Hypertension

Replacing regular salt with a salt substitute reduced the incidence of new hypertension compared with a usual salt group, without provoking hypotension, new data showed.

Among a group of older adults with normal blood pressure (BP), those who swapped table salt for a salt substitute — consisting of 62.5% sodium chloride, 25% potassium chloride, and 12.5% flavorings — were 40% less apt to develop hypertension over 2 years than were peers who continued with regular salt.

“From a public health perspective, our study results indicate that everyone in the whole population, either hypertensive or normotensive, can benefit from replacing regular salt with potassium-enriched salt substitute,” lead author Yangfeng Wu, MD, PhD, professor and executive associate director, Peking University Clinical Research Institute, Beijing, China, told this news organization.

“Thus, salt substitution should be considered and promoted as a whole-population strategy for prevention and control of hypertension and cardiovascular disease,” Dr. Wu said.

The study was published online on February 12 in the Journal of the American College of Cardiology.

“Considering the failing strategy to reduce the intake of salt worldwide, salt substitution is an attractive alternative. The food industry and authorities should prepare strategies for wide-scale implementation of salt substitutes,” Rik Olde Engberink, MD, PhD, with Amsterdam University Medical Center, wrote in a linked editorial.

Population Strategy for Hypertension Prevention

The DECIDE-Salt clinical trial was a cluster-randomized trial conducted in 48 residential elderly care facilities in China with 1612 participants (1230 men and 382 women) aged 55 years or older. The trial assessed the effect of two sodium reduction strategies in lowering BP — replacing salt with a salt substitute and progressive restriction of the salt supply.

In the original study, the salt substitute intervention lowered systolic/diastolic BP significantly by 7.1/1.9 mm Hg vs the usual salt group. The progressive restriction of salt had no impact on BP vs usual salt or salt substitute groups.

This post hoc analysis of DECIDE-Salt focused on 609 participants (mean age, 71 years; 74% men) who were normotensive at baseline (mean BP, 122/74 mm Hg), with 298 in the usual salt group and 313 in the salt substitute group.

Compared with the usual salt group, the salt substitute group had a lower incidence of hypertension over 2 years (adjusted hazard ratio [HR], 0.60; 95% CI, 0.39-0.92; P = .02), with no increase in episodes of hypotension (P = .76).

From baseline to 2 years, there was no change in mean systolic/diastolic BP in the salt substitution group, whereas the usual salt group experienced a significant increase in systolic/diastolic BP (mean, 7.0/2.1 mm Hg).

The post hoc results from DECIDE-Salt are in line with a previous study from Peru, which also investigated mostly normotensive participants and reported a 51% lower risk of developing hypertension in the salt substitute group, as reported previously by this news organization.

“Although the study involved only participants aged 55 years and above, the epidemic of hypertension and its relations with sodium and potassium intake are not limited to older adults. Thus, we believe the salt substitution should also be beneficial to younger adults,” Dr. Wu said.

Notable Analysis

Reached for comment, Ankur Shah, MD, Division of Kidney Disease and Hypertension, Warren Alpert Medical School of Brown University, Providence, Rhode Island, said the study is “notable due to the limited and conflicting reports on the effects of salt substitution in individuals with normal blood pressure.”

“There is a growing body of literature on the impact of salt substitution in controlling hypertension, but less is known about prevention,” Dr. Shah, who was not involved in the study, told this news organization.

“The study certainly has population-level implications, as the design of a cluster-randomized trial at the facility level makes for a clear path to implementation — sodium substitution in elderly care facilities. That said, this is also the greatest limitation — extrapolating to the general population may not be accurate,” Dr. Shah noted.

There is also a potential concern with salt substitutes in patients with kidney disease, who typically are advised to lower potassium intake.

“Supplementing potassium could result in hyperkalemia, which can be life-threatening if severe, and patients taking medications that interfere with the kidney’s ability to excrete potassium should be cautious as well,” Dr. Shah said.

This research was supported by a grant from the National Key Research and Development Program, Ministry of Science and Technology of China. China Salt General Company at Yulin provided the usual salt and salt substitute used in the study free of charge. Dr. Wu, Dr. Engberink, and Dr. Shah had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Replacing regular salt with a salt substitute reduced the incidence of new hypertension compared with a usual salt group, without provoking hypotension, new data showed.

Among a group of older adults with normal blood pressure (BP), those who swapped table salt for a salt substitute — consisting of 62.5% sodium chloride, 25% potassium chloride, and 12.5% flavorings — were 40% less apt to develop hypertension over 2 years than were peers who continued with regular salt.

“From a public health perspective, our study results indicate that everyone in the whole population, either hypertensive or normotensive, can benefit from replacing regular salt with potassium-enriched salt substitute,” lead author Yangfeng Wu, MD, PhD, professor and executive associate director, Peking University Clinical Research Institute, Beijing, China, told this news organization.

“Thus, salt substitution should be considered and promoted as a whole-population strategy for prevention and control of hypertension and cardiovascular disease,” Dr. Wu said.

The study was published online on February 12 in the Journal of the American College of Cardiology.

“Considering the failing strategy to reduce the intake of salt worldwide, salt substitution is an attractive alternative. The food industry and authorities should prepare strategies for wide-scale implementation of salt substitutes,” Rik Olde Engberink, MD, PhD, with Amsterdam University Medical Center, wrote in a linked editorial.

Population Strategy for Hypertension Prevention

The DECIDE-Salt clinical trial was a cluster-randomized trial conducted in 48 residential elderly care facilities in China with 1612 participants (1230 men and 382 women) aged 55 years or older. The trial assessed the effect of two sodium reduction strategies in lowering BP — replacing salt with a salt substitute and progressive restriction of the salt supply.

In the original study, the salt substitute intervention lowered systolic/diastolic BP significantly by 7.1/1.9 mm Hg vs the usual salt group. The progressive restriction of salt had no impact on BP vs usual salt or salt substitute groups.

This post hoc analysis of DECIDE-Salt focused on 609 participants (mean age, 71 years; 74% men) who were normotensive at baseline (mean BP, 122/74 mm Hg), with 298 in the usual salt group and 313 in the salt substitute group.

Compared with the usual salt group, the salt substitute group had a lower incidence of hypertension over 2 years (adjusted hazard ratio [HR], 0.60; 95% CI, 0.39-0.92; P = .02), with no increase in episodes of hypotension (P = .76).

From baseline to 2 years, there was no change in mean systolic/diastolic BP in the salt substitution group, whereas the usual salt group experienced a significant increase in systolic/diastolic BP (mean, 7.0/2.1 mm Hg).

The post hoc results from DECIDE-Salt are in line with a previous study from Peru, which also investigated mostly normotensive participants and reported a 51% lower risk of developing hypertension in the salt substitute group, as reported previously by this news organization.

“Although the study involved only participants aged 55 years and above, the epidemic of hypertension and its relations with sodium and potassium intake are not limited to older adults. Thus, we believe the salt substitution should also be beneficial to younger adults,” Dr. Wu said.

Notable Analysis

Reached for comment, Ankur Shah, MD, Division of Kidney Disease and Hypertension, Warren Alpert Medical School of Brown University, Providence, Rhode Island, said the study is “notable due to the limited and conflicting reports on the effects of salt substitution in individuals with normal blood pressure.”

“There is a growing body of literature on the impact of salt substitution in controlling hypertension, but less is known about prevention,” Dr. Shah, who was not involved in the study, told this news organization.

“The study certainly has population-level implications, as the design of a cluster-randomized trial at the facility level makes for a clear path to implementation — sodium substitution in elderly care facilities. That said, this is also the greatest limitation — extrapolating to the general population may not be accurate,” Dr. Shah noted.

There is also a potential concern with salt substitutes in patients with kidney disease, who typically are advised to lower potassium intake.

“Supplementing potassium could result in hyperkalemia, which can be life-threatening if severe, and patients taking medications that interfere with the kidney’s ability to excrete potassium should be cautious as well,” Dr. Shah said.

This research was supported by a grant from the National Key Research and Development Program, Ministry of Science and Technology of China. China Salt General Company at Yulin provided the usual salt and salt substitute used in the study free of charge. Dr. Wu, Dr. Engberink, and Dr. Shah had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Replacing regular salt with a salt substitute reduced the incidence of new hypertension compared with a usual salt group, without provoking hypotension, new data showed.

Among a group of older adults with normal blood pressure (BP), those who swapped table salt for a salt substitute — consisting of 62.5% sodium chloride, 25% potassium chloride, and 12.5% flavorings — were 40% less apt to develop hypertension over 2 years than were peers who continued with regular salt.

“From a public health perspective, our study results indicate that everyone in the whole population, either hypertensive or normotensive, can benefit from replacing regular salt with potassium-enriched salt substitute,” lead author Yangfeng Wu, MD, PhD, professor and executive associate director, Peking University Clinical Research Institute, Beijing, China, told this news organization.

“Thus, salt substitution should be considered and promoted as a whole-population strategy for prevention and control of hypertension and cardiovascular disease,” Dr. Wu said.

The study was published online on February 12 in the Journal of the American College of Cardiology.

“Considering the failing strategy to reduce the intake of salt worldwide, salt substitution is an attractive alternative. The food industry and authorities should prepare strategies for wide-scale implementation of salt substitutes,” Rik Olde Engberink, MD, PhD, with Amsterdam University Medical Center, wrote in a linked editorial.

Population Strategy for Hypertension Prevention

The DECIDE-Salt clinical trial was a cluster-randomized trial conducted in 48 residential elderly care facilities in China with 1612 participants (1230 men and 382 women) aged 55 years or older. The trial assessed the effect of two sodium reduction strategies in lowering BP — replacing salt with a salt substitute and progressive restriction of the salt supply.

In the original study, the salt substitute intervention lowered systolic/diastolic BP significantly by 7.1/1.9 mm Hg vs the usual salt group. The progressive restriction of salt had no impact on BP vs usual salt or salt substitute groups.

This post hoc analysis of DECIDE-Salt focused on 609 participants (mean age, 71 years; 74% men) who were normotensive at baseline (mean BP, 122/74 mm Hg), with 298 in the usual salt group and 313 in the salt substitute group.

Compared with the usual salt group, the salt substitute group had a lower incidence of hypertension over 2 years (adjusted hazard ratio [HR], 0.60; 95% CI, 0.39-0.92; P = .02), with no increase in episodes of hypotension (P = .76).

From baseline to 2 years, there was no change in mean systolic/diastolic BP in the salt substitution group, whereas the usual salt group experienced a significant increase in systolic/diastolic BP (mean, 7.0/2.1 mm Hg).

The post hoc results from DECIDE-Salt are in line with a previous study from Peru, which also investigated mostly normotensive participants and reported a 51% lower risk of developing hypertension in the salt substitute group, as reported previously by this news organization.

“Although the study involved only participants aged 55 years and above, the epidemic of hypertension and its relations with sodium and potassium intake are not limited to older adults. Thus, we believe the salt substitution should also be beneficial to younger adults,” Dr. Wu said.

Notable Analysis

Reached for comment, Ankur Shah, MD, Division of Kidney Disease and Hypertension, Warren Alpert Medical School of Brown University, Providence, Rhode Island, said the study is “notable due to the limited and conflicting reports on the effects of salt substitution in individuals with normal blood pressure.”

“There is a growing body of literature on the impact of salt substitution in controlling hypertension, but less is known about prevention,” Dr. Shah, who was not involved in the study, told this news organization.

“The study certainly has population-level implications, as the design of a cluster-randomized trial at the facility level makes for a clear path to implementation — sodium substitution in elderly care facilities. That said, this is also the greatest limitation — extrapolating to the general population may not be accurate,” Dr. Shah noted.

There is also a potential concern with salt substitutes in patients with kidney disease, who typically are advised to lower potassium intake.

“Supplementing potassium could result in hyperkalemia, which can be life-threatening if severe, and patients taking medications that interfere with the kidney’s ability to excrete potassium should be cautious as well,” Dr. Shah said.

This research was supported by a grant from the National Key Research and Development Program, Ministry of Science and Technology of China. China Salt General Company at Yulin provided the usual salt and salt substitute used in the study free of charge. Dr. Wu, Dr. Engberink, and Dr. Shah had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

For adults with obesity and uncontrolled hypertension, bariatric surgery is an effective and durable strategy to control high blood pressure (BP), final, 5-year follow-up data from the GATEWAY trial suggested.

In the trial, those who underwent bariatric surgery had lower body mass index (BMI) and were on fewer antihypertensive medications after 5 years while maintaining normal BP than those who only used antihypertensive medications.

The results show that “bariatric and metabolic surgery can be very effective in the treatment of patients with obesity and hypertension in the long term,” chief investigator Carlos Aurelio Schiavon, MD, with the Research Institute, Heart Hospital, São Paulo, Brazil, told this news organization. 

“The most important clinical implication of this trial is that we must treat obesity to accomplish success when treating patients with cardiovascular diseases, such as hypertension and obesity,” Dr. Schiavon said.

The study was published online on February 5, 2024, in the Journal of the American College of Cardiology. 
 

A Gateway to Lasting BP Control

GATEWAY enrolled 100 adults (76% women) with grade 1/2 obesity (BMI, 30 to < 40 kg/m²; mean, 37 kg/m²) who were on at least two antihypertensive medications at maximum doses at baseline.

Half were randomly allocated to laparoscopic Roux-en-Y gastric-bypass surgery (RYGB) plus medications and half to medication alone. The primary outcome was at least a 30% reduction of antihypertensive medications while maintaining BP < 140/90 mm Hg. Five-year results were based on 37 patients in the surgery group and 32 in the medication only group. 

After 5 years, BMI was 28.01 kg/m² for those who had surgery vs 36.40 kg/m² for those on medication alone (P < .001).

Patients who underwent RYGB had an 80.7% reduction in the number of antihypertensive medications they were taking while maintaining BP < 140/90 mm Hg compared with a 13.7% reduction in those on medication alone.

After 5 years, surgery patients were taking a mean of 0.80 antihypertensive medications vs 2.97 in the medication only group to control BP at or below the target. 

Despite using less antihypertensive medications in the RYGB, ambulatory BP monitoring data revealed similar 24-hour, daytime, and nighttime BP profiles compared with medication alone. 

The rate of hypertension remission (controlled BP without medication) was nearly 20-fold higher in the surgery group than in the medication only group (46.9% vs 2.4%; P < .001).

In addition, the rate of apparent resistant hypertension was lower with than without surgery (0% vs 15.2%). The surgery group also showed evidence of less atrial remodeling. 

The 5-year results were consistent with the 1-year GATEWAY results Dr. Schiavon presented at the American Heart Association 2017 scientific sessions, as reported by this news organization. They also mirrored the results reported at 3 years. 

Limitations of the study include its single-center, open-label design with a small sample size and loss of follow-up in some patients.

“Taken together, these results support the long-term effective role of bariatric surgery in reducing the burden of hypertension and related polypharmacy, which is frequently observed in patients with obesity and is a cause of concern for them,” the authors wrote. 

“In clinical practice, obesity is an overlooked condition. As a consequence, there is a frequent failure in approaching obesity as a crucial step for mitigating the risk of important cardiovascular risk factors including hypertension. Our results underscore the importance of approaching obesity in reducing hypertension rates,” they added. 
 

Important Data, Lingering Questions 

The coauthors of an accompanying editorial said this study provides “important long-term data on the benefits of gastric bypass on weight loss and blood pressure control, but questions remain.”

Yet, Michael Hall, MD, MSc, with University of Mississippi Medical Center in Jackson, and coauthors noted that the study only included patients undergoing RYGB; it remains unclear if other bariatric surgery procedures would have the same long-term results.

“Sleeve gastrectomy has become more common than RYGB because it is less complex and has earlier recovery and similar effectiveness for treating obesity and type 2 diabetes,” they pointed out. “Further comparative randomized controlled trials are needed to determine whether sleeve gastrectomy is as effective as RYGB for long-term BP control.”

As reported previously by this news organization, in SLEEVEPASS, there was greater weight loss and higher likelihood of hypertension remission with RYGB than with sleeve gastrectomy (24% vs 8%; P = .04), although BP control was not the primary outcome. 

The GATEWAY study was supported by a grant from Ethicon. Dr. Schiavon received a research grant from Ethicon and has received lecture fees from Ethicon and Medtronic. The editorial writers had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

For adults with obesity and uncontrolled hypertension, bariatric surgery is an effective and durable strategy to control high blood pressure (BP), final, 5-year follow-up data from the GATEWAY trial suggested.

In the trial, those who underwent bariatric surgery had lower body mass index (BMI) and were on fewer antihypertensive medications after 5 years while maintaining normal BP than those who only used antihypertensive medications.

The results show that “bariatric and metabolic surgery can be very effective in the treatment of patients with obesity and hypertension in the long term,” chief investigator Carlos Aurelio Schiavon, MD, with the Research Institute, Heart Hospital, São Paulo, Brazil, told this news organization. 

“The most important clinical implication of this trial is that we must treat obesity to accomplish success when treating patients with cardiovascular diseases, such as hypertension and obesity,” Dr. Schiavon said.

The study was published online on February 5, 2024, in the Journal of the American College of Cardiology. 
 

A Gateway to Lasting BP Control

GATEWAY enrolled 100 adults (76% women) with grade 1/2 obesity (BMI, 30 to < 40 kg/m²; mean, 37 kg/m²) who were on at least two antihypertensive medications at maximum doses at baseline.

Half were randomly allocated to laparoscopic Roux-en-Y gastric-bypass surgery (RYGB) plus medications and half to medication alone. The primary outcome was at least a 30% reduction of antihypertensive medications while maintaining BP < 140/90 mm Hg. Five-year results were based on 37 patients in the surgery group and 32 in the medication only group. 

After 5 years, BMI was 28.01 kg/m² for those who had surgery vs 36.40 kg/m² for those on medication alone (P < .001).

Patients who underwent RYGB had an 80.7% reduction in the number of antihypertensive medications they were taking while maintaining BP < 140/90 mm Hg compared with a 13.7% reduction in those on medication alone.

After 5 years, surgery patients were taking a mean of 0.80 antihypertensive medications vs 2.97 in the medication only group to control BP at or below the target. 

Despite using less antihypertensive medications in the RYGB, ambulatory BP monitoring data revealed similar 24-hour, daytime, and nighttime BP profiles compared with medication alone. 

The rate of hypertension remission (controlled BP without medication) was nearly 20-fold higher in the surgery group than in the medication only group (46.9% vs 2.4%; P < .001).

In addition, the rate of apparent resistant hypertension was lower with than without surgery (0% vs 15.2%). The surgery group also showed evidence of less atrial remodeling. 

The 5-year results were consistent with the 1-year GATEWAY results Dr. Schiavon presented at the American Heart Association 2017 scientific sessions, as reported by this news organization. They also mirrored the results reported at 3 years. 

Limitations of the study include its single-center, open-label design with a small sample size and loss of follow-up in some patients.

“Taken together, these results support the long-term effective role of bariatric surgery in reducing the burden of hypertension and related polypharmacy, which is frequently observed in patients with obesity and is a cause of concern for them,” the authors wrote. 

“In clinical practice, obesity is an overlooked condition. As a consequence, there is a frequent failure in approaching obesity as a crucial step for mitigating the risk of important cardiovascular risk factors including hypertension. Our results underscore the importance of approaching obesity in reducing hypertension rates,” they added. 
 

Important Data, Lingering Questions 

The coauthors of an accompanying editorial said this study provides “important long-term data on the benefits of gastric bypass on weight loss and blood pressure control, but questions remain.”

Yet, Michael Hall, MD, MSc, with University of Mississippi Medical Center in Jackson, and coauthors noted that the study only included patients undergoing RYGB; it remains unclear if other bariatric surgery procedures would have the same long-term results.

“Sleeve gastrectomy has become more common than RYGB because it is less complex and has earlier recovery and similar effectiveness for treating obesity and type 2 diabetes,” they pointed out. “Further comparative randomized controlled trials are needed to determine whether sleeve gastrectomy is as effective as RYGB for long-term BP control.”

As reported previously by this news organization, in SLEEVEPASS, there was greater weight loss and higher likelihood of hypertension remission with RYGB than with sleeve gastrectomy (24% vs 8%; P = .04), although BP control was not the primary outcome. 

The GATEWAY study was supported by a grant from Ethicon. Dr. Schiavon received a research grant from Ethicon and has received lecture fees from Ethicon and Medtronic. The editorial writers had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

For adults with obesity and uncontrolled hypertension, bariatric surgery is an effective and durable strategy to control high blood pressure (BP), final, 5-year follow-up data from the GATEWAY trial suggested.

In the trial, those who underwent bariatric surgery had lower body mass index (BMI) and were on fewer antihypertensive medications after 5 years while maintaining normal BP than those who only used antihypertensive medications.

The results show that “bariatric and metabolic surgery can be very effective in the treatment of patients with obesity and hypertension in the long term,” chief investigator Carlos Aurelio Schiavon, MD, with the Research Institute, Heart Hospital, São Paulo, Brazil, told this news organization. 

“The most important clinical implication of this trial is that we must treat obesity to accomplish success when treating patients with cardiovascular diseases, such as hypertension and obesity,” Dr. Schiavon said.

The study was published online on February 5, 2024, in the Journal of the American College of Cardiology. 
 

A Gateway to Lasting BP Control

GATEWAY enrolled 100 adults (76% women) with grade 1/2 obesity (BMI, 30 to < 40 kg/m²; mean, 37 kg/m²) who were on at least two antihypertensive medications at maximum doses at baseline.

Half were randomly allocated to laparoscopic Roux-en-Y gastric-bypass surgery (RYGB) plus medications and half to medication alone. The primary outcome was at least a 30% reduction of antihypertensive medications while maintaining BP < 140/90 mm Hg. Five-year results were based on 37 patients in the surgery group and 32 in the medication only group. 

After 5 years, BMI was 28.01 kg/m² for those who had surgery vs 36.40 kg/m² for those on medication alone (P < .001).

Patients who underwent RYGB had an 80.7% reduction in the number of antihypertensive medications they were taking while maintaining BP < 140/90 mm Hg compared with a 13.7% reduction in those on medication alone.

After 5 years, surgery patients were taking a mean of 0.80 antihypertensive medications vs 2.97 in the medication only group to control BP at or below the target. 

Despite using less antihypertensive medications in the RYGB, ambulatory BP monitoring data revealed similar 24-hour, daytime, and nighttime BP profiles compared with medication alone. 

The rate of hypertension remission (controlled BP without medication) was nearly 20-fold higher in the surgery group than in the medication only group (46.9% vs 2.4%; P < .001).

In addition, the rate of apparent resistant hypertension was lower with than without surgery (0% vs 15.2%). The surgery group also showed evidence of less atrial remodeling. 

The 5-year results were consistent with the 1-year GATEWAY results Dr. Schiavon presented at the American Heart Association 2017 scientific sessions, as reported by this news organization. They also mirrored the results reported at 3 years. 

Limitations of the study include its single-center, open-label design with a small sample size and loss of follow-up in some patients.

“Taken together, these results support the long-term effective role of bariatric surgery in reducing the burden of hypertension and related polypharmacy, which is frequently observed in patients with obesity and is a cause of concern for them,” the authors wrote. 

“In clinical practice, obesity is an overlooked condition. As a consequence, there is a frequent failure in approaching obesity as a crucial step for mitigating the risk of important cardiovascular risk factors including hypertension. Our results underscore the importance of approaching obesity in reducing hypertension rates,” they added. 
 

Important Data, Lingering Questions 

The coauthors of an accompanying editorial said this study provides “important long-term data on the benefits of gastric bypass on weight loss and blood pressure control, but questions remain.”

Yet, Michael Hall, MD, MSc, with University of Mississippi Medical Center in Jackson, and coauthors noted that the study only included patients undergoing RYGB; it remains unclear if other bariatric surgery procedures would have the same long-term results.

“Sleeve gastrectomy has become more common than RYGB because it is less complex and has earlier recovery and similar effectiveness for treating obesity and type 2 diabetes,” they pointed out. “Further comparative randomized controlled trials are needed to determine whether sleeve gastrectomy is as effective as RYGB for long-term BP control.”

As reported previously by this news organization, in SLEEVEPASS, there was greater weight loss and higher likelihood of hypertension remission with RYGB than with sleeve gastrectomy (24% vs 8%; P = .04), although BP control was not the primary outcome. 

The GATEWAY study was supported by a grant from Ethicon. Dr. Schiavon received a research grant from Ethicon and has received lecture fees from Ethicon and Medtronic. The editorial writers had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggested.

The Black Women’s Health Study, which has followed 59,000 participants in the United States since the 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, told this news organization. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers and looking after family.”

Dr. Aparicio will present the data in full at the International Stroke Conference 2024 to be held in Phoenix, Arizona, Feb. 7-9.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”

The researchers analyzed data from the Black Women’s Health Study, a prospective study of 59,000 Black women from across the United States. The baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

History of hypertension, defined as physician-diagnosed hypertension with the use of an antihypertensive medication, and of stroke occurrence was determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% CI, 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggested.

The Black Women’s Health Study, which has followed 59,000 participants in the United States since the 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, told this news organization. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers and looking after family.”

Dr. Aparicio will present the data in full at the International Stroke Conference 2024 to be held in Phoenix, Arizona, Feb. 7-9.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”

The researchers analyzed data from the Black Women’s Health Study, a prospective study of 59,000 Black women from across the United States. The baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

History of hypertension, defined as physician-diagnosed hypertension with the use of an antihypertensive medication, and of stroke occurrence was determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% CI, 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggested.

The Black Women’s Health Study, which has followed 59,000 participants in the United States since the 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, told this news organization. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers and looking after family.”

Dr. Aparicio will present the data in full at the International Stroke Conference 2024 to be held in Phoenix, Arizona, Feb. 7-9.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”

The researchers analyzed data from the Black Women’s Health Study, a prospective study of 59,000 Black women from across the United States. The baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

History of hypertension, defined as physician-diagnosed hypertension with the use of an antihypertensive medication, and of stroke occurrence was determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% CI, 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

In patients with chronic kidney disease (CKD) and type 2 diabetes, baseline insulin resistance was associated with increased cardiovascular (CV) but not kidney risk and did not affect the efficacy of finerenone. 

METHODOLOGY:

• Insulin resistance is implicated in CV disease in patients with CKD, but its role in CKD progression is less clear.
• This post hoc analysis of FIDELITY, a pooled analysis of the  and  trials, randomly assigned patients with type 2 diabetes and CKD (who received optimized renin-angiotensin system blockade) to receive finerenone (10 mg or 20 mg) once daily or placebo and followed them for a median of 3 years.
• An estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated for 12,964 patients (median age, 65 years), using waist circumference, hypertension status, and glycated hemoglobin.
• Outcomes included a CV composite (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite (time to renal failure, a sustained decrease ≥ 57% in the initial estimated glomerular filtration rate, or renal death).

TAKEAWAY:

• The median eGDR was 4.1 mg/kg/min. The 50% of patients with a lower eGDR were considered insulin resistant, whereas the remaining half with a higher eGDR were considered insulin sensitive.
• The incidence rate of CV outcomes was higher among patients with insulin resistance in both the finerenone group (incidence rate per 100 patient-years, 5.18 vs 3.47 among insulin-sensitive patients) and the placebo group (6.34 vs 3.76), but eGDR showed no association with kidney outcomes.
• The efficacy of finerenone vs placebo on CV (Wald test P = .063) and kidney outcomes (Wald test P = .51) did not change significantly across the range of baseline eGDR values.
• The incidences of treatment-emergent adverse events and severe adverse events with finerenone were similar between the insulin-resistant and insulin-sensitive subgroups.

IN PRACTICE:

“The efficacy and safety of finerenone were not modified by baseline insulin resistance. A higher risk of CV — but not kidney outcomes was observed in patients with CKD and T2D with greater insulin resistance,” the authors wrote.

SOURCE:

This study was led by Thomas Ebert of the Medical Department III — Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany, and published online in Diabetes Care.

LIMITATIONS:

This study was not adequately powered to evaluate the statistical significance of the association of eGDR with CV and kidney outcomes and was hypothesis-generating. Further studies are needed to examine whether the effects of insulin resistance differ between individuals with diabetes vs those with advanced CKD with or without diabetes.

DISCLOSURES:

The FIDELIO-DKD and FIGARO-DKD trials were conducted and sponsored by Bayer AG. Three authors declared being full-time employees of Bayer. Several authors declared receiving personal fees, consulting fees, grants, or research support from; holding patents with; or having ownership interests in various pharmaceutical companies, including Bayer.

A version of this article appeared on Medscape.com.

TOPLINE:

In patients with chronic kidney disease (CKD) and type 2 diabetes, baseline insulin resistance was associated with increased cardiovascular (CV) but not kidney risk and did not affect the efficacy of finerenone. 

METHODOLOGY:

• Insulin resistance is implicated in CV disease in patients with CKD, but its role in CKD progression is less clear.
• This post hoc analysis of FIDELITY, a pooled analysis of the  and  trials, randomly assigned patients with type 2 diabetes and CKD (who received optimized renin-angiotensin system blockade) to receive finerenone (10 mg or 20 mg) once daily or placebo and followed them for a median of 3 years.
• An estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated for 12,964 patients (median age, 65 years), using waist circumference, hypertension status, and glycated hemoglobin.
• Outcomes included a CV composite (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite (time to renal failure, a sustained decrease ≥ 57% in the initial estimated glomerular filtration rate, or renal death).

TAKEAWAY:

• The median eGDR was 4.1 mg/kg/min. The 50% of patients with a lower eGDR were considered insulin resistant, whereas the remaining half with a higher eGDR were considered insulin sensitive.
• The incidence rate of CV outcomes was higher among patients with insulin resistance in both the finerenone group (incidence rate per 100 patient-years, 5.18 vs 3.47 among insulin-sensitive patients) and the placebo group (6.34 vs 3.76), but eGDR showed no association with kidney outcomes.
• The efficacy of finerenone vs placebo on CV (Wald test P = .063) and kidney outcomes (Wald test P = .51) did not change significantly across the range of baseline eGDR values.
• The incidences of treatment-emergent adverse events and severe adverse events with finerenone were similar between the insulin-resistant and insulin-sensitive subgroups.

IN PRACTICE:

“The efficacy and safety of finerenone were not modified by baseline insulin resistance. A higher risk of CV — but not kidney outcomes was observed in patients with CKD and T2D with greater insulin resistance,” the authors wrote.

SOURCE:

This study was led by Thomas Ebert of the Medical Department III — Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany, and published online in Diabetes Care.

LIMITATIONS:

This study was not adequately powered to evaluate the statistical significance of the association of eGDR with CV and kidney outcomes and was hypothesis-generating. Further studies are needed to examine whether the effects of insulin resistance differ between individuals with diabetes vs those with advanced CKD with or without diabetes.

DISCLOSURES:

The FIDELIO-DKD and FIGARO-DKD trials were conducted and sponsored by Bayer AG. Three authors declared being full-time employees of Bayer. Several authors declared receiving personal fees, consulting fees, grants, or research support from; holding patents with; or having ownership interests in various pharmaceutical companies, including Bayer.

A version of this article appeared on Medscape.com.

TOPLINE:

In patients with chronic kidney disease (CKD) and type 2 diabetes, baseline insulin resistance was associated with increased cardiovascular (CV) but not kidney risk and did not affect the efficacy of finerenone. 

METHODOLOGY:

• Insulin resistance is implicated in CV disease in patients with CKD, but its role in CKD progression is less clear.
• This post hoc analysis of FIDELITY, a pooled analysis of the  and  trials, randomly assigned patients with type 2 diabetes and CKD (who received optimized renin-angiotensin system blockade) to receive finerenone (10 mg or 20 mg) once daily or placebo and followed them for a median of 3 years.
• An estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated for 12,964 patients (median age, 65 years), using waist circumference, hypertension status, and glycated hemoglobin.
• Outcomes included a CV composite (time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite (time to renal failure, a sustained decrease ≥ 57% in the initial estimated glomerular filtration rate, or renal death).

TAKEAWAY:

• The median eGDR was 4.1 mg/kg/min. The 50% of patients with a lower eGDR were considered insulin resistant, whereas the remaining half with a higher eGDR were considered insulin sensitive.
• The incidence rate of CV outcomes was higher among patients with insulin resistance in both the finerenone group (incidence rate per 100 patient-years, 5.18 vs 3.47 among insulin-sensitive patients) and the placebo group (6.34 vs 3.76), but eGDR showed no association with kidney outcomes.
• The efficacy of finerenone vs placebo on CV (Wald test P = .063) and kidney outcomes (Wald test P = .51) did not change significantly across the range of baseline eGDR values.
• The incidences of treatment-emergent adverse events and severe adverse events with finerenone were similar between the insulin-resistant and insulin-sensitive subgroups.

IN PRACTICE:

“The efficacy and safety of finerenone were not modified by baseline insulin resistance. A higher risk of CV — but not kidney outcomes was observed in patients with CKD and T2D with greater insulin resistance,” the authors wrote.

SOURCE:

This study was led by Thomas Ebert of the Medical Department III — Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany, and published online in Diabetes Care.

LIMITATIONS:

This study was not adequately powered to evaluate the statistical significance of the association of eGDR with CV and kidney outcomes and was hypothesis-generating. Further studies are needed to examine whether the effects of insulin resistance differ between individuals with diabetes vs those with advanced CKD with or without diabetes.

DISCLOSURES:

The FIDELIO-DKD and FIGARO-DKD trials were conducted and sponsored by Bayer AG. Three authors declared being full-time employees of Bayer. Several authors declared receiving personal fees, consulting fees, grants, or research support from; holding patents with; or having ownership interests in various pharmaceutical companies, including Bayer.

A version of this article appeared on Medscape.com.

People who habitually add salt to their meals at the table may unknowingly be risking their kidneys, according to a study utilizing UK Biobank data. Chronic salt additions are associated with an elevated risk of developing chronic kidney disease (CKD), as revealed by researchers led by Rui Tang, a doctoral candidate in epidemiology at Tulane University in New Orleans, Louisiana. The study was published in JAMA Network Open.

Large Study Sample

In a population-based cohort study comprising over 460,000 UK Biobank participants aged 37-73 years, the researchers explored the association between adding table salt to food and increased CKD risk.

Participants indicated how often they added salt to their meals: Never or rarely, sometimes, often, or always. The follow-up period exceeded a decade, and median duration was 11.8 years. During this time, approximately 22,000 new CKD cases were documented. Data analysis revealed a significantly higher CKD risk among those who frequently added salt.

The extent of risk elevation varied with the frequency of salt additions. Even occasional salters had a 7% higher risk than those who never or rarely added salt. For frequent salters, the risk increased by 12%, and for those who always added salt, it rose to 29%. These results were adjusted for age and gender.

Worse Overall Health

The research group noted that individuals who frequently added salt were generally less healthy, adopting an unhealthier lifestyle and having lower socioeconomic status. They exhibited higher body mass index (BMI), were more likely to smoke, had diabetes or cardiovascular diseases, and had reduced estimated glomerular filtration rate (eGFR) at the beginning of the study. Moreover, their Townsend Deprivation Index, indicating material deprivation, was higher.

Considering these factors, the researchers adjusted the results not only for age and gender but also for ethnicity, Townsend Deprivation Index, eGFR, BMI, smoking status, alcohol consumption, physical activity, elevated cholesterol levels, diabetes, cardiovascular diseases, hypertension, infectious diseases, immune system disorders, and the use of nephrotoxic medications.

Association Persists

Even after accounting for these factors, a significant, albeit attenuated, association between salt additions and CKD risk remained. The risk increased by 2% for occasional salters, 5% for frequent salters, and 6% for those who always added salt.

The research group concluded that adding salt to meals could be associated with an increased risk for CKD in the general population. However, they highlighted several limitations that should be considered when interpreting the study results.

Reducing Salt 

Primarily, self-reported frequency of salt addition doesn’t precisely reflect actual salt consumption. While earlier studies validated the accuracy of this variable, the researchers acknowledged the possibility that frequent salt addition may merely be a marker for an unhealthy lifestyle.

Nevertheless, the authors speculated that reducing the frequency of salt additions to meals could contribute to lowering CKD risk in the general population. They suggested validating their results in post hoc analyses or follow-up studies from clinical trials.
 

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

People who habitually add salt to their meals at the table may unknowingly be risking their kidneys, according to a study utilizing UK Biobank data. Chronic salt additions are associated with an elevated risk of developing chronic kidney disease (CKD), as revealed by researchers led by Rui Tang, a doctoral candidate in epidemiology at Tulane University in New Orleans, Louisiana. The study was published in JAMA Network Open.

Large Study Sample

In a population-based cohort study comprising over 460,000 UK Biobank participants aged 37-73 years, the researchers explored the association between adding table salt to food and increased CKD risk.

Participants indicated how often they added salt to their meals: Never or rarely, sometimes, often, or always. The follow-up period exceeded a decade, and median duration was 11.8 years. During this time, approximately 22,000 new CKD cases were documented. Data analysis revealed a significantly higher CKD risk among those who frequently added salt.

The extent of risk elevation varied with the frequency of salt additions. Even occasional salters had a 7% higher risk than those who never or rarely added salt. For frequent salters, the risk increased by 12%, and for those who always added salt, it rose to 29%. These results were adjusted for age and gender.

Worse Overall Health

The research group noted that individuals who frequently added salt were generally less healthy, adopting an unhealthier lifestyle and having lower socioeconomic status. They exhibited higher body mass index (BMI), were more likely to smoke, had diabetes or cardiovascular diseases, and had reduced estimated glomerular filtration rate (eGFR) at the beginning of the study. Moreover, their Townsend Deprivation Index, indicating material deprivation, was higher.

Considering these factors, the researchers adjusted the results not only for age and gender but also for ethnicity, Townsend Deprivation Index, eGFR, BMI, smoking status, alcohol consumption, physical activity, elevated cholesterol levels, diabetes, cardiovascular diseases, hypertension, infectious diseases, immune system disorders, and the use of nephrotoxic medications.

Association Persists

Even after accounting for these factors, a significant, albeit attenuated, association between salt additions and CKD risk remained. The risk increased by 2% for occasional salters, 5% for frequent salters, and 6% for those who always added salt.

The research group concluded that adding salt to meals could be associated with an increased risk for CKD in the general population. However, they highlighted several limitations that should be considered when interpreting the study results.

Reducing Salt 

Primarily, self-reported frequency of salt addition doesn’t precisely reflect actual salt consumption. While earlier studies validated the accuracy of this variable, the researchers acknowledged the possibility that frequent salt addition may merely be a marker for an unhealthy lifestyle.

Nevertheless, the authors speculated that reducing the frequency of salt additions to meals could contribute to lowering CKD risk in the general population. They suggested validating their results in post hoc analyses or follow-up studies from clinical trials.
 

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

People who habitually add salt to their meals at the table may unknowingly be risking their kidneys, according to a study utilizing UK Biobank data. Chronic salt additions are associated with an elevated risk of developing chronic kidney disease (CKD), as revealed by researchers led by Rui Tang, a doctoral candidate in epidemiology at Tulane University in New Orleans, Louisiana. The study was published in JAMA Network Open.

Large Study Sample

In a population-based cohort study comprising over 460,000 UK Biobank participants aged 37-73 years, the researchers explored the association between adding table salt to food and increased CKD risk.

Participants indicated how often they added salt to their meals: Never or rarely, sometimes, often, or always. The follow-up period exceeded a decade, and median duration was 11.8 years. During this time, approximately 22,000 new CKD cases were documented. Data analysis revealed a significantly higher CKD risk among those who frequently added salt.

The extent of risk elevation varied with the frequency of salt additions. Even occasional salters had a 7% higher risk than those who never or rarely added salt. For frequent salters, the risk increased by 12%, and for those who always added salt, it rose to 29%. These results were adjusted for age and gender.

Worse Overall Health

The research group noted that individuals who frequently added salt were generally less healthy, adopting an unhealthier lifestyle and having lower socioeconomic status. They exhibited higher body mass index (BMI), were more likely to smoke, had diabetes or cardiovascular diseases, and had reduced estimated glomerular filtration rate (eGFR) at the beginning of the study. Moreover, their Townsend Deprivation Index, indicating material deprivation, was higher.

Considering these factors, the researchers adjusted the results not only for age and gender but also for ethnicity, Townsend Deprivation Index, eGFR, BMI, smoking status, alcohol consumption, physical activity, elevated cholesterol levels, diabetes, cardiovascular diseases, hypertension, infectious diseases, immune system disorders, and the use of nephrotoxic medications.

Association Persists

Even after accounting for these factors, a significant, albeit attenuated, association between salt additions and CKD risk remained. The risk increased by 2% for occasional salters, 5% for frequent salters, and 6% for those who always added salt.

The research group concluded that adding salt to meals could be associated with an increased risk for CKD in the general population. However, they highlighted several limitations that should be considered when interpreting the study results.

Reducing Salt 

Primarily, self-reported frequency of salt addition doesn’t precisely reflect actual salt consumption. While earlier studies validated the accuracy of this variable, the researchers acknowledged the possibility that frequent salt addition may merely be a marker for an unhealthy lifestyle.

Nevertheless, the authors speculated that reducing the frequency of salt additions to meals could contribute to lowering CKD risk in the general population. They suggested validating their results in post hoc analyses or follow-up studies from clinical trials.
 

This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.

Primary aldosteronism (PA) is a frequently overlooked yet common cause of secondary hypertension, presenting significant risk for cardiovascular morbidity and mortality.

But fewer than 4% of at-risk patients receive the recommended screening for PA, leaving a substantial gap in early detection and management, according to Adina F. Turcu, MD, MS, associate professor in endocrinology and internal medicine at University of Michigan Health in Ann Arbor. 

In response to this clinical challenge, Dr. Turcu and her colleagues developed a best-practice advisory (BPA) to identify patients who were at risk for PA and embedded it into electronic health record at University of Michigan ambulatory clinics. Her team found that use of the tool led to increased rates of screening for PA, particularly among primary care physicians.

Over a 15-month period, Dr. Turcu and her colleagues tested the BPA through a quality improvement study, identifying 14,603 unique candidates for PA screening, with a mean age of 65.5 years and a diverse representation of ethnic backgrounds. 

Notably, 48.1% of these candidates had treatment-resistant hypertension, 43.5% exhibited hypokalemia, 10.5% were younger than 35 years, and 3.1% had adrenal nodules. Of these candidates, 14.0% received orders for PA screening, with 70.5% completing the recommended screening within the system, and 17.4% receiving positive screening results. 

The study, conducted over 6 months in 2023, targeted adults with hypertension and at least one of the following: Those who took four or more antihypertensive medications, exhibited hypokalemia, were younger than age 35 years, or had adrenal nodules. Patients previously tested for PA were excluded from the analysis. 

The noninterruptive BPA was triggered during outpatient visits with clinicians who specialized in hypertension. The advisory would then offer an order set for PA screening and provide a link to interpretation guidance for results. Clinicians had the option to use, ignore, or decline the BPA.

“Although we were hoping for broader uptake of this EHR-embedded BPA, we were delighted to see an increase in PA screening rates to 14% of identified candidates as compared to an average of less than 3% in retrospective studies of similar populations, including in our own institution prior to implementing this BPA,” Dr. Turcu told this news organization.

Physician specialty played a crucial role in the utilization of the BPA. Internists and family medicine physicians accounted for the majority of screening orders, placing 40.0% and 28.1% of these, respectively. Family practitioners and internists predominantly used the embedded order set (80.3% and 68.9%, respectively).

“Hypertension often gets treated rather than screening for [causes of] secondary hypertension prior to treatment,” said Kaniksha Desai, MD, clinical associate professor and endocrinology quality director at Stanford University School of Medicine, Stanford, California, who was not involved in the research. But “primary hyperaldosteronism is a condition that can be treated surgically and has increased long term cardiovascular consequences if not identified. While guidelines recommend screening at-risk patients, this often can get lost in translation in clinical practice due to many factors, including time constraints and volume of patients.” 

Patients who did vs did not undergo screening were more likely to be women, Black, and younger than age 35 years. Additionally, the likelihood of screening was higher among patients with obesity and dyslipidemia, whereas it was lower in those with chronic kidney disease and established cardiovascular complications.

According to Dr. Turcu, the findings from this study suggest that noninterruptive BPAs, especially when integrated into primary care workflows, hold promise as effective tools for PA screening.

When coupled with artificial intelligence to optimize detection yield, these refined BPAs could significantly contribute to personalized care for hypertension, the investigators said. 

“Considering that in the United States almost one in two adults has hypertension, such automatized tools become instrumental to busy clinicians, particularly those in primary care,” Dr. Turcu said. “Our results indicate a promising opportunity to meaningfully improve PA awareness and enhance its diagnosis.” 

Dr. Turcu reported receiving grants from the National Heart, Lung, and Blood Institute and Doris Duke Foundation, served as an investigator in a CinCor Pharma clinical trial, and received financial support to her institution during the conduct of the study. Dr. Desai reported no relevant financial disclosures. 
 

A version of this article appeared on Medscape.com.

Primary aldosteronism (PA) is a frequently overlooked yet common cause of secondary hypertension, presenting significant risk for cardiovascular morbidity and mortality.

But fewer than 4% of at-risk patients receive the recommended screening for PA, leaving a substantial gap in early detection and management, according to Adina F. Turcu, MD, MS, associate professor in endocrinology and internal medicine at University of Michigan Health in Ann Arbor. 

In response to this clinical challenge, Dr. Turcu and her colleagues developed a best-practice advisory (BPA) to identify patients who were at risk for PA and embedded it into electronic health record at University of Michigan ambulatory clinics. Her team found that use of the tool led to increased rates of screening for PA, particularly among primary care physicians.

Over a 15-month period, Dr. Turcu and her colleagues tested the BPA through a quality improvement study, identifying 14,603 unique candidates for PA screening, with a mean age of 65.5 years and a diverse representation of ethnic backgrounds. 

Notably, 48.1% of these candidates had treatment-resistant hypertension, 43.5% exhibited hypokalemia, 10.5% were younger than 35 years, and 3.1% had adrenal nodules. Of these candidates, 14.0% received orders for PA screening, with 70.5% completing the recommended screening within the system, and 17.4% receiving positive screening results. 

The study, conducted over 6 months in 2023, targeted adults with hypertension and at least one of the following: Those who took four or more antihypertensive medications, exhibited hypokalemia, were younger than age 35 years, or had adrenal nodules. Patients previously tested for PA were excluded from the analysis. 

The noninterruptive BPA was triggered during outpatient visits with clinicians who specialized in hypertension. The advisory would then offer an order set for PA screening and provide a link to interpretation guidance for results. Clinicians had the option to use, ignore, or decline the BPA.

“Although we were hoping for broader uptake of this EHR-embedded BPA, we were delighted to see an increase in PA screening rates to 14% of identified candidates as compared to an average of less than 3% in retrospective studies of similar populations, including in our own institution prior to implementing this BPA,” Dr. Turcu told this news organization.

Physician specialty played a crucial role in the utilization of the BPA. Internists and family medicine physicians accounted for the majority of screening orders, placing 40.0% and 28.1% of these, respectively. Family practitioners and internists predominantly used the embedded order set (80.3% and 68.9%, respectively).

“Hypertension often gets treated rather than screening for [causes of] secondary hypertension prior to treatment,” said Kaniksha Desai, MD, clinical associate professor and endocrinology quality director at Stanford University School of Medicine, Stanford, California, who was not involved in the research. But “primary hyperaldosteronism is a condition that can be treated surgically and has increased long term cardiovascular consequences if not identified. While guidelines recommend screening at-risk patients, this often can get lost in translation in clinical practice due to many factors, including time constraints and volume of patients.” 

Patients who did vs did not undergo screening were more likely to be women, Black, and younger than age 35 years. Additionally, the likelihood of screening was higher among patients with obesity and dyslipidemia, whereas it was lower in those with chronic kidney disease and established cardiovascular complications.

According to Dr. Turcu, the findings from this study suggest that noninterruptive BPAs, especially when integrated into primary care workflows, hold promise as effective tools for PA screening.

When coupled with artificial intelligence to optimize detection yield, these refined BPAs could significantly contribute to personalized care for hypertension, the investigators said. 

“Considering that in the United States almost one in two adults has hypertension, such automatized tools become instrumental to busy clinicians, particularly those in primary care,” Dr. Turcu said. “Our results indicate a promising opportunity to meaningfully improve PA awareness and enhance its diagnosis.” 

Dr. Turcu reported receiving grants from the National Heart, Lung, and Blood Institute and Doris Duke Foundation, served as an investigator in a CinCor Pharma clinical trial, and received financial support to her institution during the conduct of the study. Dr. Desai reported no relevant financial disclosures. 
 

A version of this article appeared on Medscape.com.

Primary aldosteronism (PA) is a frequently overlooked yet common cause of secondary hypertension, presenting significant risk for cardiovascular morbidity and mortality.

But fewer than 4% of at-risk patients receive the recommended screening for PA, leaving a substantial gap in early detection and management, according to Adina F. Turcu, MD, MS, associate professor in endocrinology and internal medicine at University of Michigan Health in Ann Arbor. 

In response to this clinical challenge, Dr. Turcu and her colleagues developed a best-practice advisory (BPA) to identify patients who were at risk for PA and embedded it into electronic health record at University of Michigan ambulatory clinics. Her team found that use of the tool led to increased rates of screening for PA, particularly among primary care physicians.

Over a 15-month period, Dr. Turcu and her colleagues tested the BPA through a quality improvement study, identifying 14,603 unique candidates for PA screening, with a mean age of 65.5 years and a diverse representation of ethnic backgrounds. 

Notably, 48.1% of these candidates had treatment-resistant hypertension, 43.5% exhibited hypokalemia, 10.5% were younger than 35 years, and 3.1% had adrenal nodules. Of these candidates, 14.0% received orders for PA screening, with 70.5% completing the recommended screening within the system, and 17.4% receiving positive screening results. 

The study, conducted over 6 months in 2023, targeted adults with hypertension and at least one of the following: Those who took four or more antihypertensive medications, exhibited hypokalemia, were younger than age 35 years, or had adrenal nodules. Patients previously tested for PA were excluded from the analysis. 

The noninterruptive BPA was triggered during outpatient visits with clinicians who specialized in hypertension. The advisory would then offer an order set for PA screening and provide a link to interpretation guidance for results. Clinicians had the option to use, ignore, or decline the BPA.

“Although we were hoping for broader uptake of this EHR-embedded BPA, we were delighted to see an increase in PA screening rates to 14% of identified candidates as compared to an average of less than 3% in retrospective studies of similar populations, including in our own institution prior to implementing this BPA,” Dr. Turcu told this news organization.

Physician specialty played a crucial role in the utilization of the BPA. Internists and family medicine physicians accounted for the majority of screening orders, placing 40.0% and 28.1% of these, respectively. Family practitioners and internists predominantly used the embedded order set (80.3% and 68.9%, respectively).

“Hypertension often gets treated rather than screening for [causes of] secondary hypertension prior to treatment,” said Kaniksha Desai, MD, clinical associate professor and endocrinology quality director at Stanford University School of Medicine, Stanford, California, who was not involved in the research. But “primary hyperaldosteronism is a condition that can be treated surgically and has increased long term cardiovascular consequences if not identified. While guidelines recommend screening at-risk patients, this often can get lost in translation in clinical practice due to many factors, including time constraints and volume of patients.” 

Patients who did vs did not undergo screening were more likely to be women, Black, and younger than age 35 years. Additionally, the likelihood of screening was higher among patients with obesity and dyslipidemia, whereas it was lower in those with chronic kidney disease and established cardiovascular complications.

According to Dr. Turcu, the findings from this study suggest that noninterruptive BPAs, especially when integrated into primary care workflows, hold promise as effective tools for PA screening.

When coupled with artificial intelligence to optimize detection yield, these refined BPAs could significantly contribute to personalized care for hypertension, the investigators said. 

“Considering that in the United States almost one in two adults has hypertension, such automatized tools become instrumental to busy clinicians, particularly those in primary care,” Dr. Turcu said. “Our results indicate a promising opportunity to meaningfully improve PA awareness and enhance its diagnosis.” 

Dr. Turcu reported receiving grants from the National Heart, Lung, and Blood Institute and Doris Duke Foundation, served as an investigator in a CinCor Pharma clinical trial, and received financial support to her institution during the conduct of the study. Dr. Desai reported no relevant financial disclosures. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Severe sleep irregularity often occurs with obstructive sleep apnea (OSA), and this combination approximately doubled the odds of hypertension in middle-aged individuals.

METHODOLOGY:

• OSA has demonstrated an association with hypertension, but data on the impact of sleep irregularity on this relationship are lacking.
• The researchers used the recently developed sleep regularity index (SRI) to determine sleep patterns using a scale of 0-100 (with higher numbers indicating greater regularity) to assess relationships between OSA, sleep patterns, and hypertension in 602 adults with a mean age of 57 years.
• The study’s goal was an assessment of the associations between sleep regularity, OSA, and hypertension in a community sample of adults with normal circadian patterns.

TAKEAWAY:

• The odds of OSA were significantly greater for individuals with mildly irregular or severely irregular sleep than for regular sleepers (odds ratios, 1.97 and 2.06, respectively).
• Individuals with OSA and severely irregular sleep had the highest odds of hypertension compared with individuals with no OSA and regular sleep (OR, 2.34).
• However, participants with OSA and regular sleep or mildly irregular sleep had no significant increase in hypertension risk.

IN PRACTICE:

“Irregular sleep may be an important marker of OSA-related sleep disruption and may be an important modifiable health target,” the researchers wrote.

SOURCE:

The study was led by Kelly Sansom, a PhD candidate at the Centre for Sleep Science at the University of Western Australia, Albany. The study was published online in the journal Sleep.

LIMITATIONS:

The cross-sectional design prevented conclusions of causality, and the SRI is a nonspecific measure that may capture a range of phenotypes with one score; other limitations included the small sample sizes of sleep regularity groups and the use of actigraphy to collect sleep times.

DISCLOSURES:

The study was supported by an Australian Government Research Training Program Scholarship and the Raine Study PhD Top-up Scholarship; the Raine Study Scholarship is supported by the NHMRC, the Centre for Sleep Science, School of Anatomy, Physiology & Human Biology of the University of Western Australia, and the Lions Eye Institute. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Severe sleep irregularity often occurs with obstructive sleep apnea (OSA), and this combination approximately doubled the odds of hypertension in middle-aged individuals.

METHODOLOGY:

• OSA has demonstrated an association with hypertension, but data on the impact of sleep irregularity on this relationship are lacking.
• The researchers used the recently developed sleep regularity index (SRI) to determine sleep patterns using a scale of 0-100 (with higher numbers indicating greater regularity) to assess relationships between OSA, sleep patterns, and hypertension in 602 adults with a mean age of 57 years.
• The study’s goal was an assessment of the associations between sleep regularity, OSA, and hypertension in a community sample of adults with normal circadian patterns.

TAKEAWAY:

• The odds of OSA were significantly greater for individuals with mildly irregular or severely irregular sleep than for regular sleepers (odds ratios, 1.97 and 2.06, respectively).
• Individuals with OSA and severely irregular sleep had the highest odds of hypertension compared with individuals with no OSA and regular sleep (OR, 2.34).
• However, participants with OSA and regular sleep or mildly irregular sleep had no significant increase in hypertension risk.

IN PRACTICE:

“Irregular sleep may be an important marker of OSA-related sleep disruption and may be an important modifiable health target,” the researchers wrote.

SOURCE:

The study was led by Kelly Sansom, a PhD candidate at the Centre for Sleep Science at the University of Western Australia, Albany. The study was published online in the journal Sleep.

LIMITATIONS:

The cross-sectional design prevented conclusions of causality, and the SRI is a nonspecific measure that may capture a range of phenotypes with one score; other limitations included the small sample sizes of sleep regularity groups and the use of actigraphy to collect sleep times.

DISCLOSURES:

The study was supported by an Australian Government Research Training Program Scholarship and the Raine Study PhD Top-up Scholarship; the Raine Study Scholarship is supported by the NHMRC, the Centre for Sleep Science, School of Anatomy, Physiology & Human Biology of the University of Western Australia, and the Lions Eye Institute. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Severe sleep irregularity often occurs with obstructive sleep apnea (OSA), and this combination approximately doubled the odds of hypertension in middle-aged individuals.

METHODOLOGY:

• OSA has demonstrated an association with hypertension, but data on the impact of sleep irregularity on this relationship are lacking.
• The researchers used the recently developed sleep regularity index (SRI) to determine sleep patterns using a scale of 0-100 (with higher numbers indicating greater regularity) to assess relationships between OSA, sleep patterns, and hypertension in 602 adults with a mean age of 57 years.
• The study’s goal was an assessment of the associations between sleep regularity, OSA, and hypertension in a community sample of adults with normal circadian patterns.

TAKEAWAY:

• The odds of OSA were significantly greater for individuals with mildly irregular or severely irregular sleep than for regular sleepers (odds ratios, 1.97 and 2.06, respectively).
• Individuals with OSA and severely irregular sleep had the highest odds of hypertension compared with individuals with no OSA and regular sleep (OR, 2.34).
• However, participants with OSA and regular sleep or mildly irregular sleep had no significant increase in hypertension risk.

IN PRACTICE:

“Irregular sleep may be an important marker of OSA-related sleep disruption and may be an important modifiable health target,” the researchers wrote.

SOURCE:

The study was led by Kelly Sansom, a PhD candidate at the Centre for Sleep Science at the University of Western Australia, Albany. The study was published online in the journal Sleep.

LIMITATIONS:

The cross-sectional design prevented conclusions of causality, and the SRI is a nonspecific measure that may capture a range of phenotypes with one score; other limitations included the small sample sizes of sleep regularity groups and the use of actigraphy to collect sleep times.

DISCLOSURES:

The study was supported by an Australian Government Research Training Program Scholarship and the Raine Study PhD Top-up Scholarship; the Raine Study Scholarship is supported by the NHMRC, the Centre for Sleep Science, School of Anatomy, Physiology & Human Biology of the University of Western Australia, and the Lions Eye Institute. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

This is Dr. JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. I’d like to talk about a recent report in the journal Hypertension that raises questions about whether blood pressure (BP) guidelines should be revisited and whether sex-specific thresholds and targets should be considered. Current BP guidelines are sex-agnostic.

This study was done in the large-scale nationally representative NHANES cohort. It included more than 53,000 US men and women. The average age was about 45 years, with an average duration of follow-up of 9.5 years. During that time, about 2400 cardiovascular (CVD) deaths were documented at baseline. The BP was measured three times, and the results were averaged. About 20% of the cohort were taking antihypertensive medications, and 80% were not.

Sex differences were observed in the association between BP and CVD mortality. The systolic BP associated with the lowest risk for CVD death was 110-119 mm Hg in men and 100-109 mm Hg in women. In men, however, compared with a reference category of systolic BP of 100-109 mm Hg, the risk for CVD death began to increase significantly at a systolic BP ≥ 160 mm Hg, at which point, the hazard ratio was 1.76, or 76% higher risk.

In women, the risk for CVD death began to increase significantly at a lower threshold. Compared with a reference category of systolic BP of 100-109 mm Hg, women whose systolic BP was 130-139 mm Hg had a significant 61% increase in CVD death, and among those with a systolic BP of 140-159 mm Hg, the risk was increased by 75%. With a systolic BP ≥ 160 mm Hg, CVD deaths among women were more than doubled, with a hazard ratio of 2.13.

Overall, these findings suggest sex differences, with women having an increased risk for CVD death beginning at a lower elevation of their systolic BP. For diastolic BP, both men and women showed the typical U-shaped curve and the diastolic BP associated with the lowest risk for CVD death was 70-80 mm Hg.

If these findings can be replicated with additional research and other large-scale cohort studies, and randomized trials show differences in lowering BP, then sex-specific BP guidelines could have advantages and should be seriously considered. Furthermore, some of the CVD risk scores and risk modeling should perhaps use sex-specific blood pressure thresholds.Dr. Manson received study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

This is Dr. JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. I’d like to talk about a recent report in the journal Hypertension that raises questions about whether blood pressure (BP) guidelines should be revisited and whether sex-specific thresholds and targets should be considered. Current BP guidelines are sex-agnostic.

This study was done in the large-scale nationally representative NHANES cohort. It included more than 53,000 US men and women. The average age was about 45 years, with an average duration of follow-up of 9.5 years. During that time, about 2400 cardiovascular (CVD) deaths were documented at baseline. The BP was measured three times, and the results were averaged. About 20% of the cohort were taking antihypertensive medications, and 80% were not.

Sex differences were observed in the association between BP and CVD mortality. The systolic BP associated with the lowest risk for CVD death was 110-119 mm Hg in men and 100-109 mm Hg in women. In men, however, compared with a reference category of systolic BP of 100-109 mm Hg, the risk for CVD death began to increase significantly at a systolic BP ≥ 160 mm Hg, at which point, the hazard ratio was 1.76, or 76% higher risk.

In women, the risk for CVD death began to increase significantly at a lower threshold. Compared with a reference category of systolic BP of 100-109 mm Hg, women whose systolic BP was 130-139 mm Hg had a significant 61% increase in CVD death, and among those with a systolic BP of 140-159 mm Hg, the risk was increased by 75%. With a systolic BP ≥ 160 mm Hg, CVD deaths among women were more than doubled, with a hazard ratio of 2.13.

Overall, these findings suggest sex differences, with women having an increased risk for CVD death beginning at a lower elevation of their systolic BP. For diastolic BP, both men and women showed the typical U-shaped curve and the diastolic BP associated with the lowest risk for CVD death was 70-80 mm Hg.

If these findings can be replicated with additional research and other large-scale cohort studies, and randomized trials show differences in lowering BP, then sex-specific BP guidelines could have advantages and should be seriously considered. Furthermore, some of the CVD risk scores and risk modeling should perhaps use sex-specific blood pressure thresholds.Dr. Manson received study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

This is Dr. JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. I’d like to talk about a recent report in the journal Hypertension that raises questions about whether blood pressure (BP) guidelines should be revisited and whether sex-specific thresholds and targets should be considered. Current BP guidelines are sex-agnostic.

This study was done in the large-scale nationally representative NHANES cohort. It included more than 53,000 US men and women. The average age was about 45 years, with an average duration of follow-up of 9.5 years. During that time, about 2400 cardiovascular (CVD) deaths were documented at baseline. The BP was measured three times, and the results were averaged. About 20% of the cohort were taking antihypertensive medications, and 80% were not.

Sex differences were observed in the association between BP and CVD mortality. The systolic BP associated with the lowest risk for CVD death was 110-119 mm Hg in men and 100-109 mm Hg in women. In men, however, compared with a reference category of systolic BP of 100-109 mm Hg, the risk for CVD death began to increase significantly at a systolic BP ≥ 160 mm Hg, at which point, the hazard ratio was 1.76, or 76% higher risk.

In women, the risk for CVD death began to increase significantly at a lower threshold. Compared with a reference category of systolic BP of 100-109 mm Hg, women whose systolic BP was 130-139 mm Hg had a significant 61% increase in CVD death, and among those with a systolic BP of 140-159 mm Hg, the risk was increased by 75%. With a systolic BP ≥ 160 mm Hg, CVD deaths among women were more than doubled, with a hazard ratio of 2.13.

Overall, these findings suggest sex differences, with women having an increased risk for CVD death beginning at a lower elevation of their systolic BP. For diastolic BP, both men and women showed the typical U-shaped curve and the diastolic BP associated with the lowest risk for CVD death was 70-80 mm Hg.

If these findings can be replicated with additional research and other large-scale cohort studies, and randomized trials show differences in lowering BP, then sex-specific BP guidelines could have advantages and should be seriously considered. Furthermore, some of the CVD risk scores and risk modeling should perhaps use sex-specific blood pressure thresholds.Dr. Manson received study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

Adults who used thiazide diuretics for hypertension were more likely than were those who used nonthiazide agents to develop hyponatremia within 2 years of starting treatment, a new study of more than 180,000 people has found.

Although thiazide diuretics generally are well-tolerated in the routine treatment of uncomplicated hypertension, severe adverse effects are possible, and their frequency has not been examined, according to Niklas Worm Andersson, MD, of Statens Serum Institut, in Copenhagen, Denmark, and his colleagues.

“Thiazide diuretics are commonly used drugs for the treatment of uncomplicated hypertension, and hyponatremia is a known potential side effect to thiazide treatment, but the frequency of this adverse event is inconsistently reported across drug labels,” Dr. Andersson told this news organization.

Product labels for thiazide diuretics list hyponatremia as a potential adverse event that can occur rarely (defined as a range from less than 1 in 10,000 to less than 1 in 100 individuals), but the extent of the burden is unclear given the wide range of symptoms of the condition, the researchers write. 

In a study published in Annals of Internal Medicine, Dr. Andersson and his colleagues reviewed data from population-based registries in Denmark of adults aged 40 years or older with uncomplicated hypertension, no recent prescriptions for antihypertensives, and no previous history of hyponatremia. They emulated two target trials. One trial compared the incidence of hyponatremia in new users of bendroflumethiazide (BFZ) vs a calcium-channel blocker (CCB). The other emulation compared the incidence of hyponatremia in new users of hydrochlorothiazide (HCTZ) plus a renin-angiotensin system (RAS) inhibitor vs a RAS inhibitor without HCTZ. 

The primary outcome was hyponatremia, defined as blood sodium < 130 mmol/L, within 2 years of starting treatment. 

The 2-year incidence of hyponatremia for the two thiazide diuretics was 3.83% for BFZ and 3.51% for HCTZ-RAS inhibitor. The risk difference in the incidence of hyponatremia was 1.35% for BFZ vs CCB and 1.38% for HCTZ-RAS inhibitor vs RAS inhibitor, the researchers reported. 

The study population included 37,786 new users of BFZ who were compared with 44,963 new users of CCBs as well as 11,943 new users of HCTZ-RAS inhibitors who were compared with 85,784 new users of RAS inhibitors only. 

Overall, older age and a greater number of comorbidities increased the cumulative hyponatremia in new users of thiazide-based hypertensives. The risk differences among individuals aged 80 years or older were 4.80% in the BFZ vs CCB study and 5.52% in the HCTZ-RAS inhibitor vs RAS inhibitor study. Among participants with three or more comorbidities, the risk differences in the two studies were 5.24% and 2.91%, respectively, Dr. Andersson’s group found.

The findings were limited by several factors, mainly the potential for confounding on the basis of the assumption that filled prescriptions equaled drug use, the researchers noted. Other limitations included the focus on new users and a Danish population only, which might limit generalizability, and a lack of data on blood pressure measures.

However, the results suggest a greater risk for hyponatremia with thiazide diuretics than what the drug labels indicate, especially early in treatment, the researchers concluded.

 

Data Reinforce Need for Vigilance in the Clinic

“Our findings highlight the continued need for clinical awareness and monitoring of this adverse drug reaction; particularly during the first months of treatment, in persons who are older or who have comorbidities,” Dr. Andersson told this news organization. “Further mapping of potential subpopulations at risk in terms of specific comorbidities is important to improve the prevention of this adverse event.”

“The thiazide diuretics have been recommended as first-line therapy for hypertension, and it was important to evaluate the potential development of hyponatremia, especially in the older patients given the potentially serious health effects caused by hyponatremia,” said Noel Deep, MD, a general internist in private practice in Antigo, Wisconsin. Dr. Deep, who was not involved in the study, also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo. 

The current study findings were not surprising, Dr. Deep added. “I have seen this occur in my patients, especially in the older female patients,” he said. “The results reinforce my practice of monitoring the electrolytes and renal function in 1-2 weeks after starting a thiazide diuretic, and then at regular intervals.”

In practice, clinicians should be aware of the potential development of hyponatremia and monitor and address the electrolyte abnormalities, Dr. Deep said. “While thiazide and thiazide-like diuretics are an important component of our treatment options for patients with hypertension and other conditions, we should also ensure that we are cognizant of and address the potential side effects or electrolyte imbalances caused by the medications.” 

The study was funded by the Independent Research Fund Denmark, Helsefonden, Dagmar Marshalls Fond, Gangstedfonden, A.P. Møller and Chastine Mc-Kinney Møller Foundation, Brødrene Hartmanns Fond, and Snedkermester Sophus Jacobsen og hustru Astrid Jacobsens Fond.

The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose.

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

Adults who used thiazide diuretics for hypertension were more likely than were those who used nonthiazide agents to develop hyponatremia within 2 years of starting treatment, a new study of more than 180,000 people has found.

Although thiazide diuretics generally are well-tolerated in the routine treatment of uncomplicated hypertension, severe adverse effects are possible, and their frequency has not been examined, according to Niklas Worm Andersson, MD, of Statens Serum Institut, in Copenhagen, Denmark, and his colleagues.

“Thiazide diuretics are commonly used drugs for the treatment of uncomplicated hypertension, and hyponatremia is a known potential side effect to thiazide treatment, but the frequency of this adverse event is inconsistently reported across drug labels,” Dr. Andersson told this news organization.

Product labels for thiazide diuretics list hyponatremia as a potential adverse event that can occur rarely (defined as a range from less than 1 in 10,000 to less than 1 in 100 individuals), but the extent of the burden is unclear given the wide range of symptoms of the condition, the researchers write. 

In a study published in Annals of Internal Medicine, Dr. Andersson and his colleagues reviewed data from population-based registries in Denmark of adults aged 40 years or older with uncomplicated hypertension, no recent prescriptions for antihypertensives, and no previous history of hyponatremia. They emulated two target trials. One trial compared the incidence of hyponatremia in new users of bendroflumethiazide (BFZ) vs a calcium-channel blocker (CCB). The other emulation compared the incidence of hyponatremia in new users of hydrochlorothiazide (HCTZ) plus a renin-angiotensin system (RAS) inhibitor vs a RAS inhibitor without HCTZ. 

The primary outcome was hyponatremia, defined as blood sodium < 130 mmol/L, within 2 years of starting treatment. 

The 2-year incidence of hyponatremia for the two thiazide diuretics was 3.83% for BFZ and 3.51% for HCTZ-RAS inhibitor. The risk difference in the incidence of hyponatremia was 1.35% for BFZ vs CCB and 1.38% for HCTZ-RAS inhibitor vs RAS inhibitor, the researchers reported. 

The study population included 37,786 new users of BFZ who were compared with 44,963 new users of CCBs as well as 11,943 new users of HCTZ-RAS inhibitors who were compared with 85,784 new users of RAS inhibitors only. 

Overall, older age and a greater number of comorbidities increased the cumulative hyponatremia in new users of thiazide-based hypertensives. The risk differences among individuals aged 80 years or older were 4.80% in the BFZ vs CCB study and 5.52% in the HCTZ-RAS inhibitor vs RAS inhibitor study. Among participants with three or more comorbidities, the risk differences in the two studies were 5.24% and 2.91%, respectively, Dr. Andersson’s group found.

The findings were limited by several factors, mainly the potential for confounding on the basis of the assumption that filled prescriptions equaled drug use, the researchers noted. Other limitations included the focus on new users and a Danish population only, which might limit generalizability, and a lack of data on blood pressure measures.

However, the results suggest a greater risk for hyponatremia with thiazide diuretics than what the drug labels indicate, especially early in treatment, the researchers concluded.

 

Data Reinforce Need for Vigilance in the Clinic

“Our findings highlight the continued need for clinical awareness and monitoring of this adverse drug reaction; particularly during the first months of treatment, in persons who are older or who have comorbidities,” Dr. Andersson told this news organization. “Further mapping of potential subpopulations at risk in terms of specific comorbidities is important to improve the prevention of this adverse event.”

“The thiazide diuretics have been recommended as first-line therapy for hypertension, and it was important to evaluate the potential development of hyponatremia, especially in the older patients given the potentially serious health effects caused by hyponatremia,” said Noel Deep, MD, a general internist in private practice in Antigo, Wisconsin. Dr. Deep, who was not involved in the study, also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo. 

The current study findings were not surprising, Dr. Deep added. “I have seen this occur in my patients, especially in the older female patients,” he said. “The results reinforce my practice of monitoring the electrolytes and renal function in 1-2 weeks after starting a thiazide diuretic, and then at regular intervals.”

In practice, clinicians should be aware of the potential development of hyponatremia and monitor and address the electrolyte abnormalities, Dr. Deep said. “While thiazide and thiazide-like diuretics are an important component of our treatment options for patients with hypertension and other conditions, we should also ensure that we are cognizant of and address the potential side effects or electrolyte imbalances caused by the medications.” 

The study was funded by the Independent Research Fund Denmark, Helsefonden, Dagmar Marshalls Fond, Gangstedfonden, A.P. Møller and Chastine Mc-Kinney Møller Foundation, Brødrene Hartmanns Fond, and Snedkermester Sophus Jacobsen og hustru Astrid Jacobsens Fond.

The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose.

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

Adults who used thiazide diuretics for hypertension were more likely than were those who used nonthiazide agents to develop hyponatremia within 2 years of starting treatment, a new study of more than 180,000 people has found.

Although thiazide diuretics generally are well-tolerated in the routine treatment of uncomplicated hypertension, severe adverse effects are possible, and their frequency has not been examined, according to Niklas Worm Andersson, MD, of Statens Serum Institut, in Copenhagen, Denmark, and his colleagues.

“Thiazide diuretics are commonly used drugs for the treatment of uncomplicated hypertension, and hyponatremia is a known potential side effect to thiazide treatment, but the frequency of this adverse event is inconsistently reported across drug labels,” Dr. Andersson told this news organization.

Product labels for thiazide diuretics list hyponatremia as a potential adverse event that can occur rarely (defined as a range from less than 1 in 10,000 to less than 1 in 100 individuals), but the extent of the burden is unclear given the wide range of symptoms of the condition, the researchers write. 

In a study published in Annals of Internal Medicine, Dr. Andersson and his colleagues reviewed data from population-based registries in Denmark of adults aged 40 years or older with uncomplicated hypertension, no recent prescriptions for antihypertensives, and no previous history of hyponatremia. They emulated two target trials. One trial compared the incidence of hyponatremia in new users of bendroflumethiazide (BFZ) vs a calcium-channel blocker (CCB). The other emulation compared the incidence of hyponatremia in new users of hydrochlorothiazide (HCTZ) plus a renin-angiotensin system (RAS) inhibitor vs a RAS inhibitor without HCTZ. 

The primary outcome was hyponatremia, defined as blood sodium < 130 mmol/L, within 2 years of starting treatment. 

The 2-year incidence of hyponatremia for the two thiazide diuretics was 3.83% for BFZ and 3.51% for HCTZ-RAS inhibitor. The risk difference in the incidence of hyponatremia was 1.35% for BFZ vs CCB and 1.38% for HCTZ-RAS inhibitor vs RAS inhibitor, the researchers reported. 

The study population included 37,786 new users of BFZ who were compared with 44,963 new users of CCBs as well as 11,943 new users of HCTZ-RAS inhibitors who were compared with 85,784 new users of RAS inhibitors only. 

Overall, older age and a greater number of comorbidities increased the cumulative hyponatremia in new users of thiazide-based hypertensives. The risk differences among individuals aged 80 years or older were 4.80% in the BFZ vs CCB study and 5.52% in the HCTZ-RAS inhibitor vs RAS inhibitor study. Among participants with three or more comorbidities, the risk differences in the two studies were 5.24% and 2.91%, respectively, Dr. Andersson’s group found.

The findings were limited by several factors, mainly the potential for confounding on the basis of the assumption that filled prescriptions equaled drug use, the researchers noted. Other limitations included the focus on new users and a Danish population only, which might limit generalizability, and a lack of data on blood pressure measures.

However, the results suggest a greater risk for hyponatremia with thiazide diuretics than what the drug labels indicate, especially early in treatment, the researchers concluded.

 

Data Reinforce Need for Vigilance in the Clinic

“Our findings highlight the continued need for clinical awareness and monitoring of this adverse drug reaction; particularly during the first months of treatment, in persons who are older or who have comorbidities,” Dr. Andersson told this news organization. “Further mapping of potential subpopulations at risk in terms of specific comorbidities is important to improve the prevention of this adverse event.”

“The thiazide diuretics have been recommended as first-line therapy for hypertension, and it was important to evaluate the potential development of hyponatremia, especially in the older patients given the potentially serious health effects caused by hyponatremia,” said Noel Deep, MD, a general internist in private practice in Antigo, Wisconsin. Dr. Deep, who was not involved in the study, also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo. 

The current study findings were not surprising, Dr. Deep added. “I have seen this occur in my patients, especially in the older female patients,” he said. “The results reinforce my practice of monitoring the electrolytes and renal function in 1-2 weeks after starting a thiazide diuretic, and then at regular intervals.”

In practice, clinicians should be aware of the potential development of hyponatremia and monitor and address the electrolyte abnormalities, Dr. Deep said. “While thiazide and thiazide-like diuretics are an important component of our treatment options for patients with hypertension and other conditions, we should also ensure that we are cognizant of and address the potential side effects or electrolyte imbalances caused by the medications.” 

The study was funded by the Independent Research Fund Denmark, Helsefonden, Dagmar Marshalls Fond, Gangstedfonden, A.P. Møller and Chastine Mc-Kinney Møller Foundation, Brødrene Hartmanns Fond, and Snedkermester Sophus Jacobsen og hustru Astrid Jacobsens Fond.

The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose.

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

In a new report, the Midwest Institute for Clinical and Economic Review’s (ICER) Comparative Effectiveness Public Advisory Council concluded that the Merck drug sotatercept, currently under review by the US Food and Drug Administration (FDA), has a high certainty of at least a small net health benefit to patients with pulmonary arterial hypertension (PAH) when added to background therapy. The limited availability of evidence means that the benefit could range from minimal to substantial, according to the authors. 

Sotatercept, administered by injection every 3 weeks, is a first-in-class activin signaling inhibitor. It counters cell proliferation and decreases inflammation in vessel walls, which may lead to improved pulmonary blood flow. The US FDA is considering it for approval through a biologics license application, with a decision expected by March 26, 2024.

There remains a great deal of uncertainty surrounding the long-term benefits of sotatercept. It’s possible that the drug is disease-modifying, but there isn’t yet any proof, according to Greg Curfman, MD, who attended a virtual ICER public meeting on December 1 that summarized the report and accepted public comments. “I’m still wondering the extent to which disease-modifying issue here is more aspirational at this point than really documented,” said Dr. Curfman, who is an associated professor of medicine at Harvard Medical School and executive editor of the Journal of the American Medical Association.

Current PAH treatment consists of vasodilators, including phosphodiesterase-5 inhibitors (PDE5i), guanylate cyclase stimulators, endothelin receptor antagonists (ERA), prostacyclin analogues (prostanoids), and a prostacyclin receptor agonist. The 2022 European Society of Cardiology and the European Respiratory Society clinical practice guideline recommends that low- and intermediate-risk patients should be started on ERA/PDE5i combination therapy, while high-risk patients should also be given an intravenous or subcutaneous prostacyclin analogue, referred to as triple therapy.

Sotatercept’s regulatory approval hinges on the phase 3 STELLAR trial, which included 323 patients with World Health Organization functional class (WHO-FC) II and III PAH who were randomized to 0.75 mg/kg sotatercept in addition to background double or triple therapy, or background therapy alone. The mean age was 48 years, and the mean time since diagnosis was 8.8 years. About 40% received infused prostacyclin therapy at baseline. At 24 weeks, the median change in 6-min walking distance (6mWD) was 40.8 m longer in the sotatercept group. More patients in the sotatercept group experienced WHO-FC improvement (29.4% vs 13.8%). Those in the sotatercept group also experienced an 84% reduction in risk for clinical worsening or death. PAH-specific quality of life scales did not show a difference between the two groups. Open-label extension trials have shown that benefits are maintained for up to 2 years. Adverse events likely related to sotatercept included telangiectasias, increased hemoglobin levels, and bleeding events.

Along with its benefits, the report authors suggest that the subcutaneous delivery of sotatercept may be less burdensome to patients than some other PAH treatments, especially inhaled and intravenous prostanoids. “However, uncertainty remains about sotatercept’s efficacy in sicker populations and in those with connective tissue disease, and about the durability of effect,” the authors wrote.

A lack of long-term data leaves open the question of its effect on mortality and unknown adverse effects.

Using a de novo decision analytic model, the authors estimated that sotatercept treatment would lead to a longer time without symptoms at rest and more quality-adjusted life years, life years, and equal value life years. They determined the health benefit price benchmark for sotatercept to be between $18,700 and $36,200 per year. “The long-term conventional cost-effectiveness of sotatercept is largely dependent on the long-term effect of sotatercept on improving functional class and slowing the worsening in functional class; however, controlled trial evidence for sotatercept is limited to 24 weeks. Long-term data are necessary to reduce the uncertainty in sotatercept’s long-term effect on improving functional class and slowing the worsening in functional class,” the authors wrote. 

During the online meeting, Dr. Curfman took note of the fact that the STELLAR trial reported a median value of increase in 6mWD, rather than a mean, and the 40-m improvement is close to the value accepted as clinically meaningful. “So that tells us that half the patients had less than a clinically important improvement in the six-minute walk distance. We should be putting that in perspective,” said Dr. Curfman.

Another attendee pointed out that the open-label PULSAR extension trial showed that the proportion of patients in the sotatercept arm who were functional class I rose from 7.5% at the end of the trial to 20.6% at the end of the open-label period and wondered if that could be a sign of disease-modifying activity. “I think that’s a remarkable piece of data. I don’t recall seeing that in any other open label [trial of a PAH therapy] — that much of an improvement in getting to our best functional status,” said Marc Simon, MD, professor of medicine and director of the Pulmonary Hypertension Center at the University of California, San Francisco, who was a coauthor of the report.

Dr. Curfman has no relevant financial disclosures. Dr. Simon has consulted for Merck.

A version of this article appeared on Medscape.com.

In a new report, the Midwest Institute for Clinical and Economic Review’s (ICER) Comparative Effectiveness Public Advisory Council concluded that the Merck drug sotatercept, currently under review by the US Food and Drug Administration (FDA), has a high certainty of at least a small net health benefit to patients with pulmonary arterial hypertension (PAH) when added to background therapy. The limited availability of evidence means that the benefit could range from minimal to substantial, according to the authors. 

Sotatercept, administered by injection every 3 weeks, is a first-in-class activin signaling inhibitor. It counters cell proliferation and decreases inflammation in vessel walls, which may lead to improved pulmonary blood flow. The US FDA is considering it for approval through a biologics license application, with a decision expected by March 26, 2024.

There remains a great deal of uncertainty surrounding the long-term benefits of sotatercept. It’s possible that the drug is disease-modifying, but there isn’t yet any proof, according to Greg Curfman, MD, who attended a virtual ICER public meeting on December 1 that summarized the report and accepted public comments. “I’m still wondering the extent to which disease-modifying issue here is more aspirational at this point than really documented,” said Dr. Curfman, who is an associated professor of medicine at Harvard Medical School and executive editor of the Journal of the American Medical Association.

Current PAH treatment consists of vasodilators, including phosphodiesterase-5 inhibitors (PDE5i), guanylate cyclase stimulators, endothelin receptor antagonists (ERA), prostacyclin analogues (prostanoids), and a prostacyclin receptor agonist. The 2022 European Society of Cardiology and the European Respiratory Society clinical practice guideline recommends that low- and intermediate-risk patients should be started on ERA/PDE5i combination therapy, while high-risk patients should also be given an intravenous or subcutaneous prostacyclin analogue, referred to as triple therapy.

Sotatercept’s regulatory approval hinges on the phase 3 STELLAR trial, which included 323 patients with World Health Organization functional class (WHO-FC) II and III PAH who were randomized to 0.75 mg/kg sotatercept in addition to background double or triple therapy, or background therapy alone. The mean age was 48 years, and the mean time since diagnosis was 8.8 years. About 40% received infused prostacyclin therapy at baseline. At 24 weeks, the median change in 6-min walking distance (6mWD) was 40.8 m longer in the sotatercept group. More patients in the sotatercept group experienced WHO-FC improvement (29.4% vs 13.8%). Those in the sotatercept group also experienced an 84% reduction in risk for clinical worsening or death. PAH-specific quality of life scales did not show a difference between the two groups. Open-label extension trials have shown that benefits are maintained for up to 2 years. Adverse events likely related to sotatercept included telangiectasias, increased hemoglobin levels, and bleeding events.

Along with its benefits, the report authors suggest that the subcutaneous delivery of sotatercept may be less burdensome to patients than some other PAH treatments, especially inhaled and intravenous prostanoids. “However, uncertainty remains about sotatercept’s efficacy in sicker populations and in those with connective tissue disease, and about the durability of effect,” the authors wrote.

A lack of long-term data leaves open the question of its effect on mortality and unknown adverse effects.

Using a de novo decision analytic model, the authors estimated that sotatercept treatment would lead to a longer time without symptoms at rest and more quality-adjusted life years, life years, and equal value life years. They determined the health benefit price benchmark for sotatercept to be between $18,700 and $36,200 per year. “The long-term conventional cost-effectiveness of sotatercept is largely dependent on the long-term effect of sotatercept on improving functional class and slowing the worsening in functional class; however, controlled trial evidence for sotatercept is limited to 24 weeks. Long-term data are necessary to reduce the uncertainty in sotatercept’s long-term effect on improving functional class and slowing the worsening in functional class,” the authors wrote. 

During the online meeting, Dr. Curfman took note of the fact that the STELLAR trial reported a median value of increase in 6mWD, rather than a mean, and the 40-m improvement is close to the value accepted as clinically meaningful. “So that tells us that half the patients had less than a clinically important improvement in the six-minute walk distance. We should be putting that in perspective,” said Dr. Curfman.

Another attendee pointed out that the open-label PULSAR extension trial showed that the proportion of patients in the sotatercept arm who were functional class I rose from 7.5% at the end of the trial to 20.6% at the end of the open-label period and wondered if that could be a sign of disease-modifying activity. “I think that’s a remarkable piece of data. I don’t recall seeing that in any other open label [trial of a PAH therapy] — that much of an improvement in getting to our best functional status,” said Marc Simon, MD, professor of medicine and director of the Pulmonary Hypertension Center at the University of California, San Francisco, who was a coauthor of the report.

Dr. Curfman has no relevant financial disclosures. Dr. Simon has consulted for Merck.

A version of this article appeared on Medscape.com.

In a new report, the Midwest Institute for Clinical and Economic Review’s (ICER) Comparative Effectiveness Public Advisory Council concluded that the Merck drug sotatercept, currently under review by the US Food and Drug Administration (FDA), has a high certainty of at least a small net health benefit to patients with pulmonary arterial hypertension (PAH) when added to background therapy. The limited availability of evidence means that the benefit could range from minimal to substantial, according to the authors. 

Sotatercept, administered by injection every 3 weeks, is a first-in-class activin signaling inhibitor. It counters cell proliferation and decreases inflammation in vessel walls, which may lead to improved pulmonary blood flow. The US FDA is considering it for approval through a biologics license application, with a decision expected by March 26, 2024.

There remains a great deal of uncertainty surrounding the long-term benefits of sotatercept. It’s possible that the drug is disease-modifying, but there isn’t yet any proof, according to Greg Curfman, MD, who attended a virtual ICER public meeting on December 1 that summarized the report and accepted public comments. “I’m still wondering the extent to which disease-modifying issue here is more aspirational at this point than really documented,” said Dr. Curfman, who is an associated professor of medicine at Harvard Medical School and executive editor of the Journal of the American Medical Association.

Current PAH treatment consists of vasodilators, including phosphodiesterase-5 inhibitors (PDE5i), guanylate cyclase stimulators, endothelin receptor antagonists (ERA), prostacyclin analogues (prostanoids), and a prostacyclin receptor agonist. The 2022 European Society of Cardiology and the European Respiratory Society clinical practice guideline recommends that low- and intermediate-risk patients should be started on ERA/PDE5i combination therapy, while high-risk patients should also be given an intravenous or subcutaneous prostacyclin analogue, referred to as triple therapy.

Sotatercept’s regulatory approval hinges on the phase 3 STELLAR trial, which included 323 patients with World Health Organization functional class (WHO-FC) II and III PAH who were randomized to 0.75 mg/kg sotatercept in addition to background double or triple therapy, or background therapy alone. The mean age was 48 years, and the mean time since diagnosis was 8.8 years. About 40% received infused prostacyclin therapy at baseline. At 24 weeks, the median change in 6-min walking distance (6mWD) was 40.8 m longer in the sotatercept group. More patients in the sotatercept group experienced WHO-FC improvement (29.4% vs 13.8%). Those in the sotatercept group also experienced an 84% reduction in risk for clinical worsening or death. PAH-specific quality of life scales did not show a difference between the two groups. Open-label extension trials have shown that benefits are maintained for up to 2 years. Adverse events likely related to sotatercept included telangiectasias, increased hemoglobin levels, and bleeding events.

Along with its benefits, the report authors suggest that the subcutaneous delivery of sotatercept may be less burdensome to patients than some other PAH treatments, especially inhaled and intravenous prostanoids. “However, uncertainty remains about sotatercept’s efficacy in sicker populations and in those with connective tissue disease, and about the durability of effect,” the authors wrote.

A lack of long-term data leaves open the question of its effect on mortality and unknown adverse effects.

Using a de novo decision analytic model, the authors estimated that sotatercept treatment would lead to a longer time without symptoms at rest and more quality-adjusted life years, life years, and equal value life years. They determined the health benefit price benchmark for sotatercept to be between $18,700 and $36,200 per year. “The long-term conventional cost-effectiveness of sotatercept is largely dependent on the long-term effect of sotatercept on improving functional class and slowing the worsening in functional class; however, controlled trial evidence for sotatercept is limited to 24 weeks. Long-term data are necessary to reduce the uncertainty in sotatercept’s long-term effect on improving functional class and slowing the worsening in functional class,” the authors wrote. 

During the online meeting, Dr. Curfman took note of the fact that the STELLAR trial reported a median value of increase in 6mWD, rather than a mean, and the 40-m improvement is close to the value accepted as clinically meaningful. “So that tells us that half the patients had less than a clinically important improvement in the six-minute walk distance. We should be putting that in perspective,” said Dr. Curfman.

Another attendee pointed out that the open-label PULSAR extension trial showed that the proportion of patients in the sotatercept arm who were functional class I rose from 7.5% at the end of the trial to 20.6% at the end of the open-label period and wondered if that could be a sign of disease-modifying activity. “I think that’s a remarkable piece of data. I don’t recall seeing that in any other open label [trial of a PAH therapy] — that much of an improvement in getting to our best functional status,” said Marc Simon, MD, professor of medicine and director of the Pulmonary Hypertension Center at the University of California, San Francisco, who was a coauthor of the report.

Dr. Curfman has no relevant financial disclosures. Dr. Simon has consulted for Merck.

A version of this article appeared on Medscape.com.