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Hypertension worsened by commonly used prescription meds
Nearly half of these American adults had hypertension, and in this subgroup, 18.5% reported using a prescription drug known to increase blood pressure. The most widely used class of agents with this effect was antidepressants, used by 8.7%; followed by nonsteroidal anti-inflammatory drugs (NSAIDs), used by 6.5%; steroids, 1.9%; estrogens, 1.7%; and several other agents each used by fewer than 1% of the study cohort, John Vitarello, MD, said during a press briefing on reports from the upcoming annual scientific sessions of the American College of Cardiology.
He and his associates estimated that this use of prescription drugs known to raise blood pressure could be what stands in the way of some 560,000-2.2 million Americans from having their hypertension under control, depending on the exact blood pressure impact that various pressure-increasing drugs have and presuming that half of those on blood pressure increasing agents could stop them and switch to alternative agents, said Dr. Vitarello, a researcher at Beth Israel Deaconess Medical Center in Boston.
He also highlighted that the study assessed only prescription drugs and did not examine OTC drug use, which may be especially relevant for the many people who regularly take NSAIDs.
“Clinicians should review the prescription and OTC drug use of patients with hypertension and consider stopping drugs that increase blood pressure or switching the patient to alternatives” that are blood pressure neutral, Dr. Vitarello said during the briefing. He cautioned that maintaining hypertensive patients on agents that raise their blood pressure can result in “prescribing cascades” where taking drugs that boost blood pressure results in need for intensified antihypertensive treatment.
An opportunity for NSAID alternatives
“This study hopefully raises awareness that there is a very high use of medications that increase blood pressure, and use of OTC agents could increase the rate even higher” said Eugene Yang, MD, a cardiologist and codirector of the Cardiovascular Wellness and Prevention Program of the University of Washington, Seattle. Substituting for certain antidepressant agents may often not be realistic, but an opportunity exists for reducing NSAID use, a class also linked with an increased risk for bleeding and other adverse effects, Dr. Yang said during the briefing. Minimizing use of NSAIDs including ibuprofen and naproxen use “is something to think about,” he suggested.
“The effect of NSAIDs on blood pressure is not well studied and can vary from person to person” noted Dr. Vitarello, who added that higher NSAID dosages and more prolonged use likely increase the risk for an adverse effect on blood pressure. One reasonable option is to encourage patients to use an alternative class of pain reliever such as acetaminophen.
It remains “a challenge” to discern differences in adverse blood pressure effects, and in all adverse cardiovascular effects among different NSAIDs, said Dr. Yang. Results from “some studies show that certain NSAIDs may be safer, but other studies did not. We need to be very careful using NSAIDs because, on average, they increase blood pressure by about 3 mm Hg. We need to be mindful to try to prescribe alternative agents, like acetaminophen.”
A decade of data from NHANES
The analysis run by Dr. Vitarello and associates used data from 27,599 American adults included in the NHANES during 2009-2018, and focused on the 44% who either had an average blood pressure measurement of at least 130/80 mm Hg or reported having ever been told by a clinician that they had hypertension. The NHANES assessments included the prescription medications taken by each participant. The prevalence of using at least one prescription drug known to raise blood pressure was 24% among women and 14% among men, and 4% of those with hypertension were on two or more pressure-increasing agents.
The researchers based their identification of pressure-increasing prescription drugs on the list included in the 2017 guideline for managing high blood pressure from the American College of Cardiology and American Heart Association. This list specifies that the antidepressants that raise blood pressure are the monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants.
Dr. Vitarello and Dr. Yang had no disclosures.
Nearly half of these American adults had hypertension, and in this subgroup, 18.5% reported using a prescription drug known to increase blood pressure. The most widely used class of agents with this effect was antidepressants, used by 8.7%; followed by nonsteroidal anti-inflammatory drugs (NSAIDs), used by 6.5%; steroids, 1.9%; estrogens, 1.7%; and several other agents each used by fewer than 1% of the study cohort, John Vitarello, MD, said during a press briefing on reports from the upcoming annual scientific sessions of the American College of Cardiology.
He and his associates estimated that this use of prescription drugs known to raise blood pressure could be what stands in the way of some 560,000-2.2 million Americans from having their hypertension under control, depending on the exact blood pressure impact that various pressure-increasing drugs have and presuming that half of those on blood pressure increasing agents could stop them and switch to alternative agents, said Dr. Vitarello, a researcher at Beth Israel Deaconess Medical Center in Boston.
He also highlighted that the study assessed only prescription drugs and did not examine OTC drug use, which may be especially relevant for the many people who regularly take NSAIDs.
“Clinicians should review the prescription and OTC drug use of patients with hypertension and consider stopping drugs that increase blood pressure or switching the patient to alternatives” that are blood pressure neutral, Dr. Vitarello said during the briefing. He cautioned that maintaining hypertensive patients on agents that raise their blood pressure can result in “prescribing cascades” where taking drugs that boost blood pressure results in need for intensified antihypertensive treatment.
An opportunity for NSAID alternatives
“This study hopefully raises awareness that there is a very high use of medications that increase blood pressure, and use of OTC agents could increase the rate even higher” said Eugene Yang, MD, a cardiologist and codirector of the Cardiovascular Wellness and Prevention Program of the University of Washington, Seattle. Substituting for certain antidepressant agents may often not be realistic, but an opportunity exists for reducing NSAID use, a class also linked with an increased risk for bleeding and other adverse effects, Dr. Yang said during the briefing. Minimizing use of NSAIDs including ibuprofen and naproxen use “is something to think about,” he suggested.
“The effect of NSAIDs on blood pressure is not well studied and can vary from person to person” noted Dr. Vitarello, who added that higher NSAID dosages and more prolonged use likely increase the risk for an adverse effect on blood pressure. One reasonable option is to encourage patients to use an alternative class of pain reliever such as acetaminophen.
It remains “a challenge” to discern differences in adverse blood pressure effects, and in all adverse cardiovascular effects among different NSAIDs, said Dr. Yang. Results from “some studies show that certain NSAIDs may be safer, but other studies did not. We need to be very careful using NSAIDs because, on average, they increase blood pressure by about 3 mm Hg. We need to be mindful to try to prescribe alternative agents, like acetaminophen.”
A decade of data from NHANES
The analysis run by Dr. Vitarello and associates used data from 27,599 American adults included in the NHANES during 2009-2018, and focused on the 44% who either had an average blood pressure measurement of at least 130/80 mm Hg or reported having ever been told by a clinician that they had hypertension. The NHANES assessments included the prescription medications taken by each participant. The prevalence of using at least one prescription drug known to raise blood pressure was 24% among women and 14% among men, and 4% of those with hypertension were on two or more pressure-increasing agents.
The researchers based their identification of pressure-increasing prescription drugs on the list included in the 2017 guideline for managing high blood pressure from the American College of Cardiology and American Heart Association. This list specifies that the antidepressants that raise blood pressure are the monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants.
Dr. Vitarello and Dr. Yang had no disclosures.
Nearly half of these American adults had hypertension, and in this subgroup, 18.5% reported using a prescription drug known to increase blood pressure. The most widely used class of agents with this effect was antidepressants, used by 8.7%; followed by nonsteroidal anti-inflammatory drugs (NSAIDs), used by 6.5%; steroids, 1.9%; estrogens, 1.7%; and several other agents each used by fewer than 1% of the study cohort, John Vitarello, MD, said during a press briefing on reports from the upcoming annual scientific sessions of the American College of Cardiology.
He and his associates estimated that this use of prescription drugs known to raise blood pressure could be what stands in the way of some 560,000-2.2 million Americans from having their hypertension under control, depending on the exact blood pressure impact that various pressure-increasing drugs have and presuming that half of those on blood pressure increasing agents could stop them and switch to alternative agents, said Dr. Vitarello, a researcher at Beth Israel Deaconess Medical Center in Boston.
He also highlighted that the study assessed only prescription drugs and did not examine OTC drug use, which may be especially relevant for the many people who regularly take NSAIDs.
“Clinicians should review the prescription and OTC drug use of patients with hypertension and consider stopping drugs that increase blood pressure or switching the patient to alternatives” that are blood pressure neutral, Dr. Vitarello said during the briefing. He cautioned that maintaining hypertensive patients on agents that raise their blood pressure can result in “prescribing cascades” where taking drugs that boost blood pressure results in need for intensified antihypertensive treatment.
An opportunity for NSAID alternatives
“This study hopefully raises awareness that there is a very high use of medications that increase blood pressure, and use of OTC agents could increase the rate even higher” said Eugene Yang, MD, a cardiologist and codirector of the Cardiovascular Wellness and Prevention Program of the University of Washington, Seattle. Substituting for certain antidepressant agents may often not be realistic, but an opportunity exists for reducing NSAID use, a class also linked with an increased risk for bleeding and other adverse effects, Dr. Yang said during the briefing. Minimizing use of NSAIDs including ibuprofen and naproxen use “is something to think about,” he suggested.
“The effect of NSAIDs on blood pressure is not well studied and can vary from person to person” noted Dr. Vitarello, who added that higher NSAID dosages and more prolonged use likely increase the risk for an adverse effect on blood pressure. One reasonable option is to encourage patients to use an alternative class of pain reliever such as acetaminophen.
It remains “a challenge” to discern differences in adverse blood pressure effects, and in all adverse cardiovascular effects among different NSAIDs, said Dr. Yang. Results from “some studies show that certain NSAIDs may be safer, but other studies did not. We need to be very careful using NSAIDs because, on average, they increase blood pressure by about 3 mm Hg. We need to be mindful to try to prescribe alternative agents, like acetaminophen.”
A decade of data from NHANES
The analysis run by Dr. Vitarello and associates used data from 27,599 American adults included in the NHANES during 2009-2018, and focused on the 44% who either had an average blood pressure measurement of at least 130/80 mm Hg or reported having ever been told by a clinician that they had hypertension. The NHANES assessments included the prescription medications taken by each participant. The prevalence of using at least one prescription drug known to raise blood pressure was 24% among women and 14% among men, and 4% of those with hypertension were on two or more pressure-increasing agents.
The researchers based their identification of pressure-increasing prescription drugs on the list included in the 2017 guideline for managing high blood pressure from the American College of Cardiology and American Heart Association. This list specifies that the antidepressants that raise blood pressure are the monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants.
Dr. Vitarello and Dr. Yang had no disclosures.
FROM ACC 2021
Exercise plus liraglutide better for maintaining weight loss than either strategy alone
For persons with obesity who lost a substantial amount of weight on a low-calorie diet, the combination of exercise and medication significantly improved weight-loss maintenance, and more so than either strategy alone, according to results of a randomized, head-to-head trial.
A year after starting moderate to vigorous exercise coupled with liraglutide treatment, study participants had a weight loss 9.5 kg more than those who received placebo and usual activity, study results show.
Reductions in both weight and fat loss seen with exercise and liraglutide was roughly twice as much as what was achieved at 1 year with the strategies of liraglutide or exercise alone, according to authors of the study, which appears in the New England Journal of Medicine .
Although the findings may not apply to those who can’t or won’t perform moderate to vigorous exercise, the intervention in this study was nevertheless feasible in this group of persons with obesity who had a very low level of fitness, according to the authors.
Hope for healthy weight loss maintenance
Investigator Signe S. Torekov, PhD, said in an interview that these results provide hope that more-intensive exercise regimens, with or without medication, can be useful and well accepted among individuals struggling with obesity.
“When we started our study, we were told, ‘you are never going to have people with obesity exercising that much, and for that long’ – but people were actually very happy about the exercise,” said Dr. Torekov, a professor in the department of biomedical sciences at the University of Copenhagen.
“If you actually set up a program where people are monitored and you have a feedback system, then exercise is an excellent component in obesity treatment that should be much more actively used – not only for its weight-lowering component, but also for improving health and quality of life,” she said in an interview.
Weight-management specialist John D. Clark, MD, PhD, said results of this study can be used to help inform patients about how successful different strategies incorporating exercise and medication may be following initial weight loss.
“When patients plateau on a consistent, calorie-restricted dietary plan, we can educate them and manage expectations about what options may be available to them after their initial weight loss,” said Dr. Clark, of the University of Texas, Dallas.
“If the patient’s goal specifically is weight loss at all costs, then I may suggest, ‘let’s consider liraglutide or liraglutide in combination with exercise,’ ” he said in an interview. “Exercise improves body composition, even if it may not on its own be as successful in the next phase of their weight-loss journey, as shown in this study.”
Obesity and weight-loss challenges
Although it’s not uncommon for obese patients to lose a large amount of weight, keeping the weight off is frequently a challenge unless the patient follows a structured weight maintenance program, according to Dr. Torekov and coauthors.
The rapid weight regain seen in many obese patients could be a result of reductions in total energy expenditure or increased appetite. Exercise is one strategy to sustain weight loss, though according to the authors, very few studies have looked at exercise in isolation to quantify its contribution to maintenance.
Accordingly, the present study sought to determine whether exercise, medication, or the combination thereof works best to keep weight off.
The study incorporated liraglutide, a GLP-1 receptor agonist indicated for chronic weight management, along with a reduced-calorie diet and increased physical activity, in adults with elevated body mass index and at least one weight-related comorbidity.
The investigator-initiated phase 3 trial included 215 adults with a body mass index of 32-43. Individuals with type 2 diabetes were excluded. All participants followed an 8-week, low-calorie diet comprising 800 calories per day.
Participants who lost 5% or more of their body weight were then randomized to 1 year of exercise plus liraglutide, exercise plus placebo, usual activity plus liraglutide, or usual activity plus placebo.
The exercise program – which was structured but flexible, according to investigators – included group exercise sessions that incorporated 30 minutes of indoor cycling and 15 minutes of circuit training 2 days each week. Participants wore heart rate monitors during exercise to make sure they reached targets for moderate to vigorous intensity.
Instructors trained in exercise physiology planned and monitored individualized exercise programs for each participant in the exercise-medication or exercise-only arms of the study.
Participants in all groups attended 12 one-on-one consultations where body weight was measured and dietetic support was provided.
Weight loss with exercise and medication
Out of 215 individuals enrolled in the study, 195 lost at least 5% of body weight and continued on to the randomized portion, the investigators reported. During the diet phase, they lost a mean of 13.1 kg, translating into a 12% mean reduction in body weight.
The mean frequency of exercise was 2.4 times per week in the exercise-plus-medication group and 2.5 times per week in the exercise-only group. About one-third of the exercise took place in the group sessions, and there was no difference in relative intensity between group and individual exercise regimens, the investigators said.
Individuals in the exercise plus medication group continued to lose more weight, such that, at the end of 1 year, the weight loss decreased even further, by a mean of –3.4 kg. By contrast, weight increased by a mean of 6.1 kg for the placebo group, adding up to a treatment difference of –9.5 kg (95% confidence interval, –13.1 to –5.9; P < .001), according to the report.
That treatment effect was also seen, but more muted, in the exercise- and liraglutide-only groups, at –4.1 kg and –6.8 kg, respectively.
A significant treatment effect was observed for exercise plus liraglutide, compared with exercise alone, at –5.4 kg (P = .004), while the treatment effect for the combination versus liraglutide alone was not significant at –2.7 kg (P = .13), the data show.
Body-fat reduction at 52 weeks was –3.9 percentage points for exercise plus liraglutide as compared with placebo, or roughly twice the reductions seen in the exercise- and liraglutide-alone groups, the investigators said, adding that the combination preserved lean mass.
Reductions in hemoglobin A1c, which are generally thought to reduce diabetes risk, were reduced in both the liraglutide and liraglutide-exercise combination group, according to their report.
The research was supported in part by grants from the Novo Nordisk Foundation.
For persons with obesity who lost a substantial amount of weight on a low-calorie diet, the combination of exercise and medication significantly improved weight-loss maintenance, and more so than either strategy alone, according to results of a randomized, head-to-head trial.
A year after starting moderate to vigorous exercise coupled with liraglutide treatment, study participants had a weight loss 9.5 kg more than those who received placebo and usual activity, study results show.
Reductions in both weight and fat loss seen with exercise and liraglutide was roughly twice as much as what was achieved at 1 year with the strategies of liraglutide or exercise alone, according to authors of the study, which appears in the New England Journal of Medicine .
Although the findings may not apply to those who can’t or won’t perform moderate to vigorous exercise, the intervention in this study was nevertheless feasible in this group of persons with obesity who had a very low level of fitness, according to the authors.
Hope for healthy weight loss maintenance
Investigator Signe S. Torekov, PhD, said in an interview that these results provide hope that more-intensive exercise regimens, with or without medication, can be useful and well accepted among individuals struggling with obesity.
“When we started our study, we were told, ‘you are never going to have people with obesity exercising that much, and for that long’ – but people were actually very happy about the exercise,” said Dr. Torekov, a professor in the department of biomedical sciences at the University of Copenhagen.
“If you actually set up a program where people are monitored and you have a feedback system, then exercise is an excellent component in obesity treatment that should be much more actively used – not only for its weight-lowering component, but also for improving health and quality of life,” she said in an interview.
Weight-management specialist John D. Clark, MD, PhD, said results of this study can be used to help inform patients about how successful different strategies incorporating exercise and medication may be following initial weight loss.
“When patients plateau on a consistent, calorie-restricted dietary plan, we can educate them and manage expectations about what options may be available to them after their initial weight loss,” said Dr. Clark, of the University of Texas, Dallas.
“If the patient’s goal specifically is weight loss at all costs, then I may suggest, ‘let’s consider liraglutide or liraglutide in combination with exercise,’ ” he said in an interview. “Exercise improves body composition, even if it may not on its own be as successful in the next phase of their weight-loss journey, as shown in this study.”
Obesity and weight-loss challenges
Although it’s not uncommon for obese patients to lose a large amount of weight, keeping the weight off is frequently a challenge unless the patient follows a structured weight maintenance program, according to Dr. Torekov and coauthors.
The rapid weight regain seen in many obese patients could be a result of reductions in total energy expenditure or increased appetite. Exercise is one strategy to sustain weight loss, though according to the authors, very few studies have looked at exercise in isolation to quantify its contribution to maintenance.
Accordingly, the present study sought to determine whether exercise, medication, or the combination thereof works best to keep weight off.
The study incorporated liraglutide, a GLP-1 receptor agonist indicated for chronic weight management, along with a reduced-calorie diet and increased physical activity, in adults with elevated body mass index and at least one weight-related comorbidity.
The investigator-initiated phase 3 trial included 215 adults with a body mass index of 32-43. Individuals with type 2 diabetes were excluded. All participants followed an 8-week, low-calorie diet comprising 800 calories per day.
Participants who lost 5% or more of their body weight were then randomized to 1 year of exercise plus liraglutide, exercise plus placebo, usual activity plus liraglutide, or usual activity plus placebo.
The exercise program – which was structured but flexible, according to investigators – included group exercise sessions that incorporated 30 minutes of indoor cycling and 15 minutes of circuit training 2 days each week. Participants wore heart rate monitors during exercise to make sure they reached targets for moderate to vigorous intensity.
Instructors trained in exercise physiology planned and monitored individualized exercise programs for each participant in the exercise-medication or exercise-only arms of the study.
Participants in all groups attended 12 one-on-one consultations where body weight was measured and dietetic support was provided.
Weight loss with exercise and medication
Out of 215 individuals enrolled in the study, 195 lost at least 5% of body weight and continued on to the randomized portion, the investigators reported. During the diet phase, they lost a mean of 13.1 kg, translating into a 12% mean reduction in body weight.
The mean frequency of exercise was 2.4 times per week in the exercise-plus-medication group and 2.5 times per week in the exercise-only group. About one-third of the exercise took place in the group sessions, and there was no difference in relative intensity between group and individual exercise regimens, the investigators said.
Individuals in the exercise plus medication group continued to lose more weight, such that, at the end of 1 year, the weight loss decreased even further, by a mean of –3.4 kg. By contrast, weight increased by a mean of 6.1 kg for the placebo group, adding up to a treatment difference of –9.5 kg (95% confidence interval, –13.1 to –5.9; P < .001), according to the report.
That treatment effect was also seen, but more muted, in the exercise- and liraglutide-only groups, at –4.1 kg and –6.8 kg, respectively.
A significant treatment effect was observed for exercise plus liraglutide, compared with exercise alone, at –5.4 kg (P = .004), while the treatment effect for the combination versus liraglutide alone was not significant at –2.7 kg (P = .13), the data show.
Body-fat reduction at 52 weeks was –3.9 percentage points for exercise plus liraglutide as compared with placebo, or roughly twice the reductions seen in the exercise- and liraglutide-alone groups, the investigators said, adding that the combination preserved lean mass.
Reductions in hemoglobin A1c, which are generally thought to reduce diabetes risk, were reduced in both the liraglutide and liraglutide-exercise combination group, according to their report.
The research was supported in part by grants from the Novo Nordisk Foundation.
For persons with obesity who lost a substantial amount of weight on a low-calorie diet, the combination of exercise and medication significantly improved weight-loss maintenance, and more so than either strategy alone, according to results of a randomized, head-to-head trial.
A year after starting moderate to vigorous exercise coupled with liraglutide treatment, study participants had a weight loss 9.5 kg more than those who received placebo and usual activity, study results show.
Reductions in both weight and fat loss seen with exercise and liraglutide was roughly twice as much as what was achieved at 1 year with the strategies of liraglutide or exercise alone, according to authors of the study, which appears in the New England Journal of Medicine .
Although the findings may not apply to those who can’t or won’t perform moderate to vigorous exercise, the intervention in this study was nevertheless feasible in this group of persons with obesity who had a very low level of fitness, according to the authors.
Hope for healthy weight loss maintenance
Investigator Signe S. Torekov, PhD, said in an interview that these results provide hope that more-intensive exercise regimens, with or without medication, can be useful and well accepted among individuals struggling with obesity.
“When we started our study, we were told, ‘you are never going to have people with obesity exercising that much, and for that long’ – but people were actually very happy about the exercise,” said Dr. Torekov, a professor in the department of biomedical sciences at the University of Copenhagen.
“If you actually set up a program where people are monitored and you have a feedback system, then exercise is an excellent component in obesity treatment that should be much more actively used – not only for its weight-lowering component, but also for improving health and quality of life,” she said in an interview.
Weight-management specialist John D. Clark, MD, PhD, said results of this study can be used to help inform patients about how successful different strategies incorporating exercise and medication may be following initial weight loss.
“When patients plateau on a consistent, calorie-restricted dietary plan, we can educate them and manage expectations about what options may be available to them after their initial weight loss,” said Dr. Clark, of the University of Texas, Dallas.
“If the patient’s goal specifically is weight loss at all costs, then I may suggest, ‘let’s consider liraglutide or liraglutide in combination with exercise,’ ” he said in an interview. “Exercise improves body composition, even if it may not on its own be as successful in the next phase of their weight-loss journey, as shown in this study.”
Obesity and weight-loss challenges
Although it’s not uncommon for obese patients to lose a large amount of weight, keeping the weight off is frequently a challenge unless the patient follows a structured weight maintenance program, according to Dr. Torekov and coauthors.
The rapid weight regain seen in many obese patients could be a result of reductions in total energy expenditure or increased appetite. Exercise is one strategy to sustain weight loss, though according to the authors, very few studies have looked at exercise in isolation to quantify its contribution to maintenance.
Accordingly, the present study sought to determine whether exercise, medication, or the combination thereof works best to keep weight off.
The study incorporated liraglutide, a GLP-1 receptor agonist indicated for chronic weight management, along with a reduced-calorie diet and increased physical activity, in adults with elevated body mass index and at least one weight-related comorbidity.
The investigator-initiated phase 3 trial included 215 adults with a body mass index of 32-43. Individuals with type 2 diabetes were excluded. All participants followed an 8-week, low-calorie diet comprising 800 calories per day.
Participants who lost 5% or more of their body weight were then randomized to 1 year of exercise plus liraglutide, exercise plus placebo, usual activity plus liraglutide, or usual activity plus placebo.
The exercise program – which was structured but flexible, according to investigators – included group exercise sessions that incorporated 30 minutes of indoor cycling and 15 minutes of circuit training 2 days each week. Participants wore heart rate monitors during exercise to make sure they reached targets for moderate to vigorous intensity.
Instructors trained in exercise physiology planned and monitored individualized exercise programs for each participant in the exercise-medication or exercise-only arms of the study.
Participants in all groups attended 12 one-on-one consultations where body weight was measured and dietetic support was provided.
Weight loss with exercise and medication
Out of 215 individuals enrolled in the study, 195 lost at least 5% of body weight and continued on to the randomized portion, the investigators reported. During the diet phase, they lost a mean of 13.1 kg, translating into a 12% mean reduction in body weight.
The mean frequency of exercise was 2.4 times per week in the exercise-plus-medication group and 2.5 times per week in the exercise-only group. About one-third of the exercise took place in the group sessions, and there was no difference in relative intensity between group and individual exercise regimens, the investigators said.
Individuals in the exercise plus medication group continued to lose more weight, such that, at the end of 1 year, the weight loss decreased even further, by a mean of –3.4 kg. By contrast, weight increased by a mean of 6.1 kg for the placebo group, adding up to a treatment difference of –9.5 kg (95% confidence interval, –13.1 to –5.9; P < .001), according to the report.
That treatment effect was also seen, but more muted, in the exercise- and liraglutide-only groups, at –4.1 kg and –6.8 kg, respectively.
A significant treatment effect was observed for exercise plus liraglutide, compared with exercise alone, at –5.4 kg (P = .004), while the treatment effect for the combination versus liraglutide alone was not significant at –2.7 kg (P = .13), the data show.
Body-fat reduction at 52 weeks was –3.9 percentage points for exercise plus liraglutide as compared with placebo, or roughly twice the reductions seen in the exercise- and liraglutide-alone groups, the investigators said, adding that the combination preserved lean mass.
Reductions in hemoglobin A1c, which are generally thought to reduce diabetes risk, were reduced in both the liraglutide and liraglutide-exercise combination group, according to their report.
The research was supported in part by grants from the Novo Nordisk Foundation.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Look beyond liver biopsy for NAFLD diagnosis
Nonalcoholic fatty liver disease (NAFLD) was present in approximately two-thirds of patients who did not undergo a liver biopsy. These patients were more likely to be non-White and older, as well as have normal ALT levels, which shows potential gaps in knowledge about this population.
Data from studies of patients diagnosed with NAFLD that require biopsy among their inclusion criteria may be subject to selection and detection bias, wrote A. Sidney Barritt, MD, of the University of North Carolina at Chapel Hill, and colleagues. The researchers sought to compare characteristics of patients with NAFLD who were diagnosed using clinical criteria and those diagnosed via liver biopsy.
In a study published in Hepatology Communications, the researchers reviewed data from TARGET-NASH, a longitudinal, observational cohort study designed to follow patients with NAFLD in clinical practice to provide data on the effectiveness of treatments.
“TARGET-NASH represents a large cohort of NAFLD patients from multiple sites and can provide us with real world information on progression of disease in patients with NAFLD and particular risk factors that may be clinically relevant,” Zachary Henry, MD, MS, of the division of gastroenterology & hepatology at the University of Virginia Health System in Charlottesville, said in an interview. “This is one of the first studies from this database, and as time goes on, we will see more large-population data like this to answer specific questions for NAFLD patient.”
Surprising findings
The researchers included 3,474 patients aged 18 years and older who were enrolled in the TARGET-NASH study between Aug. 1, 2016, and March 4, 2019. The study participants were classified according to severity of liver disease: nonalcoholic fatty liver (30%), nonalcoholic steatohepatitis (37%), and NAFLD cirrhosis (33%).
A total of 766 patients were diagnosed with NASH based on clinical criteria without biopsy, and all met the criteria for abnormal ALT and steatosis based on imaging. In addition, these patients had at least one secondary diagnostic criteria: body mass index greater than 30 kg/m2 (74%), type 2 diabetes (42%), and dyslipidemia (54%). Significant independent predictors of liver biopsy included younger age, White race, female gender, diabetes, and elevated levels of ALT.
Elevated ALT increased the odds of liver biopsy by 14% per 10-point rise, according to the study. A machine learning model showed that non-White patients with ALT less than 69 IU/mL had a 6% chance of liver biopsy. By comparison, White patients had a 21% chance of biopsy with ALT between 29 IU/mL and 69 IU/mL that dropped to 10% if the ALT was less than 29 IU/mL.
However, ALT remains a “suboptimal surrogate” for disease severity, the researchers noted. “How a normal ALT is defined and how a normal ALT range may vary across different laboratories may play a role in its utility as a diagnostic tool as well.”
Dr. Henry was surprised by this finding: “With the advent of noninvasive measures of fibrosis, such as the NAFLD fibrosis score, Fibrosis-4, and transient elastography, I thought these would have a more significant role in that decision as opposed to ALT levels.”
Notably, mental health diagnoses accounted for nearly half (49%) of comorbid conditions, followed by cardiovascular disease (19%), and osteoarthritis (10%). The prevalence of these conditions emphasizes the challenges of managing patients with NAFLD with diet and exercise alone because mental and physical problems may impede progress, the researchers wrote.
The study findings were limited by several factors including the inability to determine health care provider intent, as well as undocumented factors related to patients and providers that might influence a biopsy decision, such as assessment of disease severity, the researchers noted. In addition, they noted that the mostly White study population treated in specialty settings might not generalize to other populations or primary care.
However, the findings are strengthened by the large study population and real-world setting, the researchers emphasized. “These data provide context for the selection bias that may be present in many registries and randomized, controlled trials of therapies for NAFLD, where biopsy is required for inclusion,” and show potential knowledge gaps about the patient population less likely to undergo biopsy.
Knowledge gaps and implications
The study is important because of the need to identify patient factors that predict histologic versus clinical diagnosis of NAFLD as the number of patient registries and clinical trials for NAFLD increase, Bubu Banini, MD, of Yale University, New Haven, Conn., said in an interview. “This information helps to elucidate selection and ascertainment bias and place findings from NAFLD registries and clinical trials into context.”
Dr. Banini said that some of the findings were to be expected, while others were not.
“Historically, males and non-Whites are less likely to participate in registries and clinical trials, compared to females and Whites. However, I was surprised to find that these discrepancies further paralleled the likelihood of undergoing liver biopsy even among those who chose to participate. In addition, while mental health disorders (such as anxiety and depression) are a fairly prevalent comorbidity in patients with NAFLD, I was surprised to find that NAFLD patients with mental health disorders were more likely to undergo liver biopsy compared to those without these disorders. I would have expected the reverse,” he noted.
“These findings highlight the gaps in knowledge regarding the impact of demographic and psychosocial factors on choice and assess to care among patients with NAFLD, and the need for further studies to address these gaps,” she emphasized.
“A number of [studies] such as TARGET-NASH are doing away with the requirement for liver biopsy for participation; hence, it is less likely that selection bias related to liver biopsy would be a problem in these [studies] if clinical diagnosis is considered as a surrogate for histological diagnosis,” Dr. Banini added.
“On the contrary, many NAFLD clinical trials require liver biopsy for inclusion.” As nicely demonstrated in the current study, “this inclusion criterion may introduce selection bias,” she said. “Awareness of potential biases would hopefully inform the design and recruitment strategy for registries and clinical trials in order to overcome these issues.”
“I think the results of this study may actually point to a larger issue within medicine in general, which is a difference in care provided to minority communities,” Dr. Henry said. “Whether this is intentional, related to unconscious bias on the part of providers, or related to a significant mistrust between minority communities and their health care providers is unclear but certainly needs to be addressed.”
He noted that the purpose of TARGET-NASH is to enroll all patients with NAFLD regardless of biopsy. “Over time, as we have more data on these patients, we will have a better understanding of both diagnostic and therapeutic decisions in patients with NAFLD.”
The study was supported by Target RWE, sponsor of the TARGET-NASH study. TARGET-NASH is a collaboration of academic and community investigators and the pharmaceutical industry. Lead author Dr. Barritt had no financial conflicts to disclose, but many study coauthors disclosed relationships with multiple pharmaceutical companies, including those involved in the TARGET-NASH study. Dr. Banini currently serves on the NASH advisory board for Boehringer Ingelheim. Dr. Henry reported no disclosures, although his institution is one of the enrollment sites for TARGET-NASH.
Nonalcoholic fatty liver disease (NAFLD) was present in approximately two-thirds of patients who did not undergo a liver biopsy. These patients were more likely to be non-White and older, as well as have normal ALT levels, which shows potential gaps in knowledge about this population.
Data from studies of patients diagnosed with NAFLD that require biopsy among their inclusion criteria may be subject to selection and detection bias, wrote A. Sidney Barritt, MD, of the University of North Carolina at Chapel Hill, and colleagues. The researchers sought to compare characteristics of patients with NAFLD who were diagnosed using clinical criteria and those diagnosed via liver biopsy.
In a study published in Hepatology Communications, the researchers reviewed data from TARGET-NASH, a longitudinal, observational cohort study designed to follow patients with NAFLD in clinical practice to provide data on the effectiveness of treatments.
“TARGET-NASH represents a large cohort of NAFLD patients from multiple sites and can provide us with real world information on progression of disease in patients with NAFLD and particular risk factors that may be clinically relevant,” Zachary Henry, MD, MS, of the division of gastroenterology & hepatology at the University of Virginia Health System in Charlottesville, said in an interview. “This is one of the first studies from this database, and as time goes on, we will see more large-population data like this to answer specific questions for NAFLD patient.”
Surprising findings
The researchers included 3,474 patients aged 18 years and older who were enrolled in the TARGET-NASH study between Aug. 1, 2016, and March 4, 2019. The study participants were classified according to severity of liver disease: nonalcoholic fatty liver (30%), nonalcoholic steatohepatitis (37%), and NAFLD cirrhosis (33%).
A total of 766 patients were diagnosed with NASH based on clinical criteria without biopsy, and all met the criteria for abnormal ALT and steatosis based on imaging. In addition, these patients had at least one secondary diagnostic criteria: body mass index greater than 30 kg/m2 (74%), type 2 diabetes (42%), and dyslipidemia (54%). Significant independent predictors of liver biopsy included younger age, White race, female gender, diabetes, and elevated levels of ALT.
Elevated ALT increased the odds of liver biopsy by 14% per 10-point rise, according to the study. A machine learning model showed that non-White patients with ALT less than 69 IU/mL had a 6% chance of liver biopsy. By comparison, White patients had a 21% chance of biopsy with ALT between 29 IU/mL and 69 IU/mL that dropped to 10% if the ALT was less than 29 IU/mL.
However, ALT remains a “suboptimal surrogate” for disease severity, the researchers noted. “How a normal ALT is defined and how a normal ALT range may vary across different laboratories may play a role in its utility as a diagnostic tool as well.”
Dr. Henry was surprised by this finding: “With the advent of noninvasive measures of fibrosis, such as the NAFLD fibrosis score, Fibrosis-4, and transient elastography, I thought these would have a more significant role in that decision as opposed to ALT levels.”
Notably, mental health diagnoses accounted for nearly half (49%) of comorbid conditions, followed by cardiovascular disease (19%), and osteoarthritis (10%). The prevalence of these conditions emphasizes the challenges of managing patients with NAFLD with diet and exercise alone because mental and physical problems may impede progress, the researchers wrote.
The study findings were limited by several factors including the inability to determine health care provider intent, as well as undocumented factors related to patients and providers that might influence a biopsy decision, such as assessment of disease severity, the researchers noted. In addition, they noted that the mostly White study population treated in specialty settings might not generalize to other populations or primary care.
However, the findings are strengthened by the large study population and real-world setting, the researchers emphasized. “These data provide context for the selection bias that may be present in many registries and randomized, controlled trials of therapies for NAFLD, where biopsy is required for inclusion,” and show potential knowledge gaps about the patient population less likely to undergo biopsy.
Knowledge gaps and implications
The study is important because of the need to identify patient factors that predict histologic versus clinical diagnosis of NAFLD as the number of patient registries and clinical trials for NAFLD increase, Bubu Banini, MD, of Yale University, New Haven, Conn., said in an interview. “This information helps to elucidate selection and ascertainment bias and place findings from NAFLD registries and clinical trials into context.”
Dr. Banini said that some of the findings were to be expected, while others were not.
“Historically, males and non-Whites are less likely to participate in registries and clinical trials, compared to females and Whites. However, I was surprised to find that these discrepancies further paralleled the likelihood of undergoing liver biopsy even among those who chose to participate. In addition, while mental health disorders (such as anxiety and depression) are a fairly prevalent comorbidity in patients with NAFLD, I was surprised to find that NAFLD patients with mental health disorders were more likely to undergo liver biopsy compared to those without these disorders. I would have expected the reverse,” he noted.
“These findings highlight the gaps in knowledge regarding the impact of demographic and psychosocial factors on choice and assess to care among patients with NAFLD, and the need for further studies to address these gaps,” she emphasized.
“A number of [studies] such as TARGET-NASH are doing away with the requirement for liver biopsy for participation; hence, it is less likely that selection bias related to liver biopsy would be a problem in these [studies] if clinical diagnosis is considered as a surrogate for histological diagnosis,” Dr. Banini added.
“On the contrary, many NAFLD clinical trials require liver biopsy for inclusion.” As nicely demonstrated in the current study, “this inclusion criterion may introduce selection bias,” she said. “Awareness of potential biases would hopefully inform the design and recruitment strategy for registries and clinical trials in order to overcome these issues.”
“I think the results of this study may actually point to a larger issue within medicine in general, which is a difference in care provided to minority communities,” Dr. Henry said. “Whether this is intentional, related to unconscious bias on the part of providers, or related to a significant mistrust between minority communities and their health care providers is unclear but certainly needs to be addressed.”
He noted that the purpose of TARGET-NASH is to enroll all patients with NAFLD regardless of biopsy. “Over time, as we have more data on these patients, we will have a better understanding of both diagnostic and therapeutic decisions in patients with NAFLD.”
The study was supported by Target RWE, sponsor of the TARGET-NASH study. TARGET-NASH is a collaboration of academic and community investigators and the pharmaceutical industry. Lead author Dr. Barritt had no financial conflicts to disclose, but many study coauthors disclosed relationships with multiple pharmaceutical companies, including those involved in the TARGET-NASH study. Dr. Banini currently serves on the NASH advisory board for Boehringer Ingelheim. Dr. Henry reported no disclosures, although his institution is one of the enrollment sites for TARGET-NASH.
Nonalcoholic fatty liver disease (NAFLD) was present in approximately two-thirds of patients who did not undergo a liver biopsy. These patients were more likely to be non-White and older, as well as have normal ALT levels, which shows potential gaps in knowledge about this population.
Data from studies of patients diagnosed with NAFLD that require biopsy among their inclusion criteria may be subject to selection and detection bias, wrote A. Sidney Barritt, MD, of the University of North Carolina at Chapel Hill, and colleagues. The researchers sought to compare characteristics of patients with NAFLD who were diagnosed using clinical criteria and those diagnosed via liver biopsy.
In a study published in Hepatology Communications, the researchers reviewed data from TARGET-NASH, a longitudinal, observational cohort study designed to follow patients with NAFLD in clinical practice to provide data on the effectiveness of treatments.
“TARGET-NASH represents a large cohort of NAFLD patients from multiple sites and can provide us with real world information on progression of disease in patients with NAFLD and particular risk factors that may be clinically relevant,” Zachary Henry, MD, MS, of the division of gastroenterology & hepatology at the University of Virginia Health System in Charlottesville, said in an interview. “This is one of the first studies from this database, and as time goes on, we will see more large-population data like this to answer specific questions for NAFLD patient.”
Surprising findings
The researchers included 3,474 patients aged 18 years and older who were enrolled in the TARGET-NASH study between Aug. 1, 2016, and March 4, 2019. The study participants were classified according to severity of liver disease: nonalcoholic fatty liver (30%), nonalcoholic steatohepatitis (37%), and NAFLD cirrhosis (33%).
A total of 766 patients were diagnosed with NASH based on clinical criteria without biopsy, and all met the criteria for abnormal ALT and steatosis based on imaging. In addition, these patients had at least one secondary diagnostic criteria: body mass index greater than 30 kg/m2 (74%), type 2 diabetes (42%), and dyslipidemia (54%). Significant independent predictors of liver biopsy included younger age, White race, female gender, diabetes, and elevated levels of ALT.
Elevated ALT increased the odds of liver biopsy by 14% per 10-point rise, according to the study. A machine learning model showed that non-White patients with ALT less than 69 IU/mL had a 6% chance of liver biopsy. By comparison, White patients had a 21% chance of biopsy with ALT between 29 IU/mL and 69 IU/mL that dropped to 10% if the ALT was less than 29 IU/mL.
However, ALT remains a “suboptimal surrogate” for disease severity, the researchers noted. “How a normal ALT is defined and how a normal ALT range may vary across different laboratories may play a role in its utility as a diagnostic tool as well.”
Dr. Henry was surprised by this finding: “With the advent of noninvasive measures of fibrosis, such as the NAFLD fibrosis score, Fibrosis-4, and transient elastography, I thought these would have a more significant role in that decision as opposed to ALT levels.”
Notably, mental health diagnoses accounted for nearly half (49%) of comorbid conditions, followed by cardiovascular disease (19%), and osteoarthritis (10%). The prevalence of these conditions emphasizes the challenges of managing patients with NAFLD with diet and exercise alone because mental and physical problems may impede progress, the researchers wrote.
The study findings were limited by several factors including the inability to determine health care provider intent, as well as undocumented factors related to patients and providers that might influence a biopsy decision, such as assessment of disease severity, the researchers noted. In addition, they noted that the mostly White study population treated in specialty settings might not generalize to other populations or primary care.
However, the findings are strengthened by the large study population and real-world setting, the researchers emphasized. “These data provide context for the selection bias that may be present in many registries and randomized, controlled trials of therapies for NAFLD, where biopsy is required for inclusion,” and show potential knowledge gaps about the patient population less likely to undergo biopsy.
Knowledge gaps and implications
The study is important because of the need to identify patient factors that predict histologic versus clinical diagnosis of NAFLD as the number of patient registries and clinical trials for NAFLD increase, Bubu Banini, MD, of Yale University, New Haven, Conn., said in an interview. “This information helps to elucidate selection and ascertainment bias and place findings from NAFLD registries and clinical trials into context.”
Dr. Banini said that some of the findings were to be expected, while others were not.
“Historically, males and non-Whites are less likely to participate in registries and clinical trials, compared to females and Whites. However, I was surprised to find that these discrepancies further paralleled the likelihood of undergoing liver biopsy even among those who chose to participate. In addition, while mental health disorders (such as anxiety and depression) are a fairly prevalent comorbidity in patients with NAFLD, I was surprised to find that NAFLD patients with mental health disorders were more likely to undergo liver biopsy compared to those without these disorders. I would have expected the reverse,” he noted.
“These findings highlight the gaps in knowledge regarding the impact of demographic and psychosocial factors on choice and assess to care among patients with NAFLD, and the need for further studies to address these gaps,” she emphasized.
“A number of [studies] such as TARGET-NASH are doing away with the requirement for liver biopsy for participation; hence, it is less likely that selection bias related to liver biopsy would be a problem in these [studies] if clinical diagnosis is considered as a surrogate for histological diagnosis,” Dr. Banini added.
“On the contrary, many NAFLD clinical trials require liver biopsy for inclusion.” As nicely demonstrated in the current study, “this inclusion criterion may introduce selection bias,” she said. “Awareness of potential biases would hopefully inform the design and recruitment strategy for registries and clinical trials in order to overcome these issues.”
“I think the results of this study may actually point to a larger issue within medicine in general, which is a difference in care provided to minority communities,” Dr. Henry said. “Whether this is intentional, related to unconscious bias on the part of providers, or related to a significant mistrust between minority communities and their health care providers is unclear but certainly needs to be addressed.”
He noted that the purpose of TARGET-NASH is to enroll all patients with NAFLD regardless of biopsy. “Over time, as we have more data on these patients, we will have a better understanding of both diagnostic and therapeutic decisions in patients with NAFLD.”
The study was supported by Target RWE, sponsor of the TARGET-NASH study. TARGET-NASH is a collaboration of academic and community investigators and the pharmaceutical industry. Lead author Dr. Barritt had no financial conflicts to disclose, but many study coauthors disclosed relationships with multiple pharmaceutical companies, including those involved in the TARGET-NASH study. Dr. Banini currently serves on the NASH advisory board for Boehringer Ingelheim. Dr. Henry reported no disclosures, although his institution is one of the enrollment sites for TARGET-NASH.
FROM HEPATOLOGY COMMUNICATIONS
Weight-related COVID-19 severity starts in normal BMI range, especially in young
The risk of severe outcomes with COVID-19 increases with excess weight in a linear manner beginning in normal body mass index ranges, with the effect apparently independent of obesity-related diseases such as diabetes, and stronger among younger people and Black persons, new research shows.
“Even a small increase in body mass index above 23 kg/m² is a risk factor for adverse outcomes after infection with SARS-CoV-2,” the authors reported.
“Excess weight is a modifiable risk factor and investment in the treatment of overweight and obesity, and long-term preventive strategies could help reduce the severity of COVID-19 disease,” they wrote.
The findings shed important new light in the ongoing efforts to understand COVID-19 effects, Krishnan Bhaskaran, PhD, said in an interview.
“These results confirm and add detail to the established links between overweight and obesity and COVID-19, and also add new information on risks among people with low BMI levels,” said Dr. Bhaskaran, an epidemiologist at the London School of Hygiene & Tropical Medicine, who authored an accompanying editorial.
Obesity has been well established as a major risk factor for poor outcomes among people with COVID-19; however, less is known about the risk of severe outcomes over the broader spectrum of excess weight, and its relationship with other factors.
For the prospective, community-based study, Carmen Piernas, PhD, of the University of Oxford (England) and colleagues evaluated data on nearly 7 million individuals registered in the U.K. QResearch database during Jan. 24–April 30, 2020.
Overall, patients had a mean BMI of 27 kg/m². Among them, 13,503 (.20%) were admitted to the hospital during the study period, 1,601 (.02%) were admitted to an ICU and 5,479 (.08%) died after testing positive for SARS-CoV-2.
Risk rises from BMI of 23 kg/m²
In looking at the risk of hospital admission with COVID-19, the authors found a J-shaped relationship with BMI, with the risk increased with a BMI of 20 kg/m² or lower, as well as an increased risk beginning with a BMI of 23 kg/m² – considered normal weight – or higher (hazard ratio, 1.05).
The risk of death from COVID-19 was also J-shaped, however the association with increases in BMI started higher – at 28 kg/m² (adjusted HR 1.04).
In terms of the risk of ICU admission with COVID-19, the curve was not J-shaped, with just a linear association of admission with increasing BMI beginning at 23 kg/m2 (adjusted HR 1.10).
“It was surprising to see that the lowest risk of severe COVID-19 was found at a BMI of 23, and each extra BMI unit was associated with significantly higher risk, but we don’t really know yet what the reason is for this,” Dr. Piernas said in an interview.
The association between increasing BMI and risk of hospital admission for COVID-19 beginning at a BMI of 23 kg/m² was more significant among younger people aged 20-39 years than in those aged 80-100 years, with an adjusted HR for hospital admission per BMI unit above 23 kg/m² of 1.09 versus 1.01 (P < .0001).
In addition, the risk associated with BMI and hospital admission was stronger in people who were Black, compared with those who were White (1.07 vs. 1.04), as was the risk of death due to COVID-19 (1.08 vs. 1.04; P < .0001 for both).
“For the risk of death, Blacks have an 8% higher risk with each extra BMI unit, whereas Whites have a 4% increase, which is half the risk,” Dr. Piernas said.
Notably, the increased risks of hospital admission and ICU due to COVID-19 seen with increases in BMI were slightly lower among people with type 2 diabetes, hypertension, and cardiovascular disease compared with patients who did not have those comorbidities, suggesting the association with BMI is not explained by those risk factors.
Dr. Piernas speculated that the effect could reflect that people with diabetes or cardiovascular disease already have a preexisting condition which makes them more susceptible to SARS-CoV-2.
Hence, “the association with BMI in this group may not be as strong as the association found among those without those conditions, in which BMI explains a higher proportion of this increased risk, given the absence of these preexisting conditions.”
Similarly, the effect of BMI on COVID-19 outcomes in younger patients may appear stronger because their rates of other comorbidities are much lower than in older patients.
“Among older people, preexisting conditions and perhaps a weaker immune system may explain their much higher rates of severe COVID outcomes,” Dr. Piernas noted.
Furthermore, older patients may have frailty and high comorbidities that could explain their lower rates of ICU admission with COVID-19, Dr. Bhaskaran added in further comments.
The findings overall underscore that excess weight can represent a risk in COVID-19 outcomes that is, importantly, modifiable, and “suggest that supporting people to reach and maintain a healthy weight is likely to help people reduce their risk of experiencing severe outcomes from this disease, now or in any future waves,” he concluded.
Dr. Piernas and Dr. Bhaskaran had no disclosures to report. Coauthors’ disclosures are detailed in the published study.
The risk of severe outcomes with COVID-19 increases with excess weight in a linear manner beginning in normal body mass index ranges, with the effect apparently independent of obesity-related diseases such as diabetes, and stronger among younger people and Black persons, new research shows.
“Even a small increase in body mass index above 23 kg/m² is a risk factor for adverse outcomes after infection with SARS-CoV-2,” the authors reported.
“Excess weight is a modifiable risk factor and investment in the treatment of overweight and obesity, and long-term preventive strategies could help reduce the severity of COVID-19 disease,” they wrote.
The findings shed important new light in the ongoing efforts to understand COVID-19 effects, Krishnan Bhaskaran, PhD, said in an interview.
“These results confirm and add detail to the established links between overweight and obesity and COVID-19, and also add new information on risks among people with low BMI levels,” said Dr. Bhaskaran, an epidemiologist at the London School of Hygiene & Tropical Medicine, who authored an accompanying editorial.
Obesity has been well established as a major risk factor for poor outcomes among people with COVID-19; however, less is known about the risk of severe outcomes over the broader spectrum of excess weight, and its relationship with other factors.
For the prospective, community-based study, Carmen Piernas, PhD, of the University of Oxford (England) and colleagues evaluated data on nearly 7 million individuals registered in the U.K. QResearch database during Jan. 24–April 30, 2020.
Overall, patients had a mean BMI of 27 kg/m². Among them, 13,503 (.20%) were admitted to the hospital during the study period, 1,601 (.02%) were admitted to an ICU and 5,479 (.08%) died after testing positive for SARS-CoV-2.
Risk rises from BMI of 23 kg/m²
In looking at the risk of hospital admission with COVID-19, the authors found a J-shaped relationship with BMI, with the risk increased with a BMI of 20 kg/m² or lower, as well as an increased risk beginning with a BMI of 23 kg/m² – considered normal weight – or higher (hazard ratio, 1.05).
The risk of death from COVID-19 was also J-shaped, however the association with increases in BMI started higher – at 28 kg/m² (adjusted HR 1.04).
In terms of the risk of ICU admission with COVID-19, the curve was not J-shaped, with just a linear association of admission with increasing BMI beginning at 23 kg/m2 (adjusted HR 1.10).
“It was surprising to see that the lowest risk of severe COVID-19 was found at a BMI of 23, and each extra BMI unit was associated with significantly higher risk, but we don’t really know yet what the reason is for this,” Dr. Piernas said in an interview.
The association between increasing BMI and risk of hospital admission for COVID-19 beginning at a BMI of 23 kg/m² was more significant among younger people aged 20-39 years than in those aged 80-100 years, with an adjusted HR for hospital admission per BMI unit above 23 kg/m² of 1.09 versus 1.01 (P < .0001).
In addition, the risk associated with BMI and hospital admission was stronger in people who were Black, compared with those who were White (1.07 vs. 1.04), as was the risk of death due to COVID-19 (1.08 vs. 1.04; P < .0001 for both).
“For the risk of death, Blacks have an 8% higher risk with each extra BMI unit, whereas Whites have a 4% increase, which is half the risk,” Dr. Piernas said.
Notably, the increased risks of hospital admission and ICU due to COVID-19 seen with increases in BMI were slightly lower among people with type 2 diabetes, hypertension, and cardiovascular disease compared with patients who did not have those comorbidities, suggesting the association with BMI is not explained by those risk factors.
Dr. Piernas speculated that the effect could reflect that people with diabetes or cardiovascular disease already have a preexisting condition which makes them more susceptible to SARS-CoV-2.
Hence, “the association with BMI in this group may not be as strong as the association found among those without those conditions, in which BMI explains a higher proportion of this increased risk, given the absence of these preexisting conditions.”
Similarly, the effect of BMI on COVID-19 outcomes in younger patients may appear stronger because their rates of other comorbidities are much lower than in older patients.
“Among older people, preexisting conditions and perhaps a weaker immune system may explain their much higher rates of severe COVID outcomes,” Dr. Piernas noted.
Furthermore, older patients may have frailty and high comorbidities that could explain their lower rates of ICU admission with COVID-19, Dr. Bhaskaran added in further comments.
The findings overall underscore that excess weight can represent a risk in COVID-19 outcomes that is, importantly, modifiable, and “suggest that supporting people to reach and maintain a healthy weight is likely to help people reduce their risk of experiencing severe outcomes from this disease, now or in any future waves,” he concluded.
Dr. Piernas and Dr. Bhaskaran had no disclosures to report. Coauthors’ disclosures are detailed in the published study.
The risk of severe outcomes with COVID-19 increases with excess weight in a linear manner beginning in normal body mass index ranges, with the effect apparently independent of obesity-related diseases such as diabetes, and stronger among younger people and Black persons, new research shows.
“Even a small increase in body mass index above 23 kg/m² is a risk factor for adverse outcomes after infection with SARS-CoV-2,” the authors reported.
“Excess weight is a modifiable risk factor and investment in the treatment of overweight and obesity, and long-term preventive strategies could help reduce the severity of COVID-19 disease,” they wrote.
The findings shed important new light in the ongoing efforts to understand COVID-19 effects, Krishnan Bhaskaran, PhD, said in an interview.
“These results confirm and add detail to the established links between overweight and obesity and COVID-19, and also add new information on risks among people with low BMI levels,” said Dr. Bhaskaran, an epidemiologist at the London School of Hygiene & Tropical Medicine, who authored an accompanying editorial.
Obesity has been well established as a major risk factor for poor outcomes among people with COVID-19; however, less is known about the risk of severe outcomes over the broader spectrum of excess weight, and its relationship with other factors.
For the prospective, community-based study, Carmen Piernas, PhD, of the University of Oxford (England) and colleagues evaluated data on nearly 7 million individuals registered in the U.K. QResearch database during Jan. 24–April 30, 2020.
Overall, patients had a mean BMI of 27 kg/m². Among them, 13,503 (.20%) were admitted to the hospital during the study period, 1,601 (.02%) were admitted to an ICU and 5,479 (.08%) died after testing positive for SARS-CoV-2.
Risk rises from BMI of 23 kg/m²
In looking at the risk of hospital admission with COVID-19, the authors found a J-shaped relationship with BMI, with the risk increased with a BMI of 20 kg/m² or lower, as well as an increased risk beginning with a BMI of 23 kg/m² – considered normal weight – or higher (hazard ratio, 1.05).
The risk of death from COVID-19 was also J-shaped, however the association with increases in BMI started higher – at 28 kg/m² (adjusted HR 1.04).
In terms of the risk of ICU admission with COVID-19, the curve was not J-shaped, with just a linear association of admission with increasing BMI beginning at 23 kg/m2 (adjusted HR 1.10).
“It was surprising to see that the lowest risk of severe COVID-19 was found at a BMI of 23, and each extra BMI unit was associated with significantly higher risk, but we don’t really know yet what the reason is for this,” Dr. Piernas said in an interview.
The association between increasing BMI and risk of hospital admission for COVID-19 beginning at a BMI of 23 kg/m² was more significant among younger people aged 20-39 years than in those aged 80-100 years, with an adjusted HR for hospital admission per BMI unit above 23 kg/m² of 1.09 versus 1.01 (P < .0001).
In addition, the risk associated with BMI and hospital admission was stronger in people who were Black, compared with those who were White (1.07 vs. 1.04), as was the risk of death due to COVID-19 (1.08 vs. 1.04; P < .0001 for both).
“For the risk of death, Blacks have an 8% higher risk with each extra BMI unit, whereas Whites have a 4% increase, which is half the risk,” Dr. Piernas said.
Notably, the increased risks of hospital admission and ICU due to COVID-19 seen with increases in BMI were slightly lower among people with type 2 diabetes, hypertension, and cardiovascular disease compared with patients who did not have those comorbidities, suggesting the association with BMI is not explained by those risk factors.
Dr. Piernas speculated that the effect could reflect that people with diabetes or cardiovascular disease already have a preexisting condition which makes them more susceptible to SARS-CoV-2.
Hence, “the association with BMI in this group may not be as strong as the association found among those without those conditions, in which BMI explains a higher proportion of this increased risk, given the absence of these preexisting conditions.”
Similarly, the effect of BMI on COVID-19 outcomes in younger patients may appear stronger because their rates of other comorbidities are much lower than in older patients.
“Among older people, preexisting conditions and perhaps a weaker immune system may explain their much higher rates of severe COVID outcomes,” Dr. Piernas noted.
Furthermore, older patients may have frailty and high comorbidities that could explain their lower rates of ICU admission with COVID-19, Dr. Bhaskaran added in further comments.
The findings overall underscore that excess weight can represent a risk in COVID-19 outcomes that is, importantly, modifiable, and “suggest that supporting people to reach and maintain a healthy weight is likely to help people reduce their risk of experiencing severe outcomes from this disease, now or in any future waves,” he concluded.
Dr. Piernas and Dr. Bhaskaran had no disclosures to report. Coauthors’ disclosures are detailed in the published study.
FROM LANCET DIABETES & ENDOCRINOLOGY
Being overweight ups risk of severe COVID-19 in hospital
In a global meta-analysis of more than 7,000 patients who were hospitalized with COVID-19, individuals with overweight or obesity were more likely to need respiratory support but were not more likely to die in the hospital, compared to individuals of normal weight.
Compared to patients without diabetes, those with diabetes had higher odds of needing invasive respiratory support (with intubation) but not for needing noninvasive respiratory support or of dying in the hospital.
“Surprisingly,” among patients with diabetes, being overweight or having obesity did not further increase the odds of any of these outcomes, the researchers wrote. The finding needs to be confirmed in larger studies, they said, because the sample sizes in these subanalyses were small and the confidence intervals were large.
The study by Danielle K. Longmore, PhD, of Murdoch Children’s Research Institute (MCRI), Melbourne, and colleagues from the International BMI-COVID consortium, was published online April 15 in Diabetes Care.
This new research “adds to the known data on the associations between obesity and severe COVID-19 disease and extends these findings” to patients who are overweight and/or have diabetes, Dr. Longmore, a pediatric endocrinologist with a clinical and research interest in childhood and youth obesity, said in an interview.
Immunologist Siroon Bekkering, PhD, of Radboud University Medical Center, Nijmegen, the Netherlands, explained that never before have so much data of different types regarding obesity been combined in one large study. Dr. Bekkering is a coauthor of the article and was a principal investigator.
“Several national and international observations already showed the important role of overweight and obesity in a more severe COVID-19 course. This study adds to those observations by combining data from several countries with the possibility to look at the risk factors separately,” she said in a statement from her institution.
“Regardless of other risk factors (such as heart disease or diabetes), we now see that too high a BMI [body mass index] can actually lead to a more severe course in [coronavirus] infection,” she said.
Study implications: Data show that overweight, obesity add to risk
These latest findings highlight the urgent need to develop public health policies to address socioeconomic and psychological drivers of obesity, Dr. Longmore said.
“Although taking steps to address obesity in the short term is unlikely to have an immediate impact in the COVID-19 pandemic, it will likely reduce the disease burden in future viral pandemics and reduce risks of complications like heart disease and stroke,” she observed in a statement issued by MCRI.
Coauthor Kirsty R. Short, PhD, a research fellow at the University of Queensland, Brisbane, Australia, noted that “obesity is associated with numerous poor health outcomes, including increased risk of cardiometabolic and respiratory disease and more severe viral disease including influenza, dengue, and SARS-CoV-1.
“Given the large scale of this study,” she said, “we have conclusively shown that being overweight or obese are independent risk factors for worse outcomes in adults hospitalized with COVID-19.”
“At the moment, the World Health Organization has not had enough high-quality data to include being overweight or obese as a risk factor for severe COVID-19 disease,” added another author, David P. Burgner, PhD, a pediatric infectious diseases clinician scientist from MCRI.
“Our study should help inform decisions about which higher-risk groups should be vaccinated as a priority,” he observed.
Does being overweight up risk of worse COVID-19 outcomes?
About 13% of the world’s population are overweight, and 40% have obesity. There are wide between-country variations in these data, and about 90% of patients with type 2 diabetes are overweight or obese, the researchers noted.
The Organisation for Economic Co-operation and Development reported that the prevalence of obesity in 2016-2017 was 5.7% to 8.9% in Asia, 9.8% to 16.8% in Europe, 26.5% in South Africa, and 40.0% in the United States, they added.
Obesity is common and has emerged as an important risk factor for severe COVID-19. However, most previous studies of COVID-19 and elevated BMI were conducted in single centers and did not focus on patients with overweight.
To investigate, the researchers identified 7,244 patients (two-thirds were overweight or obese) who were hospitalized with COVID-19 in 69 hospitals (18 sites) in 11 countries from Jan. 17, 2020, to June 2, 2020.
Most patients were hospitalized with COVID-19 in the Netherlands (2,260), followed by New York City (1,682), Switzerland (920), St. Louis (805), Norway, Italy, China, South Africa, Indonesia, Denmark, Los Angeles, Austria, and Singapore.
Just over half (60%) of the individuals were male, and 52% were older than 65.
Overall, 34.8% were overweight, and 30.8% had obesity, but the average weight varied considerably between countries and sites.
Increased need for respiratory support, same mortality risk
Compared with patients with normal weight, patients who were overweight had a 44% increased risk of needing supplemental oxygen/noninvasive ventilation, and those with obesity had a 75% increased risk of this, after adjustment for age (< 65, ≥ 65), sex, hypertension, diabetes, or preexisting cardiovascular disease or respiratory conditions.
Patients who were overweight had a 22% increased risk of needing invasive (mechanical) ventilation, and those with obesity had a 73% increased risk of this, after multivariable adjustment.
Being overweight or having obesity was not associated with a significantly increased risk of dying in the hospital, however.
“In other viral respiratory infections, such as influenza, there is a similar pattern of increased requirement for ventilatory support but lower in-hospital mortality among individuals with obesity, when compared to those with normal range BMI,” Dr. Longmore noted. She said that larger studies are needed to further explore this finding regarding COVID-19.
Compared to patients without diabetes, those with diabetes had a 21% increased risk of requiring invasive ventilation, but they did not have an increased risk of needing noninvasive ventilation or of dying in the hospital.
As in previous studies, individuals who had cardiovascular and preexisting respiratory diseases were not at greater risk of needing oxygen or mechanical ventilation but were at increased risk for in-hospital death. Men had a greater risk of needing invasive mechanical ventilation, and individuals who were older than 65 had an increased risk of requiring oxygen or of dying in the hospital.
A living meta-analysis, call for more collaborators
“We consider this a ‘living meta-analysis’ and invite other centers to join us,” Dr. Longmore said. “We hope to update the analyses as more data are contributed.”
No specific project funded the study. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a global meta-analysis of more than 7,000 patients who were hospitalized with COVID-19, individuals with overweight or obesity were more likely to need respiratory support but were not more likely to die in the hospital, compared to individuals of normal weight.
Compared to patients without diabetes, those with diabetes had higher odds of needing invasive respiratory support (with intubation) but not for needing noninvasive respiratory support or of dying in the hospital.
“Surprisingly,” among patients with diabetes, being overweight or having obesity did not further increase the odds of any of these outcomes, the researchers wrote. The finding needs to be confirmed in larger studies, they said, because the sample sizes in these subanalyses were small and the confidence intervals were large.
The study by Danielle K. Longmore, PhD, of Murdoch Children’s Research Institute (MCRI), Melbourne, and colleagues from the International BMI-COVID consortium, was published online April 15 in Diabetes Care.
This new research “adds to the known data on the associations between obesity and severe COVID-19 disease and extends these findings” to patients who are overweight and/or have diabetes, Dr. Longmore, a pediatric endocrinologist with a clinical and research interest in childhood and youth obesity, said in an interview.
Immunologist Siroon Bekkering, PhD, of Radboud University Medical Center, Nijmegen, the Netherlands, explained that never before have so much data of different types regarding obesity been combined in one large study. Dr. Bekkering is a coauthor of the article and was a principal investigator.
“Several national and international observations already showed the important role of overweight and obesity in a more severe COVID-19 course. This study adds to those observations by combining data from several countries with the possibility to look at the risk factors separately,” she said in a statement from her institution.
“Regardless of other risk factors (such as heart disease or diabetes), we now see that too high a BMI [body mass index] can actually lead to a more severe course in [coronavirus] infection,” she said.
Study implications: Data show that overweight, obesity add to risk
These latest findings highlight the urgent need to develop public health policies to address socioeconomic and psychological drivers of obesity, Dr. Longmore said.
“Although taking steps to address obesity in the short term is unlikely to have an immediate impact in the COVID-19 pandemic, it will likely reduce the disease burden in future viral pandemics and reduce risks of complications like heart disease and stroke,” she observed in a statement issued by MCRI.
Coauthor Kirsty R. Short, PhD, a research fellow at the University of Queensland, Brisbane, Australia, noted that “obesity is associated with numerous poor health outcomes, including increased risk of cardiometabolic and respiratory disease and more severe viral disease including influenza, dengue, and SARS-CoV-1.
“Given the large scale of this study,” she said, “we have conclusively shown that being overweight or obese are independent risk factors for worse outcomes in adults hospitalized with COVID-19.”
“At the moment, the World Health Organization has not had enough high-quality data to include being overweight or obese as a risk factor for severe COVID-19 disease,” added another author, David P. Burgner, PhD, a pediatric infectious diseases clinician scientist from MCRI.
“Our study should help inform decisions about which higher-risk groups should be vaccinated as a priority,” he observed.
Does being overweight up risk of worse COVID-19 outcomes?
About 13% of the world’s population are overweight, and 40% have obesity. There are wide between-country variations in these data, and about 90% of patients with type 2 diabetes are overweight or obese, the researchers noted.
The Organisation for Economic Co-operation and Development reported that the prevalence of obesity in 2016-2017 was 5.7% to 8.9% in Asia, 9.8% to 16.8% in Europe, 26.5% in South Africa, and 40.0% in the United States, they added.
Obesity is common and has emerged as an important risk factor for severe COVID-19. However, most previous studies of COVID-19 and elevated BMI were conducted in single centers and did not focus on patients with overweight.
To investigate, the researchers identified 7,244 patients (two-thirds were overweight or obese) who were hospitalized with COVID-19 in 69 hospitals (18 sites) in 11 countries from Jan. 17, 2020, to June 2, 2020.
Most patients were hospitalized with COVID-19 in the Netherlands (2,260), followed by New York City (1,682), Switzerland (920), St. Louis (805), Norway, Italy, China, South Africa, Indonesia, Denmark, Los Angeles, Austria, and Singapore.
Just over half (60%) of the individuals were male, and 52% were older than 65.
Overall, 34.8% were overweight, and 30.8% had obesity, but the average weight varied considerably between countries and sites.
Increased need for respiratory support, same mortality risk
Compared with patients with normal weight, patients who were overweight had a 44% increased risk of needing supplemental oxygen/noninvasive ventilation, and those with obesity had a 75% increased risk of this, after adjustment for age (< 65, ≥ 65), sex, hypertension, diabetes, or preexisting cardiovascular disease or respiratory conditions.
Patients who were overweight had a 22% increased risk of needing invasive (mechanical) ventilation, and those with obesity had a 73% increased risk of this, after multivariable adjustment.
Being overweight or having obesity was not associated with a significantly increased risk of dying in the hospital, however.
“In other viral respiratory infections, such as influenza, there is a similar pattern of increased requirement for ventilatory support but lower in-hospital mortality among individuals with obesity, when compared to those with normal range BMI,” Dr. Longmore noted. She said that larger studies are needed to further explore this finding regarding COVID-19.
Compared to patients without diabetes, those with diabetes had a 21% increased risk of requiring invasive ventilation, but they did not have an increased risk of needing noninvasive ventilation or of dying in the hospital.
As in previous studies, individuals who had cardiovascular and preexisting respiratory diseases were not at greater risk of needing oxygen or mechanical ventilation but were at increased risk for in-hospital death. Men had a greater risk of needing invasive mechanical ventilation, and individuals who were older than 65 had an increased risk of requiring oxygen or of dying in the hospital.
A living meta-analysis, call for more collaborators
“We consider this a ‘living meta-analysis’ and invite other centers to join us,” Dr. Longmore said. “We hope to update the analyses as more data are contributed.”
No specific project funded the study. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a global meta-analysis of more than 7,000 patients who were hospitalized with COVID-19, individuals with overweight or obesity were more likely to need respiratory support but were not more likely to die in the hospital, compared to individuals of normal weight.
Compared to patients without diabetes, those with diabetes had higher odds of needing invasive respiratory support (with intubation) but not for needing noninvasive respiratory support or of dying in the hospital.
“Surprisingly,” among patients with diabetes, being overweight or having obesity did not further increase the odds of any of these outcomes, the researchers wrote. The finding needs to be confirmed in larger studies, they said, because the sample sizes in these subanalyses were small and the confidence intervals were large.
The study by Danielle K. Longmore, PhD, of Murdoch Children’s Research Institute (MCRI), Melbourne, and colleagues from the International BMI-COVID consortium, was published online April 15 in Diabetes Care.
This new research “adds to the known data on the associations between obesity and severe COVID-19 disease and extends these findings” to patients who are overweight and/or have diabetes, Dr. Longmore, a pediatric endocrinologist with a clinical and research interest in childhood and youth obesity, said in an interview.
Immunologist Siroon Bekkering, PhD, of Radboud University Medical Center, Nijmegen, the Netherlands, explained that never before have so much data of different types regarding obesity been combined in one large study. Dr. Bekkering is a coauthor of the article and was a principal investigator.
“Several national and international observations already showed the important role of overweight and obesity in a more severe COVID-19 course. This study adds to those observations by combining data from several countries with the possibility to look at the risk factors separately,” she said in a statement from her institution.
“Regardless of other risk factors (such as heart disease or diabetes), we now see that too high a BMI [body mass index] can actually lead to a more severe course in [coronavirus] infection,” she said.
Study implications: Data show that overweight, obesity add to risk
These latest findings highlight the urgent need to develop public health policies to address socioeconomic and psychological drivers of obesity, Dr. Longmore said.
“Although taking steps to address obesity in the short term is unlikely to have an immediate impact in the COVID-19 pandemic, it will likely reduce the disease burden in future viral pandemics and reduce risks of complications like heart disease and stroke,” she observed in a statement issued by MCRI.
Coauthor Kirsty R. Short, PhD, a research fellow at the University of Queensland, Brisbane, Australia, noted that “obesity is associated with numerous poor health outcomes, including increased risk of cardiometabolic and respiratory disease and more severe viral disease including influenza, dengue, and SARS-CoV-1.
“Given the large scale of this study,” she said, “we have conclusively shown that being overweight or obese are independent risk factors for worse outcomes in adults hospitalized with COVID-19.”
“At the moment, the World Health Organization has not had enough high-quality data to include being overweight or obese as a risk factor for severe COVID-19 disease,” added another author, David P. Burgner, PhD, a pediatric infectious diseases clinician scientist from MCRI.
“Our study should help inform decisions about which higher-risk groups should be vaccinated as a priority,” he observed.
Does being overweight up risk of worse COVID-19 outcomes?
About 13% of the world’s population are overweight, and 40% have obesity. There are wide between-country variations in these data, and about 90% of patients with type 2 diabetes are overweight or obese, the researchers noted.
The Organisation for Economic Co-operation and Development reported that the prevalence of obesity in 2016-2017 was 5.7% to 8.9% in Asia, 9.8% to 16.8% in Europe, 26.5% in South Africa, and 40.0% in the United States, they added.
Obesity is common and has emerged as an important risk factor for severe COVID-19. However, most previous studies of COVID-19 and elevated BMI were conducted in single centers and did not focus on patients with overweight.
To investigate, the researchers identified 7,244 patients (two-thirds were overweight or obese) who were hospitalized with COVID-19 in 69 hospitals (18 sites) in 11 countries from Jan. 17, 2020, to June 2, 2020.
Most patients were hospitalized with COVID-19 in the Netherlands (2,260), followed by New York City (1,682), Switzerland (920), St. Louis (805), Norway, Italy, China, South Africa, Indonesia, Denmark, Los Angeles, Austria, and Singapore.
Just over half (60%) of the individuals were male, and 52% were older than 65.
Overall, 34.8% were overweight, and 30.8% had obesity, but the average weight varied considerably between countries and sites.
Increased need for respiratory support, same mortality risk
Compared with patients with normal weight, patients who were overweight had a 44% increased risk of needing supplemental oxygen/noninvasive ventilation, and those with obesity had a 75% increased risk of this, after adjustment for age (< 65, ≥ 65), sex, hypertension, diabetes, or preexisting cardiovascular disease or respiratory conditions.
Patients who were overweight had a 22% increased risk of needing invasive (mechanical) ventilation, and those with obesity had a 73% increased risk of this, after multivariable adjustment.
Being overweight or having obesity was not associated with a significantly increased risk of dying in the hospital, however.
“In other viral respiratory infections, such as influenza, there is a similar pattern of increased requirement for ventilatory support but lower in-hospital mortality among individuals with obesity, when compared to those with normal range BMI,” Dr. Longmore noted. She said that larger studies are needed to further explore this finding regarding COVID-19.
Compared to patients without diabetes, those with diabetes had a 21% increased risk of requiring invasive ventilation, but they did not have an increased risk of needing noninvasive ventilation or of dying in the hospital.
As in previous studies, individuals who had cardiovascular and preexisting respiratory diseases were not at greater risk of needing oxygen or mechanical ventilation but were at increased risk for in-hospital death. Men had a greater risk of needing invasive mechanical ventilation, and individuals who were older than 65 had an increased risk of requiring oxygen or of dying in the hospital.
A living meta-analysis, call for more collaborators
“We consider this a ‘living meta-analysis’ and invite other centers to join us,” Dr. Longmore said. “We hope to update the analyses as more data are contributed.”
No specific project funded the study. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AHA statement flags CV risk of hormonal cancer therapies
Hormonal therapies for the treatment of hormone-dependent breast and prostate cancer could raise the risk for myocardial infarction and stroke, and patients need to be closely monitored to allow early detection and treatment of cardiovascular disease (CVD), the American Heart Association says in a new scientific statement.
“The statement provides data on the risks of each type of hormonal therapy so clinicians can use it as a guide to help manage cardiovascular risks during cancer treatment,” Tochi Okwuosa, DO, chair of the writing group, said in a news release.
“A team-based approach to patient care that includes the oncology team, cardiologist, primary care clinician, dietitian, endocrinologist, and other health care professionals as appropriate is needed to work with each patient to manage and reduce the increased risk of heart disease and strokes associated with hormonal therapy in breast and prostate cancer treatment,” said Dr. Okwuosa, director of cardio-oncology services, Rush University Medical Center, Chicago.
The scientific statement was published online April 26 in Circulation: Genomic and Precision Medicine.
Hormone-dependent cancers, such as prostate and breast cancer, are the most common noncutaneous cancers in the United States and around the world. As hormonal therapies have markedly improved survival in these patients, CVD has emerged as a leading cause illness and death.
The increased CVD burden might be explained by the increasing average age of cancer survivors, leading to higher rates of age-related CV risk factors and coronary artery disease.
The writing group reviewed existing evidence from observational studies and randomized controlled trials on the cardiovascular impact of anticancer hormonal therapies.
Among the key findings:
- In patients with breast cancer, has been shown to increase the risk for venous thromboembolic events, but to have somewhat protective to neutral effects on CVD risk burden and CVD events. Conversely, aromatase inhibitors have been shown to increase the risk for CVD risk factors and events, including MI and stroke.
- Androgen-deprivation therapy for prostate cancer appears to increase the risk for CV events, although gonadotrophin-releasing hormone (GnRH) antagonists are associated with a lower risk for CV events than are GnRH agonists. The oral antiandrogens appear to be associated with increased CVD risk as well, particularly when used for complete androgen blockade as combination GnRH/anti-androgen therapy.
- The duration of hormonal therapies has a significant impact on CVD risk; the longer patients receive hormonal therapy, the greater the risk. More research is needed to better define the risks associated with duration of treatment.
- The data are mixed on the impact of preexisting CV risk factors and CVD on CV events associated with hormonal therapy. Although the presence of baseline CV risk factors and CVD can increase CV events associated with aromatase inhibitors, it is not clear that tamoxifen does.
- Studies suggest that patients with prostate cancer and baseline CVD and CV risk factors have increased rates of CV events when treated with androgen-deprivation therapy.
- Although the prolonged use of some hormonal therapies worsens CV risk factors and , the effects of the duration of therapy on CV events are less clear.
The writing group noted that there are no definitive guidelines for the monitoring and management of hormonal therapy-related CVD risks.
The authors encourage clinicians to be alert for worsening CV problems in those with preexisting heart disease or risk factors, and to recognize that even patients without preexisting CV problems are at higher risk because of their exposure to hormonal therapies.
“For patients who have two or more cardiovascular risk factors, it is likely that referral to a cardiologist would be appropriate prior to beginning hormone treatment. For patients already receiving hormonal therapies, a discussion with the oncology team can help to determine if a cardiology referral is recommended,” Dr. Okwuosa said in the news release.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardio-Oncology Subcommittee of the Council on Clinical Cardiology and the Council on Genomic and Precision Medicine; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Council on Cardiovascular Radiology and Intervention.
The research had no commercial funding. Dr. Okwuosa has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Hormonal therapies for the treatment of hormone-dependent breast and prostate cancer could raise the risk for myocardial infarction and stroke, and patients need to be closely monitored to allow early detection and treatment of cardiovascular disease (CVD), the American Heart Association says in a new scientific statement.
“The statement provides data on the risks of each type of hormonal therapy so clinicians can use it as a guide to help manage cardiovascular risks during cancer treatment,” Tochi Okwuosa, DO, chair of the writing group, said in a news release.
“A team-based approach to patient care that includes the oncology team, cardiologist, primary care clinician, dietitian, endocrinologist, and other health care professionals as appropriate is needed to work with each patient to manage and reduce the increased risk of heart disease and strokes associated with hormonal therapy in breast and prostate cancer treatment,” said Dr. Okwuosa, director of cardio-oncology services, Rush University Medical Center, Chicago.
The scientific statement was published online April 26 in Circulation: Genomic and Precision Medicine.
Hormone-dependent cancers, such as prostate and breast cancer, are the most common noncutaneous cancers in the United States and around the world. As hormonal therapies have markedly improved survival in these patients, CVD has emerged as a leading cause illness and death.
The increased CVD burden might be explained by the increasing average age of cancer survivors, leading to higher rates of age-related CV risk factors and coronary artery disease.
The writing group reviewed existing evidence from observational studies and randomized controlled trials on the cardiovascular impact of anticancer hormonal therapies.
Among the key findings:
- In patients with breast cancer, has been shown to increase the risk for venous thromboembolic events, but to have somewhat protective to neutral effects on CVD risk burden and CVD events. Conversely, aromatase inhibitors have been shown to increase the risk for CVD risk factors and events, including MI and stroke.
- Androgen-deprivation therapy for prostate cancer appears to increase the risk for CV events, although gonadotrophin-releasing hormone (GnRH) antagonists are associated with a lower risk for CV events than are GnRH agonists. The oral antiandrogens appear to be associated with increased CVD risk as well, particularly when used for complete androgen blockade as combination GnRH/anti-androgen therapy.
- The duration of hormonal therapies has a significant impact on CVD risk; the longer patients receive hormonal therapy, the greater the risk. More research is needed to better define the risks associated with duration of treatment.
- The data are mixed on the impact of preexisting CV risk factors and CVD on CV events associated with hormonal therapy. Although the presence of baseline CV risk factors and CVD can increase CV events associated with aromatase inhibitors, it is not clear that tamoxifen does.
- Studies suggest that patients with prostate cancer and baseline CVD and CV risk factors have increased rates of CV events when treated with androgen-deprivation therapy.
- Although the prolonged use of some hormonal therapies worsens CV risk factors and , the effects of the duration of therapy on CV events are less clear.
The writing group noted that there are no definitive guidelines for the monitoring and management of hormonal therapy-related CVD risks.
The authors encourage clinicians to be alert for worsening CV problems in those with preexisting heart disease or risk factors, and to recognize that even patients without preexisting CV problems are at higher risk because of their exposure to hormonal therapies.
“For patients who have two or more cardiovascular risk factors, it is likely that referral to a cardiologist would be appropriate prior to beginning hormone treatment. For patients already receiving hormonal therapies, a discussion with the oncology team can help to determine if a cardiology referral is recommended,” Dr. Okwuosa said in the news release.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardio-Oncology Subcommittee of the Council on Clinical Cardiology and the Council on Genomic and Precision Medicine; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Council on Cardiovascular Radiology and Intervention.
The research had no commercial funding. Dr. Okwuosa has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Hormonal therapies for the treatment of hormone-dependent breast and prostate cancer could raise the risk for myocardial infarction and stroke, and patients need to be closely monitored to allow early detection and treatment of cardiovascular disease (CVD), the American Heart Association says in a new scientific statement.
“The statement provides data on the risks of each type of hormonal therapy so clinicians can use it as a guide to help manage cardiovascular risks during cancer treatment,” Tochi Okwuosa, DO, chair of the writing group, said in a news release.
“A team-based approach to patient care that includes the oncology team, cardiologist, primary care clinician, dietitian, endocrinologist, and other health care professionals as appropriate is needed to work with each patient to manage and reduce the increased risk of heart disease and strokes associated with hormonal therapy in breast and prostate cancer treatment,” said Dr. Okwuosa, director of cardio-oncology services, Rush University Medical Center, Chicago.
The scientific statement was published online April 26 in Circulation: Genomic and Precision Medicine.
Hormone-dependent cancers, such as prostate and breast cancer, are the most common noncutaneous cancers in the United States and around the world. As hormonal therapies have markedly improved survival in these patients, CVD has emerged as a leading cause illness and death.
The increased CVD burden might be explained by the increasing average age of cancer survivors, leading to higher rates of age-related CV risk factors and coronary artery disease.
The writing group reviewed existing evidence from observational studies and randomized controlled trials on the cardiovascular impact of anticancer hormonal therapies.
Among the key findings:
- In patients with breast cancer, has been shown to increase the risk for venous thromboembolic events, but to have somewhat protective to neutral effects on CVD risk burden and CVD events. Conversely, aromatase inhibitors have been shown to increase the risk for CVD risk factors and events, including MI and stroke.
- Androgen-deprivation therapy for prostate cancer appears to increase the risk for CV events, although gonadotrophin-releasing hormone (GnRH) antagonists are associated with a lower risk for CV events than are GnRH agonists. The oral antiandrogens appear to be associated with increased CVD risk as well, particularly when used for complete androgen blockade as combination GnRH/anti-androgen therapy.
- The duration of hormonal therapies has a significant impact on CVD risk; the longer patients receive hormonal therapy, the greater the risk. More research is needed to better define the risks associated with duration of treatment.
- The data are mixed on the impact of preexisting CV risk factors and CVD on CV events associated with hormonal therapy. Although the presence of baseline CV risk factors and CVD can increase CV events associated with aromatase inhibitors, it is not clear that tamoxifen does.
- Studies suggest that patients with prostate cancer and baseline CVD and CV risk factors have increased rates of CV events when treated with androgen-deprivation therapy.
- Although the prolonged use of some hormonal therapies worsens CV risk factors and , the effects of the duration of therapy on CV events are less clear.
The writing group noted that there are no definitive guidelines for the monitoring and management of hormonal therapy-related CVD risks.
The authors encourage clinicians to be alert for worsening CV problems in those with preexisting heart disease or risk factors, and to recognize that even patients without preexisting CV problems are at higher risk because of their exposure to hormonal therapies.
“For patients who have two or more cardiovascular risk factors, it is likely that referral to a cardiologist would be appropriate prior to beginning hormone treatment. For patients already receiving hormonal therapies, a discussion with the oncology team can help to determine if a cardiology referral is recommended,” Dr. Okwuosa said in the news release.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Cardio-Oncology Subcommittee of the Council on Clinical Cardiology and the Council on Genomic and Precision Medicine; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Council on Cardiovascular Radiology and Intervention.
The research had no commercial funding. Dr. Okwuosa has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AHA statement on obesity emphasizes abdominal fat, AFib
An updated American Heart Association scientific statement on the role of obesity in cardiovascular disease provides the first new guidance in 15 years, drawing on evidence that’s emerged in that time to clarify the potential of newer drug therapies and interventions like bariatric surgery and lifestyle modifications to curtail cardiovascular disease risks.
“The timing of this information is important because the obesity epidemic contributes significantly to the global burden of cardiovascular disease and numerous chronic health conditions that also impact heart disease,” said Tiffany Powell-Wiley, MD, MPH, chair of the volunteer statement writing group.
“One of the big takeaways that I hope people get from the statement is really making it clear that obesity is a complex disease, and that it is multifactorial,” Dr. Powell-Wiley said in an interview. “There are not just biological reasons why individuals have obesity, but there are environmental, psychosocial, and really multilevel factors that contribute to the development and course of obesity.”
Most significantly, Dr. Powell-Wiley said, “we want to emphasize that we really want to have cardiologists think about and focus on abdominal obesity in particular.”
A metric for cardiovascular risk that seems to gain credibility in the statement is the relationship of waist circumference to height regardless of overall weight. “That is a very important finding that we can now really think of waist circumference as an important measure in our clinical practice,” said Dr. Powell-Wiley, chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory in the division of intramural research at the National Heart, Lung, and Blood Institute. “We want to get across to providers that this is something that should be measured and should be followed over time, based on data from the last 15 years that waist circumference and abdominal obesity are associated with higher cardiovascular risk regardless of body mass index.”
The statement provides potentially groundbreaking advice on atrial fibrillation as a consequence of weight, noted Dr. Powell-Wiley. “Up until recently, we haven’t really thought about weight management as a part of managing Afib [atrial fibrillation],” she said. “This statement highlights the need to think about weight management in addition to anticoagulation as part of the pieces for managing Afib.”
Evidence on interventions
The statement, published in Circulation, also dives into the evidence surrounding the varied interventions for managing weight.
“The biggest area where there’s much more data is bariatric surgery,” said Dr. Powell-Wiley. “There’s clear evidence that bariatric surgery lowers cardio mortality and all-cause mortality for patients, but we’ve also seen data around lifestyle interventions, with the Look AHEAD trial, which showed that while there were improvements in CV [cardiovascular] risk factors, we didn’t see the reduction in CV mortality that we wanted to see.”
The statement noted that the Look AHEAD trial (for Action for Health in Diabetes) of people with type 2 diabetes failed to show a significant reduction in major adverse cardiac events or CV mortality after almost 10 years of an intensive weight-loss intervention. Dr. Powell-Wiley added that the result seemed to be related more to the lack of weight loss with lifestyle interventions when compared with bariatric surgery.
The statement also addressed the effectiveness of drug treatments for weight control in managing CV risk, and while the evidence supporting pharmacotherapy specifically for weight loss has been mixed, emerging treatments have shown promise, Dr. Powell-Wiley said. “I think we now have some bright spots with new therapies that have been developed for diabetes and heart failure, such as the SGLT2 inhibitors as well as the GLP-1 agonists, and how they can also appear to improve weight and likely will improve CV mortality in patients with obesity.”
The “obesity paradox,” which Dr. Powell-Wiley noted is “definitely a controversial topic,” is also addressed in the statement. “We try to explain what it is and what we know about it right now,” she said. “We know for instance that patients with obesity, particularly those who have class 1 obesity or patients who are overweight, seem to do better in the short term in relation to coronary artery disease and heart failure, but the reasons for that are not necessarily clear.”
The statement also provides evidence-based insights on the use of diagnostic tools, including stress echocardiography and cardiac MRI as well as coronary angiography, and the clinical significance of specific echocardiographic changes in obese patients.
The writing committee also identified areas that need future research. “It’s really important to emphasize what we learned about the complexity of obesity over this time period,” Dr. Powell-Wiley said. “But again, we don’t have all the answers; there’s a lot more work to be done to understand what type of lifestyle intervention might be most beneficial, especially with addressing abdominal obesity, and how these new therapeutics around heart failure and diabetes may be useful in patients with obesity.
Obesity in adolescents is another area that needs further research, Dr. Powell-Wiley said. “How do we prevent obesity in those populations when we know they’re at risk for so much as they get older? Once you have obesity it’s hard to change that trajectory.”
The scientific statement was prepared by the volunteer writing group on behalf of the AHA’s Council on Lifestyle and Cardiometabolic Health, the Council on Cardiovascular and Stroke Nursing, the Council on Clinical Cardiology, the Council on Epidemiology and Prevention, and the Stroke Council. Committee vice chair Paul Poirier, MD, PhD, reported financial relationships with Abbott, Amgen, AstraZeneca, Bausch Health, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Novo Nordisk, Sanofi, Servier, and HLS Therapeutics. One committee member disclosed a financial relationship with AstraZeneca. Dr. Powell-Wiley and the other committee members have no relationships to disclose.
An updated American Heart Association scientific statement on the role of obesity in cardiovascular disease provides the first new guidance in 15 years, drawing on evidence that’s emerged in that time to clarify the potential of newer drug therapies and interventions like bariatric surgery and lifestyle modifications to curtail cardiovascular disease risks.
“The timing of this information is important because the obesity epidemic contributes significantly to the global burden of cardiovascular disease and numerous chronic health conditions that also impact heart disease,” said Tiffany Powell-Wiley, MD, MPH, chair of the volunteer statement writing group.
“One of the big takeaways that I hope people get from the statement is really making it clear that obesity is a complex disease, and that it is multifactorial,” Dr. Powell-Wiley said in an interview. “There are not just biological reasons why individuals have obesity, but there are environmental, psychosocial, and really multilevel factors that contribute to the development and course of obesity.”
Most significantly, Dr. Powell-Wiley said, “we want to emphasize that we really want to have cardiologists think about and focus on abdominal obesity in particular.”
A metric for cardiovascular risk that seems to gain credibility in the statement is the relationship of waist circumference to height regardless of overall weight. “That is a very important finding that we can now really think of waist circumference as an important measure in our clinical practice,” said Dr. Powell-Wiley, chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory in the division of intramural research at the National Heart, Lung, and Blood Institute. “We want to get across to providers that this is something that should be measured and should be followed over time, based on data from the last 15 years that waist circumference and abdominal obesity are associated with higher cardiovascular risk regardless of body mass index.”
The statement provides potentially groundbreaking advice on atrial fibrillation as a consequence of weight, noted Dr. Powell-Wiley. “Up until recently, we haven’t really thought about weight management as a part of managing Afib [atrial fibrillation],” she said. “This statement highlights the need to think about weight management in addition to anticoagulation as part of the pieces for managing Afib.”
Evidence on interventions
The statement, published in Circulation, also dives into the evidence surrounding the varied interventions for managing weight.
“The biggest area where there’s much more data is bariatric surgery,” said Dr. Powell-Wiley. “There’s clear evidence that bariatric surgery lowers cardio mortality and all-cause mortality for patients, but we’ve also seen data around lifestyle interventions, with the Look AHEAD trial, which showed that while there were improvements in CV [cardiovascular] risk factors, we didn’t see the reduction in CV mortality that we wanted to see.”
The statement noted that the Look AHEAD trial (for Action for Health in Diabetes) of people with type 2 diabetes failed to show a significant reduction in major adverse cardiac events or CV mortality after almost 10 years of an intensive weight-loss intervention. Dr. Powell-Wiley added that the result seemed to be related more to the lack of weight loss with lifestyle interventions when compared with bariatric surgery.
The statement also addressed the effectiveness of drug treatments for weight control in managing CV risk, and while the evidence supporting pharmacotherapy specifically for weight loss has been mixed, emerging treatments have shown promise, Dr. Powell-Wiley said. “I think we now have some bright spots with new therapies that have been developed for diabetes and heart failure, such as the SGLT2 inhibitors as well as the GLP-1 agonists, and how they can also appear to improve weight and likely will improve CV mortality in patients with obesity.”
The “obesity paradox,” which Dr. Powell-Wiley noted is “definitely a controversial topic,” is also addressed in the statement. “We try to explain what it is and what we know about it right now,” she said. “We know for instance that patients with obesity, particularly those who have class 1 obesity or patients who are overweight, seem to do better in the short term in relation to coronary artery disease and heart failure, but the reasons for that are not necessarily clear.”
The statement also provides evidence-based insights on the use of diagnostic tools, including stress echocardiography and cardiac MRI as well as coronary angiography, and the clinical significance of specific echocardiographic changes in obese patients.
The writing committee also identified areas that need future research. “It’s really important to emphasize what we learned about the complexity of obesity over this time period,” Dr. Powell-Wiley said. “But again, we don’t have all the answers; there’s a lot more work to be done to understand what type of lifestyle intervention might be most beneficial, especially with addressing abdominal obesity, and how these new therapeutics around heart failure and diabetes may be useful in patients with obesity.
Obesity in adolescents is another area that needs further research, Dr. Powell-Wiley said. “How do we prevent obesity in those populations when we know they’re at risk for so much as they get older? Once you have obesity it’s hard to change that trajectory.”
The scientific statement was prepared by the volunteer writing group on behalf of the AHA’s Council on Lifestyle and Cardiometabolic Health, the Council on Cardiovascular and Stroke Nursing, the Council on Clinical Cardiology, the Council on Epidemiology and Prevention, and the Stroke Council. Committee vice chair Paul Poirier, MD, PhD, reported financial relationships with Abbott, Amgen, AstraZeneca, Bausch Health, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Novo Nordisk, Sanofi, Servier, and HLS Therapeutics. One committee member disclosed a financial relationship with AstraZeneca. Dr. Powell-Wiley and the other committee members have no relationships to disclose.
An updated American Heart Association scientific statement on the role of obesity in cardiovascular disease provides the first new guidance in 15 years, drawing on evidence that’s emerged in that time to clarify the potential of newer drug therapies and interventions like bariatric surgery and lifestyle modifications to curtail cardiovascular disease risks.
“The timing of this information is important because the obesity epidemic contributes significantly to the global burden of cardiovascular disease and numerous chronic health conditions that also impact heart disease,” said Tiffany Powell-Wiley, MD, MPH, chair of the volunteer statement writing group.
“One of the big takeaways that I hope people get from the statement is really making it clear that obesity is a complex disease, and that it is multifactorial,” Dr. Powell-Wiley said in an interview. “There are not just biological reasons why individuals have obesity, but there are environmental, psychosocial, and really multilevel factors that contribute to the development and course of obesity.”
Most significantly, Dr. Powell-Wiley said, “we want to emphasize that we really want to have cardiologists think about and focus on abdominal obesity in particular.”
A metric for cardiovascular risk that seems to gain credibility in the statement is the relationship of waist circumference to height regardless of overall weight. “That is a very important finding that we can now really think of waist circumference as an important measure in our clinical practice,” said Dr. Powell-Wiley, chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory in the division of intramural research at the National Heart, Lung, and Blood Institute. “We want to get across to providers that this is something that should be measured and should be followed over time, based on data from the last 15 years that waist circumference and abdominal obesity are associated with higher cardiovascular risk regardless of body mass index.”
The statement provides potentially groundbreaking advice on atrial fibrillation as a consequence of weight, noted Dr. Powell-Wiley. “Up until recently, we haven’t really thought about weight management as a part of managing Afib [atrial fibrillation],” she said. “This statement highlights the need to think about weight management in addition to anticoagulation as part of the pieces for managing Afib.”
Evidence on interventions
The statement, published in Circulation, also dives into the evidence surrounding the varied interventions for managing weight.
“The biggest area where there’s much more data is bariatric surgery,” said Dr. Powell-Wiley. “There’s clear evidence that bariatric surgery lowers cardio mortality and all-cause mortality for patients, but we’ve also seen data around lifestyle interventions, with the Look AHEAD trial, which showed that while there were improvements in CV [cardiovascular] risk factors, we didn’t see the reduction in CV mortality that we wanted to see.”
The statement noted that the Look AHEAD trial (for Action for Health in Diabetes) of people with type 2 diabetes failed to show a significant reduction in major adverse cardiac events or CV mortality after almost 10 years of an intensive weight-loss intervention. Dr. Powell-Wiley added that the result seemed to be related more to the lack of weight loss with lifestyle interventions when compared with bariatric surgery.
The statement also addressed the effectiveness of drug treatments for weight control in managing CV risk, and while the evidence supporting pharmacotherapy specifically for weight loss has been mixed, emerging treatments have shown promise, Dr. Powell-Wiley said. “I think we now have some bright spots with new therapies that have been developed for diabetes and heart failure, such as the SGLT2 inhibitors as well as the GLP-1 agonists, and how they can also appear to improve weight and likely will improve CV mortality in patients with obesity.”
The “obesity paradox,” which Dr. Powell-Wiley noted is “definitely a controversial topic,” is also addressed in the statement. “We try to explain what it is and what we know about it right now,” she said. “We know for instance that patients with obesity, particularly those who have class 1 obesity or patients who are overweight, seem to do better in the short term in relation to coronary artery disease and heart failure, but the reasons for that are not necessarily clear.”
The statement also provides evidence-based insights on the use of diagnostic tools, including stress echocardiography and cardiac MRI as well as coronary angiography, and the clinical significance of specific echocardiographic changes in obese patients.
The writing committee also identified areas that need future research. “It’s really important to emphasize what we learned about the complexity of obesity over this time period,” Dr. Powell-Wiley said. “But again, we don’t have all the answers; there’s a lot more work to be done to understand what type of lifestyle intervention might be most beneficial, especially with addressing abdominal obesity, and how these new therapeutics around heart failure and diabetes may be useful in patients with obesity.
Obesity in adolescents is another area that needs further research, Dr. Powell-Wiley said. “How do we prevent obesity in those populations when we know they’re at risk for so much as they get older? Once you have obesity it’s hard to change that trajectory.”
The scientific statement was prepared by the volunteer writing group on behalf of the AHA’s Council on Lifestyle and Cardiometabolic Health, the Council on Cardiovascular and Stroke Nursing, the Council on Clinical Cardiology, the Council on Epidemiology and Prevention, and the Stroke Council. Committee vice chair Paul Poirier, MD, PhD, reported financial relationships with Abbott, Amgen, AstraZeneca, Bausch Health, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Novo Nordisk, Sanofi, Servier, and HLS Therapeutics. One committee member disclosed a financial relationship with AstraZeneca. Dr. Powell-Wiley and the other committee members have no relationships to disclose.
FROM CIRCULATION
Cushing’s death rate ‘unacceptable,’ triple that of general population
Excess mortality among people with endogenous Cushing’s syndrome (CS) has declined in the past 20 years yet remains three times higher than in the general population, new research finds.
Among more than 90,000 individuals with endogenous CS, the overall proportion of mortality – defined as the ratio of the number of deaths from CS divided by the total number of CS patients – was 0.05, and the standardized mortality rate was an “unacceptable” three times that of the general population, Padiporn Limumpornpetch, MD, reported on March 20 at ENDO 2021: The Endocrine Society Annual Meeting.
Excess deaths were higher among those with adrenal CS, compared with those with Cushing’s disease. The most common causes of death among those with CS were cardiovascular diseases, cerebrovascular accident, infection, and malignancy, noted Dr. Limumpornpetch, of Songkla University, Hat Yai, Thailand, who is also a PhD student at the University of Leeds, United Kingdom.
“While mortality has improved since 2000, it is still significantly compromised compared to the background population ... The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of thromboembolism, infection control, and a normalized cortisol level,” she said.
Asked to comment, Maria Fleseriu, MD, told this news organization that the new data show “we are making improvements in the care of patients with CS and thus outcomes, but we are not there yet ... This meta-analysis highlights the whole spectrum of acute and life-threatening complications in CS and their high prevalence, even before disease diagnosis and after successful surgery.”
She noted that although she wasn’t surprised by the overall results, “the improvement over time was indeed lower than I expected. However, interestingly here, the risk of mortality in adrenal Cushing’s was unexpectedly high despite patients with adrenal cancer being excluded.”
Dr. Fleseriu, who is director of the Pituitary Center at Oregon Health and Science University, Portland, advised, “Management of hyperglycemia and diabetes, hypertension, hypokalemia, hyperlipidemia, and other cardiovascular risk factors is generally undertaken in accordance with standard of clinical care.”
“But we should focus more on optimizing more aggressively this care in addition to the specific Cushing’s treatment,” she stressed.
In addition, she noted, “Medical therapy for CS may be needed even prior to surgery in severe and/or prolonged hypercortisolism to decrease complications ... We definitely need a multidisciplinary approach to address complications and etiologic treatment as well as the reduced long-term quality of life in patients with CS.”
Largest study in scale and scope of Cushing’s syndrome mortality
Endogenous Cushing’s syndrome occurs when the body overproduces cortisol. The most common cause of the latter is a tumor of the pituitary gland (Cushing’s disease), but another cause is a usually benign tumor of the adrenal glands (adrenal Cushing’s syndrome). Surgery is the mainstay of initial treatment of Cushing’s syndrome. If an operation to remove the tumor fails to cause remission, medications are available.
Prior to this new meta-analysis, there had been limited data on mortality among patients with endogenous CS. Research has mostly been limited to single-cohort studies. A previous systematic review/meta-analysis comprised only seven articles with 780 patients. All the studies were conducted prior to 2012, and most were limited to Cushing’s disease.
“In 2021, we lacked a detailed understanding of patient outcomes and mortality because of the rarity of Cushing’s syndrome,” Dr. Limumpornpetch noted.
The current meta-analysis included 91 articles that reported mortality among patients with endogenous CS. There was a total of 19,181 patients from 92 study cohorts, including 49 studies on CD (n = 14,971), 24 studies on adrenal CS (n = 2304), and 19 studies that included both (n = 1906).
Among 21 studies that reported standardized mortality rate (SMR) data, including 13 CD studies (n = 2160) and seven on adrenal CS (n = 1531), the overall increase in mortality compared to the background population was a significant 3.00 (range, 1.15-7.84).
This SMR was higher among patients with adrenal Cushing’s syndrome (3.3) versus Cushing’s disease (2.8) (P = .003) and among patients who had active disease (5.7) versus those whose disease was in remission (2.3) (P < .001).
The SMR was also worse among patients with Cushing’s disease with larger tumors (macroadenomas), at 7.4, than among patients with very small tumors (microadenomas), at 1.9 (P = .004).
The proportion of death was 0.05 for CS overall, with 0.04 for CD and 0.02 for adrenal adenomas.
Compared to studies published prior to the year 2000, more recent studies seem to reflect advances in treatment and care. The overall proportion of death for all CS cohorts dropped from 0.10 to 0.03 (P < .001); for all CD cohorts, it dropped from 0.14 to 0.03; and for adrenal CS cohorts, it dropped from 0.09 to 0.03 (P = .04).
Causes of death were cardiovascular diseases (29.5% of cases), cerebrovascular accident (11.5%), infection (10.5%), and malignancy (10.1%). Less common causes of death were gastrointestinal bleeding and acute pancreatitis (3.7%), active CS (3.5%), adrenal insufficiency (2.5%), suicide (2.5%), and surgery (1.6%).
Overall, in the CS groups, the proportion of deaths within 30 days of surgery dropped from 0.04 prior to 2000 to 0.01 since (P = .07). For CD, the proportion dropped from 0.02 to 0.01 (P = .25).
Preventing perioperative mortality: Consider thromboprophylaxis
Dr. Fleseriu told this news organization that she believes hypercoagulability is “the least recognized complication with a big role in mortality.” Because most of the perioperative mortality is due to venous thromboembolism and infections, “thromboprophylaxis should be considered for CS patients with severe hypercortisolism and/or postoperatively, based on individual risk factors of thromboembolism and bleeding.”
Recently, Dr. Fleseriu’s group showed in a single retrospective study that the risk for arterial and venous thromboembolic events among patients with CS was approximately 20%. Many patients experienced more than one event. Risk was higher 30 to 60 days postoperatively.
The odds ratio of venous thromoboembolism among patients with CS was 18 times higher than in the normal population.
“Due to the additional thrombotic risk of surgery or any invasive procedure, anticoagulation prophylaxis should be at least considered in all patients with Cushing’s syndrome and balanced with individual bleeding risk,” Dr. Fleseriu advised.
A recent Pituitary Society workshop discussed the management of complications of CS at length; proceedings will be published soon, she noted.
Dr. Limumpornpetch commented, “We look forward to the day when our interdisciplinary approach to managing these challenging patients can deliver outcomes similar to the background population.”
Dr. Limumpornpetch has disclosed no relevant financial relationships. Dr. Fleseriu has been a scientific consultant to Recordati, Sparrow, and Strongbridge and has received grants (inst) from Novartis and Strongbridge.
A version of this article first appeared on Medscape.com.
Excess mortality among people with endogenous Cushing’s syndrome (CS) has declined in the past 20 years yet remains three times higher than in the general population, new research finds.
Among more than 90,000 individuals with endogenous CS, the overall proportion of mortality – defined as the ratio of the number of deaths from CS divided by the total number of CS patients – was 0.05, and the standardized mortality rate was an “unacceptable” three times that of the general population, Padiporn Limumpornpetch, MD, reported on March 20 at ENDO 2021: The Endocrine Society Annual Meeting.
Excess deaths were higher among those with adrenal CS, compared with those with Cushing’s disease. The most common causes of death among those with CS were cardiovascular diseases, cerebrovascular accident, infection, and malignancy, noted Dr. Limumpornpetch, of Songkla University, Hat Yai, Thailand, who is also a PhD student at the University of Leeds, United Kingdom.
“While mortality has improved since 2000, it is still significantly compromised compared to the background population ... The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of thromboembolism, infection control, and a normalized cortisol level,” she said.
Asked to comment, Maria Fleseriu, MD, told this news organization that the new data show “we are making improvements in the care of patients with CS and thus outcomes, but we are not there yet ... This meta-analysis highlights the whole spectrum of acute and life-threatening complications in CS and their high prevalence, even before disease diagnosis and after successful surgery.”
She noted that although she wasn’t surprised by the overall results, “the improvement over time was indeed lower than I expected. However, interestingly here, the risk of mortality in adrenal Cushing’s was unexpectedly high despite patients with adrenal cancer being excluded.”
Dr. Fleseriu, who is director of the Pituitary Center at Oregon Health and Science University, Portland, advised, “Management of hyperglycemia and diabetes, hypertension, hypokalemia, hyperlipidemia, and other cardiovascular risk factors is generally undertaken in accordance with standard of clinical care.”
“But we should focus more on optimizing more aggressively this care in addition to the specific Cushing’s treatment,” she stressed.
In addition, she noted, “Medical therapy for CS may be needed even prior to surgery in severe and/or prolonged hypercortisolism to decrease complications ... We definitely need a multidisciplinary approach to address complications and etiologic treatment as well as the reduced long-term quality of life in patients with CS.”
Largest study in scale and scope of Cushing’s syndrome mortality
Endogenous Cushing’s syndrome occurs when the body overproduces cortisol. The most common cause of the latter is a tumor of the pituitary gland (Cushing’s disease), but another cause is a usually benign tumor of the adrenal glands (adrenal Cushing’s syndrome). Surgery is the mainstay of initial treatment of Cushing’s syndrome. If an operation to remove the tumor fails to cause remission, medications are available.
Prior to this new meta-analysis, there had been limited data on mortality among patients with endogenous CS. Research has mostly been limited to single-cohort studies. A previous systematic review/meta-analysis comprised only seven articles with 780 patients. All the studies were conducted prior to 2012, and most were limited to Cushing’s disease.
“In 2021, we lacked a detailed understanding of patient outcomes and mortality because of the rarity of Cushing’s syndrome,” Dr. Limumpornpetch noted.
The current meta-analysis included 91 articles that reported mortality among patients with endogenous CS. There was a total of 19,181 patients from 92 study cohorts, including 49 studies on CD (n = 14,971), 24 studies on adrenal CS (n = 2304), and 19 studies that included both (n = 1906).
Among 21 studies that reported standardized mortality rate (SMR) data, including 13 CD studies (n = 2160) and seven on adrenal CS (n = 1531), the overall increase in mortality compared to the background population was a significant 3.00 (range, 1.15-7.84).
This SMR was higher among patients with adrenal Cushing’s syndrome (3.3) versus Cushing’s disease (2.8) (P = .003) and among patients who had active disease (5.7) versus those whose disease was in remission (2.3) (P < .001).
The SMR was also worse among patients with Cushing’s disease with larger tumors (macroadenomas), at 7.4, than among patients with very small tumors (microadenomas), at 1.9 (P = .004).
The proportion of death was 0.05 for CS overall, with 0.04 for CD and 0.02 for adrenal adenomas.
Compared to studies published prior to the year 2000, more recent studies seem to reflect advances in treatment and care. The overall proportion of death for all CS cohorts dropped from 0.10 to 0.03 (P < .001); for all CD cohorts, it dropped from 0.14 to 0.03; and for adrenal CS cohorts, it dropped from 0.09 to 0.03 (P = .04).
Causes of death were cardiovascular diseases (29.5% of cases), cerebrovascular accident (11.5%), infection (10.5%), and malignancy (10.1%). Less common causes of death were gastrointestinal bleeding and acute pancreatitis (3.7%), active CS (3.5%), adrenal insufficiency (2.5%), suicide (2.5%), and surgery (1.6%).
Overall, in the CS groups, the proportion of deaths within 30 days of surgery dropped from 0.04 prior to 2000 to 0.01 since (P = .07). For CD, the proportion dropped from 0.02 to 0.01 (P = .25).
Preventing perioperative mortality: Consider thromboprophylaxis
Dr. Fleseriu told this news organization that she believes hypercoagulability is “the least recognized complication with a big role in mortality.” Because most of the perioperative mortality is due to venous thromboembolism and infections, “thromboprophylaxis should be considered for CS patients with severe hypercortisolism and/or postoperatively, based on individual risk factors of thromboembolism and bleeding.”
Recently, Dr. Fleseriu’s group showed in a single retrospective study that the risk for arterial and venous thromboembolic events among patients with CS was approximately 20%. Many patients experienced more than one event. Risk was higher 30 to 60 days postoperatively.
The odds ratio of venous thromoboembolism among patients with CS was 18 times higher than in the normal population.
“Due to the additional thrombotic risk of surgery or any invasive procedure, anticoagulation prophylaxis should be at least considered in all patients with Cushing’s syndrome and balanced with individual bleeding risk,” Dr. Fleseriu advised.
A recent Pituitary Society workshop discussed the management of complications of CS at length; proceedings will be published soon, she noted.
Dr. Limumpornpetch commented, “We look forward to the day when our interdisciplinary approach to managing these challenging patients can deliver outcomes similar to the background population.”
Dr. Limumpornpetch has disclosed no relevant financial relationships. Dr. Fleseriu has been a scientific consultant to Recordati, Sparrow, and Strongbridge and has received grants (inst) from Novartis and Strongbridge.
A version of this article first appeared on Medscape.com.
Excess mortality among people with endogenous Cushing’s syndrome (CS) has declined in the past 20 years yet remains three times higher than in the general population, new research finds.
Among more than 90,000 individuals with endogenous CS, the overall proportion of mortality – defined as the ratio of the number of deaths from CS divided by the total number of CS patients – was 0.05, and the standardized mortality rate was an “unacceptable” three times that of the general population, Padiporn Limumpornpetch, MD, reported on March 20 at ENDO 2021: The Endocrine Society Annual Meeting.
Excess deaths were higher among those with adrenal CS, compared with those with Cushing’s disease. The most common causes of death among those with CS were cardiovascular diseases, cerebrovascular accident, infection, and malignancy, noted Dr. Limumpornpetch, of Songkla University, Hat Yai, Thailand, who is also a PhD student at the University of Leeds, United Kingdom.
“While mortality has improved since 2000, it is still significantly compromised compared to the background population ... The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of thromboembolism, infection control, and a normalized cortisol level,” she said.
Asked to comment, Maria Fleseriu, MD, told this news organization that the new data show “we are making improvements in the care of patients with CS and thus outcomes, but we are not there yet ... This meta-analysis highlights the whole spectrum of acute and life-threatening complications in CS and their high prevalence, even before disease diagnosis and after successful surgery.”
She noted that although she wasn’t surprised by the overall results, “the improvement over time was indeed lower than I expected. However, interestingly here, the risk of mortality in adrenal Cushing’s was unexpectedly high despite patients with adrenal cancer being excluded.”
Dr. Fleseriu, who is director of the Pituitary Center at Oregon Health and Science University, Portland, advised, “Management of hyperglycemia and diabetes, hypertension, hypokalemia, hyperlipidemia, and other cardiovascular risk factors is generally undertaken in accordance with standard of clinical care.”
“But we should focus more on optimizing more aggressively this care in addition to the specific Cushing’s treatment,” she stressed.
In addition, she noted, “Medical therapy for CS may be needed even prior to surgery in severe and/or prolonged hypercortisolism to decrease complications ... We definitely need a multidisciplinary approach to address complications and etiologic treatment as well as the reduced long-term quality of life in patients with CS.”
Largest study in scale and scope of Cushing’s syndrome mortality
Endogenous Cushing’s syndrome occurs when the body overproduces cortisol. The most common cause of the latter is a tumor of the pituitary gland (Cushing’s disease), but another cause is a usually benign tumor of the adrenal glands (adrenal Cushing’s syndrome). Surgery is the mainstay of initial treatment of Cushing’s syndrome. If an operation to remove the tumor fails to cause remission, medications are available.
Prior to this new meta-analysis, there had been limited data on mortality among patients with endogenous CS. Research has mostly been limited to single-cohort studies. A previous systematic review/meta-analysis comprised only seven articles with 780 patients. All the studies were conducted prior to 2012, and most were limited to Cushing’s disease.
“In 2021, we lacked a detailed understanding of patient outcomes and mortality because of the rarity of Cushing’s syndrome,” Dr. Limumpornpetch noted.
The current meta-analysis included 91 articles that reported mortality among patients with endogenous CS. There was a total of 19,181 patients from 92 study cohorts, including 49 studies on CD (n = 14,971), 24 studies on adrenal CS (n = 2304), and 19 studies that included both (n = 1906).
Among 21 studies that reported standardized mortality rate (SMR) data, including 13 CD studies (n = 2160) and seven on adrenal CS (n = 1531), the overall increase in mortality compared to the background population was a significant 3.00 (range, 1.15-7.84).
This SMR was higher among patients with adrenal Cushing’s syndrome (3.3) versus Cushing’s disease (2.8) (P = .003) and among patients who had active disease (5.7) versus those whose disease was in remission (2.3) (P < .001).
The SMR was also worse among patients with Cushing’s disease with larger tumors (macroadenomas), at 7.4, than among patients with very small tumors (microadenomas), at 1.9 (P = .004).
The proportion of death was 0.05 for CS overall, with 0.04 for CD and 0.02 for adrenal adenomas.
Compared to studies published prior to the year 2000, more recent studies seem to reflect advances in treatment and care. The overall proportion of death for all CS cohorts dropped from 0.10 to 0.03 (P < .001); for all CD cohorts, it dropped from 0.14 to 0.03; and for adrenal CS cohorts, it dropped from 0.09 to 0.03 (P = .04).
Causes of death were cardiovascular diseases (29.5% of cases), cerebrovascular accident (11.5%), infection (10.5%), and malignancy (10.1%). Less common causes of death were gastrointestinal bleeding and acute pancreatitis (3.7%), active CS (3.5%), adrenal insufficiency (2.5%), suicide (2.5%), and surgery (1.6%).
Overall, in the CS groups, the proportion of deaths within 30 days of surgery dropped from 0.04 prior to 2000 to 0.01 since (P = .07). For CD, the proportion dropped from 0.02 to 0.01 (P = .25).
Preventing perioperative mortality: Consider thromboprophylaxis
Dr. Fleseriu told this news organization that she believes hypercoagulability is “the least recognized complication with a big role in mortality.” Because most of the perioperative mortality is due to venous thromboembolism and infections, “thromboprophylaxis should be considered for CS patients with severe hypercortisolism and/or postoperatively, based on individual risk factors of thromboembolism and bleeding.”
Recently, Dr. Fleseriu’s group showed in a single retrospective study that the risk for arterial and venous thromboembolic events among patients with CS was approximately 20%. Many patients experienced more than one event. Risk was higher 30 to 60 days postoperatively.
The odds ratio of venous thromoboembolism among patients with CS was 18 times higher than in the normal population.
“Due to the additional thrombotic risk of surgery or any invasive procedure, anticoagulation prophylaxis should be at least considered in all patients with Cushing’s syndrome and balanced with individual bleeding risk,” Dr. Fleseriu advised.
A recent Pituitary Society workshop discussed the management of complications of CS at length; proceedings will be published soon, she noted.
Dr. Limumpornpetch commented, “We look forward to the day when our interdisciplinary approach to managing these challenging patients can deliver outcomes similar to the background population.”
Dr. Limumpornpetch has disclosed no relevant financial relationships. Dr. Fleseriu has been a scientific consultant to Recordati, Sparrow, and Strongbridge and has received grants (inst) from Novartis and Strongbridge.
A version of this article first appeared on Medscape.com.
Severe obesity persists, takes high cardiovascular toll
In a U.K. cohort of more than 260,000 mostly middle-aged adults in primary care with overweight or obesity, body mass index remained relatively stable over a decade.
However, compared to overweight individuals, those with severe (class 3) obesity were more socioeconomically disadvantaged and had triple the risk for incident heart failure or all-cause or cardiovascular disease (CVD)–related mortality in a study published online April 15 in BMC Public Health.
“This is the first study to evaluate the long-term impact of overweight and obese individuals’ BMI trajectory on cardiovascular endpoints, heart failure, and mortality outcomes,” wrote Barbara Iyen, PhD, University of Nottingham, England, and colleagues.
The findings emphasize “the high cardiovascular toll exacted by continuing failure to tackle obesity, particularly among more socioeconomically deprived populations,” they warned.
“We have found that despite widespread efforts to prevent and manage obesity, the majority of adults who are overweight or obese in the general population continue to remain so in the long term,” Dr. Iyen said in a statement from her university.
“More effective policies and weight-management interventions are needed urgently to address this increasing burden and associated adverse health outcomes,” she stressed.
Invited to comment, Sadiya S. Khan, MD, Northwestern University, Chicago, said in an interview: “This research adds to the growing body of evidence [that] earlier and more intensive interventions for weight loss are necessary to promote cardiovascular health and reduce morbidity and mortality.
“Adjunctive pharmacotherapy and bariatric surgery are both options that should be considered in addition to intensive lifestyle interventions in overweight and obesity groups,” she added.
“I would always advocate for earlier prevention efforts focused on weight loss, because years lived with obesity are associated with future CVD, so every year counts,” Dr. Khan said.
Does BMI remain elevated, predict worse heart health?
Although obesity is a well-recognized risk factor for CVD, long-term changes in BMI and the impact of BMI on the risk for heart failure, CVD, and mortality have not been quantified among adults with overweight and obesity, Dr. Iyen and colleagues explained.
The researchers examined data from the UK Clinical Practice Research Datalink and secondary care and mortality records to determine BMI trajectories among adults with overweight or obesity and to quantify the risk for heart failure, CVD (defined as coronary heart disease, stroke, transient ischemic attack, or peripheral vascular disease, CVD-related mortality, and all-cause mortality.
They identified 264,230 adults with overweight or obesity who were seen in 790 primary care practices in the United Kingdom from 1999 to 2018 and who did not initially have heart failure or CVD and for whom baseline BMI measurements and at least one other BMI measurement 2, 5, 8, and 10 years later was available.
The researchers divided the cohort into four groups on the basis of initial BMI: overweight (36% of patients; mean BMI, 28.7 kg/m2); class 1 obesity (40%; mean BMI, 33.7 kg/m2); class 2 obesity (19%; mean BMI, 39.9 kg/m2), and class 3 obesity (5%; mean BMI, 49.1 kg/m2).
The mean age of the individuals was 50 years, and 64% were White. Race/ethnicity data were unavailable for 31%. Asian Indian, Asian, and Black patients comprised 5% of the cohort.
“Strong significant gradient in heart failure risk”
Compared to the overweight (reference) group, the severe-obesity group comprised a higher percentage of women (74% vs. 70%), and the prevalence of comorbidities and socioeconomic deprivation was higher.
BMI remained relatively stable in each BMI group. The mean BMI increase was 1.06 kg/m2 during a median follow-up of 10.9 years.
There were 30,400 incident cases of CVD, 7,662 incident cases of heart failure, and 24,022 deaths, of which 2,827 (11.8%) were from CVD.
The risk for heart failure and CVD-related or all-cause mortality increased with increasing obesity severity.
Compared with overweight individuals, those with class 3 obesity were at significantly increased risk for heart failure (hazard ratio [HR], 3.26), all-cause mortality (HR, 2.72), and CVD-related mortality (HR, 3.31) after adjustment for age, sex, and comorbidities (hypertension, type 2 diabetes, atrial fibrillation, and chronic kidney disease).
The risk for stroke/TIA or coronary heart disease was similar among those with severe obesity and the other individuals. The risk for PVD was significantly lower (HR, 0.73).
The reduced risk for PVD in the most severely obese group is similar to findings in the Framingham heart study, the authors noted, and may be due to underdiagnosis or differences in the underlying mechanism.
Compelling evidence of poor health outcomes associated with obesity
Study limitations include the fact that the findings may not be generalizable to other race/ethnicity groups, the lack of information on diet and exercise, and the fact that BMI was used as a surrogate of adiposity. As such, it does not account for an age-related decrease in heavier-than-fat muscle mass and differences between sexes and ethnic groups.
The finding of stable obesity over time accords with two smaller studies that included Canadian and American adults.
The current study did not uncover an obesity paradox, unlike some studies that included patients with preexisting CVD or a history of acute coronary events. Those studies reported better clinical outcomes among patients with overweight or obesity.
The current study included individuals who did not initially have CVD. Those with more severe obesity were younger than individuals with overweight at the time of the occurrence of incident CVD (age 64 vs. 66) and at the age of death (age 67 vs. age 75), which “provides compelling evidence of poor health outcomes associated with obesity,” the authors emphasized.
“Further research is ... needed to explore whether interventions to change BMI trajectories would have an impact on future CVD outcomes,” they concluded.
Dr. Iyen’s clinical academic lectureship is fully funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and are not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. Dr. Khan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a U.K. cohort of more than 260,000 mostly middle-aged adults in primary care with overweight or obesity, body mass index remained relatively stable over a decade.
However, compared to overweight individuals, those with severe (class 3) obesity were more socioeconomically disadvantaged and had triple the risk for incident heart failure or all-cause or cardiovascular disease (CVD)–related mortality in a study published online April 15 in BMC Public Health.
“This is the first study to evaluate the long-term impact of overweight and obese individuals’ BMI trajectory on cardiovascular endpoints, heart failure, and mortality outcomes,” wrote Barbara Iyen, PhD, University of Nottingham, England, and colleagues.
The findings emphasize “the high cardiovascular toll exacted by continuing failure to tackle obesity, particularly among more socioeconomically deprived populations,” they warned.
“We have found that despite widespread efforts to prevent and manage obesity, the majority of adults who are overweight or obese in the general population continue to remain so in the long term,” Dr. Iyen said in a statement from her university.
“More effective policies and weight-management interventions are needed urgently to address this increasing burden and associated adverse health outcomes,” she stressed.
Invited to comment, Sadiya S. Khan, MD, Northwestern University, Chicago, said in an interview: “This research adds to the growing body of evidence [that] earlier and more intensive interventions for weight loss are necessary to promote cardiovascular health and reduce morbidity and mortality.
“Adjunctive pharmacotherapy and bariatric surgery are both options that should be considered in addition to intensive lifestyle interventions in overweight and obesity groups,” she added.
“I would always advocate for earlier prevention efforts focused on weight loss, because years lived with obesity are associated with future CVD, so every year counts,” Dr. Khan said.
Does BMI remain elevated, predict worse heart health?
Although obesity is a well-recognized risk factor for CVD, long-term changes in BMI and the impact of BMI on the risk for heart failure, CVD, and mortality have not been quantified among adults with overweight and obesity, Dr. Iyen and colleagues explained.
The researchers examined data from the UK Clinical Practice Research Datalink and secondary care and mortality records to determine BMI trajectories among adults with overweight or obesity and to quantify the risk for heart failure, CVD (defined as coronary heart disease, stroke, transient ischemic attack, or peripheral vascular disease, CVD-related mortality, and all-cause mortality.
They identified 264,230 adults with overweight or obesity who were seen in 790 primary care practices in the United Kingdom from 1999 to 2018 and who did not initially have heart failure or CVD and for whom baseline BMI measurements and at least one other BMI measurement 2, 5, 8, and 10 years later was available.
The researchers divided the cohort into four groups on the basis of initial BMI: overweight (36% of patients; mean BMI, 28.7 kg/m2); class 1 obesity (40%; mean BMI, 33.7 kg/m2); class 2 obesity (19%; mean BMI, 39.9 kg/m2), and class 3 obesity (5%; mean BMI, 49.1 kg/m2).
The mean age of the individuals was 50 years, and 64% were White. Race/ethnicity data were unavailable for 31%. Asian Indian, Asian, and Black patients comprised 5% of the cohort.
“Strong significant gradient in heart failure risk”
Compared to the overweight (reference) group, the severe-obesity group comprised a higher percentage of women (74% vs. 70%), and the prevalence of comorbidities and socioeconomic deprivation was higher.
BMI remained relatively stable in each BMI group. The mean BMI increase was 1.06 kg/m2 during a median follow-up of 10.9 years.
There were 30,400 incident cases of CVD, 7,662 incident cases of heart failure, and 24,022 deaths, of which 2,827 (11.8%) were from CVD.
The risk for heart failure and CVD-related or all-cause mortality increased with increasing obesity severity.
Compared with overweight individuals, those with class 3 obesity were at significantly increased risk for heart failure (hazard ratio [HR], 3.26), all-cause mortality (HR, 2.72), and CVD-related mortality (HR, 3.31) after adjustment for age, sex, and comorbidities (hypertension, type 2 diabetes, atrial fibrillation, and chronic kidney disease).
The risk for stroke/TIA or coronary heart disease was similar among those with severe obesity and the other individuals. The risk for PVD was significantly lower (HR, 0.73).
The reduced risk for PVD in the most severely obese group is similar to findings in the Framingham heart study, the authors noted, and may be due to underdiagnosis or differences in the underlying mechanism.
Compelling evidence of poor health outcomes associated with obesity
Study limitations include the fact that the findings may not be generalizable to other race/ethnicity groups, the lack of information on diet and exercise, and the fact that BMI was used as a surrogate of adiposity. As such, it does not account for an age-related decrease in heavier-than-fat muscle mass and differences between sexes and ethnic groups.
The finding of stable obesity over time accords with two smaller studies that included Canadian and American adults.
The current study did not uncover an obesity paradox, unlike some studies that included patients with preexisting CVD or a history of acute coronary events. Those studies reported better clinical outcomes among patients with overweight or obesity.
The current study included individuals who did not initially have CVD. Those with more severe obesity were younger than individuals with overweight at the time of the occurrence of incident CVD (age 64 vs. 66) and at the age of death (age 67 vs. age 75), which “provides compelling evidence of poor health outcomes associated with obesity,” the authors emphasized.
“Further research is ... needed to explore whether interventions to change BMI trajectories would have an impact on future CVD outcomes,” they concluded.
Dr. Iyen’s clinical academic lectureship is fully funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and are not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. Dr. Khan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a U.K. cohort of more than 260,000 mostly middle-aged adults in primary care with overweight or obesity, body mass index remained relatively stable over a decade.
However, compared to overweight individuals, those with severe (class 3) obesity were more socioeconomically disadvantaged and had triple the risk for incident heart failure or all-cause or cardiovascular disease (CVD)–related mortality in a study published online April 15 in BMC Public Health.
“This is the first study to evaluate the long-term impact of overweight and obese individuals’ BMI trajectory on cardiovascular endpoints, heart failure, and mortality outcomes,” wrote Barbara Iyen, PhD, University of Nottingham, England, and colleagues.
The findings emphasize “the high cardiovascular toll exacted by continuing failure to tackle obesity, particularly among more socioeconomically deprived populations,” they warned.
“We have found that despite widespread efforts to prevent and manage obesity, the majority of adults who are overweight or obese in the general population continue to remain so in the long term,” Dr. Iyen said in a statement from her university.
“More effective policies and weight-management interventions are needed urgently to address this increasing burden and associated adverse health outcomes,” she stressed.
Invited to comment, Sadiya S. Khan, MD, Northwestern University, Chicago, said in an interview: “This research adds to the growing body of evidence [that] earlier and more intensive interventions for weight loss are necessary to promote cardiovascular health and reduce morbidity and mortality.
“Adjunctive pharmacotherapy and bariatric surgery are both options that should be considered in addition to intensive lifestyle interventions in overweight and obesity groups,” she added.
“I would always advocate for earlier prevention efforts focused on weight loss, because years lived with obesity are associated with future CVD, so every year counts,” Dr. Khan said.
Does BMI remain elevated, predict worse heart health?
Although obesity is a well-recognized risk factor for CVD, long-term changes in BMI and the impact of BMI on the risk for heart failure, CVD, and mortality have not been quantified among adults with overweight and obesity, Dr. Iyen and colleagues explained.
The researchers examined data from the UK Clinical Practice Research Datalink and secondary care and mortality records to determine BMI trajectories among adults with overweight or obesity and to quantify the risk for heart failure, CVD (defined as coronary heart disease, stroke, transient ischemic attack, or peripheral vascular disease, CVD-related mortality, and all-cause mortality.
They identified 264,230 adults with overweight or obesity who were seen in 790 primary care practices in the United Kingdom from 1999 to 2018 and who did not initially have heart failure or CVD and for whom baseline BMI measurements and at least one other BMI measurement 2, 5, 8, and 10 years later was available.
The researchers divided the cohort into four groups on the basis of initial BMI: overweight (36% of patients; mean BMI, 28.7 kg/m2); class 1 obesity (40%; mean BMI, 33.7 kg/m2); class 2 obesity (19%; mean BMI, 39.9 kg/m2), and class 3 obesity (5%; mean BMI, 49.1 kg/m2).
The mean age of the individuals was 50 years, and 64% were White. Race/ethnicity data were unavailable for 31%. Asian Indian, Asian, and Black patients comprised 5% of the cohort.
“Strong significant gradient in heart failure risk”
Compared to the overweight (reference) group, the severe-obesity group comprised a higher percentage of women (74% vs. 70%), and the prevalence of comorbidities and socioeconomic deprivation was higher.
BMI remained relatively stable in each BMI group. The mean BMI increase was 1.06 kg/m2 during a median follow-up of 10.9 years.
There were 30,400 incident cases of CVD, 7,662 incident cases of heart failure, and 24,022 deaths, of which 2,827 (11.8%) were from CVD.
The risk for heart failure and CVD-related or all-cause mortality increased with increasing obesity severity.
Compared with overweight individuals, those with class 3 obesity were at significantly increased risk for heart failure (hazard ratio [HR], 3.26), all-cause mortality (HR, 2.72), and CVD-related mortality (HR, 3.31) after adjustment for age, sex, and comorbidities (hypertension, type 2 diabetes, atrial fibrillation, and chronic kidney disease).
The risk for stroke/TIA or coronary heart disease was similar among those with severe obesity and the other individuals. The risk for PVD was significantly lower (HR, 0.73).
The reduced risk for PVD in the most severely obese group is similar to findings in the Framingham heart study, the authors noted, and may be due to underdiagnosis or differences in the underlying mechanism.
Compelling evidence of poor health outcomes associated with obesity
Study limitations include the fact that the findings may not be generalizable to other race/ethnicity groups, the lack of information on diet and exercise, and the fact that BMI was used as a surrogate of adiposity. As such, it does not account for an age-related decrease in heavier-than-fat muscle mass and differences between sexes and ethnic groups.
The finding of stable obesity over time accords with two smaller studies that included Canadian and American adults.
The current study did not uncover an obesity paradox, unlike some studies that included patients with preexisting CVD or a history of acute coronary events. Those studies reported better clinical outcomes among patients with overweight or obesity.
The current study included individuals who did not initially have CVD. Those with more severe obesity were younger than individuals with overweight at the time of the occurrence of incident CVD (age 64 vs. 66) and at the age of death (age 67 vs. age 75), which “provides compelling evidence of poor health outcomes associated with obesity,” the authors emphasized.
“Further research is ... needed to explore whether interventions to change BMI trajectories would have an impact on future CVD outcomes,” they concluded.
Dr. Iyen’s clinical academic lectureship is fully funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and are not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. Dr. Khan has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Eating more fat may boost borderline low testosterone
Low-fat diets appear to decrease testosterone levels in men, but further randomized, controlled trials are needed to confirm this effect, the authors of a meta-analysis of six small intervention studies concluded.
A total of 206 healthy men with normal testosterone received a high-fat diet followed by a low-fat diet (or vice versa), and their mean total testosterone levels were 10%-15% lower (but still in the normal range) during the low-fat diet.
The study by registered nutritionist Joseph Whittaker, MSc, University of Worcester (England), and statistician Kexin Wu, MSc, University of Warwick, Coventry, England, was published online in the Journal of Steroid Biochemistry and Molecular Biology.
“I think our results are consistent and fairly strong, but they are not strong enough to give blanket recommendations,” Mr. Whittaker said in an interview.
However, “if somebody has low testosterone, particularly borderline, they could try increasing their fat intake, maybe on a Mediterranean diet,” he said, and see if that works to increase their testosterone by 60 ng/dL, the weighted mean difference in total testosterone levels between the low-fat versus high-fat diet interventions in this meta-analysis.
“A Mediterranean diet is a good way to increase ‘healthy fats,’ mono- and polyunsaturated fatty acids, which will likely decrease cardiovascular disease risk, and boost testosterone at the same time,” Mr. Whittaker noted.
Olive oil has been shown to boost testosterone more than butter, and it also reduces CVD, he continued. Nuts are high in “healthy fats” and consistently decrease CVD and mortality and may boost testosterone. Other sources of “good fat” in a healthy diet include avocado, and red meat and poultry in moderation.
“It is controversial, but our results also indicate that foods with saturated fatty acids may boost testosterone,” he added, noting however that such foods are also associated with an increase in cholesterol.
Is waning testosterone explained by leaner diet?
Men need healthy testosterone levels for good physical performance, mental health, and sexual health, and low levels are associated with a higher risk of heart disease, diabetes, and Alzheimer’s disease, according to a statement about this research issued by the University of Worcester.
Although testosterone levels do decline with advancing age, there has also been an additional age-independent and persistent decline in testosterone levels that began roughly after nutrition guidelines began recommending a lower-fat diet in 1965.
Fat consumption dropped from 45% of the diet in 1965 to 35% of the diet in 1991, and stayed around that lower level through to 2011.
However, it is not clear if this decrease in dietary fat intake might explain part of the concurrent decline in men’s testosterone levels.
Mr. Whittaker and Mr. Wu conducted a systematic literature review and identified six crossover intervention studies that compared testosterone levels during low-fat versus high-fat diets – Dorgan 1996, Wang 2005, Hamalainen 1984, Hill 1980, Reed 1987, and Hill 1979 – and then they combined these studies in a meta-analysis.
Five studies each enrolled 6-43 healthy men from North America, the United Kingdom, and Scandinavia, and the sixth study (Hill 1980) enrolled 34 healthy men from North America and 39 farm laborers from South Africa.
Overall, on average, the men were aged 34-54 years and slightly overweight (a mean body mass index of roughly 27 kg/m2) with normal testosterone (i.e., >300 ng/dL, based on the 2018 American Urological Association guidelines criteria).
Most men received a high-fat diet (40% of calories from fat) first, followed by a low-fat diet (on average 20% of calories from fat; range, 7%-25%), but the subgroup of men from South Africa received the low-fat diet first.
To put this into context, U.K. guidelines recommend a fat intake of less than 35% of daily calories, and U.S. guidelines recommend a fat intake of 20%-35% of daily calories.
The low-and high-fat interventions ranged from 2 to 10 weeks.
Lowest testosterone levels with low-fat vegetarian diets
Overall, on average, the men’s total testosterone was 475 mg/dL when they were consuming a low-fat diet and 532 mg/dL when they were consuming a high-fat diet.
However, the South African men had higher testosterone levels when they consumed a low-fat diet. This suggests that “men with European ancestry may experience a greater decrease in testosterone in response to a low-fat diet,” the researchers wrote.
The decrease in total testosterone in the low-fat versus high-fat diet was largest (26%) in the two studies of men who consumed a vegetarian diet (Hill 1979 and Hill 1980). These diets may have been low in zinc, since a marginal zinc deficiency has been shown to decrease total testosterone, Mr. Whittaker and Mr. Wu speculated.
The meta-analysis also showed that levels of free testosterone, urinary testosterone, and dihydrotestosterone declined during the low-fat diet, whereas levels of luteinizing hormone or sex hormone binding globulin were similar with both diets.
Men with low testosterone and overweight, obesity
What nutritional advice should practitioners give to men who have low testosterone and overweight/obesity?
“If you are very overweight, losing weight is going to dramatically improve your testosterone,” Mr. Whittaker said.
However, proponents of various diets are often in stark disagreement about the merits of a low-fat versus low-carbohydrate diet to lose weight.
“In general,” he continued, “the literature shows low-carb (high-fat) diets are better for weight loss [although many will disagree with that statement].”
Although nutrition guidelines have stressed the importance of limiting fat intake, fat in the diet is also associated with lower triglyceride levels and blood pressure and higher HDL cholesterol levels, and now in this study, higher testosterone levels.
More research needed
The researchers acknowledge study limitations: The meta-analysis included just a few small studies with heterogeneous designs and findings, and there was possible bias from confounding variables.
“Ideally, we would like to see a few more studies to confirm our results,” Mr. Whittaker said in the statement. “However, these studies may never come; normally researchers want to find new results, not replicate old ones. In the meantime, men with low testosterone would be wise to avoid low-fat diets.”
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Low-fat diets appear to decrease testosterone levels in men, but further randomized, controlled trials are needed to confirm this effect, the authors of a meta-analysis of six small intervention studies concluded.
A total of 206 healthy men with normal testosterone received a high-fat diet followed by a low-fat diet (or vice versa), and their mean total testosterone levels were 10%-15% lower (but still in the normal range) during the low-fat diet.
The study by registered nutritionist Joseph Whittaker, MSc, University of Worcester (England), and statistician Kexin Wu, MSc, University of Warwick, Coventry, England, was published online in the Journal of Steroid Biochemistry and Molecular Biology.
“I think our results are consistent and fairly strong, but they are not strong enough to give blanket recommendations,” Mr. Whittaker said in an interview.
However, “if somebody has low testosterone, particularly borderline, they could try increasing their fat intake, maybe on a Mediterranean diet,” he said, and see if that works to increase their testosterone by 60 ng/dL, the weighted mean difference in total testosterone levels between the low-fat versus high-fat diet interventions in this meta-analysis.
“A Mediterranean diet is a good way to increase ‘healthy fats,’ mono- and polyunsaturated fatty acids, which will likely decrease cardiovascular disease risk, and boost testosterone at the same time,” Mr. Whittaker noted.
Olive oil has been shown to boost testosterone more than butter, and it also reduces CVD, he continued. Nuts are high in “healthy fats” and consistently decrease CVD and mortality and may boost testosterone. Other sources of “good fat” in a healthy diet include avocado, and red meat and poultry in moderation.
“It is controversial, but our results also indicate that foods with saturated fatty acids may boost testosterone,” he added, noting however that such foods are also associated with an increase in cholesterol.
Is waning testosterone explained by leaner diet?
Men need healthy testosterone levels for good physical performance, mental health, and sexual health, and low levels are associated with a higher risk of heart disease, diabetes, and Alzheimer’s disease, according to a statement about this research issued by the University of Worcester.
Although testosterone levels do decline with advancing age, there has also been an additional age-independent and persistent decline in testosterone levels that began roughly after nutrition guidelines began recommending a lower-fat diet in 1965.
Fat consumption dropped from 45% of the diet in 1965 to 35% of the diet in 1991, and stayed around that lower level through to 2011.
However, it is not clear if this decrease in dietary fat intake might explain part of the concurrent decline in men’s testosterone levels.
Mr. Whittaker and Mr. Wu conducted a systematic literature review and identified six crossover intervention studies that compared testosterone levels during low-fat versus high-fat diets – Dorgan 1996, Wang 2005, Hamalainen 1984, Hill 1980, Reed 1987, and Hill 1979 – and then they combined these studies in a meta-analysis.
Five studies each enrolled 6-43 healthy men from North America, the United Kingdom, and Scandinavia, and the sixth study (Hill 1980) enrolled 34 healthy men from North America and 39 farm laborers from South Africa.
Overall, on average, the men were aged 34-54 years and slightly overweight (a mean body mass index of roughly 27 kg/m2) with normal testosterone (i.e., >300 ng/dL, based on the 2018 American Urological Association guidelines criteria).
Most men received a high-fat diet (40% of calories from fat) first, followed by a low-fat diet (on average 20% of calories from fat; range, 7%-25%), but the subgroup of men from South Africa received the low-fat diet first.
To put this into context, U.K. guidelines recommend a fat intake of less than 35% of daily calories, and U.S. guidelines recommend a fat intake of 20%-35% of daily calories.
The low-and high-fat interventions ranged from 2 to 10 weeks.
Lowest testosterone levels with low-fat vegetarian diets
Overall, on average, the men’s total testosterone was 475 mg/dL when they were consuming a low-fat diet and 532 mg/dL when they were consuming a high-fat diet.
However, the South African men had higher testosterone levels when they consumed a low-fat diet. This suggests that “men with European ancestry may experience a greater decrease in testosterone in response to a low-fat diet,” the researchers wrote.
The decrease in total testosterone in the low-fat versus high-fat diet was largest (26%) in the two studies of men who consumed a vegetarian diet (Hill 1979 and Hill 1980). These diets may have been low in zinc, since a marginal zinc deficiency has been shown to decrease total testosterone, Mr. Whittaker and Mr. Wu speculated.
The meta-analysis also showed that levels of free testosterone, urinary testosterone, and dihydrotestosterone declined during the low-fat diet, whereas levels of luteinizing hormone or sex hormone binding globulin were similar with both diets.
Men with low testosterone and overweight, obesity
What nutritional advice should practitioners give to men who have low testosterone and overweight/obesity?
“If you are very overweight, losing weight is going to dramatically improve your testosterone,” Mr. Whittaker said.
However, proponents of various diets are often in stark disagreement about the merits of a low-fat versus low-carbohydrate diet to lose weight.
“In general,” he continued, “the literature shows low-carb (high-fat) diets are better for weight loss [although many will disagree with that statement].”
Although nutrition guidelines have stressed the importance of limiting fat intake, fat in the diet is also associated with lower triglyceride levels and blood pressure and higher HDL cholesterol levels, and now in this study, higher testosterone levels.
More research needed
The researchers acknowledge study limitations: The meta-analysis included just a few small studies with heterogeneous designs and findings, and there was possible bias from confounding variables.
“Ideally, we would like to see a few more studies to confirm our results,” Mr. Whittaker said in the statement. “However, these studies may never come; normally researchers want to find new results, not replicate old ones. In the meantime, men with low testosterone would be wise to avoid low-fat diets.”
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Low-fat diets appear to decrease testosterone levels in men, but further randomized, controlled trials are needed to confirm this effect, the authors of a meta-analysis of six small intervention studies concluded.
A total of 206 healthy men with normal testosterone received a high-fat diet followed by a low-fat diet (or vice versa), and their mean total testosterone levels were 10%-15% lower (but still in the normal range) during the low-fat diet.
The study by registered nutritionist Joseph Whittaker, MSc, University of Worcester (England), and statistician Kexin Wu, MSc, University of Warwick, Coventry, England, was published online in the Journal of Steroid Biochemistry and Molecular Biology.
“I think our results are consistent and fairly strong, but they are not strong enough to give blanket recommendations,” Mr. Whittaker said in an interview.
However, “if somebody has low testosterone, particularly borderline, they could try increasing their fat intake, maybe on a Mediterranean diet,” he said, and see if that works to increase their testosterone by 60 ng/dL, the weighted mean difference in total testosterone levels between the low-fat versus high-fat diet interventions in this meta-analysis.
“A Mediterranean diet is a good way to increase ‘healthy fats,’ mono- and polyunsaturated fatty acids, which will likely decrease cardiovascular disease risk, and boost testosterone at the same time,” Mr. Whittaker noted.
Olive oil has been shown to boost testosterone more than butter, and it also reduces CVD, he continued. Nuts are high in “healthy fats” and consistently decrease CVD and mortality and may boost testosterone. Other sources of “good fat” in a healthy diet include avocado, and red meat and poultry in moderation.
“It is controversial, but our results also indicate that foods with saturated fatty acids may boost testosterone,” he added, noting however that such foods are also associated with an increase in cholesterol.
Is waning testosterone explained by leaner diet?
Men need healthy testosterone levels for good physical performance, mental health, and sexual health, and low levels are associated with a higher risk of heart disease, diabetes, and Alzheimer’s disease, according to a statement about this research issued by the University of Worcester.
Although testosterone levels do decline with advancing age, there has also been an additional age-independent and persistent decline in testosterone levels that began roughly after nutrition guidelines began recommending a lower-fat diet in 1965.
Fat consumption dropped from 45% of the diet in 1965 to 35% of the diet in 1991, and stayed around that lower level through to 2011.
However, it is not clear if this decrease in dietary fat intake might explain part of the concurrent decline in men’s testosterone levels.
Mr. Whittaker and Mr. Wu conducted a systematic literature review and identified six crossover intervention studies that compared testosterone levels during low-fat versus high-fat diets – Dorgan 1996, Wang 2005, Hamalainen 1984, Hill 1980, Reed 1987, and Hill 1979 – and then they combined these studies in a meta-analysis.
Five studies each enrolled 6-43 healthy men from North America, the United Kingdom, and Scandinavia, and the sixth study (Hill 1980) enrolled 34 healthy men from North America and 39 farm laborers from South Africa.
Overall, on average, the men were aged 34-54 years and slightly overweight (a mean body mass index of roughly 27 kg/m2) with normal testosterone (i.e., >300 ng/dL, based on the 2018 American Urological Association guidelines criteria).
Most men received a high-fat diet (40% of calories from fat) first, followed by a low-fat diet (on average 20% of calories from fat; range, 7%-25%), but the subgroup of men from South Africa received the low-fat diet first.
To put this into context, U.K. guidelines recommend a fat intake of less than 35% of daily calories, and U.S. guidelines recommend a fat intake of 20%-35% of daily calories.
The low-and high-fat interventions ranged from 2 to 10 weeks.
Lowest testosterone levels with low-fat vegetarian diets
Overall, on average, the men’s total testosterone was 475 mg/dL when they were consuming a low-fat diet and 532 mg/dL when they were consuming a high-fat diet.
However, the South African men had higher testosterone levels when they consumed a low-fat diet. This suggests that “men with European ancestry may experience a greater decrease in testosterone in response to a low-fat diet,” the researchers wrote.
The decrease in total testosterone in the low-fat versus high-fat diet was largest (26%) in the two studies of men who consumed a vegetarian diet (Hill 1979 and Hill 1980). These diets may have been low in zinc, since a marginal zinc deficiency has been shown to decrease total testosterone, Mr. Whittaker and Mr. Wu speculated.
The meta-analysis also showed that levels of free testosterone, urinary testosterone, and dihydrotestosterone declined during the low-fat diet, whereas levels of luteinizing hormone or sex hormone binding globulin were similar with both diets.
Men with low testosterone and overweight, obesity
What nutritional advice should practitioners give to men who have low testosterone and overweight/obesity?
“If you are very overweight, losing weight is going to dramatically improve your testosterone,” Mr. Whittaker said.
However, proponents of various diets are often in stark disagreement about the merits of a low-fat versus low-carbohydrate diet to lose weight.
“In general,” he continued, “the literature shows low-carb (high-fat) diets are better for weight loss [although many will disagree with that statement].”
Although nutrition guidelines have stressed the importance of limiting fat intake, fat in the diet is also associated with lower triglyceride levels and blood pressure and higher HDL cholesterol levels, and now in this study, higher testosterone levels.
More research needed
The researchers acknowledge study limitations: The meta-analysis included just a few small studies with heterogeneous designs and findings, and there was possible bias from confounding variables.
“Ideally, we would like to see a few more studies to confirm our results,” Mr. Whittaker said in the statement. “However, these studies may never come; normally researchers want to find new results, not replicate old ones. In the meantime, men with low testosterone would be wise to avoid low-fat diets.”
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.