Mitchel L. Zoler, PhD

ORLANDO — Elevated levels of hemoglobin A_1c were linked with a significantly increased risk of heart failure in a review of more than 11,000 American adults without diabetes.

“Hemoglobin A_1c may be a better biomarker to evaluate the risk of heart failure compared with fasting glucose in nondiabetic populations,” Dr. Kunihiro Matsushita said at the annual scientific sessions of the American Heart Association.

Prior study results linked higher hemoglobin A_1c levels with heart failure in patients with diabetes, but no previous study looked at this relationship in people without diabetes, said Dr. Matsushita, an epidemiologist in the Johns Hopkins Bloomberg School of Public Health, Baltimore.

Diabetes is an established risk factor for heart failure.

The new study used some of the more than 15,000 Americans aged 45-64 years who enrolled in the Atherosclerosis Risk in Communities study in four U.S. locations in 1987.

The analysis focused on the 11,196 study participants who underwent an examination in 1990-1992 that included HbA_1c measurement and did not have diabetes or heart failure at that time. Their average age was 56, and 56% were women.

When analyzed by HbA_1c level at their examination in 1990-1992, 9% had a level of less than 5%, 47% had a level of 5.0%-5.4%, 35% had a level of 5.5%-5.9%, 8% had a level of 6.0%-6.4%, and 1% had a level of 6.5% or higher.

During a median follow-up of 14 years, 871 cases of incident heart failure developed. The data showed a continuous association between baseline level of HbA_1c and subsequent heart failure.

In a model that adjusted for age, gender, and race, the rate of heart failure cases per 1,000 person-years of follow-up rose from 5 among those with a HbA_1c level of 5% to 6 in those with a level of 5.5%, 9 in those with a level of 6%, and 16 in people with a 6.5% level.

Dr. Matsushita and his associates ran additional models that adjusted for many other baseline variables, including smoking, alcohol intake, body mass index, blood pressure, cholesterol levels, kidney function, and fasting glucose.

In the fully adjusted model, people with a baseline HbA_1c of 6.0%-6.4% had a 41% increased risk of heart failure during follow-up, compared with the reference group that started with a HbA_1c level of 5.0%-5.4%. People who began with a level of 6.5% or greater had more than a twofold risk compared with the reference group. Both differences were significant.

The analysis also showed that higher levels of HbA_1c were more predictive than were high baseline levels of fasting blood glucose.

In a similar, fully adjusted model that controlled for baseline HbA_1c, people whose baseline fasting blood glucose was either 100-109 mg/dL or 110-125 mg/dL did not have a significantly higher risk of developing heart failure than did the reference group with a baseline fasting glucose level of 90-99 mg/dL.

Additional analysis by the Johns Hopkins researchers showed that the interaction between HbA_1c and heart failure did not depend on coronary heart disease to mediate the effect.

When the analysis eliminated the 482 cases of coronary heart disease that occurred during follow-up before those people developed heart failure, the significant link between baseline HbA_1c and incident heart failure remained, Dr. Matsushita said.

Dr. Matsushita reported that he and his associates had no financial relationships to disclose.

HbA_1c may be a better biomarker of heart failure risk than fasting glucose in nondiabetic populations.

Source DR. MATSUSHITA

ORLANDO — Elevated levels of hemoglobin A_1c were linked with a significantly increased risk of heart failure in a review of more than 11,000 American adults without diabetes.

“Hemoglobin A_1c may be a better biomarker to evaluate the risk of heart failure compared with fasting glucose in nondiabetic populations,” Dr. Kunihiro Matsushita said at the annual scientific sessions of the American Heart Association.

Prior study results linked higher hemoglobin A_1c levels with heart failure in patients with diabetes, but no previous study looked at this relationship in people without diabetes, said Dr. Matsushita, an epidemiologist in the Johns Hopkins Bloomberg School of Public Health, Baltimore.

Diabetes is an established risk factor for heart failure.

The new study used some of the more than 15,000 Americans aged 45-64 years who enrolled in the Atherosclerosis Risk in Communities study in four U.S. locations in 1987.

The analysis focused on the 11,196 study participants who underwent an examination in 1990-1992 that included HbA_1c measurement and did not have diabetes or heart failure at that time. Their average age was 56, and 56% were women.

When analyzed by HbA_1c level at their examination in 1990-1992, 9% had a level of less than 5%, 47% had a level of 5.0%-5.4%, 35% had a level of 5.5%-5.9%, 8% had a level of 6.0%-6.4%, and 1% had a level of 6.5% or higher.

During a median follow-up of 14 years, 871 cases of incident heart failure developed. The data showed a continuous association between baseline level of HbA_1c and subsequent heart failure.

In a model that adjusted for age, gender, and race, the rate of heart failure cases per 1,000 person-years of follow-up rose from 5 among those with a HbA_1c level of 5% to 6 in those with a level of 5.5%, 9 in those with a level of 6%, and 16 in people with a 6.5% level.

Dr. Matsushita and his associates ran additional models that adjusted for many other baseline variables, including smoking, alcohol intake, body mass index, blood pressure, cholesterol levels, kidney function, and fasting glucose.

In the fully adjusted model, people with a baseline HbA_1c of 6.0%-6.4% had a 41% increased risk of heart failure during follow-up, compared with the reference group that started with a HbA_1c level of 5.0%-5.4%. People who began with a level of 6.5% or greater had more than a twofold risk compared with the reference group. Both differences were significant.

The analysis also showed that higher levels of HbA_1c were more predictive than were high baseline levels of fasting blood glucose.

In a similar, fully adjusted model that controlled for baseline HbA_1c, people whose baseline fasting blood glucose was either 100-109 mg/dL or 110-125 mg/dL did not have a significantly higher risk of developing heart failure than did the reference group with a baseline fasting glucose level of 90-99 mg/dL.

Additional analysis by the Johns Hopkins researchers showed that the interaction between HbA_1c and heart failure did not depend on coronary heart disease to mediate the effect.

When the analysis eliminated the 482 cases of coronary heart disease that occurred during follow-up before those people developed heart failure, the significant link between baseline HbA_1c and incident heart failure remained, Dr. Matsushita said.

Dr. Matsushita reported that he and his associates had no financial relationships to disclose.

HbA_1c may be a better biomarker of heart failure risk than fasting glucose in nondiabetic populations.

Source DR. MATSUSHITA

ORLANDO — Elevated levels of hemoglobin A_1c were linked with a significantly increased risk of heart failure in a review of more than 11,000 American adults without diabetes.

“Hemoglobin A_1c may be a better biomarker to evaluate the risk of heart failure compared with fasting glucose in nondiabetic populations,” Dr. Kunihiro Matsushita said at the annual scientific sessions of the American Heart Association.

Prior study results linked higher hemoglobin A_1c levels with heart failure in patients with diabetes, but no previous study looked at this relationship in people without diabetes, said Dr. Matsushita, an epidemiologist in the Johns Hopkins Bloomberg School of Public Health, Baltimore.

Diabetes is an established risk factor for heart failure.

The new study used some of the more than 15,000 Americans aged 45-64 years who enrolled in the Atherosclerosis Risk in Communities study in four U.S. locations in 1987.

The analysis focused on the 11,196 study participants who underwent an examination in 1990-1992 that included HbA_1c measurement and did not have diabetes or heart failure at that time. Their average age was 56, and 56% were women.

When analyzed by HbA_1c level at their examination in 1990-1992, 9% had a level of less than 5%, 47% had a level of 5.0%-5.4%, 35% had a level of 5.5%-5.9%, 8% had a level of 6.0%-6.4%, and 1% had a level of 6.5% or higher.

During a median follow-up of 14 years, 871 cases of incident heart failure developed. The data showed a continuous association between baseline level of HbA_1c and subsequent heart failure.

In a model that adjusted for age, gender, and race, the rate of heart failure cases per 1,000 person-years of follow-up rose from 5 among those with a HbA_1c level of 5% to 6 in those with a level of 5.5%, 9 in those with a level of 6%, and 16 in people with a 6.5% level.

Dr. Matsushita and his associates ran additional models that adjusted for many other baseline variables, including smoking, alcohol intake, body mass index, blood pressure, cholesterol levels, kidney function, and fasting glucose.

In the fully adjusted model, people with a baseline HbA_1c of 6.0%-6.4% had a 41% increased risk of heart failure during follow-up, compared with the reference group that started with a HbA_1c level of 5.0%-5.4%. People who began with a level of 6.5% or greater had more than a twofold risk compared with the reference group. Both differences were significant.

The analysis also showed that higher levels of HbA_1c were more predictive than were high baseline levels of fasting blood glucose.

In a similar, fully adjusted model that controlled for baseline HbA_1c, people whose baseline fasting blood glucose was either 100-109 mg/dL or 110-125 mg/dL did not have a significantly higher risk of developing heart failure than did the reference group with a baseline fasting glucose level of 90-99 mg/dL.

Additional analysis by the Johns Hopkins researchers showed that the interaction between HbA_1c and heart failure did not depend on coronary heart disease to mediate the effect.

When the analysis eliminated the 482 cases of coronary heart disease that occurred during follow-up before those people developed heart failure, the significant link between baseline HbA_1c and incident heart failure remained, Dr. Matsushita said.

Dr. Matsushita reported that he and his associates had no financial relationships to disclose.

HbA_1c may be a better biomarker of heart failure risk than fasting glucose in nondiabetic populations.

Source DR. MATSUSHITA

ORLANDO — High blood levels of a brain natriuretic peptide were associated with poor cognitive function in a study of 950 community-dwelling, healthy, elderly adults.

“This is the first time this [association] has been shown,” Dr. Lori B. Daniels said at the annual scientific sessions of the American Heart Association.

Dr. Daniels, a cardiologist at the University of California, San Diego, suggested that several mechanisms that might link production of natriuretic peptide to poor cognitive function including reduced cardiac output that drops oxygen or nutrient supplies to the brain, atrial fibrillation that creates microemboli, microcirculation deficits that harm both the heart and brain, and genetic predisposition.

Cognitive function data and blood specimens were analyzed from 950 of 5,000 participants enrolled in the Rancho Bernardo study of the early 1970s.

The average age of the participants was 77 years; 61% were women. The researchers used three tests to evaluate cognitive function: The Mini-Mental State Exam (MMSE), the Trail-Making Test B, and a category fluency test that asked participants to name as many animals as they could in 1 minute.

MMSE results identified poor function in 7%, the trail-making test B identified poor function in 30%, and category fluency identified poor function in 15%.

Natriuretic peptide levels in the blood specimens were measured using a test that detects N-terminal pro-B-type natriuretic peptide (NT-proBNP). Among the 950 participants, 79% had a low level of NT-proBNP, and 21% had a high level.

In the low level group, poor cognitive scores occurred in 5%, 23%, and 12% of subjects for the three cognitive function tests, respectively. In the high level group, 17%, 54%, and 26% of the subjects scored poorly on the three tests, respectively.

When the results were adjusted for age, education, and other factors, participants with high NT-proBNP levels had significantly worse cognitive function scores on the MMSE and the Trail-Making Test B. Scores for category fluency were lower in people with high NT-proBNP in the fully-adjusted model, but the difference fell short of statistical significance.

In the fully-adjusted model, people with high levels of NT-proBNP were 82%, 75%, and 37% more likely to have poor cognitive function on the three tests, respectively, compared with people with low levels.

Dr. Daniels received research support from Roche Diagnostics, which markets an NT-proBNP assay.

ORLANDO — High blood levels of a brain natriuretic peptide were associated with poor cognitive function in a study of 950 community-dwelling, healthy, elderly adults.

“This is the first time this [association] has been shown,” Dr. Lori B. Daniels said at the annual scientific sessions of the American Heart Association.

Dr. Daniels, a cardiologist at the University of California, San Diego, suggested that several mechanisms that might link production of natriuretic peptide to poor cognitive function including reduced cardiac output that drops oxygen or nutrient supplies to the brain, atrial fibrillation that creates microemboli, microcirculation deficits that harm both the heart and brain, and genetic predisposition.

Cognitive function data and blood specimens were analyzed from 950 of 5,000 participants enrolled in the Rancho Bernardo study of the early 1970s.

The average age of the participants was 77 years; 61% were women. The researchers used three tests to evaluate cognitive function: The Mini-Mental State Exam (MMSE), the Trail-Making Test B, and a category fluency test that asked participants to name as many animals as they could in 1 minute.

MMSE results identified poor function in 7%, the trail-making test B identified poor function in 30%, and category fluency identified poor function in 15%.

Natriuretic peptide levels in the blood specimens were measured using a test that detects N-terminal pro-B-type natriuretic peptide (NT-proBNP). Among the 950 participants, 79% had a low level of NT-proBNP, and 21% had a high level.

In the low level group, poor cognitive scores occurred in 5%, 23%, and 12% of subjects for the three cognitive function tests, respectively. In the high level group, 17%, 54%, and 26% of the subjects scored poorly on the three tests, respectively.

When the results were adjusted for age, education, and other factors, participants with high NT-proBNP levels had significantly worse cognitive function scores on the MMSE and the Trail-Making Test B. Scores for category fluency were lower in people with high NT-proBNP in the fully-adjusted model, but the difference fell short of statistical significance.

In the fully-adjusted model, people with high levels of NT-proBNP were 82%, 75%, and 37% more likely to have poor cognitive function on the three tests, respectively, compared with people with low levels.

Dr. Daniels received research support from Roche Diagnostics, which markets an NT-proBNP assay.

ORLANDO — High blood levels of a brain natriuretic peptide were associated with poor cognitive function in a study of 950 community-dwelling, healthy, elderly adults.

“This is the first time this [association] has been shown,” Dr. Lori B. Daniels said at the annual scientific sessions of the American Heart Association.

Dr. Daniels, a cardiologist at the University of California, San Diego, suggested that several mechanisms that might link production of natriuretic peptide to poor cognitive function including reduced cardiac output that drops oxygen or nutrient supplies to the brain, atrial fibrillation that creates microemboli, microcirculation deficits that harm both the heart and brain, and genetic predisposition.

Cognitive function data and blood specimens were analyzed from 950 of 5,000 participants enrolled in the Rancho Bernardo study of the early 1970s.

The average age of the participants was 77 years; 61% were women. The researchers used three tests to evaluate cognitive function: The Mini-Mental State Exam (MMSE), the Trail-Making Test B, and a category fluency test that asked participants to name as many animals as they could in 1 minute.

MMSE results identified poor function in 7%, the trail-making test B identified poor function in 30%, and category fluency identified poor function in 15%.

Natriuretic peptide levels in the blood specimens were measured using a test that detects N-terminal pro-B-type natriuretic peptide (NT-proBNP). Among the 950 participants, 79% had a low level of NT-proBNP, and 21% had a high level.

In the low level group, poor cognitive scores occurred in 5%, 23%, and 12% of subjects for the three cognitive function tests, respectively. In the high level group, 17%, 54%, and 26% of the subjects scored poorly on the three tests, respectively.

When the results were adjusted for age, education, and other factors, participants with high NT-proBNP levels had significantly worse cognitive function scores on the MMSE and the Trail-Making Test B. Scores for category fluency were lower in people with high NT-proBNP in the fully-adjusted model, but the difference fell short of statistical significance.

In the fully-adjusted model, people with high levels of NT-proBNP were 82%, 75%, and 37% more likely to have poor cognitive function on the three tests, respectively, compared with people with low levels.

Dr. Daniels received research support from Roche Diagnostics, which markets an NT-proBNP assay.

PHILADELPHIA — Weight loss was linked to significant drops in serum uric acid levels in a prospective study with more than 12,000 men with high cardiovascular risk.

“Weight loss could substantially help achieve a widely accepted therapeutic uric acid target level of 6 mg/dL among men with a high cardiovascular risk profile,” Yanyan Zhu said at the annual meeting of the American College of Rheumatology.

Ms. Zhu and her associates used data from 12,510 men with a high cardiovascular risk profile enrolled in the MRFIT (Multiple Risk Factor Intervention Trial), a study begun in the early 1970s. MRFIT assessed the role of multiple risk-factor interventions, including a special diet, on mortality from coronary heart disease.

The men's mean age at baseline was 46 years. Their average body mass index was 28 kg/m

The study design had the men return annually for clinical assessments for 6 years. During follow-up, 39% had weight loss, 31% had no weight change, and 30% gained weight.

In an analysis that adjusted for baseline covariables of hypertension, diuretic use, alcohol use, and serum creatinine, men who lost weight during follow-up had a statistically significant reduction in their risk for having hyperuricemia, said Ms. Zhu, an epidemiologist at Boston University. The more weight they lost, the lower their risk for hyperuricemia. (See box.) A weight loss of at least 10 kg was associated with a 56% drop in the risk for hyperuricemia. In contrast, men who gained weight during follow-up had a significantly increased risk for hyperuricemia. Again, the risk rose with greater weight gain, with a weight gain of at least 10 kg associated with a 54% increased risk for hyperuricemia

A second analysis showed similar, significant relationships between changes in weight and changes in the serum level of uric acid. The more weight patients lost, the lower their uric acid levels fell, whereas the more weight they gained, the higher their levels rose. (See box.)

Ms. Zhu and her associates hypothesized that the impact of weight change on serum uric acid occurred through changes in uric acid production and renal excretion.

Ms. Zhu had no disclosures.

Source Elsevier Global Medical News

PHILADELPHIA — Weight loss was linked to significant drops in serum uric acid levels in a prospective study with more than 12,000 men with high cardiovascular risk.

“Weight loss could substantially help achieve a widely accepted therapeutic uric acid target level of 6 mg/dL among men with a high cardiovascular risk profile,” Yanyan Zhu said at the annual meeting of the American College of Rheumatology.

Ms. Zhu and her associates used data from 12,510 men with a high cardiovascular risk profile enrolled in the MRFIT (Multiple Risk Factor Intervention Trial), a study begun in the early 1970s. MRFIT assessed the role of multiple risk-factor interventions, including a special diet, on mortality from coronary heart disease.

The men's mean age at baseline was 46 years. Their average body mass index was 28 kg/m

The study design had the men return annually for clinical assessments for 6 years. During follow-up, 39% had weight loss, 31% had no weight change, and 30% gained weight.

In an analysis that adjusted for baseline covariables of hypertension, diuretic use, alcohol use, and serum creatinine, men who lost weight during follow-up had a statistically significant reduction in their risk for having hyperuricemia, said Ms. Zhu, an epidemiologist at Boston University. The more weight they lost, the lower their risk for hyperuricemia. (See box.) A weight loss of at least 10 kg was associated with a 56% drop in the risk for hyperuricemia. In contrast, men who gained weight during follow-up had a significantly increased risk for hyperuricemia. Again, the risk rose with greater weight gain, with a weight gain of at least 10 kg associated with a 54% increased risk for hyperuricemia

A second analysis showed similar, significant relationships between changes in weight and changes in the serum level of uric acid. The more weight patients lost, the lower their uric acid levels fell, whereas the more weight they gained, the higher their levels rose. (See box.)

Ms. Zhu and her associates hypothesized that the impact of weight change on serum uric acid occurred through changes in uric acid production and renal excretion.

Ms. Zhu had no disclosures.

Source Elsevier Global Medical News

PHILADELPHIA — Weight loss was linked to significant drops in serum uric acid levels in a prospective study with more than 12,000 men with high cardiovascular risk.

“Weight loss could substantially help achieve a widely accepted therapeutic uric acid target level of 6 mg/dL among men with a high cardiovascular risk profile,” Yanyan Zhu said at the annual meeting of the American College of Rheumatology.

Ms. Zhu and her associates used data from 12,510 men with a high cardiovascular risk profile enrolled in the MRFIT (Multiple Risk Factor Intervention Trial), a study begun in the early 1970s. MRFIT assessed the role of multiple risk-factor interventions, including a special diet, on mortality from coronary heart disease.

The men's mean age at baseline was 46 years. Their average body mass index was 28 kg/m

The study design had the men return annually for clinical assessments for 6 years. During follow-up, 39% had weight loss, 31% had no weight change, and 30% gained weight.

In an analysis that adjusted for baseline covariables of hypertension, diuretic use, alcohol use, and serum creatinine, men who lost weight during follow-up had a statistically significant reduction in their risk for having hyperuricemia, said Ms. Zhu, an epidemiologist at Boston University. The more weight they lost, the lower their risk for hyperuricemia. (See box.) A weight loss of at least 10 kg was associated with a 56% drop in the risk for hyperuricemia. In contrast, men who gained weight during follow-up had a significantly increased risk for hyperuricemia. Again, the risk rose with greater weight gain, with a weight gain of at least 10 kg associated with a 54% increased risk for hyperuricemia

A second analysis showed similar, significant relationships between changes in weight and changes in the serum level of uric acid. The more weight patients lost, the lower their uric acid levels fell, whereas the more weight they gained, the higher their levels rose. (See box.)

Ms. Zhu and her associates hypothesized that the impact of weight change on serum uric acid occurred through changes in uric acid production and renal excretion.

Ms. Zhu had no disclosures.

Source Elsevier Global Medical News

ORLANDO — Gout boosted the risk of death or hospitalization for heart failure in an observational, case-control study of more than 150,000 patients with heart failure.

Patients with heart failure and gout who were on long-term allopurinol treatment had a significantly reduced risk for death or heart failure hospitalization, Dr. George Thanassoulis said at the annual scientific sessions of the American Heart Association.

Allopurinol exerts its benefit for heart failure outcomes not by lowering blood levels of uric acid, but by inhibiting oxidative stress and the endothelial dysfunction that oxidative stress produces, said Dr. Thanassoulis, a cardiologist at Boston University and the Framingham (Mass.) Heart Study. He suggested that allopurinol inhibits xanthine oxidase, the same action that also blunts uric acid production.

The study used administrative health record data from Quebec residents aged older than 65 years. Cases were 14,327 people hospitalized for heart failure but without another heart failure hospitalization during the 3 years before the index episode, a restriction that helped ensure a uniform level of heart failure severity among the patients. Controls were 143,255 people in the Quebec database matched to the cases by follow-up duration and by calendar year.

The average age was 79 years among the cases and 77 years among the controls. Cases and controls were evenly split among men and women. Identification of gout relied on hospitalization, a physician visit, or a diagnostic code in the medical record.

During an average follow-up of 2 years, the rate of death or new heart failure hospitalization was 63% higher in the patients with gout than in those without gout, a statistically significant difference in an analysis that controlled for several demographic and clinical variables including age, gender, comorbidities, and medications.

The risk for death or heart failure hospitalization was even higher in patients who had acute gout, with a twofold higher risk in the adjusted analysis. The researchers defined acute gout as hospitalization or a physician visit for gout within 60 days of the index heart failure event.

Another pair of analyses looked at the impact of allopurinol treatment. Among patients with an index heart failure event who also had gout treatment with allopurinol, there was a significant 31% reduction in the subsequent rate of death or heart failure hospitalization in the adjusted analysis. This benefit was limited to the patients on chronic allopurinol treatment for more than 30 days. Patients on allopurinol for 30 days or less showed no significant reduction in mortality or new heart failure hospitalizations.

The allopurinol analysis also showed no link between the drug and outcomes for the entire heart failure population studied, suggesting that benefit from allopurinol is not general for all heart failure patients, only those with gout.

Dr. Thanassoulis and his associates had no conflicts of interest to disclose.

ORLANDO — Gout boosted the risk of death or hospitalization for heart failure in an observational, case-control study of more than 150,000 patients with heart failure.

Patients with heart failure and gout who were on long-term allopurinol treatment had a significantly reduced risk for death or heart failure hospitalization, Dr. George Thanassoulis said at the annual scientific sessions of the American Heart Association.

Allopurinol exerts its benefit for heart failure outcomes not by lowering blood levels of uric acid, but by inhibiting oxidative stress and the endothelial dysfunction that oxidative stress produces, said Dr. Thanassoulis, a cardiologist at Boston University and the Framingham (Mass.) Heart Study. He suggested that allopurinol inhibits xanthine oxidase, the same action that also blunts uric acid production.

The study used administrative health record data from Quebec residents aged older than 65 years. Cases were 14,327 people hospitalized for heart failure but without another heart failure hospitalization during the 3 years before the index episode, a restriction that helped ensure a uniform level of heart failure severity among the patients. Controls were 143,255 people in the Quebec database matched to the cases by follow-up duration and by calendar year.

The average age was 79 years among the cases and 77 years among the controls. Cases and controls were evenly split among men and women. Identification of gout relied on hospitalization, a physician visit, or a diagnostic code in the medical record.

During an average follow-up of 2 years, the rate of death or new heart failure hospitalization was 63% higher in the patients with gout than in those without gout, a statistically significant difference in an analysis that controlled for several demographic and clinical variables including age, gender, comorbidities, and medications.

The risk for death or heart failure hospitalization was even higher in patients who had acute gout, with a twofold higher risk in the adjusted analysis. The researchers defined acute gout as hospitalization or a physician visit for gout within 60 days of the index heart failure event.

Another pair of analyses looked at the impact of allopurinol treatment. Among patients with an index heart failure event who also had gout treatment with allopurinol, there was a significant 31% reduction in the subsequent rate of death or heart failure hospitalization in the adjusted analysis. This benefit was limited to the patients on chronic allopurinol treatment for more than 30 days. Patients on allopurinol for 30 days or less showed no significant reduction in mortality or new heart failure hospitalizations.

The allopurinol analysis also showed no link between the drug and outcomes for the entire heart failure population studied, suggesting that benefit from allopurinol is not general for all heart failure patients, only those with gout.

Dr. Thanassoulis and his associates had no conflicts of interest to disclose.

ORLANDO — Gout boosted the risk of death or hospitalization for heart failure in an observational, case-control study of more than 150,000 patients with heart failure.

Patients with heart failure and gout who were on long-term allopurinol treatment had a significantly reduced risk for death or heart failure hospitalization, Dr. George Thanassoulis said at the annual scientific sessions of the American Heart Association.

Allopurinol exerts its benefit for heart failure outcomes not by lowering blood levels of uric acid, but by inhibiting oxidative stress and the endothelial dysfunction that oxidative stress produces, said Dr. Thanassoulis, a cardiologist at Boston University and the Framingham (Mass.) Heart Study. He suggested that allopurinol inhibits xanthine oxidase, the same action that also blunts uric acid production.

The study used administrative health record data from Quebec residents aged older than 65 years. Cases were 14,327 people hospitalized for heart failure but without another heart failure hospitalization during the 3 years before the index episode, a restriction that helped ensure a uniform level of heart failure severity among the patients. Controls were 143,255 people in the Quebec database matched to the cases by follow-up duration and by calendar year.

The average age was 79 years among the cases and 77 years among the controls. Cases and controls were evenly split among men and women. Identification of gout relied on hospitalization, a physician visit, or a diagnostic code in the medical record.

During an average follow-up of 2 years, the rate of death or new heart failure hospitalization was 63% higher in the patients with gout than in those without gout, a statistically significant difference in an analysis that controlled for several demographic and clinical variables including age, gender, comorbidities, and medications.

The risk for death or heart failure hospitalization was even higher in patients who had acute gout, with a twofold higher risk in the adjusted analysis. The researchers defined acute gout as hospitalization or a physician visit for gout within 60 days of the index heart failure event.

Another pair of analyses looked at the impact of allopurinol treatment. Among patients with an index heart failure event who also had gout treatment with allopurinol, there was a significant 31% reduction in the subsequent rate of death or heart failure hospitalization in the adjusted analysis. This benefit was limited to the patients on chronic allopurinol treatment for more than 30 days. Patients on allopurinol for 30 days or less showed no significant reduction in mortality or new heart failure hospitalizations.

The allopurinol analysis also showed no link between the drug and outcomes for the entire heart failure population studied, suggesting that benefit from allopurinol is not general for all heart failure patients, only those with gout.

Dr. Thanassoulis and his associates had no conflicts of interest to disclose.

ORLANDO — Patients with heart failure had a greater than twofold increased risk of developing diabetes compared with people without heart failure in a review of more than 4,600 individuals in the Framingham Offspring Study.

The analysis also showed a strong association between severity of heart failure symptoms and risk for new-onset diabetes: Patients with higher New York Association Class heart failure faced a greater risk for developing diabetes than did patients with less severe heart failure symptoms, Dr. Ankit Rathod said at the annual scientific sessions of the American Heart Association.

The hypothesized causal link between heart failure and diabetes is the neurohormonal, sympathetic activation that characterizes heart failure. This leads to norepinephrine release, which can trigger insulin resistance and hence increased susceptibility to developing diabetes, said Dr. Rathod, an internist at Wayne State University in Detroit. In addition, patients with more severe heart failure symptoms have reduced activity, which might exacerbate insulin resistance and the risk for developing diabetes.

“I believe the connections between insulin resistance and neurohormonal activation are a real phenomenon,” said Dr. Clyde W. Yancy, medical director of the Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas. Treatment with drugs that block neurohormonal activation also cut development of diabetes, such as with ramipril in the HOPE study (N. Engl. J. Med 2000;342:145–53) and treatment with carvedilol in the CAPRICORN study (Lancet 2001;357:1385–90), he said.

Dr. Rathod collected data from the more than 4,900 people enrolled into the Framingham Offspring Study in 1971. He and his associates excluded people with a history of diabetes or heart failure at enrollment, and those who had missing data on their subsequent rate of new-onset diabetes. The 4,614 people included in the study had an average age of 35; about half were women.

During an average follow-up of 24 years, 123 developed heart failure, and 468 developed new-onset diabetes. Forty-one of the 123 patients (33%) who developed heart failure later developed diabetes, compared with 427 new cases of diabetes among the other 4,491 people (10%).

In a multivariate analysis that adjusted for baseline demographic and clinical differences, including drug treatments and baseline blood glucose levels, patients who first developed heart failure had a statistically significant 2.5-fold increased risk for later developing diabetes compared with the people who did not have heart failure.

Dr. Rathod and Dr. Yancy said they had no conflicts of interest.

Forty-one of the 123 patients (33%) who developed heart failure later developed diabetes.

Source DR. RATHOD

ORLANDO — Patients with heart failure had a greater than twofold increased risk of developing diabetes compared with people without heart failure in a review of more than 4,600 individuals in the Framingham Offspring Study.

The analysis also showed a strong association between severity of heart failure symptoms and risk for new-onset diabetes: Patients with higher New York Association Class heart failure faced a greater risk for developing diabetes than did patients with less severe heart failure symptoms, Dr. Ankit Rathod said at the annual scientific sessions of the American Heart Association.

The hypothesized causal link between heart failure and diabetes is the neurohormonal, sympathetic activation that characterizes heart failure. This leads to norepinephrine release, which can trigger insulin resistance and hence increased susceptibility to developing diabetes, said Dr. Rathod, an internist at Wayne State University in Detroit. In addition, patients with more severe heart failure symptoms have reduced activity, which might exacerbate insulin resistance and the risk for developing diabetes.

“I believe the connections between insulin resistance and neurohormonal activation are a real phenomenon,” said Dr. Clyde W. Yancy, medical director of the Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas. Treatment with drugs that block neurohormonal activation also cut development of diabetes, such as with ramipril in the HOPE study (N. Engl. J. Med 2000;342:145–53) and treatment with carvedilol in the CAPRICORN study (Lancet 2001;357:1385–90), he said.

Dr. Rathod collected data from the more than 4,900 people enrolled into the Framingham Offspring Study in 1971. He and his associates excluded people with a history of diabetes or heart failure at enrollment, and those who had missing data on their subsequent rate of new-onset diabetes. The 4,614 people included in the study had an average age of 35; about half were women.

During an average follow-up of 24 years, 123 developed heart failure, and 468 developed new-onset diabetes. Forty-one of the 123 patients (33%) who developed heart failure later developed diabetes, compared with 427 new cases of diabetes among the other 4,491 people (10%).

In a multivariate analysis that adjusted for baseline demographic and clinical differences, including drug treatments and baseline blood glucose levels, patients who first developed heart failure had a statistically significant 2.5-fold increased risk for later developing diabetes compared with the people who did not have heart failure.

Dr. Rathod and Dr. Yancy said they had no conflicts of interest.

Forty-one of the 123 patients (33%) who developed heart failure later developed diabetes.

Source DR. RATHOD

ORLANDO — Patients with heart failure had a greater than twofold increased risk of developing diabetes compared with people without heart failure in a review of more than 4,600 individuals in the Framingham Offspring Study.

The analysis also showed a strong association between severity of heart failure symptoms and risk for new-onset diabetes: Patients with higher New York Association Class heart failure faced a greater risk for developing diabetes than did patients with less severe heart failure symptoms, Dr. Ankit Rathod said at the annual scientific sessions of the American Heart Association.

The hypothesized causal link between heart failure and diabetes is the neurohormonal, sympathetic activation that characterizes heart failure. This leads to norepinephrine release, which can trigger insulin resistance and hence increased susceptibility to developing diabetes, said Dr. Rathod, an internist at Wayne State University in Detroit. In addition, patients with more severe heart failure symptoms have reduced activity, which might exacerbate insulin resistance and the risk for developing diabetes.

“I believe the connections between insulin resistance and neurohormonal activation are a real phenomenon,” said Dr. Clyde W. Yancy, medical director of the Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas. Treatment with drugs that block neurohormonal activation also cut development of diabetes, such as with ramipril in the HOPE study (N. Engl. J. Med 2000;342:145–53) and treatment with carvedilol in the CAPRICORN study (Lancet 2001;357:1385–90), he said.

Dr. Rathod collected data from the more than 4,900 people enrolled into the Framingham Offspring Study in 1971. He and his associates excluded people with a history of diabetes or heart failure at enrollment, and those who had missing data on their subsequent rate of new-onset diabetes. The 4,614 people included in the study had an average age of 35; about half were women.

During an average follow-up of 24 years, 123 developed heart failure, and 468 developed new-onset diabetes. Forty-one of the 123 patients (33%) who developed heart failure later developed diabetes, compared with 427 new cases of diabetes among the other 4,491 people (10%).

In a multivariate analysis that adjusted for baseline demographic and clinical differences, including drug treatments and baseline blood glucose levels, patients who first developed heart failure had a statistically significant 2.5-fold increased risk for later developing diabetes compared with the people who did not have heart failure.

Dr. Rathod and Dr. Yancy said they had no conflicts of interest.

Forty-one of the 123 patients (33%) who developed heart failure later developed diabetes.

Source DR. RATHOD

ORLANDO — Infection following acute hospitalization for ST-segment elevation myocardial infarction was linked with prolonged hospitalization and significantly increased risk of death, in a review of patients in Florida hospitals in 2006.

The incidence of in-hospital infection among the 11,879 patients for ST-segment elevation myocardial infarction (STEMI) was 17%, with more than a third of these patients having two or more infections while hospitalized, Michelle C. Nash and her associates reported in a poster at the annual scientific sessions of the American Heart Association. The most common infections were urinary tract (in 6%), pneumonia (5%), surgical site (4%), and bloodstream (3%). Other infections collectively affected another 4% of the patients.

Among STEMI patients without an infection, 16% had a length of stay of 7 days or more. The percentage of infected patients who required hospitalization for a week or longer ranged from a low of 45% in those with surgical site infections to a high of 76% in those with bloodstream infections, said Ms. Nash, a researcher in the department of epidemiology and biostatistics at the University of South Florida in Tampa, and her associates (see table, p. 24).

In addition, while surgical site and some other infections led to mortality rates nearly identical to the 7% rate in STEMI patients who never developed an infection, other types of infection led to a substantially increased in-hospital mortality rate, such as the 31% rate in patients with bloodstream infections and the 20% rate in those with pneumonia.

In-hospital infections boosted the risk that STEMI patients would need mechanical ventilation or would develop renal failure or heart failure. “Notably, patients with miscellaneous infections, not those with pneumonia, had the greatest risk for mechanical ventilation” at 25%, compared with 5% in patients who developed pneumonia, the researchers said.

Their analysis also examined demographic and clinical features that appeared to be linked with an increased susceptibility to infection. The pattern of factors significantly associated with infection varied depending on infection site.

▸ Bloodstream infection. Patients treated with an indwelling arterial or venous catheter and those on dialysis were at increased risk for bloodstream infections. Both of these factors boosted the risk for a bloodstream infection by nearly sevenfold, compared with STEMI patients who did not receive these treatments. Other risk factors included chronic obstructive pulmonary disease (COPD), valve disorders, and blood transfusion, each of which roughly doubled the risk for a bloodstream infection.

▸ Pneumonia. Major risk factors for pneumonia included chronic bronchitis, an indwelling arterial or venous catheter, and dialysis, each of which quadrupled the risk. Other significant risk factors included alcohol abuse and COPD—each of which more than doubled the risk—and chronic kidney disease and an operative procedure, each of which raised the risk for pneumonia by about 50%.

▸ Surgical site infection. Cardiac catheterization and dialysis each raised the rate of surgical site infection by more than 2.5-fold, compared with STEMI patients not receiving these procedures. Other significant risk factors included an indwelling arterial or venous catheter and blood transfusion, which boosted the risk by 50%–100%. Two factors were found to significantly reduce the rate of surgical site infections: Percutaneous coronary intervention cut the risk by more than a third, and cigarette smoking cut the infection risk by 30%.

▸ Urinary tract infection. Female gender had the biggest impact on the risk of urinary tract infections, boosting the risk by nearly 2.5-fold. Dialysis also raised the risk more than twofold. Several other factors significantly raised the risk for urinary tract infection by 47%–94%: COPD, diabetes, chronic kidney disease, an operative procedure, an indwelling arterial or venous catheter, and blood transfusion. In addition, the risk for a urinary tract infection rose by a significant 27% for every 5-year increment in age. Finally, cigarette smoking significantly cut the risk by a third.

Ms. Nash and her associates said that they had no financial support from commercial sources to disclose.

Elsevier Global Medical News

ORLANDO — Infection following acute hospitalization for ST-segment elevation myocardial infarction was linked with prolonged hospitalization and significantly increased risk of death, in a review of patients in Florida hospitals in 2006.

The incidence of in-hospital infection among the 11,879 patients for ST-segment elevation myocardial infarction (STEMI) was 17%, with more than a third of these patients having two or more infections while hospitalized, Michelle C. Nash and her associates reported in a poster at the annual scientific sessions of the American Heart Association. The most common infections were urinary tract (in 6%), pneumonia (5%), surgical site (4%), and bloodstream (3%). Other infections collectively affected another 4% of the patients.

Among STEMI patients without an infection, 16% had a length of stay of 7 days or more. The percentage of infected patients who required hospitalization for a week or longer ranged from a low of 45% in those with surgical site infections to a high of 76% in those with bloodstream infections, said Ms. Nash, a researcher in the department of epidemiology and biostatistics at the University of South Florida in Tampa, and her associates (see table, p. 24).

In addition, while surgical site and some other infections led to mortality rates nearly identical to the 7% rate in STEMI patients who never developed an infection, other types of infection led to a substantially increased in-hospital mortality rate, such as the 31% rate in patients with bloodstream infections and the 20% rate in those with pneumonia.

In-hospital infections boosted the risk that STEMI patients would need mechanical ventilation or would develop renal failure or heart failure. “Notably, patients with miscellaneous infections, not those with pneumonia, had the greatest risk for mechanical ventilation” at 25%, compared with 5% in patients who developed pneumonia, the researchers said.

Their analysis also examined demographic and clinical features that appeared to be linked with an increased susceptibility to infection. The pattern of factors significantly associated with infection varied depending on infection site.

▸ Bloodstream infection. Patients treated with an indwelling arterial or venous catheter and those on dialysis were at increased risk for bloodstream infections. Both of these factors boosted the risk for a bloodstream infection by nearly sevenfold, compared with STEMI patients who did not receive these treatments. Other risk factors included chronic obstructive pulmonary disease (COPD), valve disorders, and blood transfusion, each of which roughly doubled the risk for a bloodstream infection.

▸ Pneumonia. Major risk factors for pneumonia included chronic bronchitis, an indwelling arterial or venous catheter, and dialysis, each of which quadrupled the risk. Other significant risk factors included alcohol abuse and COPD—each of which more than doubled the risk—and chronic kidney disease and an operative procedure, each of which raised the risk for pneumonia by about 50%.

▸ Surgical site infection. Cardiac catheterization and dialysis each raised the rate of surgical site infection by more than 2.5-fold, compared with STEMI patients not receiving these procedures. Other significant risk factors included an indwelling arterial or venous catheter and blood transfusion, which boosted the risk by 50%–100%. Two factors were found to significantly reduce the rate of surgical site infections: Percutaneous coronary intervention cut the risk by more than a third, and cigarette smoking cut the infection risk by 30%.

▸ Urinary tract infection. Female gender had the biggest impact on the risk of urinary tract infections, boosting the risk by nearly 2.5-fold. Dialysis also raised the risk more than twofold. Several other factors significantly raised the risk for urinary tract infection by 47%–94%: COPD, diabetes, chronic kidney disease, an operative procedure, an indwelling arterial or venous catheter, and blood transfusion. In addition, the risk for a urinary tract infection rose by a significant 27% for every 5-year increment in age. Finally, cigarette smoking significantly cut the risk by a third.

Ms. Nash and her associates said that they had no financial support from commercial sources to disclose.

Elsevier Global Medical News

ORLANDO — Infection following acute hospitalization for ST-segment elevation myocardial infarction was linked with prolonged hospitalization and significantly increased risk of death, in a review of patients in Florida hospitals in 2006.

The incidence of in-hospital infection among the 11,879 patients for ST-segment elevation myocardial infarction (STEMI) was 17%, with more than a third of these patients having two or more infections while hospitalized, Michelle C. Nash and her associates reported in a poster at the annual scientific sessions of the American Heart Association. The most common infections were urinary tract (in 6%), pneumonia (5%), surgical site (4%), and bloodstream (3%). Other infections collectively affected another 4% of the patients.

Among STEMI patients without an infection, 16% had a length of stay of 7 days or more. The percentage of infected patients who required hospitalization for a week or longer ranged from a low of 45% in those with surgical site infections to a high of 76% in those with bloodstream infections, said Ms. Nash, a researcher in the department of epidemiology and biostatistics at the University of South Florida in Tampa, and her associates (see table, p. 24).

In addition, while surgical site and some other infections led to mortality rates nearly identical to the 7% rate in STEMI patients who never developed an infection, other types of infection led to a substantially increased in-hospital mortality rate, such as the 31% rate in patients with bloodstream infections and the 20% rate in those with pneumonia.

In-hospital infections boosted the risk that STEMI patients would need mechanical ventilation or would develop renal failure or heart failure. “Notably, patients with miscellaneous infections, not those with pneumonia, had the greatest risk for mechanical ventilation” at 25%, compared with 5% in patients who developed pneumonia, the researchers said.

Their analysis also examined demographic and clinical features that appeared to be linked with an increased susceptibility to infection. The pattern of factors significantly associated with infection varied depending on infection site.

▸ Bloodstream infection. Patients treated with an indwelling arterial or venous catheter and those on dialysis were at increased risk for bloodstream infections. Both of these factors boosted the risk for a bloodstream infection by nearly sevenfold, compared with STEMI patients who did not receive these treatments. Other risk factors included chronic obstructive pulmonary disease (COPD), valve disorders, and blood transfusion, each of which roughly doubled the risk for a bloodstream infection.

▸ Pneumonia. Major risk factors for pneumonia included chronic bronchitis, an indwelling arterial or venous catheter, and dialysis, each of which quadrupled the risk. Other significant risk factors included alcohol abuse and COPD—each of which more than doubled the risk—and chronic kidney disease and an operative procedure, each of which raised the risk for pneumonia by about 50%.

▸ Surgical site infection. Cardiac catheterization and dialysis each raised the rate of surgical site infection by more than 2.5-fold, compared with STEMI patients not receiving these procedures. Other significant risk factors included an indwelling arterial or venous catheter and blood transfusion, which boosted the risk by 50%–100%. Two factors were found to significantly reduce the rate of surgical site infections: Percutaneous coronary intervention cut the risk by more than a third, and cigarette smoking cut the infection risk by 30%.

▸ Urinary tract infection. Female gender had the biggest impact on the risk of urinary tract infections, boosting the risk by nearly 2.5-fold. Dialysis also raised the risk more than twofold. Several other factors significantly raised the risk for urinary tract infection by 47%–94%: COPD, diabetes, chronic kidney disease, an operative procedure, an indwelling arterial or venous catheter, and blood transfusion. In addition, the risk for a urinary tract infection rose by a significant 27% for every 5-year increment in age. Finally, cigarette smoking significantly cut the risk by a third.

Ms. Nash and her associates said that they had no financial support from commercial sources to disclose.

Elsevier Global Medical News

The criteria for selecting obese adolescents as candidates for bariatric surgery have loosened in recent years, say some surgeons, while other surgeons had already applied the looser criteria for several years. Now that the adolescent field has converged on a roughly uniform body mass index standard that's the same as for adults—at least 35 kg/m

The goal, they agree, is to offer bariatric surgery to adolescents (usually defined as patients aged 13–17 years) safely but at a stage when the surgery has the best potential to normalize patients' weight so that comorbidities improve and possibly resolve.

An aggressive approach may also help avoid another problem. “No one can explain why, but there is a plateauing effect of all bariatric surgery, be it gastric bypass, gastric sleeve, or gastric banding. Patients lose about 15 BMI [body mass index] points but no more,” said Dr. Evan P. Nadler, director of the bariatric surgery program at Children's National Medical Center in Washington. 'The chances of getting patients near a normal body weight once they reach a BMI of 45 or 50 are quite small.”

The reasons behind this limit to the effect of bariatric surgery remain elusive. Many surgeons believe that the adaptable human body kicks in a thermostatlike resetting that maintains a certain body weight starting about a year after the large initial loss following surgery. Another factor may be that many patients have lifestyle regression at some point after surgery.

Regardless of the cause, the apparent limit to weight loss for most patients suggests to pediatric surgeons that bariatric surgery has the greatest potential to normalize BMI, and thereby prevent comorbidities, when applied relatively early, before BMI grows too high and before end-organ damage is irreversible.

“If you get to younger patients, they may still be in a window of opportunity for their end-organ disease to essentially be reversed,” Dr. Marc P. Michalsky said. “Our hope is that perhaps in adolescents, without decades of cardiac disease, hypertension, and liver disease, once their weight is off you may see more resolution of that disease than in adults. That's the hypothesis, but we haven't proven it yet,” said Dr. Michalsky, surgical director of the center for healthy weight and nutrition at Nationwide Children's Hospital in Columbus, Ohio.

“It's a new concept to think of surgery as preventive medicine, but it is preventive in the sense that patients have more severe comorbidities if you wait,” said Dr. Ai-Xuan Holterman, director of pediatric surgery at Rush University Medical Center in Chicago.

“You could argue that in a 14-year-old who is obese but has no comorbidities, there is no urgency to do surgery. But we know what the natural trajectory of these patients will be. If a patient is older than 14 and morbidly obese, even if their comorbidities are relatively minor, I think that surgery is an appropriate option,” Dr. Nadler said in an interview.

Another benefit of early surgery is that “the risk of operating on a patient at a BMI of 45 is a lot different than operating on someone with a BMI of 60,” he added.

Still, U.S. studies have yet to report outcomes from bariatric surgery in adolescents at more than 3 years of follow-up.

A series of 61 patients, with an average age of 17, underwent gastric bypass surgery (Roux-en-Y) at Cincinnati Children's Hospital Medical Center between August 2002 and January 2007. The analysis showed that the average percentage of lost BMI was about 37% across all weight categories, and that two-thirds of the variance in BMI 1 year after surgery was attributable to the variance in baseline BMI (J. Pediatr. 2010;156:103–8).

The shift in surgical criteria for adolescents means that most surgeons now follow the same guidelines that have been standard for adult patients for nearly 2 decades. Serious comorbidities that lower the threshold to 35 kg/m

In 2004, a group of surgeons who at the time primarily favored gastric bypass for their adolescent patients published recommendations that called for limiting bariatric surgery for adolescents to those with a BMI of at least 40 kg/m

Dr. Nadler and his associates published their own endorsement for applying the adult BMI criteria for bariatric surgery to adolescents in another paper that appeared last year (J. Pediatr. Surg. 2009;44:1869–76).

“What is crucial is that you're not operating just because of BMI or weight, but that there is a compelling health indication,” said Dr. Inge, surgical director of the surgical weight loss program for teens at Cincinnati Children's. He cited preliminary evidence collected by his collaborators that, for example, “the pediatric heart may be more resilient to remodeling” than an adult's heart, and more likely to return to normal following significant weight loss. “There may be a window of opportunity to act before there is more permanent damage to the heart,” Dr. Inge said in an interview.

Comorbidities that are “more or less reversible” with bariatric surgery in adolescents and are the most common indications for surgery are diabetes, sleep apnea, and nonalcoholic steatohepatitis. Others in this category include hypertension, pseudotumor cerebri, gastro-esophageal reflux disease, asthma, and poor self-esteem, said Dr. Janey S.A. Pratt, a bariatric surgeon at Massachusetts General Hospital in Boston. However, she noted, other obesity-linked conditions are generally not reversible, including glomerulosclerosis of the kidney, gallstones, flat feet, major orthopedic deformities, precocious puberty, and some body-image issues.

“The most important reason to operate on obese adolescents is … to treat or prevent the comorbidities associated with excess weight,” Dr. Pratt said. “Will all of the adolescents we operate on be obese as adults?” Dr. Pratt cited results from a recent study in which 100% of children with a BMI above the 99th percentile after age 10 years had BMIs greater than 35 kg/m

Disclosures: Dr. Inge has received research funding from Ethicon Inc. Dr. Pratt has served as a consultant to Covidien. Dr. Nadler received research support from Allergan. Dr. Holterman and Dr. Michalsky had no financial disclosures.

'It's a new concept to think of surgery as preventive medicine, but it is preventive.'

Source DR. HOLTERMAN

All children with a BMI above the 99th percentile after age 10 had BMIs greater than 35 kg/m

Source DR. PRATT

'There may be a window of opportunity to act before there is more permanent damage to the heart.'

Source DR. INGE

The criteria for selecting obese adolescents as candidates for bariatric surgery have loosened in recent years, say some surgeons, while other surgeons had already applied the looser criteria for several years. Now that the adolescent field has converged on a roughly uniform body mass index standard that's the same as for adults—at least 35 kg/m

The goal, they agree, is to offer bariatric surgery to adolescents (usually defined as patients aged 13–17 years) safely but at a stage when the surgery has the best potential to normalize patients' weight so that comorbidities improve and possibly resolve.

An aggressive approach may also help avoid another problem. “No one can explain why, but there is a plateauing effect of all bariatric surgery, be it gastric bypass, gastric sleeve, or gastric banding. Patients lose about 15 BMI [body mass index] points but no more,” said Dr. Evan P. Nadler, director of the bariatric surgery program at Children's National Medical Center in Washington. 'The chances of getting patients near a normal body weight once they reach a BMI of 45 or 50 are quite small.”

The reasons behind this limit to the effect of bariatric surgery remain elusive. Many surgeons believe that the adaptable human body kicks in a thermostatlike resetting that maintains a certain body weight starting about a year after the large initial loss following surgery. Another factor may be that many patients have lifestyle regression at some point after surgery.

Regardless of the cause, the apparent limit to weight loss for most patients suggests to pediatric surgeons that bariatric surgery has the greatest potential to normalize BMI, and thereby prevent comorbidities, when applied relatively early, before BMI grows too high and before end-organ damage is irreversible.

“If you get to younger patients, they may still be in a window of opportunity for their end-organ disease to essentially be reversed,” Dr. Marc P. Michalsky said. “Our hope is that perhaps in adolescents, without decades of cardiac disease, hypertension, and liver disease, once their weight is off you may see more resolution of that disease than in adults. That's the hypothesis, but we haven't proven it yet,” said Dr. Michalsky, surgical director of the center for healthy weight and nutrition at Nationwide Children's Hospital in Columbus, Ohio.

“It's a new concept to think of surgery as preventive medicine, but it is preventive in the sense that patients have more severe comorbidities if you wait,” said Dr. Ai-Xuan Holterman, director of pediatric surgery at Rush University Medical Center in Chicago.

“You could argue that in a 14-year-old who is obese but has no comorbidities, there is no urgency to do surgery. But we know what the natural trajectory of these patients will be. If a patient is older than 14 and morbidly obese, even if their comorbidities are relatively minor, I think that surgery is an appropriate option,” Dr. Nadler said in an interview.

Another benefit of early surgery is that “the risk of operating on a patient at a BMI of 45 is a lot different than operating on someone with a BMI of 60,” he added.

Still, U.S. studies have yet to report outcomes from bariatric surgery in adolescents at more than 3 years of follow-up.

A series of 61 patients, with an average age of 17, underwent gastric bypass surgery (Roux-en-Y) at Cincinnati Children's Hospital Medical Center between August 2002 and January 2007. The analysis showed that the average percentage of lost BMI was about 37% across all weight categories, and that two-thirds of the variance in BMI 1 year after surgery was attributable to the variance in baseline BMI (J. Pediatr. 2010;156:103–8).

The shift in surgical criteria for adolescents means that most surgeons now follow the same guidelines that have been standard for adult patients for nearly 2 decades. Serious comorbidities that lower the threshold to 35 kg/m

In 2004, a group of surgeons who at the time primarily favored gastric bypass for their adolescent patients published recommendations that called for limiting bariatric surgery for adolescents to those with a BMI of at least 40 kg/m

Dr. Nadler and his associates published their own endorsement for applying the adult BMI criteria for bariatric surgery to adolescents in another paper that appeared last year (J. Pediatr. Surg. 2009;44:1869–76).

“What is crucial is that you're not operating just because of BMI or weight, but that there is a compelling health indication,” said Dr. Inge, surgical director of the surgical weight loss program for teens at Cincinnati Children's. He cited preliminary evidence collected by his collaborators that, for example, “the pediatric heart may be more resilient to remodeling” than an adult's heart, and more likely to return to normal following significant weight loss. “There may be a window of opportunity to act before there is more permanent damage to the heart,” Dr. Inge said in an interview.

Comorbidities that are “more or less reversible” with bariatric surgery in adolescents and are the most common indications for surgery are diabetes, sleep apnea, and nonalcoholic steatohepatitis. Others in this category include hypertension, pseudotumor cerebri, gastro-esophageal reflux disease, asthma, and poor self-esteem, said Dr. Janey S.A. Pratt, a bariatric surgeon at Massachusetts General Hospital in Boston. However, she noted, other obesity-linked conditions are generally not reversible, including glomerulosclerosis of the kidney, gallstones, flat feet, major orthopedic deformities, precocious puberty, and some body-image issues.

“The most important reason to operate on obese adolescents is … to treat or prevent the comorbidities associated with excess weight,” Dr. Pratt said. “Will all of the adolescents we operate on be obese as adults?” Dr. Pratt cited results from a recent study in which 100% of children with a BMI above the 99th percentile after age 10 years had BMIs greater than 35 kg/m

Disclosures: Dr. Inge has received research funding from Ethicon Inc. Dr. Pratt has served as a consultant to Covidien. Dr. Nadler received research support from Allergan. Dr. Holterman and Dr. Michalsky had no financial disclosures.

'It's a new concept to think of surgery as preventive medicine, but it is preventive.'

Source DR. HOLTERMAN

All children with a BMI above the 99th percentile after age 10 had BMIs greater than 35 kg/m

Source DR. PRATT

'There may be a window of opportunity to act before there is more permanent damage to the heart.'

Source DR. INGE

The criteria for selecting obese adolescents as candidates for bariatric surgery have loosened in recent years, say some surgeons, while other surgeons had already applied the looser criteria for several years. Now that the adolescent field has converged on a roughly uniform body mass index standard that's the same as for adults—at least 35 kg/m

The goal, they agree, is to offer bariatric surgery to adolescents (usually defined as patients aged 13–17 years) safely but at a stage when the surgery has the best potential to normalize patients' weight so that comorbidities improve and possibly resolve.

An aggressive approach may also help avoid another problem. “No one can explain why, but there is a plateauing effect of all bariatric surgery, be it gastric bypass, gastric sleeve, or gastric banding. Patients lose about 15 BMI [body mass index] points but no more,” said Dr. Evan P. Nadler, director of the bariatric surgery program at Children's National Medical Center in Washington. 'The chances of getting patients near a normal body weight once they reach a BMI of 45 or 50 are quite small.”

The reasons behind this limit to the effect of bariatric surgery remain elusive. Many surgeons believe that the adaptable human body kicks in a thermostatlike resetting that maintains a certain body weight starting about a year after the large initial loss following surgery. Another factor may be that many patients have lifestyle regression at some point after surgery.

Regardless of the cause, the apparent limit to weight loss for most patients suggests to pediatric surgeons that bariatric surgery has the greatest potential to normalize BMI, and thereby prevent comorbidities, when applied relatively early, before BMI grows too high and before end-organ damage is irreversible.

“If you get to younger patients, they may still be in a window of opportunity for their end-organ disease to essentially be reversed,” Dr. Marc P. Michalsky said. “Our hope is that perhaps in adolescents, without decades of cardiac disease, hypertension, and liver disease, once their weight is off you may see more resolution of that disease than in adults. That's the hypothesis, but we haven't proven it yet,” said Dr. Michalsky, surgical director of the center for healthy weight and nutrition at Nationwide Children's Hospital in Columbus, Ohio.

“It's a new concept to think of surgery as preventive medicine, but it is preventive in the sense that patients have more severe comorbidities if you wait,” said Dr. Ai-Xuan Holterman, director of pediatric surgery at Rush University Medical Center in Chicago.

“You could argue that in a 14-year-old who is obese but has no comorbidities, there is no urgency to do surgery. But we know what the natural trajectory of these patients will be. If a patient is older than 14 and morbidly obese, even if their comorbidities are relatively minor, I think that surgery is an appropriate option,” Dr. Nadler said in an interview.

Another benefit of early surgery is that “the risk of operating on a patient at a BMI of 45 is a lot different than operating on someone with a BMI of 60,” he added.

Still, U.S. studies have yet to report outcomes from bariatric surgery in adolescents at more than 3 years of follow-up.

A series of 61 patients, with an average age of 17, underwent gastric bypass surgery (Roux-en-Y) at Cincinnati Children's Hospital Medical Center between August 2002 and January 2007. The analysis showed that the average percentage of lost BMI was about 37% across all weight categories, and that two-thirds of the variance in BMI 1 year after surgery was attributable to the variance in baseline BMI (J. Pediatr. 2010;156:103–8).

The shift in surgical criteria for adolescents means that most surgeons now follow the same guidelines that have been standard for adult patients for nearly 2 decades. Serious comorbidities that lower the threshold to 35 kg/m

In 2004, a group of surgeons who at the time primarily favored gastric bypass for their adolescent patients published recommendations that called for limiting bariatric surgery for adolescents to those with a BMI of at least 40 kg/m

Dr. Nadler and his associates published their own endorsement for applying the adult BMI criteria for bariatric surgery to adolescents in another paper that appeared last year (J. Pediatr. Surg. 2009;44:1869–76).

“What is crucial is that you're not operating just because of BMI or weight, but that there is a compelling health indication,” said Dr. Inge, surgical director of the surgical weight loss program for teens at Cincinnati Children's. He cited preliminary evidence collected by his collaborators that, for example, “the pediatric heart may be more resilient to remodeling” than an adult's heart, and more likely to return to normal following significant weight loss. “There may be a window of opportunity to act before there is more permanent damage to the heart,” Dr. Inge said in an interview.

Comorbidities that are “more or less reversible” with bariatric surgery in adolescents and are the most common indications for surgery are diabetes, sleep apnea, and nonalcoholic steatohepatitis. Others in this category include hypertension, pseudotumor cerebri, gastro-esophageal reflux disease, asthma, and poor self-esteem, said Dr. Janey S.A. Pratt, a bariatric surgeon at Massachusetts General Hospital in Boston. However, she noted, other obesity-linked conditions are generally not reversible, including glomerulosclerosis of the kidney, gallstones, flat feet, major orthopedic deformities, precocious puberty, and some body-image issues.

“The most important reason to operate on obese adolescents is … to treat or prevent the comorbidities associated with excess weight,” Dr. Pratt said. “Will all of the adolescents we operate on be obese as adults?” Dr. Pratt cited results from a recent study in which 100% of children with a BMI above the 99th percentile after age 10 years had BMIs greater than 35 kg/m

Disclosures: Dr. Inge has received research funding from Ethicon Inc. Dr. Pratt has served as a consultant to Covidien. Dr. Nadler received research support from Allergan. Dr. Holterman and Dr. Michalsky had no financial disclosures.

'It's a new concept to think of surgery as preventive medicine, but it is preventive.'

Source DR. HOLTERMAN

All children with a BMI above the 99th percentile after age 10 had BMIs greater than 35 kg/m

Source DR. PRATT

'There may be a window of opportunity to act before there is more permanent damage to the heart.'

Source DR. INGE

Major Finding: At 24 weeks, Patient Global Assessment scores improved in 50% of the 304 heart failure patients receiving intravenous iron and in 28% of the 155 patients on placebo.

Data Source: FAIR-HF, placebo-controlled phase III study of 459 patients, from 75 sites in 11 countries, randomized to iron or placebo.

Disclosures: The study was sponsored by Vifor Pharma, a Swiss company that markets Ferinject in Europe. Dr. Anker has received fees from Vifor; he also has received fees from Roche and Amgen.

ORLANDO — The clinical benefits from intravenous iron in chronic heart failure seen in a placebo-controlled study of 459 patients abruptly made iron repletion a new, plausible treatment for a sizeable fraction of heart failure patients.

“This is a new therapeutic concept. When patients [with heart failure] are symptomatic, physicians should think about iron deficiency,” Dr. Stefan D. Anker said at the annual scientific sessions of the American Heart Association. The study results also showed that the boost from iron occurred regardless of whether patients were anemic before starting treatment, a finding that suggests iron helps patients by a mechanism that does not involve hemoglobin.

The study findings “are very intriguing. Iron deficiency hasn't been on our radar screen,” commented Dr. Mariell L. Jessup, professor of medicine and associate chief of clinical affairs in the division of cardiovascular medicine at the University of Pennsylvania in Philadelphia.“I think this is something that people will start to act on quickly.”

“Iron deficiency is extremely common in this population,” commented Dr. John G.F. Cleland, professor and chairman of cardiology at the University of Hull, England.

Despite the promising new results, Dr. Anker stressed that the study was not powered to adequately address safety or efficacy end points such as survival and hospitalization. Further study is needed to build up a larger experience with the tested agent, ferric carboxymaltose, in heart failure patients, although Dr. Anker's study included 150 patient-years of treatment with this drug with no hint of excess adverse events aside from an expected, modest increase in gastrointestinal disorders. Dr. Anker also expressed eagerness to test this strategy in patients with diastolic dysfunction: heart failure with preserved left ventricular function.

About 20%–30% of heart failure patients likely have iron deficiency, said Dr. Anker, professor in the Center for Cardiovascular Research at Charit University in Berlin. Dr. Cleland said this estimate probably underestimates the actual prevalence.

Iron deficiency is probably prevalent in many heart failure patients because of a combination of poor diet and poor gastrointestinal absorption, and because of increased bleeding linked with aspirin use, Dr. Cleland said.

The Ferinject Assessment in Patients With Iron Deficiency and Chronic Heart Failure (FAIR-HF) trial enrolled patients during June 2007–December 2008 at 75 sites in 11 countries. Dr. Anker and his associates screened more than 950 patients to find the 459 who fulfilled the study's criteria for heart failure and serum ferritin level. Eligible patients had either New York Heart Association class III heart failure and a left ventricular ejection fraction of 45% or less, or class II heart failure and an ejection fraction of 40% or less. Their hemoglobin at enrollment could be 95–135 g/L, and so the study included nearly equal numbers of patients with anemia (hemoglobin of 120 g/L or less) and those without (more than 120 g/L). Their average age was 68, and 82% had class III heart failure.

Patients were randomized on a two-to-one basis to receive an intravenous, bolus injection of ferric carboxymaltose equivalent to 200 mg iron weekly or placebo. Once iron repletion occurred, after 8 or 12 weeks, the dosage was scaled back to one injection every 4 weeks.

After 24 weeks, the self-reported Patient Global Assessment was at least moderately improved in 50% of the 304 patients receiving iron and in 28% of the 155 patients on placebo, a statistically significant difference for this primary end point. New York Heart Association heart failure class improved in 47% of the patients on iron and in 30% of the control patients, also a significant difference in the second primary end point. The results appeared in an article published online (N. Engl. J. Med. 2009 Nov. 17 [doi:10.1056/NEJMoa0908355

During the study, mortality rates were 3% in the iron group and 6% in the control patients, a nonsignificant difference. Hospitalization for any cardiovascular reason occurred in 10% of the iron patients and 20% of the controls, a difference that came close to, but did not reach, statistical significance. Cardiac disorders of any type were significantly more common in the control patients, 50%, than in those on iron, 28%. The most notable adverse event more common in the iron patients was gastrointestinal disorder, in 17% of the iron patients and 7% of the controls, a difference that just missed statistical significance.

Despite its promising results, the study was not powered to address safety or efficacy end points.

Source DR. ANKER

My Take

'The Effect Occurs So Quickly'

This is a remarkable result. I am especially impressed that the separation in the primary end points between the patients receiving iron and those on placebo began to be statistically significant after the first 4 weeks on treatment and then continued to separate further.

The effect occurs so quickly. This is probably the fastest separation we've seen in a clinical trial in heart failure.

MILTON PACKER, M.D., is professor of medicine at the University of Texas Southwestern Medical Center in Dallas. He has been an adviser to Actelion, Pfizer, and United Therapeutics.

Major Finding: At 24 weeks, Patient Global Assessment scores improved in 50% of the 304 heart failure patients receiving intravenous iron and in 28% of the 155 patients on placebo.

Data Source: FAIR-HF, placebo-controlled phase III study of 459 patients, from 75 sites in 11 countries, randomized to iron or placebo.

Disclosures: The study was sponsored by Vifor Pharma, a Swiss company that markets Ferinject in Europe. Dr. Anker has received fees from Vifor; he also has received fees from Roche and Amgen.

ORLANDO — The clinical benefits from intravenous iron in chronic heart failure seen in a placebo-controlled study of 459 patients abruptly made iron repletion a new, plausible treatment for a sizeable fraction of heart failure patients.

“This is a new therapeutic concept. When patients [with heart failure] are symptomatic, physicians should think about iron deficiency,” Dr. Stefan D. Anker said at the annual scientific sessions of the American Heart Association. The study results also showed that the boost from iron occurred regardless of whether patients were anemic before starting treatment, a finding that suggests iron helps patients by a mechanism that does not involve hemoglobin.

The study findings “are very intriguing. Iron deficiency hasn't been on our radar screen,” commented Dr. Mariell L. Jessup, professor of medicine and associate chief of clinical affairs in the division of cardiovascular medicine at the University of Pennsylvania in Philadelphia.“I think this is something that people will start to act on quickly.”

“Iron deficiency is extremely common in this population,” commented Dr. John G.F. Cleland, professor and chairman of cardiology at the University of Hull, England.

Despite the promising new results, Dr. Anker stressed that the study was not powered to adequately address safety or efficacy end points such as survival and hospitalization. Further study is needed to build up a larger experience with the tested agent, ferric carboxymaltose, in heart failure patients, although Dr. Anker's study included 150 patient-years of treatment with this drug with no hint of excess adverse events aside from an expected, modest increase in gastrointestinal disorders. Dr. Anker also expressed eagerness to test this strategy in patients with diastolic dysfunction: heart failure with preserved left ventricular function.

About 20%–30% of heart failure patients likely have iron deficiency, said Dr. Anker, professor in the Center for Cardiovascular Research at Charit University in Berlin. Dr. Cleland said this estimate probably underestimates the actual prevalence.

Iron deficiency is probably prevalent in many heart failure patients because of a combination of poor diet and poor gastrointestinal absorption, and because of increased bleeding linked with aspirin use, Dr. Cleland said.

The Ferinject Assessment in Patients With Iron Deficiency and Chronic Heart Failure (FAIR-HF) trial enrolled patients during June 2007–December 2008 at 75 sites in 11 countries. Dr. Anker and his associates screened more than 950 patients to find the 459 who fulfilled the study's criteria for heart failure and serum ferritin level. Eligible patients had either New York Heart Association class III heart failure and a left ventricular ejection fraction of 45% or less, or class II heart failure and an ejection fraction of 40% or less. Their hemoglobin at enrollment could be 95–135 g/L, and so the study included nearly equal numbers of patients with anemia (hemoglobin of 120 g/L or less) and those without (more than 120 g/L). Their average age was 68, and 82% had class III heart failure.

Patients were randomized on a two-to-one basis to receive an intravenous, bolus injection of ferric carboxymaltose equivalent to 200 mg iron weekly or placebo. Once iron repletion occurred, after 8 or 12 weeks, the dosage was scaled back to one injection every 4 weeks.

After 24 weeks, the self-reported Patient Global Assessment was at least moderately improved in 50% of the 304 patients receiving iron and in 28% of the 155 patients on placebo, a statistically significant difference for this primary end point. New York Heart Association heart failure class improved in 47% of the patients on iron and in 30% of the control patients, also a significant difference in the second primary end point. The results appeared in an article published online (N. Engl. J. Med. 2009 Nov. 17 [doi:10.1056/NEJMoa0908355

During the study, mortality rates were 3% in the iron group and 6% in the control patients, a nonsignificant difference. Hospitalization for any cardiovascular reason occurred in 10% of the iron patients and 20% of the controls, a difference that came close to, but did not reach, statistical significance. Cardiac disorders of any type were significantly more common in the control patients, 50%, than in those on iron, 28%. The most notable adverse event more common in the iron patients was gastrointestinal disorder, in 17% of the iron patients and 7% of the controls, a difference that just missed statistical significance.

Despite its promising results, the study was not powered to address safety or efficacy end points.

Source DR. ANKER

My Take

'The Effect Occurs So Quickly'

This is a remarkable result. I am especially impressed that the separation in the primary end points between the patients receiving iron and those on placebo began to be statistically significant after the first 4 weeks on treatment and then continued to separate further.

The effect occurs so quickly. This is probably the fastest separation we've seen in a clinical trial in heart failure.

MILTON PACKER, M.D., is professor of medicine at the University of Texas Southwestern Medical Center in Dallas. He has been an adviser to Actelion, Pfizer, and United Therapeutics.

Major Finding: At 24 weeks, Patient Global Assessment scores improved in 50% of the 304 heart failure patients receiving intravenous iron and in 28% of the 155 patients on placebo.

Data Source: FAIR-HF, placebo-controlled phase III study of 459 patients, from 75 sites in 11 countries, randomized to iron or placebo.

Disclosures: The study was sponsored by Vifor Pharma, a Swiss company that markets Ferinject in Europe. Dr. Anker has received fees from Vifor; he also has received fees from Roche and Amgen.

ORLANDO — The clinical benefits from intravenous iron in chronic heart failure seen in a placebo-controlled study of 459 patients abruptly made iron repletion a new, plausible treatment for a sizeable fraction of heart failure patients.

“This is a new therapeutic concept. When patients [with heart failure] are symptomatic, physicians should think about iron deficiency,” Dr. Stefan D. Anker said at the annual scientific sessions of the American Heart Association. The study results also showed that the boost from iron occurred regardless of whether patients were anemic before starting treatment, a finding that suggests iron helps patients by a mechanism that does not involve hemoglobin.

The study findings “are very intriguing. Iron deficiency hasn't been on our radar screen,” commented Dr. Mariell L. Jessup, professor of medicine and associate chief of clinical affairs in the division of cardiovascular medicine at the University of Pennsylvania in Philadelphia.“I think this is something that people will start to act on quickly.”

“Iron deficiency is extremely common in this population,” commented Dr. John G.F. Cleland, professor and chairman of cardiology at the University of Hull, England.

Despite the promising new results, Dr. Anker stressed that the study was not powered to adequately address safety or efficacy end points such as survival and hospitalization. Further study is needed to build up a larger experience with the tested agent, ferric carboxymaltose, in heart failure patients, although Dr. Anker's study included 150 patient-years of treatment with this drug with no hint of excess adverse events aside from an expected, modest increase in gastrointestinal disorders. Dr. Anker also expressed eagerness to test this strategy in patients with diastolic dysfunction: heart failure with preserved left ventricular function.

About 20%–30% of heart failure patients likely have iron deficiency, said Dr. Anker, professor in the Center for Cardiovascular Research at Charit University in Berlin. Dr. Cleland said this estimate probably underestimates the actual prevalence.

Iron deficiency is probably prevalent in many heart failure patients because of a combination of poor diet and poor gastrointestinal absorption, and because of increased bleeding linked with aspirin use, Dr. Cleland said.

The Ferinject Assessment in Patients With Iron Deficiency and Chronic Heart Failure (FAIR-HF) trial enrolled patients during June 2007–December 2008 at 75 sites in 11 countries. Dr. Anker and his associates screened more than 950 patients to find the 459 who fulfilled the study's criteria for heart failure and serum ferritin level. Eligible patients had either New York Heart Association class III heart failure and a left ventricular ejection fraction of 45% or less, or class II heart failure and an ejection fraction of 40% or less. Their hemoglobin at enrollment could be 95–135 g/L, and so the study included nearly equal numbers of patients with anemia (hemoglobin of 120 g/L or less) and those without (more than 120 g/L). Their average age was 68, and 82% had class III heart failure.

Patients were randomized on a two-to-one basis to receive an intravenous, bolus injection of ferric carboxymaltose equivalent to 200 mg iron weekly or placebo. Once iron repletion occurred, after 8 or 12 weeks, the dosage was scaled back to one injection every 4 weeks.

After 24 weeks, the self-reported Patient Global Assessment was at least moderately improved in 50% of the 304 patients receiving iron and in 28% of the 155 patients on placebo, a statistically significant difference for this primary end point. New York Heart Association heart failure class improved in 47% of the patients on iron and in 30% of the control patients, also a significant difference in the second primary end point. The results appeared in an article published online (N. Engl. J. Med. 2009 Nov. 17 [doi:10.1056/NEJMoa0908355

During the study, mortality rates were 3% in the iron group and 6% in the control patients, a nonsignificant difference. Hospitalization for any cardiovascular reason occurred in 10% of the iron patients and 20% of the controls, a difference that came close to, but did not reach, statistical significance. Cardiac disorders of any type were significantly more common in the control patients, 50%, than in those on iron, 28%. The most notable adverse event more common in the iron patients was gastrointestinal disorder, in 17% of the iron patients and 7% of the controls, a difference that just missed statistical significance.

Despite its promising results, the study was not powered to address safety or efficacy end points.

Source DR. ANKER

My Take

'The Effect Occurs So Quickly'

This is a remarkable result. I am especially impressed that the separation in the primary end points between the patients receiving iron and those on placebo began to be statistically significant after the first 4 weeks on treatment and then continued to separate further.

The effect occurs so quickly. This is probably the fastest separation we've seen in a clinical trial in heart failure.

MILTON PACKER, M.D., is professor of medicine at the University of Texas Southwestern Medical Center in Dallas. He has been an adviser to Actelion, Pfizer, and United Therapeutics.

Major Finding: The rate of death or new heart failure hospitalization was 63% higher in the patients with gout than in those without gout.

Data Source: The analysis used administrative health record data from residents of the province of Quebec; 14,327 cases of people hospitalized for heart failure were compared with 143,255 controls.

Disclosures: None

ORLANDO — Gout boosted the risk of death or hospitalization for heart failure in an observational, case-control study of more than 150,000 patients with heart failure.

The analysis also showed that patients with heart failure and gout who were on long-term allopurinol treatment had a significantly reduced risk for death or heart failure hospitalization, Dr. George Thanassoulis said at the annual scientific sessions of the American Heart Association.

These findings do not warrant the use of allopurinol in heart failure patients without gout, but the data suggest that if such patients are candidates for allopurinol because of coexisting gout, then the new results “increase the reasons to treat them,” said Dr. Thanassoulis, a cardiologist at Boston University and the Framingham (Mass.) Heart Study.

He hypothesized that allo-purinol benefits heart failure outcomes not by lowering blood levels of uric acid, but by inhibiting oxidative stress and the endothelial dysfunction that oxidative stress produces.

The study used administrative health record data from residents of the province of Quebec who were aged older than 65 years. Cases were 14,327 people hospitalized for heart failure but without another heart failure hospitalization during the 3 years before the index episode, a restriction that helped ensure a uniform level of heart failure severity among the patients. Controls were 143,255 people in the Quebec database matched to the cases by follow-up duration and by calendar year.

The average age was 79 years among the cases and 77 years among the controls. Both the cases and controls were evenly split among men and women. Identification of gout relied on hospitalization, a physician visit, or a diagnostic code in the medical record.

During an average follow-up of 2 years, the rate of death or new heart failure hospitalization was 63% higher in the patients with gout than in those without gout, a statistically significant difference in an analysis that controlled for several demographic and clinical variables including age, gender, comorbidities, and medications.

The risk for death or heart failure hospitalization was even higher in patients who had acute gout, with a twofold higher risk in the adjusted analysis. The researchers defined acute gout as hospitalization or a physician visit for gout within 60 days of the index heart failure event.

Another pair of analyses looked at the impact of allo-purinol treatment. Among patients with an index heart failure event who also had gout treatment with allopurinol, there was a significant 31% reduction in the subsequent rate of death or heart failure hospitalization in the adjusted analysis. This benefit was limited to the patients on chronic allopurinol treatment for more than 30 days. Patients on allopurinol for 30 days or less showed no significant reduction in mortality or new heart failure hospitalizations.

Major Finding: The rate of death or new heart failure hospitalization was 63% higher in the patients with gout than in those without gout.

Data Source: The analysis used administrative health record data from residents of the province of Quebec; 14,327 cases of people hospitalized for heart failure were compared with 143,255 controls.

Disclosures: None

ORLANDO — Gout boosted the risk of death or hospitalization for heart failure in an observational, case-control study of more than 150,000 patients with heart failure.

The analysis also showed that patients with heart failure and gout who were on long-term allopurinol treatment had a significantly reduced risk for death or heart failure hospitalization, Dr. George Thanassoulis said at the annual scientific sessions of the American Heart Association.

These findings do not warrant the use of allopurinol in heart failure patients without gout, but the data suggest that if such patients are candidates for allopurinol because of coexisting gout, then the new results “increase the reasons to treat them,” said Dr. Thanassoulis, a cardiologist at Boston University and the Framingham (Mass.) Heart Study.

He hypothesized that allo-purinol benefits heart failure outcomes not by lowering blood levels of uric acid, but by inhibiting oxidative stress and the endothelial dysfunction that oxidative stress produces.

The study used administrative health record data from residents of the province of Quebec who were aged older than 65 years. Cases were 14,327 people hospitalized for heart failure but without another heart failure hospitalization during the 3 years before the index episode, a restriction that helped ensure a uniform level of heart failure severity among the patients. Controls were 143,255 people in the Quebec database matched to the cases by follow-up duration and by calendar year.

The average age was 79 years among the cases and 77 years among the controls. Both the cases and controls were evenly split among men and women. Identification of gout relied on hospitalization, a physician visit, or a diagnostic code in the medical record.

During an average follow-up of 2 years, the rate of death or new heart failure hospitalization was 63% higher in the patients with gout than in those without gout, a statistically significant difference in an analysis that controlled for several demographic and clinical variables including age, gender, comorbidities, and medications.

The risk for death or heart failure hospitalization was even higher in patients who had acute gout, with a twofold higher risk in the adjusted analysis. The researchers defined acute gout as hospitalization or a physician visit for gout within 60 days of the index heart failure event.

Another pair of analyses looked at the impact of allo-purinol treatment. Among patients with an index heart failure event who also had gout treatment with allopurinol, there was a significant 31% reduction in the subsequent rate of death or heart failure hospitalization in the adjusted analysis. This benefit was limited to the patients on chronic allopurinol treatment for more than 30 days. Patients on allopurinol for 30 days or less showed no significant reduction in mortality or new heart failure hospitalizations.

Major Finding: The rate of death or new heart failure hospitalization was 63% higher in the patients with gout than in those without gout.

Data Source: The analysis used administrative health record data from residents of the province of Quebec; 14,327 cases of people hospitalized for heart failure were compared with 143,255 controls.

Disclosures: None

ORLANDO — Gout boosted the risk of death or hospitalization for heart failure in an observational, case-control study of more than 150,000 patients with heart failure.

The analysis also showed that patients with heart failure and gout who were on long-term allopurinol treatment had a significantly reduced risk for death or heart failure hospitalization, Dr. George Thanassoulis said at the annual scientific sessions of the American Heart Association.

These findings do not warrant the use of allopurinol in heart failure patients without gout, but the data suggest that if such patients are candidates for allopurinol because of coexisting gout, then the new results “increase the reasons to treat them,” said Dr. Thanassoulis, a cardiologist at Boston University and the Framingham (Mass.) Heart Study.

He hypothesized that allo-purinol benefits heart failure outcomes not by lowering blood levels of uric acid, but by inhibiting oxidative stress and the endothelial dysfunction that oxidative stress produces.

The study used administrative health record data from residents of the province of Quebec who were aged older than 65 years. Cases were 14,327 people hospitalized for heart failure but without another heart failure hospitalization during the 3 years before the index episode, a restriction that helped ensure a uniform level of heart failure severity among the patients. Controls were 143,255 people in the Quebec database matched to the cases by follow-up duration and by calendar year.

The average age was 79 years among the cases and 77 years among the controls. Both the cases and controls were evenly split among men and women. Identification of gout relied on hospitalization, a physician visit, or a diagnostic code in the medical record.

During an average follow-up of 2 years, the rate of death or new heart failure hospitalization was 63% higher in the patients with gout than in those without gout, a statistically significant difference in an analysis that controlled for several demographic and clinical variables including age, gender, comorbidities, and medications.

The risk for death or heart failure hospitalization was even higher in patients who had acute gout, with a twofold higher risk in the adjusted analysis. The researchers defined acute gout as hospitalization or a physician visit for gout within 60 days of the index heart failure event.

Another pair of analyses looked at the impact of allo-purinol treatment. Among patients with an index heart failure event who also had gout treatment with allopurinol, there was a significant 31% reduction in the subsequent rate of death or heart failure hospitalization in the adjusted analysis. This benefit was limited to the patients on chronic allopurinol treatment for more than 30 days. Patients on allopurinol for 30 days or less showed no significant reduction in mortality or new heart failure hospitalizations.

ORLANDO — Patients who experienced sudden cardiac death had a significantly higher rate of treatment with a sodium-channel blocking, anticonvulsant drug, compared with people who did not have sudden death, in a case-control study of more than 10,000 people.

“This finding may explain a proportion of the sudden deaths seen in epilepsy patients,” Dr. Abdennasser Bardai said at the annual scientific sessions of the American Heart Association.

About 10% of epilepsy patients have an unexpected death that is not seizure related—a phenomenon so common that it's been named “sudden unexplained death in epilepsy.” Dr. Bardai and his associates hypothesized that many of these deaths might be triggered by anticonvulsant drugs, especially those that block sodium channels such as carbamazepine, lamotrigine, and phenytoin. Although the sodium-channel blockade these drugs cause is aimed at neurons, the same property can also affect cardiac cells and may potentially cause arrhythmia.

To explore a possible link between anticonvulsant use and sudden death, the researchers used data collected in the Netherlands' Integrated Primary Care Information database. They focused on medical records for people aged 18 or older during 1995–2007 in cases for which at least 1 year's record existed.

Among the more than 478,000 people who met these criteria, 926 experienced sudden death, defined as a natural death heralded by a sudden loss of consciousness within 1 hour after the onset of acute symptoms, or an unwitnessed, unexpected death of someone seen in stable medical condition less than 24 hours before with no evidence of a noncardiac cause. The researchers matched each case with about 20 other people from the database with a similar age and identical gender, reaching a total of 9,832 controls. The average age of the cases and controls was 72 years, and 26% were men.

In a multivariate analysis that controlled for age, gender, smoking, alcohol abuse, concomitant medications, cardiovascular disease, arrhythmia, hypertension, diabetes, heart failure, and hypercholesterolemia, people who died from sudden death were 2.5-fold more likely to be on treatment with an anticonvulsant drug than were controls, a statistically significant difference, reported Dr. Bardai, a cardiovascular diseases researcher at the Academic Medical Center in Amsterdam.

In a second adjusted analysis that divided anticonvulsant drug use into agents that block sodium channels and those that don't, the sudden death cases were 2.9-fold more likely to be on a sodium-channel blocking anticonvulsant, compared with controls, a statistically significant difference.

In contrast, the fraction of sudden death cases on treatment with an anticonvulsant that doesn't block sodium channels was not significantly different from the rate at which these drugs were used by the controls.

Dr. Bardai said that he and his associates had no financial disclosures.

ORLANDO — Patients who experienced sudden cardiac death had a significantly higher rate of treatment with a sodium-channel blocking, anticonvulsant drug, compared with people who did not have sudden death, in a case-control study of more than 10,000 people.

“This finding may explain a proportion of the sudden deaths seen in epilepsy patients,” Dr. Abdennasser Bardai said at the annual scientific sessions of the American Heart Association.

About 10% of epilepsy patients have an unexpected death that is not seizure related—a phenomenon so common that it's been named “sudden unexplained death in epilepsy.” Dr. Bardai and his associates hypothesized that many of these deaths might be triggered by anticonvulsant drugs, especially those that block sodium channels such as carbamazepine, lamotrigine, and phenytoin. Although the sodium-channel blockade these drugs cause is aimed at neurons, the same property can also affect cardiac cells and may potentially cause arrhythmia.

To explore a possible link between anticonvulsant use and sudden death, the researchers used data collected in the Netherlands' Integrated Primary Care Information database. They focused on medical records for people aged 18 or older during 1995–2007 in cases for which at least 1 year's record existed.

Among the more than 478,000 people who met these criteria, 926 experienced sudden death, defined as a natural death heralded by a sudden loss of consciousness within 1 hour after the onset of acute symptoms, or an unwitnessed, unexpected death of someone seen in stable medical condition less than 24 hours before with no evidence of a noncardiac cause. The researchers matched each case with about 20 other people from the database with a similar age and identical gender, reaching a total of 9,832 controls. The average age of the cases and controls was 72 years, and 26% were men.

In a multivariate analysis that controlled for age, gender, smoking, alcohol abuse, concomitant medications, cardiovascular disease, arrhythmia, hypertension, diabetes, heart failure, and hypercholesterolemia, people who died from sudden death were 2.5-fold more likely to be on treatment with an anticonvulsant drug than were controls, a statistically significant difference, reported Dr. Bardai, a cardiovascular diseases researcher at the Academic Medical Center in Amsterdam.

In a second adjusted analysis that divided anticonvulsant drug use into agents that block sodium channels and those that don't, the sudden death cases were 2.9-fold more likely to be on a sodium-channel blocking anticonvulsant, compared with controls, a statistically significant difference.

In contrast, the fraction of sudden death cases on treatment with an anticonvulsant that doesn't block sodium channels was not significantly different from the rate at which these drugs were used by the controls.

Dr. Bardai said that he and his associates had no financial disclosures.

ORLANDO — Patients who experienced sudden cardiac death had a significantly higher rate of treatment with a sodium-channel blocking, anticonvulsant drug, compared with people who did not have sudden death, in a case-control study of more than 10,000 people.

“This finding may explain a proportion of the sudden deaths seen in epilepsy patients,” Dr. Abdennasser Bardai said at the annual scientific sessions of the American Heart Association.

About 10% of epilepsy patients have an unexpected death that is not seizure related—a phenomenon so common that it's been named “sudden unexplained death in epilepsy.” Dr. Bardai and his associates hypothesized that many of these deaths might be triggered by anticonvulsant drugs, especially those that block sodium channels such as carbamazepine, lamotrigine, and phenytoin. Although the sodium-channel blockade these drugs cause is aimed at neurons, the same property can also affect cardiac cells and may potentially cause arrhythmia.

To explore a possible link between anticonvulsant use and sudden death, the researchers used data collected in the Netherlands' Integrated Primary Care Information database. They focused on medical records for people aged 18 or older during 1995–2007 in cases for which at least 1 year's record existed.

Among the more than 478,000 people who met these criteria, 926 experienced sudden death, defined as a natural death heralded by a sudden loss of consciousness within 1 hour after the onset of acute symptoms, or an unwitnessed, unexpected death of someone seen in stable medical condition less than 24 hours before with no evidence of a noncardiac cause. The researchers matched each case with about 20 other people from the database with a similar age and identical gender, reaching a total of 9,832 controls. The average age of the cases and controls was 72 years, and 26% were men.

In a multivariate analysis that controlled for age, gender, smoking, alcohol abuse, concomitant medications, cardiovascular disease, arrhythmia, hypertension, diabetes, heart failure, and hypercholesterolemia, people who died from sudden death were 2.5-fold more likely to be on treatment with an anticonvulsant drug than were controls, a statistically significant difference, reported Dr. Bardai, a cardiovascular diseases researcher at the Academic Medical Center in Amsterdam.

In a second adjusted analysis that divided anticonvulsant drug use into agents that block sodium channels and those that don't, the sudden death cases were 2.9-fold more likely to be on a sodium-channel blocking anticonvulsant, compared with controls, a statistically significant difference.

In contrast, the fraction of sudden death cases on treatment with an anticonvulsant that doesn't block sodium channels was not significantly different from the rate at which these drugs were used by the controls.

Dr. Bardai said that he and his associates had no financial disclosures.