Cardiology

Physical activity, long recommended by health experts to reduce risk for obesity, heart disease, type 2 diabetes, high blood pressure, hypercholesterolemia, and other cardiovascular disease risk factors, is also associated with increases in the amount of calcium deposited in the coronary arteries, new observational data suggest.

In a prospective cohort study of Korean men and women 18 years and older, participants who were the most physically active had the fastest progression of their coronary artery calcium (CAC) scores at 5 years, compared with those who were the least physically active.

“People who exercise may have an increase in their coronary calcium levels, but this is not necessarily bad news. This may mean that atherosclerotic lesions in the coronary arteries are becoming more stable and less dangerous, but we need additional research to understand these changes,” Eliseo Guallar, MD, PhD, professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, the study’s corresponding author, said in an interview.

This paradoxical effect notwithstanding, doctors should continue to advise their patients to follow the physical activity guidelines for Americans that were published in 2018, Dr. Guallar said.

“Physical activity is a key component of a healthy lifestyle. Our analysis can be useful, however, if someone starts exercising and sees that his or her coronary calcium score goes up,” he said.

The study is published online September 20 in Heart.

The degree of build-up of calcium deposits in the coronary arteries is used to determine future cardiovascular disease risk and to guide treatment to prevent myocardial infarction and stroke. A CAC score of at least 100 Agatston units indicates that treatment with statins is warranted, the researchers write.

In the current study, investigators — led by Ki-Chul Sung, MD, Sungkyunkwan University School of Medicine, Seoul, Korea, and Yun Soo Hong, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore — explored the link between different degrees of physical activity and the progression of CAC scores in healthy adults.

“While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. It is not clear if exercise may itself be associated with calcification of the arteries,” the authors write.

The researchers studied 25,485 participants (22,741 men and 2,744 women) who were part of the Kangbuk Samsung Health Study. All were free of cardiovascular disease at study entry and underwent comprehensive health screening exams at one of two major health centers in Seoul and Suwon, South Korea, between March 1, 2011, and December 31, 2017.

At each exam, participants filled out a questionnaire that included questions on medical and family history, smoking habits, alcohol intake, and education level.

Participants were also quizzed at baseline about their physical activity, using the Korean version of the International Physical Activity Questionnaire Short Form (IPAQ-SF).

On the basis of that, they were categorized into one of three categories: inactive; moderately active, defined as at least 3 days of vigorous-intensity activity for at least 20 min/day or at least 5 days of moderate-intensity activity or walking for at least 30 min/ day or at least 5 days of any combination of walking and moderate- or vigorous-intensity activities, attaining at least 600 MET-min/week; or health-enhancing physically active (HEPA), defined as at least 3 days of vigorous-intensity activity, attaining at least 1,500 MET-min/week or 7 days of any combination of walking or moderate- or vigorous-intensity activities, attaining at least 3000 MET-min/week.  

Of the study participants, 47% were classified as inactive, 38% as moderately active, and 15% as HEPA.

Those who were more physically active tended to be older and less likely to smoke than less physically active participants. They also had lower total cholesterol, more hypertension, and existing evidence of calcium deposits in their coronary arteries.

A graded association between physical activity level and the prevalence and progression of coronary artery calcification was seen, irrespective of CAC scores at the start of monitoring.

At baseline, the estimated adjusted average baseline CAC scores in inactive participants was 9.45 (95% CI, 8.76 - 10.14), in moderately active participants was 10.20 (95% CI, 9.40 - 11.00), and in HEPA participants was 12.04 (95% CI, 10.81 - 13.26).

Compared with the least active participants, the estimated adjusted 5-year average increases in CAC was 3.20 (95% CI, 0.72 - 5.69) in moderately active participants and 8.16 (95% CI, 4.80 - 11.53) in HEPA participants.

A higher level of physical activity was associated with faster progression of CAC scores, both in participants with CAC score of 0 at baseline and in those with prevalent CAC.

The authors note there are several limitations to consider when interpreting their findings. These include the absence of an objective assessment of physical activity, the inability to evaluate the association between physical activity and CAC levels with incident cardiovascular events because of a lack of data, and the lack of information on incident myocardial infarction, stroke, CAC density, or volume.

Physical activity might increase coronary atherosclerosis through mechanical stress and vessel wall injury of coronary arteries; physiologic responses during exercise, such as increased blood pressure; increased parathyroid hormone levels; and changes in coronary hemodynamics and inflammation. “In addition, other factors, such as diet, vitamins, and minerals, may change with physical activity,” the authors write.

“The second possibility is that physical activity may increase CAC scores without increasing cardiovascular disease risk,” they write.

“The cardiovascular benefits of physical activity are unquestionable,” the authors emphasize, adding that the national guidelines recommend at least 150 to 300 minutes per week of moderate-intensity or 75 to 150 minutes per week of vigorous-intensity aerobic physical activity.

“Patients and physicians, however, need to consider that engaging in physical activity may accelerate the progression of coronary calcium, possibly due to plaque healing, stabilization and calcification,” they conclude.

Dr. Guallar added: “We would like to link our research to clinical outcomes, so that we can really be sure that the increase in coronary calcium scores does not imply an increase in risk.”

“Do these findings mean that we should stop using coronary artery calcium scores to assess coronary artery disease?” ask Gaurav Gulsin, MD, and Alastair James Moss, MD, University of Leicester, United Kingdom, in an accompanying editorial.

The study highlights the complexity of interpreting CAC scores in patients who have implemented recommendations for physical activity or started statin therapy, they note.

“While proponents would argue that it is an effective tool to screen for subclinical atherosclerosis in asymptomatic individuals, clinicians should be cautious regarding the overuse of this test in otherwise healthy individuals. The coronary artery calcium paradox should not result in paradoxical care for our patients,” Dr. Gulsin and Dr. Moss conclude.

Dr. Sung, Dr. Hong, and the other study authors report no relevant financial relationships. The British Heart Foundation provides funding support for Dr. Gulsin and Dr. Moss.

A version of this article first appeared on Medscape.com.

Physical activity, long recommended by health experts to reduce risk for obesity, heart disease, type 2 diabetes, high blood pressure, hypercholesterolemia, and other cardiovascular disease risk factors, is also associated with increases in the amount of calcium deposited in the coronary arteries, new observational data suggest.

In a prospective cohort study of Korean men and women 18 years and older, participants who were the most physically active had the fastest progression of their coronary artery calcium (CAC) scores at 5 years, compared with those who were the least physically active.

“People who exercise may have an increase in their coronary calcium levels, but this is not necessarily bad news. This may mean that atherosclerotic lesions in the coronary arteries are becoming more stable and less dangerous, but we need additional research to understand these changes,” Eliseo Guallar, MD, PhD, professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, the study’s corresponding author, said in an interview.

This paradoxical effect notwithstanding, doctors should continue to advise their patients to follow the physical activity guidelines for Americans that were published in 2018, Dr. Guallar said.

“Physical activity is a key component of a healthy lifestyle. Our analysis can be useful, however, if someone starts exercising and sees that his or her coronary calcium score goes up,” he said.

The study is published online September 20 in Heart.

The degree of build-up of calcium deposits in the coronary arteries is used to determine future cardiovascular disease risk and to guide treatment to prevent myocardial infarction and stroke. A CAC score of at least 100 Agatston units indicates that treatment with statins is warranted, the researchers write.

In the current study, investigators — led by Ki-Chul Sung, MD, Sungkyunkwan University School of Medicine, Seoul, Korea, and Yun Soo Hong, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore — explored the link between different degrees of physical activity and the progression of CAC scores in healthy adults.

“While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. It is not clear if exercise may itself be associated with calcification of the arteries,” the authors write.

The researchers studied 25,485 participants (22,741 men and 2,744 women) who were part of the Kangbuk Samsung Health Study. All were free of cardiovascular disease at study entry and underwent comprehensive health screening exams at one of two major health centers in Seoul and Suwon, South Korea, between March 1, 2011, and December 31, 2017.

At each exam, participants filled out a questionnaire that included questions on medical and family history, smoking habits, alcohol intake, and education level.

Participants were also quizzed at baseline about their physical activity, using the Korean version of the International Physical Activity Questionnaire Short Form (IPAQ-SF).

On the basis of that, they were categorized into one of three categories: inactive; moderately active, defined as at least 3 days of vigorous-intensity activity for at least 20 min/day or at least 5 days of moderate-intensity activity or walking for at least 30 min/ day or at least 5 days of any combination of walking and moderate- or vigorous-intensity activities, attaining at least 600 MET-min/week; or health-enhancing physically active (HEPA), defined as at least 3 days of vigorous-intensity activity, attaining at least 1,500 MET-min/week or 7 days of any combination of walking or moderate- or vigorous-intensity activities, attaining at least 3000 MET-min/week.  

Of the study participants, 47% were classified as inactive, 38% as moderately active, and 15% as HEPA.

Those who were more physically active tended to be older and less likely to smoke than less physically active participants. They also had lower total cholesterol, more hypertension, and existing evidence of calcium deposits in their coronary arteries.

A graded association between physical activity level and the prevalence and progression of coronary artery calcification was seen, irrespective of CAC scores at the start of monitoring.

At baseline, the estimated adjusted average baseline CAC scores in inactive participants was 9.45 (95% CI, 8.76 - 10.14), in moderately active participants was 10.20 (95% CI, 9.40 - 11.00), and in HEPA participants was 12.04 (95% CI, 10.81 - 13.26).

Compared with the least active participants, the estimated adjusted 5-year average increases in CAC was 3.20 (95% CI, 0.72 - 5.69) in moderately active participants and 8.16 (95% CI, 4.80 - 11.53) in HEPA participants.

A higher level of physical activity was associated with faster progression of CAC scores, both in participants with CAC score of 0 at baseline and in those with prevalent CAC.

The authors note there are several limitations to consider when interpreting their findings. These include the absence of an objective assessment of physical activity, the inability to evaluate the association between physical activity and CAC levels with incident cardiovascular events because of a lack of data, and the lack of information on incident myocardial infarction, stroke, CAC density, or volume.

Physical activity might increase coronary atherosclerosis through mechanical stress and vessel wall injury of coronary arteries; physiologic responses during exercise, such as increased blood pressure; increased parathyroid hormone levels; and changes in coronary hemodynamics and inflammation. “In addition, other factors, such as diet, vitamins, and minerals, may change with physical activity,” the authors write.

“The second possibility is that physical activity may increase CAC scores without increasing cardiovascular disease risk,” they write.

“The cardiovascular benefits of physical activity are unquestionable,” the authors emphasize, adding that the national guidelines recommend at least 150 to 300 minutes per week of moderate-intensity or 75 to 150 minutes per week of vigorous-intensity aerobic physical activity.

“Patients and physicians, however, need to consider that engaging in physical activity may accelerate the progression of coronary calcium, possibly due to plaque healing, stabilization and calcification,” they conclude.

Dr. Guallar added: “We would like to link our research to clinical outcomes, so that we can really be sure that the increase in coronary calcium scores does not imply an increase in risk.”

“Do these findings mean that we should stop using coronary artery calcium scores to assess coronary artery disease?” ask Gaurav Gulsin, MD, and Alastair James Moss, MD, University of Leicester, United Kingdom, in an accompanying editorial.

The study highlights the complexity of interpreting CAC scores in patients who have implemented recommendations for physical activity or started statin therapy, they note.

“While proponents would argue that it is an effective tool to screen for subclinical atherosclerosis in asymptomatic individuals, clinicians should be cautious regarding the overuse of this test in otherwise healthy individuals. The coronary artery calcium paradox should not result in paradoxical care for our patients,” Dr. Gulsin and Dr. Moss conclude.

Dr. Sung, Dr. Hong, and the other study authors report no relevant financial relationships. The British Heart Foundation provides funding support for Dr. Gulsin and Dr. Moss.

A version of this article first appeared on Medscape.com.

Physical activity, long recommended by health experts to reduce risk for obesity, heart disease, type 2 diabetes, high blood pressure, hypercholesterolemia, and other cardiovascular disease risk factors, is also associated with increases in the amount of calcium deposited in the coronary arteries, new observational data suggest.

In a prospective cohort study of Korean men and women 18 years and older, participants who were the most physically active had the fastest progression of their coronary artery calcium (CAC) scores at 5 years, compared with those who were the least physically active.

“People who exercise may have an increase in their coronary calcium levels, but this is not necessarily bad news. This may mean that atherosclerotic lesions in the coronary arteries are becoming more stable and less dangerous, but we need additional research to understand these changes,” Eliseo Guallar, MD, PhD, professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, the study’s corresponding author, said in an interview.

This paradoxical effect notwithstanding, doctors should continue to advise their patients to follow the physical activity guidelines for Americans that were published in 2018, Dr. Guallar said.

“Physical activity is a key component of a healthy lifestyle. Our analysis can be useful, however, if someone starts exercising and sees that his or her coronary calcium score goes up,” he said.

The study is published online September 20 in Heart.

The degree of build-up of calcium deposits in the coronary arteries is used to determine future cardiovascular disease risk and to guide treatment to prevent myocardial infarction and stroke. A CAC score of at least 100 Agatston units indicates that treatment with statins is warranted, the researchers write.

In the current study, investigators — led by Ki-Chul Sung, MD, Sungkyunkwan University School of Medicine, Seoul, Korea, and Yun Soo Hong, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore — explored the link between different degrees of physical activity and the progression of CAC scores in healthy adults.

“While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. It is not clear if exercise may itself be associated with calcification of the arteries,” the authors write.

The researchers studied 25,485 participants (22,741 men and 2,744 women) who were part of the Kangbuk Samsung Health Study. All were free of cardiovascular disease at study entry and underwent comprehensive health screening exams at one of two major health centers in Seoul and Suwon, South Korea, between March 1, 2011, and December 31, 2017.

At each exam, participants filled out a questionnaire that included questions on medical and family history, smoking habits, alcohol intake, and education level.

Participants were also quizzed at baseline about their physical activity, using the Korean version of the International Physical Activity Questionnaire Short Form (IPAQ-SF).

On the basis of that, they were categorized into one of three categories: inactive; moderately active, defined as at least 3 days of vigorous-intensity activity for at least 20 min/day or at least 5 days of moderate-intensity activity or walking for at least 30 min/ day or at least 5 days of any combination of walking and moderate- or vigorous-intensity activities, attaining at least 600 MET-min/week; or health-enhancing physically active (HEPA), defined as at least 3 days of vigorous-intensity activity, attaining at least 1,500 MET-min/week or 7 days of any combination of walking or moderate- or vigorous-intensity activities, attaining at least 3000 MET-min/week.  

Of the study participants, 47% were classified as inactive, 38% as moderately active, and 15% as HEPA.

Those who were more physically active tended to be older and less likely to smoke than less physically active participants. They also had lower total cholesterol, more hypertension, and existing evidence of calcium deposits in their coronary arteries.

A graded association between physical activity level and the prevalence and progression of coronary artery calcification was seen, irrespective of CAC scores at the start of monitoring.

At baseline, the estimated adjusted average baseline CAC scores in inactive participants was 9.45 (95% CI, 8.76 - 10.14), in moderately active participants was 10.20 (95% CI, 9.40 - 11.00), and in HEPA participants was 12.04 (95% CI, 10.81 - 13.26).

Compared with the least active participants, the estimated adjusted 5-year average increases in CAC was 3.20 (95% CI, 0.72 - 5.69) in moderately active participants and 8.16 (95% CI, 4.80 - 11.53) in HEPA participants.

A higher level of physical activity was associated with faster progression of CAC scores, both in participants with CAC score of 0 at baseline and in those with prevalent CAC.

The authors note there are several limitations to consider when interpreting their findings. These include the absence of an objective assessment of physical activity, the inability to evaluate the association between physical activity and CAC levels with incident cardiovascular events because of a lack of data, and the lack of information on incident myocardial infarction, stroke, CAC density, or volume.

Physical activity might increase coronary atherosclerosis through mechanical stress and vessel wall injury of coronary arteries; physiologic responses during exercise, such as increased blood pressure; increased parathyroid hormone levels; and changes in coronary hemodynamics and inflammation. “In addition, other factors, such as diet, vitamins, and minerals, may change with physical activity,” the authors write.

“The second possibility is that physical activity may increase CAC scores without increasing cardiovascular disease risk,” they write.

“The cardiovascular benefits of physical activity are unquestionable,” the authors emphasize, adding that the national guidelines recommend at least 150 to 300 minutes per week of moderate-intensity or 75 to 150 minutes per week of vigorous-intensity aerobic physical activity.

“Patients and physicians, however, need to consider that engaging in physical activity may accelerate the progression of coronary calcium, possibly due to plaque healing, stabilization and calcification,” they conclude.

Dr. Guallar added: “We would like to link our research to clinical outcomes, so that we can really be sure that the increase in coronary calcium scores does not imply an increase in risk.”

“Do these findings mean that we should stop using coronary artery calcium scores to assess coronary artery disease?” ask Gaurav Gulsin, MD, and Alastair James Moss, MD, University of Leicester, United Kingdom, in an accompanying editorial.

The study highlights the complexity of interpreting CAC scores in patients who have implemented recommendations for physical activity or started statin therapy, they note.

“While proponents would argue that it is an effective tool to screen for subclinical atherosclerosis in asymptomatic individuals, clinicians should be cautious regarding the overuse of this test in otherwise healthy individuals. The coronary artery calcium paradox should not result in paradoxical care for our patients,” Dr. Gulsin and Dr. Moss conclude.

Dr. Sung, Dr. Hong, and the other study authors report no relevant financial relationships. The British Heart Foundation provides funding support for Dr. Gulsin and Dr. Moss.

A version of this article first appeared on Medscape.com.

A 4-month, structured diet and exercise intervention lowered blood pressure in adults with resistant blood pressure, according to results from a randomized, clinical trial. The program also led to improvements in baroreflex sensitivity, heart rate variability, and flow-mediated dilation, compared with individuals who received only a single education session.

The intervention included instruction from a nutritionist on how to follow the Dietary Approaches to Stop Hypertension (DASH) diet, as well as restricting calories and sodium to less than 2,300 mg/day. It included weekly, 45-minute group counseling sessions, run by a clinical psychiatrist, focusing on eating behaviors. The exercise component included 30- to 45-minute sessions at 70%-85% of initial heart rate reserve, carried out three times per week at a cardiac rehabilitation facility.

“While some individuals can make the lifestyle changes on their own, a structured program of supervised exercise and dietary modification conducted by a multidisciplinary team of physicians, psychologists, nutritionists, and physical therapists/exercise physiologists found in cardiac rehabilitation programs throughout the country is likely to be more effective. There are many cardiac rehabilitation programs throughout the country that are accessible to most patients,” said lead author James Blumenthal, PhD, the J.P. Gibbons Professor in Psychiatry and Behavioral Sciences at Duke University, Durham, N.C.

The study, called Treating Resistant Hypertension Using Lifestyle Modification to Promote Health (TRIUMPH), was published in Circulation. It is one of few that have examined lifestyle interventions in resistant hypertension, defined as systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 80 mm Hg after adherence to three or more optimally-dosed antihypertensive medications of three different classes, including one diuretic.

“This is a nice study [that] emphasizes what we often forget: Lifestyle factors, especially salt intake, are important drivers of resistant hypertension. Our own studies have shown that this is predominantly a salt retaining state, and one would expect dietary salt restriction to be particularly effective in this group of patients and that is what this study showed,” said Bryan Williams, MD, who was asked to comment on the study. Dr. Williams is chair of medicine at University College London.

The results should also be reassuring to some who worried that exercise might lead to worsened blood pressure. “This study showed that in patients with resistant hypertension, though not out of control blood pressures, exercise was not only safe, but effective in lowering their blood pressure,” said Deepak L. Bhatt, MD, MPH, who was asked to comment. He is executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, and professor of medicine at Harvard Medical School, both in Boston.

The new research isn’t unique. In August, researchers in Portugal and Brazil showed that a 12-week exercise-only intervention reduced 24-hour and daytime ambulatory systolic and diastolic blood pressure. The two studies communicate the same message. “Lifestyle changes can work for resistant hypertension. So, two independent, modest-sized studies with essentially the same, positive, actionable conclusion,” said Dr. Bhatt, adding that the next step should be a larger, multicenter trial.

In the new study, 90 patients were assigned to the diet and exercise intervention and 50 to the control group. They had a mean age of 63 years, and 48% were women. Participants attended 94% of DASH diet classes and 89% of exercise sessions, and both groups had excellent adherence to medications.

The treatment group had a greater reduction in clinic systolic BP (–12.5 versus –7.1 mm Hg; P = .005) and diastolic BP (–5.9 versus –3.7 mm Hg; P = .034), as well as 24-hour ambulatory systolic BP (–7.0 versus –0.3 mm Hg; P = .001). The treatment group also had more improvement in resting baroreflex sensitivity (2.3 versus –1.1 ms/mm Hg; P = .003), high-frequency heart rate variability (0.4 versus –0.2 ln ms²; P = .025, and flow-mediated dilation (0.3% versus –1.4%, P = .022). The two groups had similar outcomes with respect to pulse wave velocity and left ventricular mass.

“Results of the TRIUMPH study suggest that policymakers should consider resistant hypertension as a new indication for cardiac rehabilitation with appropriate coverage by governmental agencies and private insurers,” Dr. Blumenthal said.

“This is an important new, evidence-based intervention for resistant hypertension. It is safe and relatively inexpensive. It should now be something physicians routinely offer these patients. Hopefully in the future, insurers will cover cardiac rehabilitation for patients with resistant hypertension,” Dr. Bhatt said.

The study also pointed towards an effective approach for patients who may be unable to sustain lifestyle changes. “Of course, not every patient will be able to maintain a healthy diet and an exercise program on their own, thus a cardiac rehabilitation program can be an excellent way to increase the likelihood of successful lifestyle modification,” Dr. Bhatt said.

TRIUMPH was sponsored by grants from the National Heart, Lung, and Blood Institute. None of the authors had disclosures to report. Dr. Bhatt disclosed having financial relationships with more than 40 pharmaceutical companies. Dr. Williams reported having no relevant financial disclosures.
 

A 4-month, structured diet and exercise intervention lowered blood pressure in adults with resistant blood pressure, according to results from a randomized, clinical trial. The program also led to improvements in baroreflex sensitivity, heart rate variability, and flow-mediated dilation, compared with individuals who received only a single education session.

The intervention included instruction from a nutritionist on how to follow the Dietary Approaches to Stop Hypertension (DASH) diet, as well as restricting calories and sodium to less than 2,300 mg/day. It included weekly, 45-minute group counseling sessions, run by a clinical psychiatrist, focusing on eating behaviors. The exercise component included 30- to 45-minute sessions at 70%-85% of initial heart rate reserve, carried out three times per week at a cardiac rehabilitation facility.

“While some individuals can make the lifestyle changes on their own, a structured program of supervised exercise and dietary modification conducted by a multidisciplinary team of physicians, psychologists, nutritionists, and physical therapists/exercise physiologists found in cardiac rehabilitation programs throughout the country is likely to be more effective. There are many cardiac rehabilitation programs throughout the country that are accessible to most patients,” said lead author James Blumenthal, PhD, the J.P. Gibbons Professor in Psychiatry and Behavioral Sciences at Duke University, Durham, N.C.

The study, called Treating Resistant Hypertension Using Lifestyle Modification to Promote Health (TRIUMPH), was published in Circulation. It is one of few that have examined lifestyle interventions in resistant hypertension, defined as systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 80 mm Hg after adherence to three or more optimally-dosed antihypertensive medications of three different classes, including one diuretic.

“This is a nice study [that] emphasizes what we often forget: Lifestyle factors, especially salt intake, are important drivers of resistant hypertension. Our own studies have shown that this is predominantly a salt retaining state, and one would expect dietary salt restriction to be particularly effective in this group of patients and that is what this study showed,” said Bryan Williams, MD, who was asked to comment on the study. Dr. Williams is chair of medicine at University College London.

The results should also be reassuring to some who worried that exercise might lead to worsened blood pressure. “This study showed that in patients with resistant hypertension, though not out of control blood pressures, exercise was not only safe, but effective in lowering their blood pressure,” said Deepak L. Bhatt, MD, MPH, who was asked to comment. He is executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, and professor of medicine at Harvard Medical School, both in Boston.

The new research isn’t unique. In August, researchers in Portugal and Brazil showed that a 12-week exercise-only intervention reduced 24-hour and daytime ambulatory systolic and diastolic blood pressure. The two studies communicate the same message. “Lifestyle changes can work for resistant hypertension. So, two independent, modest-sized studies with essentially the same, positive, actionable conclusion,” said Dr. Bhatt, adding that the next step should be a larger, multicenter trial.

In the new study, 90 patients were assigned to the diet and exercise intervention and 50 to the control group. They had a mean age of 63 years, and 48% were women. Participants attended 94% of DASH diet classes and 89% of exercise sessions, and both groups had excellent adherence to medications.

The treatment group had a greater reduction in clinic systolic BP (–12.5 versus –7.1 mm Hg; P = .005) and diastolic BP (–5.9 versus –3.7 mm Hg; P = .034), as well as 24-hour ambulatory systolic BP (–7.0 versus –0.3 mm Hg; P = .001). The treatment group also had more improvement in resting baroreflex sensitivity (2.3 versus –1.1 ms/mm Hg; P = .003), high-frequency heart rate variability (0.4 versus –0.2 ln ms²; P = .025, and flow-mediated dilation (0.3% versus –1.4%, P = .022). The two groups had similar outcomes with respect to pulse wave velocity and left ventricular mass.

“Results of the TRIUMPH study suggest that policymakers should consider resistant hypertension as a new indication for cardiac rehabilitation with appropriate coverage by governmental agencies and private insurers,” Dr. Blumenthal said.

“This is an important new, evidence-based intervention for resistant hypertension. It is safe and relatively inexpensive. It should now be something physicians routinely offer these patients. Hopefully in the future, insurers will cover cardiac rehabilitation for patients with resistant hypertension,” Dr. Bhatt said.

The study also pointed towards an effective approach for patients who may be unable to sustain lifestyle changes. “Of course, not every patient will be able to maintain a healthy diet and an exercise program on their own, thus a cardiac rehabilitation program can be an excellent way to increase the likelihood of successful lifestyle modification,” Dr. Bhatt said.

TRIUMPH was sponsored by grants from the National Heart, Lung, and Blood Institute. None of the authors had disclosures to report. Dr. Bhatt disclosed having financial relationships with more than 40 pharmaceutical companies. Dr. Williams reported having no relevant financial disclosures.
 

A 4-month, structured diet and exercise intervention lowered blood pressure in adults with resistant blood pressure, according to results from a randomized, clinical trial. The program also led to improvements in baroreflex sensitivity, heart rate variability, and flow-mediated dilation, compared with individuals who received only a single education session.

The intervention included instruction from a nutritionist on how to follow the Dietary Approaches to Stop Hypertension (DASH) diet, as well as restricting calories and sodium to less than 2,300 mg/day. It included weekly, 45-minute group counseling sessions, run by a clinical psychiatrist, focusing on eating behaviors. The exercise component included 30- to 45-minute sessions at 70%-85% of initial heart rate reserve, carried out three times per week at a cardiac rehabilitation facility.

“While some individuals can make the lifestyle changes on their own, a structured program of supervised exercise and dietary modification conducted by a multidisciplinary team of physicians, psychologists, nutritionists, and physical therapists/exercise physiologists found in cardiac rehabilitation programs throughout the country is likely to be more effective. There are many cardiac rehabilitation programs throughout the country that are accessible to most patients,” said lead author James Blumenthal, PhD, the J.P. Gibbons Professor in Psychiatry and Behavioral Sciences at Duke University, Durham, N.C.

The study, called Treating Resistant Hypertension Using Lifestyle Modification to Promote Health (TRIUMPH), was published in Circulation. It is one of few that have examined lifestyle interventions in resistant hypertension, defined as systolic blood pressure ≥ 130 mm Hg or diastolic blood pressure ≥ 80 mm Hg after adherence to three or more optimally-dosed antihypertensive medications of three different classes, including one diuretic.

“This is a nice study [that] emphasizes what we often forget: Lifestyle factors, especially salt intake, are important drivers of resistant hypertension. Our own studies have shown that this is predominantly a salt retaining state, and one would expect dietary salt restriction to be particularly effective in this group of patients and that is what this study showed,” said Bryan Williams, MD, who was asked to comment on the study. Dr. Williams is chair of medicine at University College London.

The results should also be reassuring to some who worried that exercise might lead to worsened blood pressure. “This study showed that in patients with resistant hypertension, though not out of control blood pressures, exercise was not only safe, but effective in lowering their blood pressure,” said Deepak L. Bhatt, MD, MPH, who was asked to comment. He is executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, and professor of medicine at Harvard Medical School, both in Boston.

The new research isn’t unique. In August, researchers in Portugal and Brazil showed that a 12-week exercise-only intervention reduced 24-hour and daytime ambulatory systolic and diastolic blood pressure. The two studies communicate the same message. “Lifestyle changes can work for resistant hypertension. So, two independent, modest-sized studies with essentially the same, positive, actionable conclusion,” said Dr. Bhatt, adding that the next step should be a larger, multicenter trial.

In the new study, 90 patients were assigned to the diet and exercise intervention and 50 to the control group. They had a mean age of 63 years, and 48% were women. Participants attended 94% of DASH diet classes and 89% of exercise sessions, and both groups had excellent adherence to medications.

The treatment group had a greater reduction in clinic systolic BP (–12.5 versus –7.1 mm Hg; P = .005) and diastolic BP (–5.9 versus –3.7 mm Hg; P = .034), as well as 24-hour ambulatory systolic BP (–7.0 versus –0.3 mm Hg; P = .001). The treatment group also had more improvement in resting baroreflex sensitivity (2.3 versus –1.1 ms/mm Hg; P = .003), high-frequency heart rate variability (0.4 versus –0.2 ln ms²; P = .025, and flow-mediated dilation (0.3% versus –1.4%, P = .022). The two groups had similar outcomes with respect to pulse wave velocity and left ventricular mass.

“Results of the TRIUMPH study suggest that policymakers should consider resistant hypertension as a new indication for cardiac rehabilitation with appropriate coverage by governmental agencies and private insurers,” Dr. Blumenthal said.

“This is an important new, evidence-based intervention for resistant hypertension. It is safe and relatively inexpensive. It should now be something physicians routinely offer these patients. Hopefully in the future, insurers will cover cardiac rehabilitation for patients with resistant hypertension,” Dr. Bhatt said.

The study also pointed towards an effective approach for patients who may be unable to sustain lifestyle changes. “Of course, not every patient will be able to maintain a healthy diet and an exercise program on their own, thus a cardiac rehabilitation program can be an excellent way to increase the likelihood of successful lifestyle modification,” Dr. Bhatt said.

TRIUMPH was sponsored by grants from the National Heart, Lung, and Blood Institute. None of the authors had disclosures to report. Dr. Bhatt disclosed having financial relationships with more than 40 pharmaceutical companies. Dr. Williams reported having no relevant financial disclosures.
 

Study Overview

Objective. To evaluate whether a digital intervention comprising self-monitoring of blood pressure (BP) with reminders and predetermined drug changes combined with lifestyle change support resulted in lower systolic BP in people receiving treatment for hypertension that was poorly controlled, and whether this approach was cost effective.

Design. Unmasked randomized controlled trial.

Settings and participants. Eligible participants were identified from clinical codes recorded in the electronic health records of 76 collaborating general practices from the National Institute for Health Research Clinical Research Network, a United Kingdom government agency. The practices sent invitation letters to eligible participants to come to the clinic to establish eligibility, take consent, and collect baseline data via online questionnaires.

Eligible participants were aged 18 years or older with treated hypertension, a mean baseline BP reading of more than 140/90 mm Hg and were taking no more than 3 antihypertensive drugs. Participants also needed to be willing to self-monitor and have access to the internet (with support from a family member if needed). Exclusions included BP greater than 180/110 mm Hg, atrial fibrillation, hypertension not managed by their general practitioner, chronic kidney disease stage 4-5, postural hypotension (> 20 mm Hg systolic drop), an acute cardiovascular event in the previous 3 months, terminal disease, or another condition which in the opinion of their general practitioner made participation inappropriate.

Of the 11 399 invitation letters sent out, 1389 (12%) potential participants responded positively and were screened for eligibility. Those who declined to take part could optionally give their reasons, and responses were gained from 2426 of 10 010 (24%). The mean age of those who gave a reason for declining was 73 years. The most commonly selected reasons for declining were not having access to the internet (982, 41%), not wanting to participate in a research trial (617, 25%) or an internet study (543, 22%), and not wanting to change drugs (535, 22%). Of the 1389 screened, 734 were ineligible, and 33 did not complete baseline measures and randomization. The remaining 622 people who were randomized in a 1:1 ratio to receive the HOME BP intervention (n = 305) or usual care (n = 317).

Intervention vs usual care. The HOME BP intervention for the self-management of high BP consisted of an integrated patient and health care practitioner online digital intervention, BP self-monitoring (using an Omron M3 monitor), health care practitioner directed and supervised titration of antihypertensive drugs, and user-selected lifestyle modifications. Participants were advised via automated email reminders to take 2 morning BP readings for 7 days each month and to enter online each second reading. Mean home BP was calculated, accompanied by feedback of BP results to both patients and professionals with optional evidence-based lifestyle advice (for healthy eating, physical activity, losing weight if appropriate, and salt and alcohol reduction) and motivational support through practice nurses or health care assistances (using the CARE approach – congratulate, ask, reassure, encourage).

Participants allocated to usual care were not provided with self-monitoring equipment or the HOME BP intervention but had online access to the information provided in a patient leaflet for hypertension. This information comprised definitions of hypertension, causes, and brief guidance on treatment, including lifestyle changes and drugs. These participants received routine hypertension care that typically consisted of clinic BP monitoring to titrate drugs, with appointments and drug changes made at the discretion of the general practitioner. Participants were not prevented from self-monitoring, but data on self-monitoring practices were collected at the end of the trial from patients and practitioners.

Measures and analysis. The primary outcome measure was the difference in systolic BP at 12-month follow-up between the intervention and usual care groups (adjusting for baseline BP, practice, BP target levels, and sex). Secondary outcomes included systolic and diastolic BP at 6 and 12 months, weight, modified patient enablement instrument, drug adherence, health-related quality of life, and side effects from the symptoms section of an adjusted illness perceptions questionnaire. At trial, registration participants and general practitioners were asked about their use of self-monitoring in the usual care group.

The primary analysis used general linear modelling to compare systolic BP in the intervention and usual care groups at follow-up, adjusting for baseline BP, practice (as a random effect to take into account clustering), BP target levels, and sex. Analyses were on an intention-to-treat basis and used multiple imputation for missing data. Sensitivity analyses used complete cases and a repeated measures technique. Secondary analyses used similar techniques to assess differences between groups. A within-trial economic analysis estimated cost per unit reduction in systolic BP by using similar adjustments and multiple imputation for missing values. Repeated bootstrapping was used to estimate the probability of the intervention being cost-effective at different levels of willingness to pay per unit reduction in BP.

Main results. The intervention and usual care groups did not differ significantly – participants had a mean age of 66 years and mean baseline clinical BP of 151.6/85.3 mm Hg and 151.7/86.4 mm Hg (usual care and intervention, respectively). Most participants were White British (94%), just more than half were men, and the time since diagnosis averaged around 11 years. The most deprived group (based on the English Index of Multiple Deprivation) accounted for 63/622 (10%), with the least deprived group accounting for 326/622 (52%).

After 1 year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean BP dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic BP of −3.4 mm Hg (95% CI −6.1 to −0.8 mm Hg) and a mean difference in diastolic BP of −0.5 mm Hg (−1.9 to 0.9 mm Hg). Exploratory subgroup analyses suggested that participants aged 67 years or older had a smaller effect size than those younger than 67. Similarly, while the effect sizes in the standard and diabetes target groups were similar, those older than 80 years with a higher target of 145/85 mm Hg showed little evidence of benefit. Results for other subgroups, including sex, baseline BP, deprivation, and history of self-monitoring, were similar between groups.

Engagement with the digital intervention was high, with 281/305 (92%) participants completing the 2 core training sessions, 268/305 (88%) completing a week of practice BP readings, and 243/305 (80%) completing at least 3 weeks of BP entries. Furthermore, 214/305 (70%) were still monitoring in the last 3 months of participation. However, less than 1/3 of participants chose to register on 1 of the optional lifestyle change modules. In the usual care group, a post-hoc analysis after 12 months showed that 112/234 (47%) patients reported monitoring their own BP at home at least once per month during the trial.

The difference in mean cost per patient was £38 (US $51.30, €41.9; 95% CI £27 to £47), which along with the decrease in systolic BP, gave an incremental cost per mm Hg BP reduction of £11 (£6 to £29). Bootstrapping analysis showed the intervention had high (90%) probability of being cost-effective at willingness to pay above £20 per unit reduction. The probabilities of being cost-effective for the intervention against usual care were 87%, 93%, and 97% at thresholds of £20, £30, and £50, respectively.

Conclusion. The HOME BP digital intervention for the management of hypertension by using self-monitored BP led to better control of systolic BP after 1 year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded.

Commentary

Elevated BP, also known as hypertension, is the most important, modifiable risk factor for cardiovascular disease and mortality.¹ Clinically significant effects and improvements in mortality can be achieved with relatively small reductions in BP levels. Long-established lifestyle modifications that effectively lower BP include weight loss, reduced sodium intake, increased physical activity, and limited alcohol intake. However, motivating patients to achieve lifestyle modifications is among the most difficult aspects of managing hypertension. Importantly, for individuals taking antihypertensive medication, lifestyle modification is recommended as adjunctive therapy to reduce BP. Given that target blood pressure levels are reached for less than half of adults, novel interventions are needed to improve BP control – in particular, individualized cognitive behavioral interventions are more likely to be effective than standardized, single-component interventions.

Guided self-management for hypertension as part of systematic, planned care offers the potential for improvements in adherence and in turn improved long-term patient outcomes.² Self-management can encompass a wide range of behaviors in addition to medication titration and monitoring of symptoms, such as individuals’ ability to manage physical, psychosocial and lifestyle behaviors related to their condition.³ Digital interventions leveraging apps, software, and/or technologies in particular have the potential to support people in self-management, allow for remote monitoring, and enable personalized and adaptive strategies for chronic disease management.^4-5 An example of a digital intervention in the context of guided self-management for hypertension can be a web-based program delivered by computer or phone that combines health information with decision support to help inform behavior change in patients and remote monitoring of patient status by health professionals. Well-designed digital interventions can effectively change patient health-related behaviors, improve patient knowledge and confidence for self-management of health, and lead to better health outcomes.^6-7

This study adds to the literature as a large, randomized controlled trial evaluating the effectiveness of a digital intervention in the field of hypertension and with follow-up for a year. The authors highlight that relatively few studies have been performed that combine self-monitoring with a digitally delivered cointervention, and none has shown a major effect in an adequately powered trial over a year. Results from this study showed that HOME BP, a digital intervention enabling self-management of hypertension, including self-monitoring, titration based on self-monitored BP, lifestyle advice, and behavioral support for patients and health care professionals, resulted in a worthwhile reduction of systolic BP. In addition, this reduction was achieved at modest cost based on the within trial cost effectiveness analysis.

There are many important strengths of this study, especially related to the design and analysis strategy, and some limitations. This study was designed as a randomized controlled trial with a 1 year follow-up period, although participants were unmasked to the group they were randomized to, which may have impacted their behaviors while in the study. As the authors state, the study was not only adequately powered to detect a difference in blood pressure, but also over-recruitment ensured such an effect was not missed. Recruiting from a large number of general practices ensured generalizability in terms of health care professionals. Importantly, while study participants mostly identified as predominantly White and tended to be of higher socioeconomic status, this is representative of the aged population in England and Wales. Nevertheless, generalizability of findings from this study is still limited to the demographic characteristics of the study population. Other strengths included inclusion of intention-to-treat analysis, multiple imputation for missing data, sensitivity analysis, as well as economic analysis and cost effectiveness analysis.

Of note, results from the study are only attributable to the digital interventions used in this study (digital web-based with limited mechanisms of behavior change and engagement built-in) and thus should not be generalized to all digital interventions for managing hypertension. Also, as the authors highlight, the relative importance of the different parts of the digital intervention were unable to be distinguished, although this type of analysis is important in multicomponent interventions to better understand the most effective mechanism impacting change in the primary outcome.

Applications for Clinical Practice

Results of this study demonstrated that among participants being treated with hypertension, those engaged with the HOME BP digital intervention (combining self-monitoring of blood pressure with guided self-management) had better control of systolic BP after 1 year compared to participants receiving usual care. While these findings have important implications in the management of hypertension in health care systems, its integration into clinical workflow, sustainability, long-term clinical effectiveness, and effectiveness among diverse populations is unclear. However, clinicians can still encourage and support the use of evidence-based digital tools for patient self-monitoring of BP and guided-management of lifestyle modifications to lower BP. Additionally, clinicians can proactively propose incorporating evidence-based digital interventions like HOME BP into routine clinical practice guidelines.

Financial disclosures: None.

Study Overview

Objective. To evaluate whether a digital intervention comprising self-monitoring of blood pressure (BP) with reminders and predetermined drug changes combined with lifestyle change support resulted in lower systolic BP in people receiving treatment for hypertension that was poorly controlled, and whether this approach was cost effective.

Design. Unmasked randomized controlled trial.

Settings and participants. Eligible participants were identified from clinical codes recorded in the electronic health records of 76 collaborating general practices from the National Institute for Health Research Clinical Research Network, a United Kingdom government agency. The practices sent invitation letters to eligible participants to come to the clinic to establish eligibility, take consent, and collect baseline data via online questionnaires.

Eligible participants were aged 18 years or older with treated hypertension, a mean baseline BP reading of more than 140/90 mm Hg and were taking no more than 3 antihypertensive drugs. Participants also needed to be willing to self-monitor and have access to the internet (with support from a family member if needed). Exclusions included BP greater than 180/110 mm Hg, atrial fibrillation, hypertension not managed by their general practitioner, chronic kidney disease stage 4-5, postural hypotension (> 20 mm Hg systolic drop), an acute cardiovascular event in the previous 3 months, terminal disease, or another condition which in the opinion of their general practitioner made participation inappropriate.

Of the 11 399 invitation letters sent out, 1389 (12%) potential participants responded positively and were screened for eligibility. Those who declined to take part could optionally give their reasons, and responses were gained from 2426 of 10 010 (24%). The mean age of those who gave a reason for declining was 73 years. The most commonly selected reasons for declining were not having access to the internet (982, 41%), not wanting to participate in a research trial (617, 25%) or an internet study (543, 22%), and not wanting to change drugs (535, 22%). Of the 1389 screened, 734 were ineligible, and 33 did not complete baseline measures and randomization. The remaining 622 people who were randomized in a 1:1 ratio to receive the HOME BP intervention (n = 305) or usual care (n = 317).

Intervention vs usual care. The HOME BP intervention for the self-management of high BP consisted of an integrated patient and health care practitioner online digital intervention, BP self-monitoring (using an Omron M3 monitor), health care practitioner directed and supervised titration of antihypertensive drugs, and user-selected lifestyle modifications. Participants were advised via automated email reminders to take 2 morning BP readings for 7 days each month and to enter online each second reading. Mean home BP was calculated, accompanied by feedback of BP results to both patients and professionals with optional evidence-based lifestyle advice (for healthy eating, physical activity, losing weight if appropriate, and salt and alcohol reduction) and motivational support through practice nurses or health care assistances (using the CARE approach – congratulate, ask, reassure, encourage).

Participants allocated to usual care were not provided with self-monitoring equipment or the HOME BP intervention but had online access to the information provided in a patient leaflet for hypertension. This information comprised definitions of hypertension, causes, and brief guidance on treatment, including lifestyle changes and drugs. These participants received routine hypertension care that typically consisted of clinic BP monitoring to titrate drugs, with appointments and drug changes made at the discretion of the general practitioner. Participants were not prevented from self-monitoring, but data on self-monitoring practices were collected at the end of the trial from patients and practitioners.

Measures and analysis. The primary outcome measure was the difference in systolic BP at 12-month follow-up between the intervention and usual care groups (adjusting for baseline BP, practice, BP target levels, and sex). Secondary outcomes included systolic and diastolic BP at 6 and 12 months, weight, modified patient enablement instrument, drug adherence, health-related quality of life, and side effects from the symptoms section of an adjusted illness perceptions questionnaire. At trial, registration participants and general practitioners were asked about their use of self-monitoring in the usual care group.

The primary analysis used general linear modelling to compare systolic BP in the intervention and usual care groups at follow-up, adjusting for baseline BP, practice (as a random effect to take into account clustering), BP target levels, and sex. Analyses were on an intention-to-treat basis and used multiple imputation for missing data. Sensitivity analyses used complete cases and a repeated measures technique. Secondary analyses used similar techniques to assess differences between groups. A within-trial economic analysis estimated cost per unit reduction in systolic BP by using similar adjustments and multiple imputation for missing values. Repeated bootstrapping was used to estimate the probability of the intervention being cost-effective at different levels of willingness to pay per unit reduction in BP.

Main results. The intervention and usual care groups did not differ significantly – participants had a mean age of 66 years and mean baseline clinical BP of 151.6/85.3 mm Hg and 151.7/86.4 mm Hg (usual care and intervention, respectively). Most participants were White British (94%), just more than half were men, and the time since diagnosis averaged around 11 years. The most deprived group (based on the English Index of Multiple Deprivation) accounted for 63/622 (10%), with the least deprived group accounting for 326/622 (52%).

After 1 year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean BP dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic BP of −3.4 mm Hg (95% CI −6.1 to −0.8 mm Hg) and a mean difference in diastolic BP of −0.5 mm Hg (−1.9 to 0.9 mm Hg). Exploratory subgroup analyses suggested that participants aged 67 years or older had a smaller effect size than those younger than 67. Similarly, while the effect sizes in the standard and diabetes target groups were similar, those older than 80 years with a higher target of 145/85 mm Hg showed little evidence of benefit. Results for other subgroups, including sex, baseline BP, deprivation, and history of self-monitoring, were similar between groups.

Engagement with the digital intervention was high, with 281/305 (92%) participants completing the 2 core training sessions, 268/305 (88%) completing a week of practice BP readings, and 243/305 (80%) completing at least 3 weeks of BP entries. Furthermore, 214/305 (70%) were still monitoring in the last 3 months of participation. However, less than 1/3 of participants chose to register on 1 of the optional lifestyle change modules. In the usual care group, a post-hoc analysis after 12 months showed that 112/234 (47%) patients reported monitoring their own BP at home at least once per month during the trial.

The difference in mean cost per patient was £38 (US $51.30, €41.9; 95% CI £27 to £47), which along with the decrease in systolic BP, gave an incremental cost per mm Hg BP reduction of £11 (£6 to £29). Bootstrapping analysis showed the intervention had high (90%) probability of being cost-effective at willingness to pay above £20 per unit reduction. The probabilities of being cost-effective for the intervention against usual care were 87%, 93%, and 97% at thresholds of £20, £30, and £50, respectively.

Conclusion. The HOME BP digital intervention for the management of hypertension by using self-monitored BP led to better control of systolic BP after 1 year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded.

Commentary

Elevated BP, also known as hypertension, is the most important, modifiable risk factor for cardiovascular disease and mortality.¹ Clinically significant effects and improvements in mortality can be achieved with relatively small reductions in BP levels. Long-established lifestyle modifications that effectively lower BP include weight loss, reduced sodium intake, increased physical activity, and limited alcohol intake. However, motivating patients to achieve lifestyle modifications is among the most difficult aspects of managing hypertension. Importantly, for individuals taking antihypertensive medication, lifestyle modification is recommended as adjunctive therapy to reduce BP. Given that target blood pressure levels are reached for less than half of adults, novel interventions are needed to improve BP control – in particular, individualized cognitive behavioral interventions are more likely to be effective than standardized, single-component interventions.

Guided self-management for hypertension as part of systematic, planned care offers the potential for improvements in adherence and in turn improved long-term patient outcomes.² Self-management can encompass a wide range of behaviors in addition to medication titration and monitoring of symptoms, such as individuals’ ability to manage physical, psychosocial and lifestyle behaviors related to their condition.³ Digital interventions leveraging apps, software, and/or technologies in particular have the potential to support people in self-management, allow for remote monitoring, and enable personalized and adaptive strategies for chronic disease management.^4-5 An example of a digital intervention in the context of guided self-management for hypertension can be a web-based program delivered by computer or phone that combines health information with decision support to help inform behavior change in patients and remote monitoring of patient status by health professionals. Well-designed digital interventions can effectively change patient health-related behaviors, improve patient knowledge and confidence for self-management of health, and lead to better health outcomes.^6-7

This study adds to the literature as a large, randomized controlled trial evaluating the effectiveness of a digital intervention in the field of hypertension and with follow-up for a year. The authors highlight that relatively few studies have been performed that combine self-monitoring with a digitally delivered cointervention, and none has shown a major effect in an adequately powered trial over a year. Results from this study showed that HOME BP, a digital intervention enabling self-management of hypertension, including self-monitoring, titration based on self-monitored BP, lifestyle advice, and behavioral support for patients and health care professionals, resulted in a worthwhile reduction of systolic BP. In addition, this reduction was achieved at modest cost based on the within trial cost effectiveness analysis.

There are many important strengths of this study, especially related to the design and analysis strategy, and some limitations. This study was designed as a randomized controlled trial with a 1 year follow-up period, although participants were unmasked to the group they were randomized to, which may have impacted their behaviors while in the study. As the authors state, the study was not only adequately powered to detect a difference in blood pressure, but also over-recruitment ensured such an effect was not missed. Recruiting from a large number of general practices ensured generalizability in terms of health care professionals. Importantly, while study participants mostly identified as predominantly White and tended to be of higher socioeconomic status, this is representative of the aged population in England and Wales. Nevertheless, generalizability of findings from this study is still limited to the demographic characteristics of the study population. Other strengths included inclusion of intention-to-treat analysis, multiple imputation for missing data, sensitivity analysis, as well as economic analysis and cost effectiveness analysis.

Of note, results from the study are only attributable to the digital interventions used in this study (digital web-based with limited mechanisms of behavior change and engagement built-in) and thus should not be generalized to all digital interventions for managing hypertension. Also, as the authors highlight, the relative importance of the different parts of the digital intervention were unable to be distinguished, although this type of analysis is important in multicomponent interventions to better understand the most effective mechanism impacting change in the primary outcome.

Applications for Clinical Practice

Results of this study demonstrated that among participants being treated with hypertension, those engaged with the HOME BP digital intervention (combining self-monitoring of blood pressure with guided self-management) had better control of systolic BP after 1 year compared to participants receiving usual care. While these findings have important implications in the management of hypertension in health care systems, its integration into clinical workflow, sustainability, long-term clinical effectiveness, and effectiveness among diverse populations is unclear. However, clinicians can still encourage and support the use of evidence-based digital tools for patient self-monitoring of BP and guided-management of lifestyle modifications to lower BP. Additionally, clinicians can proactively propose incorporating evidence-based digital interventions like HOME BP into routine clinical practice guidelines.

Financial disclosures: None.

Study Overview

Objective. To evaluate whether a digital intervention comprising self-monitoring of blood pressure (BP) with reminders and predetermined drug changes combined with lifestyle change support resulted in lower systolic BP in people receiving treatment for hypertension that was poorly controlled, and whether this approach was cost effective.

Design. Unmasked randomized controlled trial.

Settings and participants. Eligible participants were identified from clinical codes recorded in the electronic health records of 76 collaborating general practices from the National Institute for Health Research Clinical Research Network, a United Kingdom government agency. The practices sent invitation letters to eligible participants to come to the clinic to establish eligibility, take consent, and collect baseline data via online questionnaires.

Eligible participants were aged 18 years or older with treated hypertension, a mean baseline BP reading of more than 140/90 mm Hg and were taking no more than 3 antihypertensive drugs. Participants also needed to be willing to self-monitor and have access to the internet (with support from a family member if needed). Exclusions included BP greater than 180/110 mm Hg, atrial fibrillation, hypertension not managed by their general practitioner, chronic kidney disease stage 4-5, postural hypotension (> 20 mm Hg systolic drop), an acute cardiovascular event in the previous 3 months, terminal disease, or another condition which in the opinion of their general practitioner made participation inappropriate.

Of the 11 399 invitation letters sent out, 1389 (12%) potential participants responded positively and were screened for eligibility. Those who declined to take part could optionally give their reasons, and responses were gained from 2426 of 10 010 (24%). The mean age of those who gave a reason for declining was 73 years. The most commonly selected reasons for declining were not having access to the internet (982, 41%), not wanting to participate in a research trial (617, 25%) or an internet study (543, 22%), and not wanting to change drugs (535, 22%). Of the 1389 screened, 734 were ineligible, and 33 did not complete baseline measures and randomization. The remaining 622 people who were randomized in a 1:1 ratio to receive the HOME BP intervention (n = 305) or usual care (n = 317).

Intervention vs usual care. The HOME BP intervention for the self-management of high BP consisted of an integrated patient and health care practitioner online digital intervention, BP self-monitoring (using an Omron M3 monitor), health care practitioner directed and supervised titration of antihypertensive drugs, and user-selected lifestyle modifications. Participants were advised via automated email reminders to take 2 morning BP readings for 7 days each month and to enter online each second reading. Mean home BP was calculated, accompanied by feedback of BP results to both patients and professionals with optional evidence-based lifestyle advice (for healthy eating, physical activity, losing weight if appropriate, and salt and alcohol reduction) and motivational support through practice nurses or health care assistances (using the CARE approach – congratulate, ask, reassure, encourage).

Participants allocated to usual care were not provided with self-monitoring equipment or the HOME BP intervention but had online access to the information provided in a patient leaflet for hypertension. This information comprised definitions of hypertension, causes, and brief guidance on treatment, including lifestyle changes and drugs. These participants received routine hypertension care that typically consisted of clinic BP monitoring to titrate drugs, with appointments and drug changes made at the discretion of the general practitioner. Participants were not prevented from self-monitoring, but data on self-monitoring practices were collected at the end of the trial from patients and practitioners.

Measures and analysis. The primary outcome measure was the difference in systolic BP at 12-month follow-up between the intervention and usual care groups (adjusting for baseline BP, practice, BP target levels, and sex). Secondary outcomes included systolic and diastolic BP at 6 and 12 months, weight, modified patient enablement instrument, drug adherence, health-related quality of life, and side effects from the symptoms section of an adjusted illness perceptions questionnaire. At trial, registration participants and general practitioners were asked about their use of self-monitoring in the usual care group.

The primary analysis used general linear modelling to compare systolic BP in the intervention and usual care groups at follow-up, adjusting for baseline BP, practice (as a random effect to take into account clustering), BP target levels, and sex. Analyses were on an intention-to-treat basis and used multiple imputation for missing data. Sensitivity analyses used complete cases and a repeated measures technique. Secondary analyses used similar techniques to assess differences between groups. A within-trial economic analysis estimated cost per unit reduction in systolic BP by using similar adjustments and multiple imputation for missing values. Repeated bootstrapping was used to estimate the probability of the intervention being cost-effective at different levels of willingness to pay per unit reduction in BP.

Main results. The intervention and usual care groups did not differ significantly – participants had a mean age of 66 years and mean baseline clinical BP of 151.6/85.3 mm Hg and 151.7/86.4 mm Hg (usual care and intervention, respectively). Most participants were White British (94%), just more than half were men, and the time since diagnosis averaged around 11 years. The most deprived group (based on the English Index of Multiple Deprivation) accounted for 63/622 (10%), with the least deprived group accounting for 326/622 (52%).

After 1 year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean BP dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic BP of −3.4 mm Hg (95% CI −6.1 to −0.8 mm Hg) and a mean difference in diastolic BP of −0.5 mm Hg (−1.9 to 0.9 mm Hg). Exploratory subgroup analyses suggested that participants aged 67 years or older had a smaller effect size than those younger than 67. Similarly, while the effect sizes in the standard and diabetes target groups were similar, those older than 80 years with a higher target of 145/85 mm Hg showed little evidence of benefit. Results for other subgroups, including sex, baseline BP, deprivation, and history of self-monitoring, were similar between groups.

Engagement with the digital intervention was high, with 281/305 (92%) participants completing the 2 core training sessions, 268/305 (88%) completing a week of practice BP readings, and 243/305 (80%) completing at least 3 weeks of BP entries. Furthermore, 214/305 (70%) were still monitoring in the last 3 months of participation. However, less than 1/3 of participants chose to register on 1 of the optional lifestyle change modules. In the usual care group, a post-hoc analysis after 12 months showed that 112/234 (47%) patients reported monitoring their own BP at home at least once per month during the trial.

The difference in mean cost per patient was £38 (US $51.30, €41.9; 95% CI £27 to £47), which along with the decrease in systolic BP, gave an incremental cost per mm Hg BP reduction of £11 (£6 to £29). Bootstrapping analysis showed the intervention had high (90%) probability of being cost-effective at willingness to pay above £20 per unit reduction. The probabilities of being cost-effective for the intervention against usual care were 87%, 93%, and 97% at thresholds of £20, £30, and £50, respectively.

Conclusion. The HOME BP digital intervention for the management of hypertension by using self-monitored BP led to better control of systolic BP after 1 year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded.

Commentary

Elevated BP, also known as hypertension, is the most important, modifiable risk factor for cardiovascular disease and mortality.¹ Clinically significant effects and improvements in mortality can be achieved with relatively small reductions in BP levels. Long-established lifestyle modifications that effectively lower BP include weight loss, reduced sodium intake, increased physical activity, and limited alcohol intake. However, motivating patients to achieve lifestyle modifications is among the most difficult aspects of managing hypertension. Importantly, for individuals taking antihypertensive medication, lifestyle modification is recommended as adjunctive therapy to reduce BP. Given that target blood pressure levels are reached for less than half of adults, novel interventions are needed to improve BP control – in particular, individualized cognitive behavioral interventions are more likely to be effective than standardized, single-component interventions.

Guided self-management for hypertension as part of systematic, planned care offers the potential for improvements in adherence and in turn improved long-term patient outcomes.² Self-management can encompass a wide range of behaviors in addition to medication titration and monitoring of symptoms, such as individuals’ ability to manage physical, psychosocial and lifestyle behaviors related to their condition.³ Digital interventions leveraging apps, software, and/or technologies in particular have the potential to support people in self-management, allow for remote monitoring, and enable personalized and adaptive strategies for chronic disease management.^4-5 An example of a digital intervention in the context of guided self-management for hypertension can be a web-based program delivered by computer or phone that combines health information with decision support to help inform behavior change in patients and remote monitoring of patient status by health professionals. Well-designed digital interventions can effectively change patient health-related behaviors, improve patient knowledge and confidence for self-management of health, and lead to better health outcomes.^6-7

This study adds to the literature as a large, randomized controlled trial evaluating the effectiveness of a digital intervention in the field of hypertension and with follow-up for a year. The authors highlight that relatively few studies have been performed that combine self-monitoring with a digitally delivered cointervention, and none has shown a major effect in an adequately powered trial over a year. Results from this study showed that HOME BP, a digital intervention enabling self-management of hypertension, including self-monitoring, titration based on self-monitored BP, lifestyle advice, and behavioral support for patients and health care professionals, resulted in a worthwhile reduction of systolic BP. In addition, this reduction was achieved at modest cost based on the within trial cost effectiveness analysis.

There are many important strengths of this study, especially related to the design and analysis strategy, and some limitations. This study was designed as a randomized controlled trial with a 1 year follow-up period, although participants were unmasked to the group they were randomized to, which may have impacted their behaviors while in the study. As the authors state, the study was not only adequately powered to detect a difference in blood pressure, but also over-recruitment ensured such an effect was not missed. Recruiting from a large number of general practices ensured generalizability in terms of health care professionals. Importantly, while study participants mostly identified as predominantly White and tended to be of higher socioeconomic status, this is representative of the aged population in England and Wales. Nevertheless, generalizability of findings from this study is still limited to the demographic characteristics of the study population. Other strengths included inclusion of intention-to-treat analysis, multiple imputation for missing data, sensitivity analysis, as well as economic analysis and cost effectiveness analysis.

Of note, results from the study are only attributable to the digital interventions used in this study (digital web-based with limited mechanisms of behavior change and engagement built-in) and thus should not be generalized to all digital interventions for managing hypertension. Also, as the authors highlight, the relative importance of the different parts of the digital intervention were unable to be distinguished, although this type of analysis is important in multicomponent interventions to better understand the most effective mechanism impacting change in the primary outcome.

Applications for Clinical Practice

Results of this study demonstrated that among participants being treated with hypertension, those engaged with the HOME BP digital intervention (combining self-monitoring of blood pressure with guided self-management) had better control of systolic BP after 1 year compared to participants receiving usual care. While these findings have important implications in the management of hypertension in health care systems, its integration into clinical workflow, sustainability, long-term clinical effectiveness, and effectiveness among diverse populations is unclear. However, clinicians can still encourage and support the use of evidence-based digital tools for patient self-monitoring of BP and guided-management of lifestyle modifications to lower BP. Additionally, clinicians can proactively propose incorporating evidence-based digital interventions like HOME BP into routine clinical practice guidelines.

Financial disclosures: None.

Traumatic experiences, especially sexual assault, may put women at greater risk for poor brain health.

In the Ms Brain study, middle-aged women with trauma exposure had a greater volume of white matter hyperintensities (WMHs) than those without trauma. In addition, the differences persisted even after adjusting for depressive or post-traumatic stress symptoms. 

WMHs are “an important indicator of small vessel disease in the brain and have been linked to future stroke risk, dementia risk, and mortality,” lead investigator Rebecca Thurston, PhD, from the University of Pittsburgh, told this news organization.

“What I take from this is, really, that sexual assault has implications for women’s health, far beyond exclusively mental health outcomes, but also for their cardiovascular health, as we have shown in other work and for their stroke and dementia risk as we are seeing in the present work,” Dr. Thurston added.

The study was presented at the North American Menopause Society (NAMS) Annual Meeting in Washington, D.C., and has been accepted for publication in the journal Brain Imaging and Behavior.
 

Beyond the usual suspects

As part of the study, 145 women (mean age, 59 years) free of clinical cardiovascular disease, stroke, or dementia provided their medical history, including history of traumatic experiences, depression, and post-traumatic stress disorder and underwent magnetic resonance brain imaging for WMHs.

More than two-thirds (68%) of the women reported at least one trauma, most commonly sexual assault (23%).

In multivariate analysis, women with trauma exposure had greater WMH volume than women without trauma (P = .01), with sexual assault most strongly associated with greater WMH volume (P = .02).

The associations persisted after adjusting for depressive or post-traumatic stress symptoms.

“A history of sexual assault was particularly related to white matter hyperintensities in the parietal lobe, and these kinds of white matter hyperintensities have been linked to Alzheimer’s disease in a fairly pronounced way,” Dr. Thurston said.

“When we think about risk factors for stroke, dementia, we need to think beyond exclusively our usual suspects and also think about women [who experienced] psychological trauma and experienced sexual assault in particular. So ask about it and consider it part of your screening regimen,” she added.
 

‘Burgeoning’ literature

Commenting on the findings, Charles Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, Dell Medical School, University of Texas at Austin, and director of its Institute for Early Life Adversity Research, said the research adds to the “burgeoning literature on the long term neurobiological consequences of trauma and more specifically, sexual abuse, on brain imaging measures.”

“Our group and others reported several years ago that patients with mood disorders, more specifically bipolar disorder and major depression, had higher rates of WMH than matched controls. Those older studies did not control for a history of early life adversity such as childhood maltreatment,” Dr. Nemeroff said.

“In addition to this finding of increased WMH in subjects exposed to trauma is a very large literature documenting other central nervous system (CNS) changes in this population, including cortical thinning in certain brain areas and clearly an emerging finding that different forms of childhood maltreatment are associated with quite distinct structural brain alterations in adulthood,” he noted. 

The study was supported by grants from the National Institutes of Health. Dr. Thurston and Dr. Nemeroff have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Traumatic experiences, especially sexual assault, may put women at greater risk for poor brain health.

In the Ms Brain study, middle-aged women with trauma exposure had a greater volume of white matter hyperintensities (WMHs) than those without trauma. In addition, the differences persisted even after adjusting for depressive or post-traumatic stress symptoms. 

WMHs are “an important indicator of small vessel disease in the brain and have been linked to future stroke risk, dementia risk, and mortality,” lead investigator Rebecca Thurston, PhD, from the University of Pittsburgh, told this news organization.

“What I take from this is, really, that sexual assault has implications for women’s health, far beyond exclusively mental health outcomes, but also for their cardiovascular health, as we have shown in other work and for their stroke and dementia risk as we are seeing in the present work,” Dr. Thurston added.

The study was presented at the North American Menopause Society (NAMS) Annual Meeting in Washington, D.C., and has been accepted for publication in the journal Brain Imaging and Behavior.
 

Beyond the usual suspects

As part of the study, 145 women (mean age, 59 years) free of clinical cardiovascular disease, stroke, or dementia provided their medical history, including history of traumatic experiences, depression, and post-traumatic stress disorder and underwent magnetic resonance brain imaging for WMHs.

More than two-thirds (68%) of the women reported at least one trauma, most commonly sexual assault (23%).

In multivariate analysis, women with trauma exposure had greater WMH volume than women without trauma (P = .01), with sexual assault most strongly associated with greater WMH volume (P = .02).

The associations persisted after adjusting for depressive or post-traumatic stress symptoms.

“A history of sexual assault was particularly related to white matter hyperintensities in the parietal lobe, and these kinds of white matter hyperintensities have been linked to Alzheimer’s disease in a fairly pronounced way,” Dr. Thurston said.

“When we think about risk factors for stroke, dementia, we need to think beyond exclusively our usual suspects and also think about women [who experienced] psychological trauma and experienced sexual assault in particular. So ask about it and consider it part of your screening regimen,” she added.
 

‘Burgeoning’ literature

Commenting on the findings, Charles Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, Dell Medical School, University of Texas at Austin, and director of its Institute for Early Life Adversity Research, said the research adds to the “burgeoning literature on the long term neurobiological consequences of trauma and more specifically, sexual abuse, on brain imaging measures.”

“Our group and others reported several years ago that patients with mood disorders, more specifically bipolar disorder and major depression, had higher rates of WMH than matched controls. Those older studies did not control for a history of early life adversity such as childhood maltreatment,” Dr. Nemeroff said.

“In addition to this finding of increased WMH in subjects exposed to trauma is a very large literature documenting other central nervous system (CNS) changes in this population, including cortical thinning in certain brain areas and clearly an emerging finding that different forms of childhood maltreatment are associated with quite distinct structural brain alterations in adulthood,” he noted. 

The study was supported by grants from the National Institutes of Health. Dr. Thurston and Dr. Nemeroff have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Traumatic experiences, especially sexual assault, may put women at greater risk for poor brain health.

In the Ms Brain study, middle-aged women with trauma exposure had a greater volume of white matter hyperintensities (WMHs) than those without trauma. In addition, the differences persisted even after adjusting for depressive or post-traumatic stress symptoms. 

WMHs are “an important indicator of small vessel disease in the brain and have been linked to future stroke risk, dementia risk, and mortality,” lead investigator Rebecca Thurston, PhD, from the University of Pittsburgh, told this news organization.

“What I take from this is, really, that sexual assault has implications for women’s health, far beyond exclusively mental health outcomes, but also for their cardiovascular health, as we have shown in other work and for their stroke and dementia risk as we are seeing in the present work,” Dr. Thurston added.

The study was presented at the North American Menopause Society (NAMS) Annual Meeting in Washington, D.C., and has been accepted for publication in the journal Brain Imaging and Behavior.
 

Beyond the usual suspects

As part of the study, 145 women (mean age, 59 years) free of clinical cardiovascular disease, stroke, or dementia provided their medical history, including history of traumatic experiences, depression, and post-traumatic stress disorder and underwent magnetic resonance brain imaging for WMHs.

More than two-thirds (68%) of the women reported at least one trauma, most commonly sexual assault (23%).

In multivariate analysis, women with trauma exposure had greater WMH volume than women without trauma (P = .01), with sexual assault most strongly associated with greater WMH volume (P = .02).

The associations persisted after adjusting for depressive or post-traumatic stress symptoms.

“A history of sexual assault was particularly related to white matter hyperintensities in the parietal lobe, and these kinds of white matter hyperintensities have been linked to Alzheimer’s disease in a fairly pronounced way,” Dr. Thurston said.

“When we think about risk factors for stroke, dementia, we need to think beyond exclusively our usual suspects and also think about women [who experienced] psychological trauma and experienced sexual assault in particular. So ask about it and consider it part of your screening regimen,” she added.
 

‘Burgeoning’ literature

Commenting on the findings, Charles Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, Dell Medical School, University of Texas at Austin, and director of its Institute for Early Life Adversity Research, said the research adds to the “burgeoning literature on the long term neurobiological consequences of trauma and more specifically, sexual abuse, on brain imaging measures.”

“Our group and others reported several years ago that patients with mood disorders, more specifically bipolar disorder and major depression, had higher rates of WMH than matched controls. Those older studies did not control for a history of early life adversity such as childhood maltreatment,” Dr. Nemeroff said.

“In addition to this finding of increased WMH in subjects exposed to trauma is a very large literature documenting other central nervous system (CNS) changes in this population, including cortical thinning in certain brain areas and clearly an emerging finding that different forms of childhood maltreatment are associated with quite distinct structural brain alterations in adulthood,” he noted. 

The study was supported by grants from the National Institutes of Health. Dr. Thurston and Dr. Nemeroff have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A large multicenter study provides further evidence supporting the rationale for multidisciplinary teams for cardiogenic shock, one of the most lethal diseases in cardiovascular medicine.

The analysis of 24 critical care ICUs in the Critical Care Cardiology Trials Network showed that the presence of a shock team was independently associated with a 28% lower risk for CICU mortality (23% vs. 29%; odds ratio, 0.72; P = .016).

Patients treated by a shock team also had significantly shorter CICU stays and less need for mechanical ventilation or renal replacement therapy, as reported in the Journal of the American College of Cardiology.

“It’s observational, but the association that we’re seeing here, just because of our sample size, is the strongest that’s been published yet,” lead author Alexander Papolos, MD, MedStar Washington Hospital Center, said in an interview.

Although a causal relationship cannot be drawn, the authors suggest several factors that could explain the findings, including a shock team’s ability to rapidly diagnose and treat cardiogenic shock before multiorgan dysfunction occurs.

Centers with shock teams also used significantly more pulmonary artery catheters (60% vs. 49%; adjusted OR, 1.86; P < .001) and placed them earlier (0.3 vs. 0.66 days; P = .019).

Pulmonary artery catheter (PAC) use has declined after earlier trials like ESCAPE showed little or no benefit in other acutely ill patient groups, but positive results have been reported recently in cardiogenic shock, where a PAC is needed to determine the severity of the lesion and the phenotype, Dr. Papolos observed.

A 2018 study showed PAC use was tied to increased survival among patients with acute myocardial infarction cardiogenic shock (AMI-CS) supported with the Impella (Abiomed) device. Additionally, a 2021 study by the Cardiogenic Shock Working Group demonstrated a dose-dependent survival response based on the completeness of hemodynamic assessment by PAC prior to initiating mechanical circulatory support (MCS).

A third factor might be that a structured, team-based evaluation can facilitate timely and optimal MCS device selection, deployment, and management, suggested Dr. Papolos.

Centers with shock teams used more advanced types of MCS – defined as Impella, TandemHeart (LivaNova), extracorporeal membrane oxygenation, and temporary or durable surgical ventricular assist devices – than those without a shock team (53% vs. 43%; adjusted OR, 1.73; P = .005) and did so more often as the initial device (42% vs. 28%; P = .002).

Overall MCS use was lower at shock team centers (35% vs. 43%), driven by less frequent use of intra-aortic balloon pumps (58% vs. 72%).

“The standard, basic MCS has always been the balloon pump because it’s something that’s easy to put in at the cath lab or at the bedside,” Dr. Papolos said. “So, if you take away having all of the information and having the right people at the table to discuss what the best level of support is, then you’re going to end up with balloon pumps, and that’s what we saw here.”

The study involved 6,872 consecutive medical admissions at 24 level 1 CICU centers during an annual 2-month period from 2017 to 2019. Of these, 1,242 admissions were for cardiogenic shock and 546 (44%) were treated at one of 10 centers with a shock team.

Shock team centers had higher-acuity patients than centers without a shock team (Sequential Organ Failure Assessment score, 4 vs. 3) but a similar proportion of patients with AMI-CS (27% vs. 28%).

Among all admissions, CICU mortality was not significantly different between centers with and without a shock team.

For cardiogenic shock patients treated at centers with and without a shock team, the median CICU stay was 4.0 and 5.1 days, respectively, mechanical ventilation was used in 41% and 52%, respectively, and new renal replacement therapy in 11% and 19%, respectively (P < .001 for all).

Shock team centers used significantly more PACs for AMI-CS and non–AMI-CS admissions; advanced MCS therapy was also greater in the AMI-CS subgroup.

Lower CICU mortality at shock team centers persisted among patients with non-AMI-CS (adjusted OR, 0.67; P = .017) and AMI-CS (adjusted OR, 0.79; P = .344).

“This analysis supports that all AHA level 1 cardiac ICUs should strongly consider having a shock team,” Dr. Papolos said.

Evidence from single centers and the National Cardiogenic Shock Initiative has shown improved survival with a cardiogenic shock algorithm, but this is the first report specifically comparing no shock teams with shock teams, Perwaiz Meraj, MD, Northwell Health, Manhansett, N.Y., told this news organization.

“People may say that it’s just another paper that’s saying, ‘shock teams, shock teams, rah, rah, rah,’ but it’s important for all of us to really take a close look under the covers and see how are we best managing these patients, what teams are we putting together, and to create systems of care, where if you’re at a center that really doesn’t have the capabilities of doing this, then you should partner up with a center that does,” he said.

Notably, the 10 shock teams were present only in medium or large urban, academic medical centers with more than 500 beds. Although they followed individual protocols, survey results show service-line representation, structure, and operations were similar across centers.

They all had a centralized way to activate the shock team, the service was 24/7, and members came from areas such as critical care cardiology (100%), cardiac surgery (100%), interventional cardiology (90%), advanced heart failure (80%), and extracorporeal membrane oxygenation service (70%).

Limitations of the study include the possibility of residual confounding, the fact that the registry did not capture patients with cardiogenic shock managed outside the CICU or the time of onset of cardiogenic shock, and data were limited on inotropic strategies, sedation practices, and ventilator management, the authors wrote.

“Although many critics will continue to discuss the lack of randomized controlled trials in cardiogenic shock, this paper supports the process previously outlined of a multidisciplinary team-based approach improving survival,” Dr. Meraj and William W. O’Neill, MD, director of the Center for Structural Heart Disease and Henry Ford Health System, Detroit, and the force behind the National Cardiogenic Shock Initiative, wrote in an accompanying editorial.

They point out that the report doesn’t address the escalation of care based on invasive hemodynamics in the CICU and the protocols to prevent acute vascular/limb complications (ALI) that can arise from the use of MCS.

“Many procedural techniques and novel CICU models exist to mitigate the risk of ALI in CS patients with MCS,” they wrote. “Finally, escalation of care and support is vital to the continued success of any shock team and center.”

One coauthor has served as a consultant to Abbott. Another has served as a consultant to the Abiomed critical care advisory board. All other authors reported having no relevant financial relationships. Dr. Meraj has received research and grant funding from Abiomed, Medtronic, CSI, and Boston Scientific. Dr. O’Neill has received consulting/speaker honoraria from Abiomed, Boston Scientific, and Abbott.

A version of this article first appeared on Medscape.com.

A large multicenter study provides further evidence supporting the rationale for multidisciplinary teams for cardiogenic shock, one of the most lethal diseases in cardiovascular medicine.

The analysis of 24 critical care ICUs in the Critical Care Cardiology Trials Network showed that the presence of a shock team was independently associated with a 28% lower risk for CICU mortality (23% vs. 29%; odds ratio, 0.72; P = .016).

Patients treated by a shock team also had significantly shorter CICU stays and less need for mechanical ventilation or renal replacement therapy, as reported in the Journal of the American College of Cardiology.

“It’s observational, but the association that we’re seeing here, just because of our sample size, is the strongest that’s been published yet,” lead author Alexander Papolos, MD, MedStar Washington Hospital Center, said in an interview.

Although a causal relationship cannot be drawn, the authors suggest several factors that could explain the findings, including a shock team’s ability to rapidly diagnose and treat cardiogenic shock before multiorgan dysfunction occurs.

Centers with shock teams also used significantly more pulmonary artery catheters (60% vs. 49%; adjusted OR, 1.86; P < .001) and placed them earlier (0.3 vs. 0.66 days; P = .019).

Pulmonary artery catheter (PAC) use has declined after earlier trials like ESCAPE showed little or no benefit in other acutely ill patient groups, but positive results have been reported recently in cardiogenic shock, where a PAC is needed to determine the severity of the lesion and the phenotype, Dr. Papolos observed.

A 2018 study showed PAC use was tied to increased survival among patients with acute myocardial infarction cardiogenic shock (AMI-CS) supported with the Impella (Abiomed) device. Additionally, a 2021 study by the Cardiogenic Shock Working Group demonstrated a dose-dependent survival response based on the completeness of hemodynamic assessment by PAC prior to initiating mechanical circulatory support (MCS).

A third factor might be that a structured, team-based evaluation can facilitate timely and optimal MCS device selection, deployment, and management, suggested Dr. Papolos.

Centers with shock teams used more advanced types of MCS – defined as Impella, TandemHeart (LivaNova), extracorporeal membrane oxygenation, and temporary or durable surgical ventricular assist devices – than those without a shock team (53% vs. 43%; adjusted OR, 1.73; P = .005) and did so more often as the initial device (42% vs. 28%; P = .002).

Overall MCS use was lower at shock team centers (35% vs. 43%), driven by less frequent use of intra-aortic balloon pumps (58% vs. 72%).

“The standard, basic MCS has always been the balloon pump because it’s something that’s easy to put in at the cath lab or at the bedside,” Dr. Papolos said. “So, if you take away having all of the information and having the right people at the table to discuss what the best level of support is, then you’re going to end up with balloon pumps, and that’s what we saw here.”

The study involved 6,872 consecutive medical admissions at 24 level 1 CICU centers during an annual 2-month period from 2017 to 2019. Of these, 1,242 admissions were for cardiogenic shock and 546 (44%) were treated at one of 10 centers with a shock team.

Shock team centers had higher-acuity patients than centers without a shock team (Sequential Organ Failure Assessment score, 4 vs. 3) but a similar proportion of patients with AMI-CS (27% vs. 28%).

Among all admissions, CICU mortality was not significantly different between centers with and without a shock team.

For cardiogenic shock patients treated at centers with and without a shock team, the median CICU stay was 4.0 and 5.1 days, respectively, mechanical ventilation was used in 41% and 52%, respectively, and new renal replacement therapy in 11% and 19%, respectively (P < .001 for all).

Shock team centers used significantly more PACs for AMI-CS and non–AMI-CS admissions; advanced MCS therapy was also greater in the AMI-CS subgroup.

Lower CICU mortality at shock team centers persisted among patients with non-AMI-CS (adjusted OR, 0.67; P = .017) and AMI-CS (adjusted OR, 0.79; P = .344).

“This analysis supports that all AHA level 1 cardiac ICUs should strongly consider having a shock team,” Dr. Papolos said.

Evidence from single centers and the National Cardiogenic Shock Initiative has shown improved survival with a cardiogenic shock algorithm, but this is the first report specifically comparing no shock teams with shock teams, Perwaiz Meraj, MD, Northwell Health, Manhansett, N.Y., told this news organization.

“People may say that it’s just another paper that’s saying, ‘shock teams, shock teams, rah, rah, rah,’ but it’s important for all of us to really take a close look under the covers and see how are we best managing these patients, what teams are we putting together, and to create systems of care, where if you’re at a center that really doesn’t have the capabilities of doing this, then you should partner up with a center that does,” he said.

Notably, the 10 shock teams were present only in medium or large urban, academic medical centers with more than 500 beds. Although they followed individual protocols, survey results show service-line representation, structure, and operations were similar across centers.

They all had a centralized way to activate the shock team, the service was 24/7, and members came from areas such as critical care cardiology (100%), cardiac surgery (100%), interventional cardiology (90%), advanced heart failure (80%), and extracorporeal membrane oxygenation service (70%).

Limitations of the study include the possibility of residual confounding, the fact that the registry did not capture patients with cardiogenic shock managed outside the CICU or the time of onset of cardiogenic shock, and data were limited on inotropic strategies, sedation practices, and ventilator management, the authors wrote.

“Although many critics will continue to discuss the lack of randomized controlled trials in cardiogenic shock, this paper supports the process previously outlined of a multidisciplinary team-based approach improving survival,” Dr. Meraj and William W. O’Neill, MD, director of the Center for Structural Heart Disease and Henry Ford Health System, Detroit, and the force behind the National Cardiogenic Shock Initiative, wrote in an accompanying editorial.

They point out that the report doesn’t address the escalation of care based on invasive hemodynamics in the CICU and the protocols to prevent acute vascular/limb complications (ALI) that can arise from the use of MCS.

“Many procedural techniques and novel CICU models exist to mitigate the risk of ALI in CS patients with MCS,” they wrote. “Finally, escalation of care and support is vital to the continued success of any shock team and center.”

One coauthor has served as a consultant to Abbott. Another has served as a consultant to the Abiomed critical care advisory board. All other authors reported having no relevant financial relationships. Dr. Meraj has received research and grant funding from Abiomed, Medtronic, CSI, and Boston Scientific. Dr. O’Neill has received consulting/speaker honoraria from Abiomed, Boston Scientific, and Abbott.

A version of this article first appeared on Medscape.com.

A large multicenter study provides further evidence supporting the rationale for multidisciplinary teams for cardiogenic shock, one of the most lethal diseases in cardiovascular medicine.

The analysis of 24 critical care ICUs in the Critical Care Cardiology Trials Network showed that the presence of a shock team was independently associated with a 28% lower risk for CICU mortality (23% vs. 29%; odds ratio, 0.72; P = .016).

Patients treated by a shock team also had significantly shorter CICU stays and less need for mechanical ventilation or renal replacement therapy, as reported in the Journal of the American College of Cardiology.

“It’s observational, but the association that we’re seeing here, just because of our sample size, is the strongest that’s been published yet,” lead author Alexander Papolos, MD, MedStar Washington Hospital Center, said in an interview.

Although a causal relationship cannot be drawn, the authors suggest several factors that could explain the findings, including a shock team’s ability to rapidly diagnose and treat cardiogenic shock before multiorgan dysfunction occurs.

Centers with shock teams also used significantly more pulmonary artery catheters (60% vs. 49%; adjusted OR, 1.86; P < .001) and placed them earlier (0.3 vs. 0.66 days; P = .019).

Pulmonary artery catheter (PAC) use has declined after earlier trials like ESCAPE showed little or no benefit in other acutely ill patient groups, but positive results have been reported recently in cardiogenic shock, where a PAC is needed to determine the severity of the lesion and the phenotype, Dr. Papolos observed.

A 2018 study showed PAC use was tied to increased survival among patients with acute myocardial infarction cardiogenic shock (AMI-CS) supported with the Impella (Abiomed) device. Additionally, a 2021 study by the Cardiogenic Shock Working Group demonstrated a dose-dependent survival response based on the completeness of hemodynamic assessment by PAC prior to initiating mechanical circulatory support (MCS).

A third factor might be that a structured, team-based evaluation can facilitate timely and optimal MCS device selection, deployment, and management, suggested Dr. Papolos.

Centers with shock teams used more advanced types of MCS – defined as Impella, TandemHeart (LivaNova), extracorporeal membrane oxygenation, and temporary or durable surgical ventricular assist devices – than those without a shock team (53% vs. 43%; adjusted OR, 1.73; P = .005) and did so more often as the initial device (42% vs. 28%; P = .002).

Overall MCS use was lower at shock team centers (35% vs. 43%), driven by less frequent use of intra-aortic balloon pumps (58% vs. 72%).

“The standard, basic MCS has always been the balloon pump because it’s something that’s easy to put in at the cath lab or at the bedside,” Dr. Papolos said. “So, if you take away having all of the information and having the right people at the table to discuss what the best level of support is, then you’re going to end up with balloon pumps, and that’s what we saw here.”

The study involved 6,872 consecutive medical admissions at 24 level 1 CICU centers during an annual 2-month period from 2017 to 2019. Of these, 1,242 admissions were for cardiogenic shock and 546 (44%) were treated at one of 10 centers with a shock team.

Shock team centers had higher-acuity patients than centers without a shock team (Sequential Organ Failure Assessment score, 4 vs. 3) but a similar proportion of patients with AMI-CS (27% vs. 28%).

Among all admissions, CICU mortality was not significantly different between centers with and without a shock team.

For cardiogenic shock patients treated at centers with and without a shock team, the median CICU stay was 4.0 and 5.1 days, respectively, mechanical ventilation was used in 41% and 52%, respectively, and new renal replacement therapy in 11% and 19%, respectively (P < .001 for all).

Shock team centers used significantly more PACs for AMI-CS and non–AMI-CS admissions; advanced MCS therapy was also greater in the AMI-CS subgroup.

Lower CICU mortality at shock team centers persisted among patients with non-AMI-CS (adjusted OR, 0.67; P = .017) and AMI-CS (adjusted OR, 0.79; P = .344).

“This analysis supports that all AHA level 1 cardiac ICUs should strongly consider having a shock team,” Dr. Papolos said.

Evidence from single centers and the National Cardiogenic Shock Initiative has shown improved survival with a cardiogenic shock algorithm, but this is the first report specifically comparing no shock teams with shock teams, Perwaiz Meraj, MD, Northwell Health, Manhansett, N.Y., told this news organization.

“People may say that it’s just another paper that’s saying, ‘shock teams, shock teams, rah, rah, rah,’ but it’s important for all of us to really take a close look under the covers and see how are we best managing these patients, what teams are we putting together, and to create systems of care, where if you’re at a center that really doesn’t have the capabilities of doing this, then you should partner up with a center that does,” he said.

Notably, the 10 shock teams were present only in medium or large urban, academic medical centers with more than 500 beds. Although they followed individual protocols, survey results show service-line representation, structure, and operations were similar across centers.

They all had a centralized way to activate the shock team, the service was 24/7, and members came from areas such as critical care cardiology (100%), cardiac surgery (100%), interventional cardiology (90%), advanced heart failure (80%), and extracorporeal membrane oxygenation service (70%).

Limitations of the study include the possibility of residual confounding, the fact that the registry did not capture patients with cardiogenic shock managed outside the CICU or the time of onset of cardiogenic shock, and data were limited on inotropic strategies, sedation practices, and ventilator management, the authors wrote.

“Although many critics will continue to discuss the lack of randomized controlled trials in cardiogenic shock, this paper supports the process previously outlined of a multidisciplinary team-based approach improving survival,” Dr. Meraj and William W. O’Neill, MD, director of the Center for Structural Heart Disease and Henry Ford Health System, Detroit, and the force behind the National Cardiogenic Shock Initiative, wrote in an accompanying editorial.

They point out that the report doesn’t address the escalation of care based on invasive hemodynamics in the CICU and the protocols to prevent acute vascular/limb complications (ALI) that can arise from the use of MCS.

“Many procedural techniques and novel CICU models exist to mitigate the risk of ALI in CS patients with MCS,” they wrote. “Finally, escalation of care and support is vital to the continued success of any shock team and center.”

One coauthor has served as a consultant to Abbott. Another has served as a consultant to the Abiomed critical care advisory board. All other authors reported having no relevant financial relationships. Dr. Meraj has received research and grant funding from Abiomed, Medtronic, CSI, and Boston Scientific. Dr. O’Neill has received consulting/speaker honoraria from Abiomed, Boston Scientific, and Abbott.

A version of this article first appeared on Medscape.com.

Whereas previous scientific statements from the American Heart Association have addressed how diet, physical activity, and weight control can help prevent and manage hypertension, a new AHA statement focuses on obesity-related hypertension. 

verbaska_studio/thinkstockphotos

The document, which was published online Sept. 20, 2021, in Hypertension, also identifies knowledge gaps and suggests future research directions.

“Given [that] obesity is a major risk factor for hypertension, and hypertension is one of the greatest (if not the greatest) attributable risk factors for most cardiovascular diseases, we thought it was important to focus on weight loss strategies and update what we know about the treatment options that are available to treat obesity hypertension,” writing group chair Michael E. Hall, MD, told this news organization. 

“Medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity,” he noted in a press release from the AHA. “We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke.”

However, by acting earlier, “we may be able to prevent these complications,” added Dr. Hall, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson.

“This is not a call for greater use of one specific therapy,” he clarified. “However, we do know that more aggressive treatments including antiobesity medications or metabolic surgery are underutilized.”

According to Dr. Hall, “we treat the secondary problem [i.e., the hypertension or diabetes], but we are not treating the root cause [obesity] as aggressively.”

“Hopefully this statement will increase awareness that there are several [treatment] options [and] bring attention to this major health issue,” he said.

He added that the most important question, in his mind, is how best to tackle obesity among children and adolescents to lower their risk of hypertension and other associated complications.

The statement is aimed at both primary care providers and specialists.
 

Diet, physical activity help, but weight regain common

Losing 5%-10% of body weight can lead to a more than 5–mm Hg reduction in systolic blood pressure and a 4–mm Hg reduction in diastolic blood pressure, the statement notes. Losing 10 kg may lower systolic blood pressure by 5-20 mm Hg.

To manage weight, control hypertension, and reduce the risk of cardiovascular disease, guidelines recommend the Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH) diet, which both emphasize fruits, vegetables, legumes, nuts, and seeds, with moderate intake of fish, seafood, poultry, and dairy, and low intake of red and processed meats and sweets. The Mediterranean diet also includes olive oil and moderate consumption of (mainly red) wine.  

The effect of intermittent fasting on blood pressure control is not clear, the statement noted.

It added that typically 150-225 minutes and 225-420 minutes of physical activity per week can produce weight loss of 2-3 kg or 5-7.5 kg respectively, and 200-300 minutes of physical activity per week is needed to maintain this weight loss.

“Successful weight-loss maintenance over years therefore typically requires high levels of [physical activity] and limited sedentary time, frequent weight monitoring, and high levels of dietary restraint,” and weight regain is common, the authors summarize.
 

Other options to address obesity, hypertension

Weight-loss pharmacotherapies and metabolic surgery are other options to treat obesity and lower hypertension.

The statement reports that four drugs are approved by the Food and Drug Administration for long-term weight loss: Orlistat (Xenical, Alli), phentermine/topiramate extended release (Qsymia), naltrexone/bupropion (Contrave), and liraglutide 3.0 mg (Saxenda). On June 4, the FDA approved a fifth drug, semaglutide (Wegovy).

The long-term effects of antiobesity medications on blood pressure are mixed.

However, “prescription rates for these drugs remain low, likely because of limited insurance coverage and low levels of clinical proficiency with treating obesity,” Dr. Hall and colleagues write.

Metabolic surgery could be a weight loss option for certain patients, and it is associated with blood pressure lowering.

In the 100-patient Gastric Bypass to Treat Obese Patients With Steady Hypertension (GATEWAY) trial, published in Circulation in 2018, more patients in the Roux-en-Y gastric-bypass group than the control group (84% vs. 13%) met the primary outcome of a 30% or greater reduction in the number of blood pressure-lowering medications at 12 months while maintaining an office blood pressure less than 140/90 mm Hg.

Unanswered questions, future research directions

In 2015-2016, an estimated 18.5% of U.S. children and adolescents aged 2-19 years had obesity, the statement notes. Children with obesity have a twofold increased risk of incident hypertension, and those with severe obesity have an over fourfold increased risk of this outcome, compared with children who have a healthy weight.

Dr. Hall and colleagues emphasized that, “as the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed.”

They identified 17 unanswered questions (knowledge gaps) that can guide the direction of future research. These include:

• What new strategies and science-based guidelines are needed to curb the growing evidence of childhood obesity?
• Does intentional weight loss with pharmacotherapy or metabolic surgery in childhood and early adulthood prevent hypertension and subsequent target organ damage in later life?
• What is the optimal amount of time that clinicians should allow before recommending more aggressive weight management strategies (that is, antiobesity medications or metabolic surgery) or hypertension strategies beyond lifestyle changes?

“To me,” Dr. Hall said, “addressing childhood obesity hypertension and determining optimal timing of antiobesity therapies are the most important [issues]. Certainly, these therapies (i.e., diets, medications, surgeries) have some risks, but we don’t have a clear understanding if their benefits outweigh these risks in younger obese people or whether initiating these therapies before the onset of target organ damage such as heart failure” outweigh the risks.

Dr. Hall has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

A version of this article first appeared on Medscape.com.

Whereas previous scientific statements from the American Heart Association have addressed how diet, physical activity, and weight control can help prevent and manage hypertension, a new AHA statement focuses on obesity-related hypertension. 

verbaska_studio/thinkstockphotos

The document, which was published online Sept. 20, 2021, in Hypertension, also identifies knowledge gaps and suggests future research directions.

“Given [that] obesity is a major risk factor for hypertension, and hypertension is one of the greatest (if not the greatest) attributable risk factors for most cardiovascular diseases, we thought it was important to focus on weight loss strategies and update what we know about the treatment options that are available to treat obesity hypertension,” writing group chair Michael E. Hall, MD, told this news organization. 

“Medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity,” he noted in a press release from the AHA. “We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke.”

However, by acting earlier, “we may be able to prevent these complications,” added Dr. Hall, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson.

“This is not a call for greater use of one specific therapy,” he clarified. “However, we do know that more aggressive treatments including antiobesity medications or metabolic surgery are underutilized.”

According to Dr. Hall, “we treat the secondary problem [i.e., the hypertension or diabetes], but we are not treating the root cause [obesity] as aggressively.”

“Hopefully this statement will increase awareness that there are several [treatment] options [and] bring attention to this major health issue,” he said.

He added that the most important question, in his mind, is how best to tackle obesity among children and adolescents to lower their risk of hypertension and other associated complications.

The statement is aimed at both primary care providers and specialists.
 

Diet, physical activity help, but weight regain common

Losing 5%-10% of body weight can lead to a more than 5–mm Hg reduction in systolic blood pressure and a 4–mm Hg reduction in diastolic blood pressure, the statement notes. Losing 10 kg may lower systolic blood pressure by 5-20 mm Hg.

To manage weight, control hypertension, and reduce the risk of cardiovascular disease, guidelines recommend the Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH) diet, which both emphasize fruits, vegetables, legumes, nuts, and seeds, with moderate intake of fish, seafood, poultry, and dairy, and low intake of red and processed meats and sweets. The Mediterranean diet also includes olive oil and moderate consumption of (mainly red) wine.  

The effect of intermittent fasting on blood pressure control is not clear, the statement noted.

It added that typically 150-225 minutes and 225-420 minutes of physical activity per week can produce weight loss of 2-3 kg or 5-7.5 kg respectively, and 200-300 minutes of physical activity per week is needed to maintain this weight loss.

“Successful weight-loss maintenance over years therefore typically requires high levels of [physical activity] and limited sedentary time, frequent weight monitoring, and high levels of dietary restraint,” and weight regain is common, the authors summarize.
 

Other options to address obesity, hypertension

Weight-loss pharmacotherapies and metabolic surgery are other options to treat obesity and lower hypertension.

The statement reports that four drugs are approved by the Food and Drug Administration for long-term weight loss: Orlistat (Xenical, Alli), phentermine/topiramate extended release (Qsymia), naltrexone/bupropion (Contrave), and liraglutide 3.0 mg (Saxenda). On June 4, the FDA approved a fifth drug, semaglutide (Wegovy).

The long-term effects of antiobesity medications on blood pressure are mixed.

However, “prescription rates for these drugs remain low, likely because of limited insurance coverage and low levels of clinical proficiency with treating obesity,” Dr. Hall and colleagues write.

Metabolic surgery could be a weight loss option for certain patients, and it is associated with blood pressure lowering.

In the 100-patient Gastric Bypass to Treat Obese Patients With Steady Hypertension (GATEWAY) trial, published in Circulation in 2018, more patients in the Roux-en-Y gastric-bypass group than the control group (84% vs. 13%) met the primary outcome of a 30% or greater reduction in the number of blood pressure-lowering medications at 12 months while maintaining an office blood pressure less than 140/90 mm Hg.

Unanswered questions, future research directions

In 2015-2016, an estimated 18.5% of U.S. children and adolescents aged 2-19 years had obesity, the statement notes. Children with obesity have a twofold increased risk of incident hypertension, and those with severe obesity have an over fourfold increased risk of this outcome, compared with children who have a healthy weight.

Dr. Hall and colleagues emphasized that, “as the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed.”

They identified 17 unanswered questions (knowledge gaps) that can guide the direction of future research. These include:

• What new strategies and science-based guidelines are needed to curb the growing evidence of childhood obesity?
• Does intentional weight loss with pharmacotherapy or metabolic surgery in childhood and early adulthood prevent hypertension and subsequent target organ damage in later life?
• What is the optimal amount of time that clinicians should allow before recommending more aggressive weight management strategies (that is, antiobesity medications or metabolic surgery) or hypertension strategies beyond lifestyle changes?

“To me,” Dr. Hall said, “addressing childhood obesity hypertension and determining optimal timing of antiobesity therapies are the most important [issues]. Certainly, these therapies (i.e., diets, medications, surgeries) have some risks, but we don’t have a clear understanding if their benefits outweigh these risks in younger obese people or whether initiating these therapies before the onset of target organ damage such as heart failure” outweigh the risks.

Dr. Hall has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

A version of this article first appeared on Medscape.com.

Whereas previous scientific statements from the American Heart Association have addressed how diet, physical activity, and weight control can help prevent and manage hypertension, a new AHA statement focuses on obesity-related hypertension. 

verbaska_studio/thinkstockphotos

The document, which was published online Sept. 20, 2021, in Hypertension, also identifies knowledge gaps and suggests future research directions.

“Given [that] obesity is a major risk factor for hypertension, and hypertension is one of the greatest (if not the greatest) attributable risk factors for most cardiovascular diseases, we thought it was important to focus on weight loss strategies and update what we know about the treatment options that are available to treat obesity hypertension,” writing group chair Michael E. Hall, MD, told this news organization. 

“Medical and surgical strategies may help with long-term weight and blood pressure improvement, in addition to a heart-healthy diet and physical activity,” he noted in a press release from the AHA. “We often don’t consider medications or metabolic surgery until after there has been target organ damage, such as heart injury or having a stroke.”

However, by acting earlier, “we may be able to prevent these complications,” added Dr. Hall, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson.

“This is not a call for greater use of one specific therapy,” he clarified. “However, we do know that more aggressive treatments including antiobesity medications or metabolic surgery are underutilized.”

According to Dr. Hall, “we treat the secondary problem [i.e., the hypertension or diabetes], but we are not treating the root cause [obesity] as aggressively.”

“Hopefully this statement will increase awareness that there are several [treatment] options [and] bring attention to this major health issue,” he said.

He added that the most important question, in his mind, is how best to tackle obesity among children and adolescents to lower their risk of hypertension and other associated complications.

The statement is aimed at both primary care providers and specialists.
 

Diet, physical activity help, but weight regain common

Losing 5%-10% of body weight can lead to a more than 5–mm Hg reduction in systolic blood pressure and a 4–mm Hg reduction in diastolic blood pressure, the statement notes. Losing 10 kg may lower systolic blood pressure by 5-20 mm Hg.

To manage weight, control hypertension, and reduce the risk of cardiovascular disease, guidelines recommend the Mediterranean diet or the Dietary Approaches to Stop Hypertension (DASH) diet, which both emphasize fruits, vegetables, legumes, nuts, and seeds, with moderate intake of fish, seafood, poultry, and dairy, and low intake of red and processed meats and sweets. The Mediterranean diet also includes olive oil and moderate consumption of (mainly red) wine.  

The effect of intermittent fasting on blood pressure control is not clear, the statement noted.

It added that typically 150-225 minutes and 225-420 minutes of physical activity per week can produce weight loss of 2-3 kg or 5-7.5 kg respectively, and 200-300 minutes of physical activity per week is needed to maintain this weight loss.

“Successful weight-loss maintenance over years therefore typically requires high levels of [physical activity] and limited sedentary time, frequent weight monitoring, and high levels of dietary restraint,” and weight regain is common, the authors summarize.
 

Other options to address obesity, hypertension

Weight-loss pharmacotherapies and metabolic surgery are other options to treat obesity and lower hypertension.

The statement reports that four drugs are approved by the Food and Drug Administration for long-term weight loss: Orlistat (Xenical, Alli), phentermine/topiramate extended release (Qsymia), naltrexone/bupropion (Contrave), and liraglutide 3.0 mg (Saxenda). On June 4, the FDA approved a fifth drug, semaglutide (Wegovy).

The long-term effects of antiobesity medications on blood pressure are mixed.

However, “prescription rates for these drugs remain low, likely because of limited insurance coverage and low levels of clinical proficiency with treating obesity,” Dr. Hall and colleagues write.

Metabolic surgery could be a weight loss option for certain patients, and it is associated with blood pressure lowering.

In the 100-patient Gastric Bypass to Treat Obese Patients With Steady Hypertension (GATEWAY) trial, published in Circulation in 2018, more patients in the Roux-en-Y gastric-bypass group than the control group (84% vs. 13%) met the primary outcome of a 30% or greater reduction in the number of blood pressure-lowering medications at 12 months while maintaining an office blood pressure less than 140/90 mm Hg.

Unanswered questions, future research directions

In 2015-2016, an estimated 18.5% of U.S. children and adolescents aged 2-19 years had obesity, the statement notes. Children with obesity have a twofold increased risk of incident hypertension, and those with severe obesity have an over fourfold increased risk of this outcome, compared with children who have a healthy weight.

Dr. Hall and colleagues emphasized that, “as the prevalence of obesity continues to increase, hypertension and associated cardiorenal diseases will also increase unless more effective strategies to prevent and treat obesity are developed.”

They identified 17 unanswered questions (knowledge gaps) that can guide the direction of future research. These include:

• What new strategies and science-based guidelines are needed to curb the growing evidence of childhood obesity?
• Does intentional weight loss with pharmacotherapy or metabolic surgery in childhood and early adulthood prevent hypertension and subsequent target organ damage in later life?
• What is the optimal amount of time that clinicians should allow before recommending more aggressive weight management strategies (that is, antiobesity medications or metabolic surgery) or hypertension strategies beyond lifestyle changes?

“To me,” Dr. Hall said, “addressing childhood obesity hypertension and determining optimal timing of antiobesity therapies are the most important [issues]. Certainly, these therapies (i.e., diets, medications, surgeries) have some risks, but we don’t have a clear understanding if their benefits outweigh these risks in younger obese people or whether initiating these therapies before the onset of target organ damage such as heart failure” outweigh the risks.

Dr. Hall has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

A version of this article first appeared on Medscape.com.

EVIDENCE SUMMARY

Mixed results, quality issues do not support screening asymptomatic patients

A meta-analysis (12 observational studies; n = 1002) compared the diagnostic accuracy of panoramic radiography (PR) to Doppler ultrasonography (11 studies) or angiography (1 study) in detecting calcified carotid artery atheroma (CCAA).¹ The studies, conducted in 8 countries, were published after 2006. Patients were 29 to 71 years old without history of stroke, endarterectomy, angioplasty, or renal disease. In a pooled analysis, the sensitivity of PR to detect CCAA was 73% (range, 31%-95%; 95% CI, 69%-77%), and the specificity was 72% (range, 19%-99%; 95% CI, 68%-76%). The pooled positive predictive value was 70% (range, 37%-95%; 95% CI, 66%-74%), and negative predictive value was 75% (range, 43%-93%; 95% CI, 71%-79%). Pooled positive likelihood ratio was 2.32 (95% CI, 1.49-3.60) and negative likelihood ratio was 0.40 (95% CI, 0.25-0.63). Seven studies had high risk of patient selection bias, and most had methodologic limitations.

In a retrospective cohort study (n = 778) from the United States, researchers identified carotid artery calcifications on routine dental radiographs in patients ≥ 55 years old and prospectively performed duplex ultrasound (DUS) to assess for significant carotid stenosis (≥ 50%).² Twenty-seven patients (3.5%) had carotid artery calcifications on radiographs, and 20 of those patients underwent DUS of bilateral carotid arteries (40 sides). Of 26 sides with calcifications on radiograph, 13 (50%) had stenosis confirmed with DUS. Of the 14 sides without calcification on radiograph, 3 (21%) had stenosis on DUS. The positive predictive value for calcification on PR predicting significant carotid stenosis was between 40% and 80%.

In a cross-sectional study from Sweden, investigators sought surgical candidates for asymptomatic carotid endarterectomy and performed PRs of 1182 patients.³ Calcifications were found in 176 people; 117 of them were eligible for asymptomatic carotid endarterectomy (ages 18-74; no cancer or other serious comorbidity; and no prior stroke or transient ischemic attack) and underwent ultrasound to assess for significant carotid stenosis (≥ 50%). Of the 117 participants who underwent ultrasound, 8 (6.8%; 95% CI, 2.2%-11.5%), all men, were found to have significant carotid stenosis. Compared to a sex- and age-matched reference group (n = 119) with no calcifications on PR, the prevalence of carotid stenosis was significantly higher in men (12.5%; 95% CI, 4.2%-20.8%) and in patients who were current smokers (19%; 95% CI, 0.7%-37.4%), were taking cholesterol medications (13.1%; 95% CI 4.4%-21.8%), and had a cardiovascular event history (15.9%; 95% CI, 7%-27.2%).

Recommendations from others

The US Preventive Services Task Force ­(USPSTF) and the American Academy of Family Physicians do not mention carotid screening with radiographs but recommend against screening for carotid artery stenosis in asymptomatic adults because the risks of screening outweigh the potential benefits (USPSTF grade D; the harms outweigh the benefits).^4,5

Editor’s takeaway

If you see calcification of the carotid artery on an x-ray of an asymptomatic patient, ignore it. The positive and negative predictive values for carotid stenosis are poor, and you should not pursue further testing.

EVIDENCE SUMMARY

Mixed results, quality issues do not support screening asymptomatic patients

A meta-analysis (12 observational studies; n = 1002) compared the diagnostic accuracy of panoramic radiography (PR) to Doppler ultrasonography (11 studies) or angiography (1 study) in detecting calcified carotid artery atheroma (CCAA).¹ The studies, conducted in 8 countries, were published after 2006. Patients were 29 to 71 years old without history of stroke, endarterectomy, angioplasty, or renal disease. In a pooled analysis, the sensitivity of PR to detect CCAA was 73% (range, 31%-95%; 95% CI, 69%-77%), and the specificity was 72% (range, 19%-99%; 95% CI, 68%-76%). The pooled positive predictive value was 70% (range, 37%-95%; 95% CI, 66%-74%), and negative predictive value was 75% (range, 43%-93%; 95% CI, 71%-79%). Pooled positive likelihood ratio was 2.32 (95% CI, 1.49-3.60) and negative likelihood ratio was 0.40 (95% CI, 0.25-0.63). Seven studies had high risk of patient selection bias, and most had methodologic limitations.

In a retrospective cohort study (n = 778) from the United States, researchers identified carotid artery calcifications on routine dental radiographs in patients ≥ 55 years old and prospectively performed duplex ultrasound (DUS) to assess for significant carotid stenosis (≥ 50%).² Twenty-seven patients (3.5%) had carotid artery calcifications on radiographs, and 20 of those patients underwent DUS of bilateral carotid arteries (40 sides). Of 26 sides with calcifications on radiograph, 13 (50%) had stenosis confirmed with DUS. Of the 14 sides without calcification on radiograph, 3 (21%) had stenosis on DUS. The positive predictive value for calcification on PR predicting significant carotid stenosis was between 40% and 80%.

In a cross-sectional study from Sweden, investigators sought surgical candidates for asymptomatic carotid endarterectomy and performed PRs of 1182 patients.³ Calcifications were found in 176 people; 117 of them were eligible for asymptomatic carotid endarterectomy (ages 18-74; no cancer or other serious comorbidity; and no prior stroke or transient ischemic attack) and underwent ultrasound to assess for significant carotid stenosis (≥ 50%). Of the 117 participants who underwent ultrasound, 8 (6.8%; 95% CI, 2.2%-11.5%), all men, were found to have significant carotid stenosis. Compared to a sex- and age-matched reference group (n = 119) with no calcifications on PR, the prevalence of carotid stenosis was significantly higher in men (12.5%; 95% CI, 4.2%-20.8%) and in patients who were current smokers (19%; 95% CI, 0.7%-37.4%), were taking cholesterol medications (13.1%; 95% CI 4.4%-21.8%), and had a cardiovascular event history (15.9%; 95% CI, 7%-27.2%).

Recommendations from others

The US Preventive Services Task Force ­(USPSTF) and the American Academy of Family Physicians do not mention carotid screening with radiographs but recommend against screening for carotid artery stenosis in asymptomatic adults because the risks of screening outweigh the potential benefits (USPSTF grade D; the harms outweigh the benefits).^4,5

Editor’s takeaway

If you see calcification of the carotid artery on an x-ray of an asymptomatic patient, ignore it. The positive and negative predictive values for carotid stenosis are poor, and you should not pursue further testing.

EVIDENCE SUMMARY

Mixed results, quality issues do not support screening asymptomatic patients

A meta-analysis (12 observational studies; n = 1002) compared the diagnostic accuracy of panoramic radiography (PR) to Doppler ultrasonography (11 studies) or angiography (1 study) in detecting calcified carotid artery atheroma (CCAA).¹ The studies, conducted in 8 countries, were published after 2006. Patients were 29 to 71 years old without history of stroke, endarterectomy, angioplasty, or renal disease. In a pooled analysis, the sensitivity of PR to detect CCAA was 73% (range, 31%-95%; 95% CI, 69%-77%), and the specificity was 72% (range, 19%-99%; 95% CI, 68%-76%). The pooled positive predictive value was 70% (range, 37%-95%; 95% CI, 66%-74%), and negative predictive value was 75% (range, 43%-93%; 95% CI, 71%-79%). Pooled positive likelihood ratio was 2.32 (95% CI, 1.49-3.60) and negative likelihood ratio was 0.40 (95% CI, 0.25-0.63). Seven studies had high risk of patient selection bias, and most had methodologic limitations.

In a retrospective cohort study (n = 778) from the United States, researchers identified carotid artery calcifications on routine dental radiographs in patients ≥ 55 years old and prospectively performed duplex ultrasound (DUS) to assess for significant carotid stenosis (≥ 50%).² Twenty-seven patients (3.5%) had carotid artery calcifications on radiographs, and 20 of those patients underwent DUS of bilateral carotid arteries (40 sides). Of 26 sides with calcifications on radiograph, 13 (50%) had stenosis confirmed with DUS. Of the 14 sides without calcification on radiograph, 3 (21%) had stenosis on DUS. The positive predictive value for calcification on PR predicting significant carotid stenosis was between 40% and 80%.

In a cross-sectional study from Sweden, investigators sought surgical candidates for asymptomatic carotid endarterectomy and performed PRs of 1182 patients.³ Calcifications were found in 176 people; 117 of them were eligible for asymptomatic carotid endarterectomy (ages 18-74; no cancer or other serious comorbidity; and no prior stroke or transient ischemic attack) and underwent ultrasound to assess for significant carotid stenosis (≥ 50%). Of the 117 participants who underwent ultrasound, 8 (6.8%; 95% CI, 2.2%-11.5%), all men, were found to have significant carotid stenosis. Compared to a sex- and age-matched reference group (n = 119) with no calcifications on PR, the prevalence of carotid stenosis was significantly higher in men (12.5%; 95% CI, 4.2%-20.8%) and in patients who were current smokers (19%; 95% CI, 0.7%-37.4%), were taking cholesterol medications (13.1%; 95% CI 4.4%-21.8%), and had a cardiovascular event history (15.9%; 95% CI, 7%-27.2%).

Recommendations from others

The US Preventive Services Task Force ­(USPSTF) and the American Academy of Family Physicians do not mention carotid screening with radiographs but recommend against screening for carotid artery stenosis in asymptomatic adults because the risks of screening outweigh the potential benefits (USPSTF grade D; the harms outweigh the benefits).^4,5

Editor’s takeaway

If you see calcification of the carotid artery on an x-ray of an asymptomatic patient, ignore it. The positive and negative predictive values for carotid stenosis are poor, and you should not pursue further testing.

In patients with acute pulmonary embolism, using cutoff values other than 110 beats per minute might improve the prognostic value of heart rate at admission, a recent observational study suggests.

Courtesy of Mercy Medical Center

For identifying low-risk patients, a cutoff of 80 bpm increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from about 94% to nearly 99% among nonhypotensive patients with acute symptomatic pulmonary embolism (PE), according to results of the large, registry-based study.

Similarly, using a 140-bpm cutoff increased the specificity of the Bova score for identifying intermediate-high–risk patients from about 93% to 98% in the study, which was recently published in the journal CHEST.

“Although standard dichotomization of HR [i.e., HR less than 110 vs. greater than 110 bpm] may be useful for guideline recommendations, our results will allow for more accuracy regarding clinical decision-making,” wrote lead author Ana Jaureguízar, MD, of the University of Alcalá in Madrid, on behalf of the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) investigators.
 

Intuitive findings inform future research

These observational findings are intuitive and do at least have the potential to inform the design of future randomized clinical trials, according to Albert J. Polito, MD, chief of the division of pulmonary medicine and medical director for the lung center at Mercy Medical Center in Baltimore.

“In medicine, there is a spectrum of risk,” Dr. Polito said in an interview. “While we love our cutoffs, which in this case has traditionally always been that 110 beats per minute for heart rate, it makes sense that there would be some range of risks of bad outcomes.”

Building on the observations of the present study, subsequent prospective randomized studies could potentially aim to determine, for example, when thrombolytic therapy should be considered in nonhypotensive patients with acute PE and higher heart rates.

“It would not be easy to design, but it’s a straightforward question to ask whether patients with the highest heart rates are the ones who potentially might benefit the most from thrombolytic therapy,” Dr. Polito said.
 

Value of alternative HR cutoffs

Heart rate is a simple and easily available vital sign that is clearly linked to prognosis in patients with pulmonary embolism, authors of the RIETE registry study say in their report. Accordingly, a heart rate threshold of 110 bpm has made its way into scoring systems that seek to identify low-risk patients, such as the sPESI, and those focused on identifying higher-risk patients, such as the Bova score.

However, it has not been clear whether alternative HR cutoffs would improve upon the 110-bpm threshold, they added. At the low-risk end, more accurate scoring systems could optimize the selection of patients for home treatment, while at the intermediate-high–risk end, they could better select patients for close monitoring or advanced PE treatments.
 

Better granularity on heart rate risks?

To better define the prognostic value of different heart rate thresholds, investigators analyzed data from RIETE, a large, ongoing, multinational prospective registry including patients with objectively confirmed acute venous thromboembolism.

For 44,331 consecutive nonhypotensive symptomatic PEs, the overall rate of 30-day all-cause mortality was 5.1%, and the 30-day PE-related mortality was 1.9%, the authors report.

Significantly poorer outcomes were seen in patients with higher heart rates as compared to patients in the 80-99 bpm range, they also found. As compared to that reference range, odds ratios for 30-day all-cause death ranged from 1.5 for heart rates of 100-109, up to 2.4 for those with heart rates of 140 bpm or greater.

Likewise, patients with higher heart rates had a 1.7- to 2.4-fold greater risk of 30-day PE-related death as compared to the 80- to 99-bpm reference range, while patients with lower heart rates had lesser risk, the data published in CHEST show.
 

Toward refinement of prognostic scoring

Next, investigators sought to refine the prognostic scoring systems for low-risk PE (sPESI) and intermediate-high–risk PE (Bova).

For sPESI, they found that dropping the cutoff value from 110 to 100 bpm increased the sensitivity of the score from 93.4% to 95.3%. Going down even further to 80 bpm increased sensitivity to 98.8%, according to the report.

By going down from 110 to 80 bpm, the proportion of patients defined as low-risk dropped from 35% to 12%, according to the investigators.

For the Bova score, increasing the cutoff value from 110 to 120 bpm likewise increased specificity from 93.2% to 95%, while going up even further to 140 bpm increased specificity to 98.0%, the report shows.

In sensitivity analyses, the findings were not impacted by excluding younger patients, those who received reperfusion therapies, or those with atrial fibrillation, according to the study findings.
 

Potential implications for clinical practice

Taken together, these findings could serve as a resource to inform discussions regarding PE management that include whether home therapy or use of thrombolytic therapy is appropriate, investigators said in their report.

“For instance, among low-risk sPESI patients, those with borderline tachycardia [i.e., a heart rate between 100-109 bpm] might benefit from initial hospital observation for trending,” they wrote.

Dr. Jaureguízar reported no disclosures. One coinvestigator reported funding support from the Institute of Health Carlos III (ISCIII) and the European Development Regional Fund (ERDF). One coinvestigator reported consulting in litigation involving two models of inferior vena cava filters.

Dr. Polito reported no disclosures.

In patients with acute pulmonary embolism, using cutoff values other than 110 beats per minute might improve the prognostic value of heart rate at admission, a recent observational study suggests.

Courtesy of Mercy Medical Center

For identifying low-risk patients, a cutoff of 80 bpm increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from about 94% to nearly 99% among nonhypotensive patients with acute symptomatic pulmonary embolism (PE), according to results of the large, registry-based study.

Similarly, using a 140-bpm cutoff increased the specificity of the Bova score for identifying intermediate-high–risk patients from about 93% to 98% in the study, which was recently published in the journal CHEST.

“Although standard dichotomization of HR [i.e., HR less than 110 vs. greater than 110 bpm] may be useful for guideline recommendations, our results will allow for more accuracy regarding clinical decision-making,” wrote lead author Ana Jaureguízar, MD, of the University of Alcalá in Madrid, on behalf of the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) investigators.
 

Intuitive findings inform future research

These observational findings are intuitive and do at least have the potential to inform the design of future randomized clinical trials, according to Albert J. Polito, MD, chief of the division of pulmonary medicine and medical director for the lung center at Mercy Medical Center in Baltimore.

“In medicine, there is a spectrum of risk,” Dr. Polito said in an interview. “While we love our cutoffs, which in this case has traditionally always been that 110 beats per minute for heart rate, it makes sense that there would be some range of risks of bad outcomes.”

Building on the observations of the present study, subsequent prospective randomized studies could potentially aim to determine, for example, when thrombolytic therapy should be considered in nonhypotensive patients with acute PE and higher heart rates.

“It would not be easy to design, but it’s a straightforward question to ask whether patients with the highest heart rates are the ones who potentially might benefit the most from thrombolytic therapy,” Dr. Polito said.
 

Value of alternative HR cutoffs

Heart rate is a simple and easily available vital sign that is clearly linked to prognosis in patients with pulmonary embolism, authors of the RIETE registry study say in their report. Accordingly, a heart rate threshold of 110 bpm has made its way into scoring systems that seek to identify low-risk patients, such as the sPESI, and those focused on identifying higher-risk patients, such as the Bova score.

However, it has not been clear whether alternative HR cutoffs would improve upon the 110-bpm threshold, they added. At the low-risk end, more accurate scoring systems could optimize the selection of patients for home treatment, while at the intermediate-high–risk end, they could better select patients for close monitoring or advanced PE treatments.
 

Better granularity on heart rate risks?

To better define the prognostic value of different heart rate thresholds, investigators analyzed data from RIETE, a large, ongoing, multinational prospective registry including patients with objectively confirmed acute venous thromboembolism.

For 44,331 consecutive nonhypotensive symptomatic PEs, the overall rate of 30-day all-cause mortality was 5.1%, and the 30-day PE-related mortality was 1.9%, the authors report.

Significantly poorer outcomes were seen in patients with higher heart rates as compared to patients in the 80-99 bpm range, they also found. As compared to that reference range, odds ratios for 30-day all-cause death ranged from 1.5 for heart rates of 100-109, up to 2.4 for those with heart rates of 140 bpm or greater.

Likewise, patients with higher heart rates had a 1.7- to 2.4-fold greater risk of 30-day PE-related death as compared to the 80- to 99-bpm reference range, while patients with lower heart rates had lesser risk, the data published in CHEST show.
 

Toward refinement of prognostic scoring

Next, investigators sought to refine the prognostic scoring systems for low-risk PE (sPESI) and intermediate-high–risk PE (Bova).

For sPESI, they found that dropping the cutoff value from 110 to 100 bpm increased the sensitivity of the score from 93.4% to 95.3%. Going down even further to 80 bpm increased sensitivity to 98.8%, according to the report.

By going down from 110 to 80 bpm, the proportion of patients defined as low-risk dropped from 35% to 12%, according to the investigators.

For the Bova score, increasing the cutoff value from 110 to 120 bpm likewise increased specificity from 93.2% to 95%, while going up even further to 140 bpm increased specificity to 98.0%, the report shows.

In sensitivity analyses, the findings were not impacted by excluding younger patients, those who received reperfusion therapies, or those with atrial fibrillation, according to the study findings.
 

Potential implications for clinical practice

Taken together, these findings could serve as a resource to inform discussions regarding PE management that include whether home therapy or use of thrombolytic therapy is appropriate, investigators said in their report.

“For instance, among low-risk sPESI patients, those with borderline tachycardia [i.e., a heart rate between 100-109 bpm] might benefit from initial hospital observation for trending,” they wrote.

Dr. Jaureguízar reported no disclosures. One coinvestigator reported funding support from the Institute of Health Carlos III (ISCIII) and the European Development Regional Fund (ERDF). One coinvestigator reported consulting in litigation involving two models of inferior vena cava filters.

Dr. Polito reported no disclosures.

In patients with acute pulmonary embolism, using cutoff values other than 110 beats per minute might improve the prognostic value of heart rate at admission, a recent observational study suggests.

Courtesy of Mercy Medical Center

For identifying low-risk patients, a cutoff of 80 bpm increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from about 94% to nearly 99% among nonhypotensive patients with acute symptomatic pulmonary embolism (PE), according to results of the large, registry-based study.

Similarly, using a 140-bpm cutoff increased the specificity of the Bova score for identifying intermediate-high–risk patients from about 93% to 98% in the study, which was recently published in the journal CHEST.

“Although standard dichotomization of HR [i.e., HR less than 110 vs. greater than 110 bpm] may be useful for guideline recommendations, our results will allow for more accuracy regarding clinical decision-making,” wrote lead author Ana Jaureguízar, MD, of the University of Alcalá in Madrid, on behalf of the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) investigators.
 

Intuitive findings inform future research

These observational findings are intuitive and do at least have the potential to inform the design of future randomized clinical trials, according to Albert J. Polito, MD, chief of the division of pulmonary medicine and medical director for the lung center at Mercy Medical Center in Baltimore.

“In medicine, there is a spectrum of risk,” Dr. Polito said in an interview. “While we love our cutoffs, which in this case has traditionally always been that 110 beats per minute for heart rate, it makes sense that there would be some range of risks of bad outcomes.”

Building on the observations of the present study, subsequent prospective randomized studies could potentially aim to determine, for example, when thrombolytic therapy should be considered in nonhypotensive patients with acute PE and higher heart rates.

“It would not be easy to design, but it’s a straightforward question to ask whether patients with the highest heart rates are the ones who potentially might benefit the most from thrombolytic therapy,” Dr. Polito said.
 

Value of alternative HR cutoffs

Heart rate is a simple and easily available vital sign that is clearly linked to prognosis in patients with pulmonary embolism, authors of the RIETE registry study say in their report. Accordingly, a heart rate threshold of 110 bpm has made its way into scoring systems that seek to identify low-risk patients, such as the sPESI, and those focused on identifying higher-risk patients, such as the Bova score.

However, it has not been clear whether alternative HR cutoffs would improve upon the 110-bpm threshold, they added. At the low-risk end, more accurate scoring systems could optimize the selection of patients for home treatment, while at the intermediate-high–risk end, they could better select patients for close monitoring or advanced PE treatments.
 

Better granularity on heart rate risks?

To better define the prognostic value of different heart rate thresholds, investigators analyzed data from RIETE, a large, ongoing, multinational prospective registry including patients with objectively confirmed acute venous thromboembolism.

For 44,331 consecutive nonhypotensive symptomatic PEs, the overall rate of 30-day all-cause mortality was 5.1%, and the 30-day PE-related mortality was 1.9%, the authors report.

Significantly poorer outcomes were seen in patients with higher heart rates as compared to patients in the 80-99 bpm range, they also found. As compared to that reference range, odds ratios for 30-day all-cause death ranged from 1.5 for heart rates of 100-109, up to 2.4 for those with heart rates of 140 bpm or greater.

Likewise, patients with higher heart rates had a 1.7- to 2.4-fold greater risk of 30-day PE-related death as compared to the 80- to 99-bpm reference range, while patients with lower heart rates had lesser risk, the data published in CHEST show.
 

Toward refinement of prognostic scoring

Next, investigators sought to refine the prognostic scoring systems for low-risk PE (sPESI) and intermediate-high–risk PE (Bova).

For sPESI, they found that dropping the cutoff value from 110 to 100 bpm increased the sensitivity of the score from 93.4% to 95.3%. Going down even further to 80 bpm increased sensitivity to 98.8%, according to the report.

By going down from 110 to 80 bpm, the proportion of patients defined as low-risk dropped from 35% to 12%, according to the investigators.

For the Bova score, increasing the cutoff value from 110 to 120 bpm likewise increased specificity from 93.2% to 95%, while going up even further to 140 bpm increased specificity to 98.0%, the report shows.

In sensitivity analyses, the findings were not impacted by excluding younger patients, those who received reperfusion therapies, or those with atrial fibrillation, according to the study findings.
 

Potential implications for clinical practice

Taken together, these findings could serve as a resource to inform discussions regarding PE management that include whether home therapy or use of thrombolytic therapy is appropriate, investigators said in their report.

“For instance, among low-risk sPESI patients, those with borderline tachycardia [i.e., a heart rate between 100-109 bpm] might benefit from initial hospital observation for trending,” they wrote.

Dr. Jaureguízar reported no disclosures. One coinvestigator reported funding support from the Institute of Health Carlos III (ISCIII) and the European Development Regional Fund (ERDF). One coinvestigator reported consulting in litigation involving two models of inferior vena cava filters.

Dr. Polito reported no disclosures.

Groundbreaking results from the EMPEROR-Preserved trial did more than establish for the first time that a drug, empagliflozin, has clearly proven efficacy for treating patients with heart failure with preserved ejection fraction (HFpEF). The results also helped catalyze a paradigm shift in how heart failure thought leaders think about the role of ejection fraction for making important distinctions among patients with heart failure.

Mitchel L. Zoler, MDedge News

EMPEROR-Preserved may also be the final nail in the coffin for defining patients with heart failure as having HFpEF or heart failure with reduced ejection fraction (HFrEF).

This new consensus essentially throws out left ventricular ejection fraction (EF) as the key metric for matching patients to heart failure treatments. Experts have instead begun suggesting a more unified treatment approach for all heart failure patients regardless of their EF.
 

‘Forget about ejection fraction’

“We encourage you to forget about ejection fraction,” declared Milton Packer, MD, during discussion at a session of the annual scientific meeting of the Heart Failure Society of America. “We certainly encourage you to forget about an ejection fraction of less than 40%” as having special significance,” added Dr. Packer, a lead investigator for both the EMPEROR-Reduced and EMPEROR-Preserved trials (which researchers combined in a unified analysis with a total of 9,718 patients with heart failure called EMPEROR-Pooled), and a heart failure researcher at Baylor University Medical Center in Dallas.

“The 40% ejection fraction divide is artificial. It was created in 2003 as part of a trial design, but it has no physiological significance,” Dr. Packer explained. A much better way to distinguish systolic and diastolic heart failure is by strain assessment rather than by ejection fraction. “Strain is a measure of myocardial shortening, a measure of what the heart does. Ejection fraction is a measure of volume,” said Dr. Packer. “Sign me up to get rid of ejection fraction,” he added.

“Ejection fraction is not as valuable as we thought for distinguishing the therapeutic benefit” of heart failure drugs, agreed Marvin A. Konstam, MD, professor of medicine at Tufts University and chief physician executive of the CardioVascular Center of Tufts Medical Center, both in Boston, who spoke during a different session at the meeting.

“It would easier if we didn’t spend time parsing this number,” ejection fraction, commented Clyde W. Yancy, MD, professor of medicine and chief of cardiology at Northwestern Medicine in Chicago. “Wouldn’t it be easier if we said that every patient with heart failure needs to receive one agent from each of the four [pillar] drug classes, and put them in a polypill” at reduced dosages, he proposed, envisioning one potential consequence of jettisoning ejection fraction.

The four pillar drug classes, recently identified as essential for patients with HFrEF but until now not endorsed for patients with HFpEF, are the sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin (Jardiance); an angiotensin receptor blocker neprilysin inhibitor compound such as sacubitril/valsartan (Entresto); beta-blockers; and mineralocorticoid receptor antagonists such as spironolactone and eplerenone.
 

An opportunity for ‘simpler and easier’ treatments

“This is an opportunity to disrupt the way we’ve been doing things and think about something that is simpler and easier,” said Dr. Yancy, who chaired some of the panels serially formed by the American Heart Association and American College of Cardiology to write guidelines for treating heart failure. “An approach that would be easier to implement without worrying about staggering the start of each drug class and an incessant focus on titrating individual elements and taking 6 months to get to a certain place.”

Results from EMPEROR-Preserved and the combined EMPEROR-Pooled analysis triggered these paradigm-shifting sentiments by showing clear evidence that treatment with empagliflozin exerts consistent benefit – and is consistently safe – for patients with heart failure across a spectrum of EFs, from less than 25% to 64%, though its performance in patients with HFpEF and EFs of 65% or greater in the EMPEROR-Preserved trial remains unclear.

The consequence is that clinicians should feel comfortable prescribing empagliflozin to most patients with heart failure without regard to EF, even patients with EF values in the mid-60% range.

The EMPEROR-Preserved results showed a clear signal of attenuated benefit among patients with an EF of 65% or greater “on a population basis,” stressed Dr. Packer. “But on an individual basis, ejection fraction is not that reproducible, so measuring ejection fraction will not help you determine whom to treat or not treat. “

“There is significant variability” measuring EF using the most common modality, echocardiography, noted Javed Butler, MD, an EMPEROR coinvestigator who also spoke at the meeting session. A person with a measured EF of 65% could actually have a value that may be as low as 58% or as high as about 72%, noted Dr. Butler, who is professor and chair of medicine at the University of Mississippi, Jackson. The upshot is that any patient diagnosed with heart failure should receive an SGLT2 inhibitor “irrespective of their ejection fraction,” Dr. Butler advised.

“Ejection fraction is very crude, and probably not sufficient to identify a phenotype,” for treatment, said Dr. Yancy. “The real takeaway may be that we need to revisit what we call HFrEF, and then let that be the new standard for treatment.”

“Is [an EF of] 60% the new 40%?” asked Dr. Packer, implying that the answer was yes.
 

Results from several trials suggest redefining HFrEF

The idea that patients without traditionally defined HFrEF – an EF of 40% or less – could also benefit from other classes of heart failure drugs has been gestating for a while, and then rose to a new level with the August 2021 report of results from EMPEROR-Preserved. Two years ago, in September 2019, Dr. Butler, Dr. Packer, and a third colleague advanced the notion of redefining HFrEF by raising the ejection fraction ceiling in a published commentary.

They cited the experience with the angiotensin receptor blocker candesartan in a post hoc analysis of data collected in the CHARM-Preserved trial, which showed a strong signal of benefit in the subgroup of patients with EFs of 41%-49%, but not in those with an EF of 50% or higher. This finding prompted Dr. Konstam to express doubts about relying on EF to define heart failure subgroups in trials and guide management in a commentary published more than 3 years ago.

Another crack in the traditional EF framework came from analysis of results from the TOPCAT trial that tested spironolactone as a treatment for patients with HFpEF, according to the 2019 opinion published by Dr. Butler and Dr. Packer. Once again a post hoc analysis, this time using data from TOPCAT, suggested a benefit from the mineralocorticoid receptor antagonist spironolactone in patients with heart failure and an EF of 45%-49% (45% was the minimum EF for enrollment into the study).

Recently, data from a third trial that tested sacubitril/valsartan in patients with HFpEF, PARAGON-HF, showed benefit among patients with EFs below the study median of 57%. This finding led the Food and Drug Administration in February 2021 to amend its initial approval for sacubitril/valsartan by removing a specific EF ceiling from the drug’s indication and instead saying that patient’s receiving the drug should have a “below normal” EF.

Writing in a recent commentary, Dr. Yancy called the FDA’s action on sacubitril/valsartan “reasonable,” and that the subgroup assessment of data from the PARAGON-HF trial creates a “new, reasonably evidence-based therapy for HFpEF.” He also predicted that guideline-writing panels will “likely align with a permissive statement of indication” for sacubitril/valsartan in patients with HFpEF, especially those with EFs of less than 57%.

The idea of using an SGLT2 inhibitor like empagliflozin on all heart failure patients, and also adding agents like sacubitril/valsartan and spironolactone in patients with HFpEF and EFs in the mid-50% range or lower may take some time to catch on, but it already has one influential advocate.

“If a patient has HFpEF with an EF of less than 55%, use quadruple-class therapy,” summed up Dr. Butler during the HFSA session, while also suggesting prescribing an SGLT2 inhibitor to essentially all patients with heart failure regardless of their EF.

The EMPEROR-Preserved and EMPEROR-Reduced trials and the EMPEROR-Pooled analysis were sponsored by Boehringer Ingelheim and Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Packer has had financial relationships with BI and Lilly and numerous other companies. Dr. Konstam has served on data monitoring committees for trials funded by Boehringer Ingelheim and by Amgen, Luitpold, and Pfizer, and has been a consultant to Arena, LivaNova, Merck, SC Pharma, and Takeda. Dr. Yancy had no disclosures. Dr. Butler has had financial relationships with Boehringer Ingelheim and numerous other companies.

mzoler@mdedge.com

Groundbreaking results from the EMPEROR-Preserved trial did more than establish for the first time that a drug, empagliflozin, has clearly proven efficacy for treating patients with heart failure with preserved ejection fraction (HFpEF). The results also helped catalyze a paradigm shift in how heart failure thought leaders think about the role of ejection fraction for making important distinctions among patients with heart failure.

Mitchel L. Zoler, MDedge News

EMPEROR-Preserved may also be the final nail in the coffin for defining patients with heart failure as having HFpEF or heart failure with reduced ejection fraction (HFrEF).

This new consensus essentially throws out left ventricular ejection fraction (EF) as the key metric for matching patients to heart failure treatments. Experts have instead begun suggesting a more unified treatment approach for all heart failure patients regardless of their EF.
 

‘Forget about ejection fraction’

“We encourage you to forget about ejection fraction,” declared Milton Packer, MD, during discussion at a session of the annual scientific meeting of the Heart Failure Society of America. “We certainly encourage you to forget about an ejection fraction of less than 40%” as having special significance,” added Dr. Packer, a lead investigator for both the EMPEROR-Reduced and EMPEROR-Preserved trials (which researchers combined in a unified analysis with a total of 9,718 patients with heart failure called EMPEROR-Pooled), and a heart failure researcher at Baylor University Medical Center in Dallas.

“The 40% ejection fraction divide is artificial. It was created in 2003 as part of a trial design, but it has no physiological significance,” Dr. Packer explained. A much better way to distinguish systolic and diastolic heart failure is by strain assessment rather than by ejection fraction. “Strain is a measure of myocardial shortening, a measure of what the heart does. Ejection fraction is a measure of volume,” said Dr. Packer. “Sign me up to get rid of ejection fraction,” he added.

“Ejection fraction is not as valuable as we thought for distinguishing the therapeutic benefit” of heart failure drugs, agreed Marvin A. Konstam, MD, professor of medicine at Tufts University and chief physician executive of the CardioVascular Center of Tufts Medical Center, both in Boston, who spoke during a different session at the meeting.

“It would easier if we didn’t spend time parsing this number,” ejection fraction, commented Clyde W. Yancy, MD, professor of medicine and chief of cardiology at Northwestern Medicine in Chicago. “Wouldn’t it be easier if we said that every patient with heart failure needs to receive one agent from each of the four [pillar] drug classes, and put them in a polypill” at reduced dosages, he proposed, envisioning one potential consequence of jettisoning ejection fraction.

The four pillar drug classes, recently identified as essential for patients with HFrEF but until now not endorsed for patients with HFpEF, are the sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin (Jardiance); an angiotensin receptor blocker neprilysin inhibitor compound such as sacubitril/valsartan (Entresto); beta-blockers; and mineralocorticoid receptor antagonists such as spironolactone and eplerenone.
 

An opportunity for ‘simpler and easier’ treatments

“This is an opportunity to disrupt the way we’ve been doing things and think about something that is simpler and easier,” said Dr. Yancy, who chaired some of the panels serially formed by the American Heart Association and American College of Cardiology to write guidelines for treating heart failure. “An approach that would be easier to implement without worrying about staggering the start of each drug class and an incessant focus on titrating individual elements and taking 6 months to get to a certain place.”

Results from EMPEROR-Preserved and the combined EMPEROR-Pooled analysis triggered these paradigm-shifting sentiments by showing clear evidence that treatment with empagliflozin exerts consistent benefit – and is consistently safe – for patients with heart failure across a spectrum of EFs, from less than 25% to 64%, though its performance in patients with HFpEF and EFs of 65% or greater in the EMPEROR-Preserved trial remains unclear.

The consequence is that clinicians should feel comfortable prescribing empagliflozin to most patients with heart failure without regard to EF, even patients with EF values in the mid-60% range.

The EMPEROR-Preserved results showed a clear signal of attenuated benefit among patients with an EF of 65% or greater “on a population basis,” stressed Dr. Packer. “But on an individual basis, ejection fraction is not that reproducible, so measuring ejection fraction will not help you determine whom to treat or not treat. “

“There is significant variability” measuring EF using the most common modality, echocardiography, noted Javed Butler, MD, an EMPEROR coinvestigator who also spoke at the meeting session. A person with a measured EF of 65% could actually have a value that may be as low as 58% or as high as about 72%, noted Dr. Butler, who is professor and chair of medicine at the University of Mississippi, Jackson. The upshot is that any patient diagnosed with heart failure should receive an SGLT2 inhibitor “irrespective of their ejection fraction,” Dr. Butler advised.

“Ejection fraction is very crude, and probably not sufficient to identify a phenotype,” for treatment, said Dr. Yancy. “The real takeaway may be that we need to revisit what we call HFrEF, and then let that be the new standard for treatment.”

“Is [an EF of] 60% the new 40%?” asked Dr. Packer, implying that the answer was yes.
 

Results from several trials suggest redefining HFrEF

The idea that patients without traditionally defined HFrEF – an EF of 40% or less – could also benefit from other classes of heart failure drugs has been gestating for a while, and then rose to a new level with the August 2021 report of results from EMPEROR-Preserved. Two years ago, in September 2019, Dr. Butler, Dr. Packer, and a third colleague advanced the notion of redefining HFrEF by raising the ejection fraction ceiling in a published commentary.

They cited the experience with the angiotensin receptor blocker candesartan in a post hoc analysis of data collected in the CHARM-Preserved trial, which showed a strong signal of benefit in the subgroup of patients with EFs of 41%-49%, but not in those with an EF of 50% or higher. This finding prompted Dr. Konstam to express doubts about relying on EF to define heart failure subgroups in trials and guide management in a commentary published more than 3 years ago.

Another crack in the traditional EF framework came from analysis of results from the TOPCAT trial that tested spironolactone as a treatment for patients with HFpEF, according to the 2019 opinion published by Dr. Butler and Dr. Packer. Once again a post hoc analysis, this time using data from TOPCAT, suggested a benefit from the mineralocorticoid receptor antagonist spironolactone in patients with heart failure and an EF of 45%-49% (45% was the minimum EF for enrollment into the study).

Recently, data from a third trial that tested sacubitril/valsartan in patients with HFpEF, PARAGON-HF, showed benefit among patients with EFs below the study median of 57%. This finding led the Food and Drug Administration in February 2021 to amend its initial approval for sacubitril/valsartan by removing a specific EF ceiling from the drug’s indication and instead saying that patient’s receiving the drug should have a “below normal” EF.

Writing in a recent commentary, Dr. Yancy called the FDA’s action on sacubitril/valsartan “reasonable,” and that the subgroup assessment of data from the PARAGON-HF trial creates a “new, reasonably evidence-based therapy for HFpEF.” He also predicted that guideline-writing panels will “likely align with a permissive statement of indication” for sacubitril/valsartan in patients with HFpEF, especially those with EFs of less than 57%.

The idea of using an SGLT2 inhibitor like empagliflozin on all heart failure patients, and also adding agents like sacubitril/valsartan and spironolactone in patients with HFpEF and EFs in the mid-50% range or lower may take some time to catch on, but it already has one influential advocate.

“If a patient has HFpEF with an EF of less than 55%, use quadruple-class therapy,” summed up Dr. Butler during the HFSA session, while also suggesting prescribing an SGLT2 inhibitor to essentially all patients with heart failure regardless of their EF.

The EMPEROR-Preserved and EMPEROR-Reduced trials and the EMPEROR-Pooled analysis were sponsored by Boehringer Ingelheim and Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Packer has had financial relationships with BI and Lilly and numerous other companies. Dr. Konstam has served on data monitoring committees for trials funded by Boehringer Ingelheim and by Amgen, Luitpold, and Pfizer, and has been a consultant to Arena, LivaNova, Merck, SC Pharma, and Takeda. Dr. Yancy had no disclosures. Dr. Butler has had financial relationships with Boehringer Ingelheim and numerous other companies.

mzoler@mdedge.com

Groundbreaking results from the EMPEROR-Preserved trial did more than establish for the first time that a drug, empagliflozin, has clearly proven efficacy for treating patients with heart failure with preserved ejection fraction (HFpEF). The results also helped catalyze a paradigm shift in how heart failure thought leaders think about the role of ejection fraction for making important distinctions among patients with heart failure.

Mitchel L. Zoler, MDedge News

EMPEROR-Preserved may also be the final nail in the coffin for defining patients with heart failure as having HFpEF or heart failure with reduced ejection fraction (HFrEF).

This new consensus essentially throws out left ventricular ejection fraction (EF) as the key metric for matching patients to heart failure treatments. Experts have instead begun suggesting a more unified treatment approach for all heart failure patients regardless of their EF.
 

‘Forget about ejection fraction’

“We encourage you to forget about ejection fraction,” declared Milton Packer, MD, during discussion at a session of the annual scientific meeting of the Heart Failure Society of America. “We certainly encourage you to forget about an ejection fraction of less than 40%” as having special significance,” added Dr. Packer, a lead investigator for both the EMPEROR-Reduced and EMPEROR-Preserved trials (which researchers combined in a unified analysis with a total of 9,718 patients with heart failure called EMPEROR-Pooled), and a heart failure researcher at Baylor University Medical Center in Dallas.

“The 40% ejection fraction divide is artificial. It was created in 2003 as part of a trial design, but it has no physiological significance,” Dr. Packer explained. A much better way to distinguish systolic and diastolic heart failure is by strain assessment rather than by ejection fraction. “Strain is a measure of myocardial shortening, a measure of what the heart does. Ejection fraction is a measure of volume,” said Dr. Packer. “Sign me up to get rid of ejection fraction,” he added.

“Ejection fraction is not as valuable as we thought for distinguishing the therapeutic benefit” of heart failure drugs, agreed Marvin A. Konstam, MD, professor of medicine at Tufts University and chief physician executive of the CardioVascular Center of Tufts Medical Center, both in Boston, who spoke during a different session at the meeting.

“It would easier if we didn’t spend time parsing this number,” ejection fraction, commented Clyde W. Yancy, MD, professor of medicine and chief of cardiology at Northwestern Medicine in Chicago. “Wouldn’t it be easier if we said that every patient with heart failure needs to receive one agent from each of the four [pillar] drug classes, and put them in a polypill” at reduced dosages, he proposed, envisioning one potential consequence of jettisoning ejection fraction.

The four pillar drug classes, recently identified as essential for patients with HFrEF but until now not endorsed for patients with HFpEF, are the sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin (Jardiance); an angiotensin receptor blocker neprilysin inhibitor compound such as sacubitril/valsartan (Entresto); beta-blockers; and mineralocorticoid receptor antagonists such as spironolactone and eplerenone.
 

An opportunity for ‘simpler and easier’ treatments

“This is an opportunity to disrupt the way we’ve been doing things and think about something that is simpler and easier,” said Dr. Yancy, who chaired some of the panels serially formed by the American Heart Association and American College of Cardiology to write guidelines for treating heart failure. “An approach that would be easier to implement without worrying about staggering the start of each drug class and an incessant focus on titrating individual elements and taking 6 months to get to a certain place.”

Results from EMPEROR-Preserved and the combined EMPEROR-Pooled analysis triggered these paradigm-shifting sentiments by showing clear evidence that treatment with empagliflozin exerts consistent benefit – and is consistently safe – for patients with heart failure across a spectrum of EFs, from less than 25% to 64%, though its performance in patients with HFpEF and EFs of 65% or greater in the EMPEROR-Preserved trial remains unclear.

The consequence is that clinicians should feel comfortable prescribing empagliflozin to most patients with heart failure without regard to EF, even patients with EF values in the mid-60% range.

The EMPEROR-Preserved results showed a clear signal of attenuated benefit among patients with an EF of 65% or greater “on a population basis,” stressed Dr. Packer. “But on an individual basis, ejection fraction is not that reproducible, so measuring ejection fraction will not help you determine whom to treat or not treat. “

“There is significant variability” measuring EF using the most common modality, echocardiography, noted Javed Butler, MD, an EMPEROR coinvestigator who also spoke at the meeting session. A person with a measured EF of 65% could actually have a value that may be as low as 58% or as high as about 72%, noted Dr. Butler, who is professor and chair of medicine at the University of Mississippi, Jackson. The upshot is that any patient diagnosed with heart failure should receive an SGLT2 inhibitor “irrespective of their ejection fraction,” Dr. Butler advised.

“Ejection fraction is very crude, and probably not sufficient to identify a phenotype,” for treatment, said Dr. Yancy. “The real takeaway may be that we need to revisit what we call HFrEF, and then let that be the new standard for treatment.”

“Is [an EF of] 60% the new 40%?” asked Dr. Packer, implying that the answer was yes.
 

Results from several trials suggest redefining HFrEF

The idea that patients without traditionally defined HFrEF – an EF of 40% or less – could also benefit from other classes of heart failure drugs has been gestating for a while, and then rose to a new level with the August 2021 report of results from EMPEROR-Preserved. Two years ago, in September 2019, Dr. Butler, Dr. Packer, and a third colleague advanced the notion of redefining HFrEF by raising the ejection fraction ceiling in a published commentary.

They cited the experience with the angiotensin receptor blocker candesartan in a post hoc analysis of data collected in the CHARM-Preserved trial, which showed a strong signal of benefit in the subgroup of patients with EFs of 41%-49%, but not in those with an EF of 50% or higher. This finding prompted Dr. Konstam to express doubts about relying on EF to define heart failure subgroups in trials and guide management in a commentary published more than 3 years ago.

Another crack in the traditional EF framework came from analysis of results from the TOPCAT trial that tested spironolactone as a treatment for patients with HFpEF, according to the 2019 opinion published by Dr. Butler and Dr. Packer. Once again a post hoc analysis, this time using data from TOPCAT, suggested a benefit from the mineralocorticoid receptor antagonist spironolactone in patients with heart failure and an EF of 45%-49% (45% was the minimum EF for enrollment into the study).

Recently, data from a third trial that tested sacubitril/valsartan in patients with HFpEF, PARAGON-HF, showed benefit among patients with EFs below the study median of 57%. This finding led the Food and Drug Administration in February 2021 to amend its initial approval for sacubitril/valsartan by removing a specific EF ceiling from the drug’s indication and instead saying that patient’s receiving the drug should have a “below normal” EF.

Writing in a recent commentary, Dr. Yancy called the FDA’s action on sacubitril/valsartan “reasonable,” and that the subgroup assessment of data from the PARAGON-HF trial creates a “new, reasonably evidence-based therapy for HFpEF.” He also predicted that guideline-writing panels will “likely align with a permissive statement of indication” for sacubitril/valsartan in patients with HFpEF, especially those with EFs of less than 57%.

The idea of using an SGLT2 inhibitor like empagliflozin on all heart failure patients, and also adding agents like sacubitril/valsartan and spironolactone in patients with HFpEF and EFs in the mid-50% range or lower may take some time to catch on, but it already has one influential advocate.

“If a patient has HFpEF with an EF of less than 55%, use quadruple-class therapy,” summed up Dr. Butler during the HFSA session, while also suggesting prescribing an SGLT2 inhibitor to essentially all patients with heart failure regardless of their EF.

The EMPEROR-Preserved and EMPEROR-Reduced trials and the EMPEROR-Pooled analysis were sponsored by Boehringer Ingelheim and Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Packer has had financial relationships with BI and Lilly and numerous other companies. Dr. Konstam has served on data monitoring committees for trials funded by Boehringer Ingelheim and by Amgen, Luitpold, and Pfizer, and has been a consultant to Arena, LivaNova, Merck, SC Pharma, and Takeda. Dr. Yancy had no disclosures. Dr. Butler has had financial relationships with Boehringer Ingelheim and numerous other companies.

mzoler@mdedge.com

Patients with type 2 diabetes who underwent bariatric surgery commonly experienced remission, but there was little increase in rates of remission above a threshold of 20% total weight loss (TWL), according to a retrospective analysis of 5,928 patients with diabetes in an integrated health care system in Southern California.

The findings should reassure physicians and patients that surgery will be beneficial, according to lead author Karen Coleman, PhD, professor of health systems science at Kaiser Permanente Southern California.

Dr. Coleman has heard from many physicians saying they recommend against bariatric surgery because of concerns that patients gain weight back and therefore won’t get a long-term benefit, but this is not supported by the literature. “Hundreds of articles at this point show that this simply is not true. In addition, providers seem to think about bariatric surgery as an ‘all or none’ treatment. Gaining any weight back means that patients ‘fail.’ Weight regain is a normal part of massive weight loss; however, maintaining a certain amount of weight loss still provides benefits for patients, especially those with cardiovascular conditions like diabetes,” said Dr. Coleman.

Most patients lose 20%-30% of their body weight after bariatric surgery, but they don’t have to lose that much to see an improvement in type 2 diabetes (T2D). In addition, if patients lose that much or more, and then gain some weight back, it doesn’t eliminate benefit. “Although we did not measure weight regain, a corollary statement is that patients can regain some of the weight they lose, but if they stay around 20% of their total weight lost, then their diabetes still remits,” said Dr. Coleman.

In the past, some standards to treat severe weight loss and metabolic disease called for 50% or more TWL. More recent standards target a 30% threshold. “We want physicians to understand that they need to have more reasonable expectations of weight loss with surgery and that these reasonable expectations still result in profound improvements in cardiovascular risk, death, and quality of life. A 20% TWL threshold is easier for these patients to get to, and like other patients, they still get the benefit. So even if these patients may not have as much weight loss they can still benefit from the surgery for their diabetes,” Dr. Coleman added.

Physicians have long assumed that the effect of bariatric surgery on T2D remission is tied to weight loss, but this has been tested only recently. Previous studies found a link and suggested that 25% TWL may be the needed threshold, but more data are needed, especially for sleeve gastrectomy.

In the current study, published in Diabetes Care, 73% of patients were female. Mean age was 49.8 years, and mean body mass index was 43.8 kg/m². Fifty-seven percent underwent Roux-en-Y gastric bypass (RYGB). Follow-up averaged 5.9 years. Overall, 71% of patients had an initial remission of their diabetes (72% RYGB, 70% sleeve). The average time to remission was 1.0 years. The researchers categorized participants by percentage TWL. Compared with the 0%-5% group, each 5% increase in TWL was linked with a greater likelihood of achieving remission: 5%-10%, hazard ratio 1.22 (P = .23); 10%-15%, HR 1.97 (95% confidence interval, 1.47-2.64); 15%-20%, HR 2.33 (95% CI, 1.74-3.11); 20%-25%, HR 2.81 (95% CI, 2.11-3.75); 25%-30%, HR 2.88 (95% CI, 2.16-3.83); >30%, HR, 2.92 (95% CI, 2.19-3.88). Categories above 25% TWL had remission rates similar to those of the 20%-25% group. Those in the over 20% TWL group who were taking insulin at the time of surgery had better odds of T2D remission than did those in the 0%-5% TWL group who were not taking insulin (HR, 2.18; 95% CI, 1.64-2.88).

The study is a useful addition to the literature on the topic, according to W. Timothy Garvey, MD, director of the diabetes research center at the University of Alabama at Birmingham. “This tends to quantify it a little bit more than people might have had before,” he said.

MDedge News

Dr. Garvey noted that there were wide error bars in the outcomes grouped by TWL, and suggested that individual results of surgery may vary widely. “There are plenty of individuals in each of those bins that will require more weight loss for remission or less weight loss. That’s just the average of people in that weight loss category. So if a clinician is going to use this information, they need to take it with a grain of salt and realize that, just because they reach that 20% weight loss threshold, it doesn’t mean that their patient is going to go into remission. As a loose guide, as something to shoot for, I think this is valuable,” he added.

Dr. Coleman recommended that physicians not wait too long to suggest bariatric surgery, since patients are likely to have better outcomes if they are healthier going in. “Bariatric surgery is by far the most effective long-term treatment we have for severe obesity and we should be treating it as a secondary prevention strategy, not a last resort to save people’s lives. Bariatric surgery cannot regrow the cells in the pancreas that make insulin. So if we wait until patients with type 2 diabetes are insulin dependent to offer bariatric surgery, we are compromising the great effect surgery can have for them,” said Dr. Coleman.

Patients with type 2 diabetes who underwent bariatric surgery commonly experienced remission, but there was little increase in rates of remission above a threshold of 20% total weight loss (TWL), according to a retrospective analysis of 5,928 patients with diabetes in an integrated health care system in Southern California.

The findings should reassure physicians and patients that surgery will be beneficial, according to lead author Karen Coleman, PhD, professor of health systems science at Kaiser Permanente Southern California.

Dr. Coleman has heard from many physicians saying they recommend against bariatric surgery because of concerns that patients gain weight back and therefore won’t get a long-term benefit, but this is not supported by the literature. “Hundreds of articles at this point show that this simply is not true. In addition, providers seem to think about bariatric surgery as an ‘all or none’ treatment. Gaining any weight back means that patients ‘fail.’ Weight regain is a normal part of massive weight loss; however, maintaining a certain amount of weight loss still provides benefits for patients, especially those with cardiovascular conditions like diabetes,” said Dr. Coleman.

Most patients lose 20%-30% of their body weight after bariatric surgery, but they don’t have to lose that much to see an improvement in type 2 diabetes (T2D). In addition, if patients lose that much or more, and then gain some weight back, it doesn’t eliminate benefit. “Although we did not measure weight regain, a corollary statement is that patients can regain some of the weight they lose, but if they stay around 20% of their total weight lost, then their diabetes still remits,” said Dr. Coleman.

In the past, some standards to treat severe weight loss and metabolic disease called for 50% or more TWL. More recent standards target a 30% threshold. “We want physicians to understand that they need to have more reasonable expectations of weight loss with surgery and that these reasonable expectations still result in profound improvements in cardiovascular risk, death, and quality of life. A 20% TWL threshold is easier for these patients to get to, and like other patients, they still get the benefit. So even if these patients may not have as much weight loss they can still benefit from the surgery for their diabetes,” Dr. Coleman added.

Physicians have long assumed that the effect of bariatric surgery on T2D remission is tied to weight loss, but this has been tested only recently. Previous studies found a link and suggested that 25% TWL may be the needed threshold, but more data are needed, especially for sleeve gastrectomy.

In the current study, published in Diabetes Care, 73% of patients were female. Mean age was 49.8 years, and mean body mass index was 43.8 kg/m². Fifty-seven percent underwent Roux-en-Y gastric bypass (RYGB). Follow-up averaged 5.9 years. Overall, 71% of patients had an initial remission of their diabetes (72% RYGB, 70% sleeve). The average time to remission was 1.0 years. The researchers categorized participants by percentage TWL. Compared with the 0%-5% group, each 5% increase in TWL was linked with a greater likelihood of achieving remission: 5%-10%, hazard ratio 1.22 (P = .23); 10%-15%, HR 1.97 (95% confidence interval, 1.47-2.64); 15%-20%, HR 2.33 (95% CI, 1.74-3.11); 20%-25%, HR 2.81 (95% CI, 2.11-3.75); 25%-30%, HR 2.88 (95% CI, 2.16-3.83); >30%, HR, 2.92 (95% CI, 2.19-3.88). Categories above 25% TWL had remission rates similar to those of the 20%-25% group. Those in the over 20% TWL group who were taking insulin at the time of surgery had better odds of T2D remission than did those in the 0%-5% TWL group who were not taking insulin (HR, 2.18; 95% CI, 1.64-2.88).

The study is a useful addition to the literature on the topic, according to W. Timothy Garvey, MD, director of the diabetes research center at the University of Alabama at Birmingham. “This tends to quantify it a little bit more than people might have had before,” he said.

MDedge News

Dr. Garvey noted that there were wide error bars in the outcomes grouped by TWL, and suggested that individual results of surgery may vary widely. “There are plenty of individuals in each of those bins that will require more weight loss for remission or less weight loss. That’s just the average of people in that weight loss category. So if a clinician is going to use this information, they need to take it with a grain of salt and realize that, just because they reach that 20% weight loss threshold, it doesn’t mean that their patient is going to go into remission. As a loose guide, as something to shoot for, I think this is valuable,” he added.

Dr. Coleman recommended that physicians not wait too long to suggest bariatric surgery, since patients are likely to have better outcomes if they are healthier going in. “Bariatric surgery is by far the most effective long-term treatment we have for severe obesity and we should be treating it as a secondary prevention strategy, not a last resort to save people’s lives. Bariatric surgery cannot regrow the cells in the pancreas that make insulin. So if we wait until patients with type 2 diabetes are insulin dependent to offer bariatric surgery, we are compromising the great effect surgery can have for them,” said Dr. Coleman.

Patients with type 2 diabetes who underwent bariatric surgery commonly experienced remission, but there was little increase in rates of remission above a threshold of 20% total weight loss (TWL), according to a retrospective analysis of 5,928 patients with diabetes in an integrated health care system in Southern California.

The findings should reassure physicians and patients that surgery will be beneficial, according to lead author Karen Coleman, PhD, professor of health systems science at Kaiser Permanente Southern California.

Dr. Coleman has heard from many physicians saying they recommend against bariatric surgery because of concerns that patients gain weight back and therefore won’t get a long-term benefit, but this is not supported by the literature. “Hundreds of articles at this point show that this simply is not true. In addition, providers seem to think about bariatric surgery as an ‘all or none’ treatment. Gaining any weight back means that patients ‘fail.’ Weight regain is a normal part of massive weight loss; however, maintaining a certain amount of weight loss still provides benefits for patients, especially those with cardiovascular conditions like diabetes,” said Dr. Coleman.

Most patients lose 20%-30% of their body weight after bariatric surgery, but they don’t have to lose that much to see an improvement in type 2 diabetes (T2D). In addition, if patients lose that much or more, and then gain some weight back, it doesn’t eliminate benefit. “Although we did not measure weight regain, a corollary statement is that patients can regain some of the weight they lose, but if they stay around 20% of their total weight lost, then their diabetes still remits,” said Dr. Coleman.

In the past, some standards to treat severe weight loss and metabolic disease called for 50% or more TWL. More recent standards target a 30% threshold. “We want physicians to understand that they need to have more reasonable expectations of weight loss with surgery and that these reasonable expectations still result in profound improvements in cardiovascular risk, death, and quality of life. A 20% TWL threshold is easier for these patients to get to, and like other patients, they still get the benefit. So even if these patients may not have as much weight loss they can still benefit from the surgery for their diabetes,” Dr. Coleman added.

Physicians have long assumed that the effect of bariatric surgery on T2D remission is tied to weight loss, but this has been tested only recently. Previous studies found a link and suggested that 25% TWL may be the needed threshold, but more data are needed, especially for sleeve gastrectomy.

In the current study, published in Diabetes Care, 73% of patients were female. Mean age was 49.8 years, and mean body mass index was 43.8 kg/m². Fifty-seven percent underwent Roux-en-Y gastric bypass (RYGB). Follow-up averaged 5.9 years. Overall, 71% of patients had an initial remission of their diabetes (72% RYGB, 70% sleeve). The average time to remission was 1.0 years. The researchers categorized participants by percentage TWL. Compared with the 0%-5% group, each 5% increase in TWL was linked with a greater likelihood of achieving remission: 5%-10%, hazard ratio 1.22 (P = .23); 10%-15%, HR 1.97 (95% confidence interval, 1.47-2.64); 15%-20%, HR 2.33 (95% CI, 1.74-3.11); 20%-25%, HR 2.81 (95% CI, 2.11-3.75); 25%-30%, HR 2.88 (95% CI, 2.16-3.83); >30%, HR, 2.92 (95% CI, 2.19-3.88). Categories above 25% TWL had remission rates similar to those of the 20%-25% group. Those in the over 20% TWL group who were taking insulin at the time of surgery had better odds of T2D remission than did those in the 0%-5% TWL group who were not taking insulin (HR, 2.18; 95% CI, 1.64-2.88).

The study is a useful addition to the literature on the topic, according to W. Timothy Garvey, MD, director of the diabetes research center at the University of Alabama at Birmingham. “This tends to quantify it a little bit more than people might have had before,” he said.

MDedge News

Dr. Garvey noted that there were wide error bars in the outcomes grouped by TWL, and suggested that individual results of surgery may vary widely. “There are plenty of individuals in each of those bins that will require more weight loss for remission or less weight loss. That’s just the average of people in that weight loss category. So if a clinician is going to use this information, they need to take it with a grain of salt and realize that, just because they reach that 20% weight loss threshold, it doesn’t mean that their patient is going to go into remission. As a loose guide, as something to shoot for, I think this is valuable,” he added.

Dr. Coleman recommended that physicians not wait too long to suggest bariatric surgery, since patients are likely to have better outcomes if they are healthier going in. “Bariatric surgery is by far the most effective long-term treatment we have for severe obesity and we should be treating it as a secondary prevention strategy, not a last resort to save people’s lives. Bariatric surgery cannot regrow the cells in the pancreas that make insulin. So if we wait until patients with type 2 diabetes are insulin dependent to offer bariatric surgery, we are compromising the great effect surgery can have for them,” said Dr. Coleman.