Lipid Disorders

The relationship between estrogen levels and heart health makes it particularly important for clinicians to be aware of those patients who might be at risk for cardiovascular disease despite not having other traditional risk factors, according to a presentation Oct. 12 at the North American Menopause Society annual meeting in Atlanta.

”Endogenous estrogens are protective for cardiovascular disease in premenopausal women,” Chrisandra L. Shufelt, MD, chair of the division of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Fla., told attendees. Yet, “a substantial population of young women are dying prematurely from cardiovascular disease,” with rates of cardiovascular death increasing in women aged 35-44 even as rates have decreased in postmenopausal women and in men. One potential reason may be premature estrogen loss.

Dr. Shufelt reminded attendees of four major causes of premature estrogen loss: Natural premature menopause, surgical menopause, chemotherapy-induced menopause, and premature ovarian insufficiency. But she would go on to discuss a less widely recognized condition, functional hypothalamic amenorrhea, that also may be contributing to increased cardiovascular risk.

First, Dr. Shufelt reviewed the evidence supporting the relationship between estrogen and cardiovascular health, starting with the Framingham study’s findings that cardiovascular disease is approximately two to four times more common in postmenopausal women than in premenopausal women, depending on the age range.

“Menopause at an early age, particularly under the age of 40, matters,” Dr. Shufelt said. “So we should be discussing this with our patients.”

Surgical menopause makes a difference to cardiovascular health as well, she said. In women under age 35, for example, the risk of a nonfatal heart attack in those with a bilateral oophorectomy was 7.7 times greater than in women who retained both ovaries and their uterus, and 1.5 times greater in women who had a hysterectomy without bilateral oophorectomy.

In a 2019 study, surgical premature menopause was associated with an 87% increased risk of heart disease even after researchers accounted for age, cardiovascular risk factors, and some forms of hormone therapy. The increased risk from natural premature menopause, on the other hand, was lower – a 36% increased risk of heart disease – compared with those producing endogenous hormones. Although randomized controlled trials are unavailable and unlikely to be done, the Nurses’ Health Study and the Danish Nurses Cohort Study, both observational studies, found that heart disease risk was diminished in those taking hormone therapy after surgical premature menopause.

Recommendations for premature or early menopause, from a wide range of different medical societies including NAMS, are that women without contraindications be given estrogen-based hormone therapy until the average age of natural menopause. Though not included in the same guidance, research has also shown that estrogen after oophorectomy does not increase the risk of breast cancer in women with a BRCA1 mutation, Dr. Shufelt said. Hormone therapy for premature or early menopause should adequately replace the levels women have lost and that means younger menopausal women often need higher doses than what older women receive, such as 2 mg/day of oral estradiol rather than the standard doses of 0.5 or 1 mg/day.
 

Functional hypothalamic amenorrhea and cardiovascular risk

Dr. Shufelt then discussed functional hypothalamic amenorrhea (hypogonadotropic hypogonadism), a common type of secondary amenorrhea that affects at least 1.4 million U.S. women. Diagnosis includes lack of a period for at least 3 months in someone who previously menstruated plus lab values below 50 pg/mL for estradiol, below 10 mIU/L for follicle stimulating hormone, and below 10 mIU/L for luteinizing hormone. Causes of this reversible form of infertility can include stress, overexercising, undereating, or some combination of these, plus an underlying genetic predisposition.

“After ruling out polycystic ovary syndrome, prolactinoma, and thyroid dysfunction, clinicians need to consider the diagnosis of hypothalamic amenorrhea,” Dr. Shufelt said. This condition goes beyond low estrogen levels: Women have elevated cortisol, low thyroid levels, low leptin levels, and increased ghrelin.

”This is not going away,” Dr. Shufelt said, sharing data on stress levels among U.S. adults, particularly Gen Z and millennial adults, noting that the ongoing “national mental health crisis” may be contributing to functional hypothalamic amenorrhea.

A 2020 substudy from the Nurses’ Health Study II found an increased risk of premature death in those who didn’t have a period or always had irregular periods starting as early as 14-17 years old. The increased risk of premature death rose with age in those with irregular or absent cycles – a 37% higher risk in 18- to 22-year-olds and a 39% increased risk in 29- to 46-year-olds.

But clinicians aren’t adequately identifying the “phenotype of the hypothalamic women,” Dr. Shufelt said, despite research showing overlap between hypothalamic amenorrhea and a higher risk of cardiovascular disease. Hypothalamic amenorrhea is so understudied that the last original research on the topic was in 2008, Dr. Shufelt said in an interview. ”No research except mine has been done to evaluate heart health in these young women,” she said.

Dr. Shufelt described a study she led involving 30 women with functional hypothalamic amenorrhea, 29 women with normal menstrual cycles, and 30 women who were recently menopausal and not on hormone therapy. The women with hypothalamic amenorrhea had average stress levels but their depression scores were higher than those of the other two groups.

The results showed that women with hypothalamic amenorrhea had lower estradiol and leptin levels and higher testosterone levels compared with the control group, and they had higher cortisol levels than those of both groups. Despite having similar body mass indexes as the control and menopausal groups, women with hypothalamic amenorrhea had lower blood pressure than that of the other two groups, yet they had higher cholesterol levels than those of the control group. EndoPAT^© (Itamar Medical) testing showed that they had poor vascular function.

“In fact, one-third of the women [with hypothalamic amenorrhea] entered the trial with a diagnosis of what would be considered endothelial dysfunction,” Dr. Shufelt said. “Our results demonstrated significantly higher circulating levels of serum proinflammatory cytokines in the women with hypothalamic amenorrhea compared to eumenorrheic controls.”

Dr. Shufelt’s team then tested whether giving estradiol to the women with hypothalamic amenorrhea for 12 weeks would improve their vascular health, but they saw no significant differences between the women who received estrogen and those who received placebo.

“Endothelial function is partly mediated by estrogen, and it was expected that giving back estrogen would ‘fix’ the endothelium, but that is not what happened,” Nanette Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado at Denver, Aurora, said in interview. “The mechanisms that maintain vascular function in women are not limited to hormones,” said Dr. Santoro, who was not involved in Dr. Shufelt’s study but attended her lecture. “We need to think beyond the simple model of estrogen-good, no-estrogen-bad.”

Dr. Santoro noted how easy it is to overlook the women who may have cardiovascular risk because of hypothalamic amenorrhea.

“Because many women with functional hypothalamic amenorrhea are super athletic and do not have the typical features of people with cardiometabolic disease – such as glucose intolerance, obesity, abnormal cholesterol or triglycerides, or high blood pressure – clinicians tend to think of them as healthy and to think that simply giving back hormones will fix the problems with bone density and vascular function, but that is not enough,” Dr. Santoro said. “The cognitive-behavioral therapy model for treatment of women with functional hypothalamic amenorrhea addresses the stress-related factors that drive the disorder, and this needs to be considered the standard of care for treatment.”

Stephanie S. Faubion, MD, professor of medicine and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Fla., who was not involved in Dr. Shufelt’s presentation, also emphasized the importance of recognizing functional hypothalamic amenorrhea.

“This is an underrecognized entity to begin with, and the fact that these women appear to be at increased risk for vascular dysfunction and potentially increased risk for cardiovascular disease down the road makes it even more important for clinicians to identify them and provide interventions early on,” Dr. Faubion said in an interview. “These women need to be identified and the etiology of the amenorrhea addressed, whether it relates to overexercising, being underweight, or experiencing significant stressors that have led to the loss of menstrual cycles.”

Dr. Shufelt’s research was funded by the National Institutes of Health. She had no disclosures. Dr. Santoro is a member of the scientific advisory board for Astellas, Menogenix, Amazon Ember, and Que Oncology, and she consults for Ansh Labs. Dr. Faubion had no disclosures.

The relationship between estrogen levels and heart health makes it particularly important for clinicians to be aware of those patients who might be at risk for cardiovascular disease despite not having other traditional risk factors, according to a presentation Oct. 12 at the North American Menopause Society annual meeting in Atlanta.

”Endogenous estrogens are protective for cardiovascular disease in premenopausal women,” Chrisandra L. Shufelt, MD, chair of the division of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Fla., told attendees. Yet, “a substantial population of young women are dying prematurely from cardiovascular disease,” with rates of cardiovascular death increasing in women aged 35-44 even as rates have decreased in postmenopausal women and in men. One potential reason may be premature estrogen loss.

Dr. Shufelt reminded attendees of four major causes of premature estrogen loss: Natural premature menopause, surgical menopause, chemotherapy-induced menopause, and premature ovarian insufficiency. But she would go on to discuss a less widely recognized condition, functional hypothalamic amenorrhea, that also may be contributing to increased cardiovascular risk.

First, Dr. Shufelt reviewed the evidence supporting the relationship between estrogen and cardiovascular health, starting with the Framingham study’s findings that cardiovascular disease is approximately two to four times more common in postmenopausal women than in premenopausal women, depending on the age range.

“Menopause at an early age, particularly under the age of 40, matters,” Dr. Shufelt said. “So we should be discussing this with our patients.”

Surgical menopause makes a difference to cardiovascular health as well, she said. In women under age 35, for example, the risk of a nonfatal heart attack in those with a bilateral oophorectomy was 7.7 times greater than in women who retained both ovaries and their uterus, and 1.5 times greater in women who had a hysterectomy without bilateral oophorectomy.

In a 2019 study, surgical premature menopause was associated with an 87% increased risk of heart disease even after researchers accounted for age, cardiovascular risk factors, and some forms of hormone therapy. The increased risk from natural premature menopause, on the other hand, was lower – a 36% increased risk of heart disease – compared with those producing endogenous hormones. Although randomized controlled trials are unavailable and unlikely to be done, the Nurses’ Health Study and the Danish Nurses Cohort Study, both observational studies, found that heart disease risk was diminished in those taking hormone therapy after surgical premature menopause.

Recommendations for premature or early menopause, from a wide range of different medical societies including NAMS, are that women without contraindications be given estrogen-based hormone therapy until the average age of natural menopause. Though not included in the same guidance, research has also shown that estrogen after oophorectomy does not increase the risk of breast cancer in women with a BRCA1 mutation, Dr. Shufelt said. Hormone therapy for premature or early menopause should adequately replace the levels women have lost and that means younger menopausal women often need higher doses than what older women receive, such as 2 mg/day of oral estradiol rather than the standard doses of 0.5 or 1 mg/day.
 

Functional hypothalamic amenorrhea and cardiovascular risk

Dr. Shufelt then discussed functional hypothalamic amenorrhea (hypogonadotropic hypogonadism), a common type of secondary amenorrhea that affects at least 1.4 million U.S. women. Diagnosis includes lack of a period for at least 3 months in someone who previously menstruated plus lab values below 50 pg/mL for estradiol, below 10 mIU/L for follicle stimulating hormone, and below 10 mIU/L for luteinizing hormone. Causes of this reversible form of infertility can include stress, overexercising, undereating, or some combination of these, plus an underlying genetic predisposition.

“After ruling out polycystic ovary syndrome, prolactinoma, and thyroid dysfunction, clinicians need to consider the diagnosis of hypothalamic amenorrhea,” Dr. Shufelt said. This condition goes beyond low estrogen levels: Women have elevated cortisol, low thyroid levels, low leptin levels, and increased ghrelin.

”This is not going away,” Dr. Shufelt said, sharing data on stress levels among U.S. adults, particularly Gen Z and millennial adults, noting that the ongoing “national mental health crisis” may be contributing to functional hypothalamic amenorrhea.

A 2020 substudy from the Nurses’ Health Study II found an increased risk of premature death in those who didn’t have a period or always had irregular periods starting as early as 14-17 years old. The increased risk of premature death rose with age in those with irregular or absent cycles – a 37% higher risk in 18- to 22-year-olds and a 39% increased risk in 29- to 46-year-olds.

But clinicians aren’t adequately identifying the “phenotype of the hypothalamic women,” Dr. Shufelt said, despite research showing overlap between hypothalamic amenorrhea and a higher risk of cardiovascular disease. Hypothalamic amenorrhea is so understudied that the last original research on the topic was in 2008, Dr. Shufelt said in an interview. ”No research except mine has been done to evaluate heart health in these young women,” she said.

Dr. Shufelt described a study she led involving 30 women with functional hypothalamic amenorrhea, 29 women with normal menstrual cycles, and 30 women who were recently menopausal and not on hormone therapy. The women with hypothalamic amenorrhea had average stress levels but their depression scores were higher than those of the other two groups.

The results showed that women with hypothalamic amenorrhea had lower estradiol and leptin levels and higher testosterone levels compared with the control group, and they had higher cortisol levels than those of both groups. Despite having similar body mass indexes as the control and menopausal groups, women with hypothalamic amenorrhea had lower blood pressure than that of the other two groups, yet they had higher cholesterol levels than those of the control group. EndoPAT^© (Itamar Medical) testing showed that they had poor vascular function.

“In fact, one-third of the women [with hypothalamic amenorrhea] entered the trial with a diagnosis of what would be considered endothelial dysfunction,” Dr. Shufelt said. “Our results demonstrated significantly higher circulating levels of serum proinflammatory cytokines in the women with hypothalamic amenorrhea compared to eumenorrheic controls.”

Dr. Shufelt’s team then tested whether giving estradiol to the women with hypothalamic amenorrhea for 12 weeks would improve their vascular health, but they saw no significant differences between the women who received estrogen and those who received placebo.

“Endothelial function is partly mediated by estrogen, and it was expected that giving back estrogen would ‘fix’ the endothelium, but that is not what happened,” Nanette Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado at Denver, Aurora, said in interview. “The mechanisms that maintain vascular function in women are not limited to hormones,” said Dr. Santoro, who was not involved in Dr. Shufelt’s study but attended her lecture. “We need to think beyond the simple model of estrogen-good, no-estrogen-bad.”

Dr. Santoro noted how easy it is to overlook the women who may have cardiovascular risk because of hypothalamic amenorrhea.

“Because many women with functional hypothalamic amenorrhea are super athletic and do not have the typical features of people with cardiometabolic disease – such as glucose intolerance, obesity, abnormal cholesterol or triglycerides, or high blood pressure – clinicians tend to think of them as healthy and to think that simply giving back hormones will fix the problems with bone density and vascular function, but that is not enough,” Dr. Santoro said. “The cognitive-behavioral therapy model for treatment of women with functional hypothalamic amenorrhea addresses the stress-related factors that drive the disorder, and this needs to be considered the standard of care for treatment.”

Stephanie S. Faubion, MD, professor of medicine and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Fla., who was not involved in Dr. Shufelt’s presentation, also emphasized the importance of recognizing functional hypothalamic amenorrhea.

“This is an underrecognized entity to begin with, and the fact that these women appear to be at increased risk for vascular dysfunction and potentially increased risk for cardiovascular disease down the road makes it even more important for clinicians to identify them and provide interventions early on,” Dr. Faubion said in an interview. “These women need to be identified and the etiology of the amenorrhea addressed, whether it relates to overexercising, being underweight, or experiencing significant stressors that have led to the loss of menstrual cycles.”

Dr. Shufelt’s research was funded by the National Institutes of Health. She had no disclosures. Dr. Santoro is a member of the scientific advisory board for Astellas, Menogenix, Amazon Ember, and Que Oncology, and she consults for Ansh Labs. Dr. Faubion had no disclosures.

The relationship between estrogen levels and heart health makes it particularly important for clinicians to be aware of those patients who might be at risk for cardiovascular disease despite not having other traditional risk factors, according to a presentation Oct. 12 at the North American Menopause Society annual meeting in Atlanta.

”Endogenous estrogens are protective for cardiovascular disease in premenopausal women,” Chrisandra L. Shufelt, MD, chair of the division of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Fla., told attendees. Yet, “a substantial population of young women are dying prematurely from cardiovascular disease,” with rates of cardiovascular death increasing in women aged 35-44 even as rates have decreased in postmenopausal women and in men. One potential reason may be premature estrogen loss.

Dr. Shufelt reminded attendees of four major causes of premature estrogen loss: Natural premature menopause, surgical menopause, chemotherapy-induced menopause, and premature ovarian insufficiency. But she would go on to discuss a less widely recognized condition, functional hypothalamic amenorrhea, that also may be contributing to increased cardiovascular risk.

First, Dr. Shufelt reviewed the evidence supporting the relationship between estrogen and cardiovascular health, starting with the Framingham study’s findings that cardiovascular disease is approximately two to four times more common in postmenopausal women than in premenopausal women, depending on the age range.

“Menopause at an early age, particularly under the age of 40, matters,” Dr. Shufelt said. “So we should be discussing this with our patients.”

Surgical menopause makes a difference to cardiovascular health as well, she said. In women under age 35, for example, the risk of a nonfatal heart attack in those with a bilateral oophorectomy was 7.7 times greater than in women who retained both ovaries and their uterus, and 1.5 times greater in women who had a hysterectomy without bilateral oophorectomy.

In a 2019 study, surgical premature menopause was associated with an 87% increased risk of heart disease even after researchers accounted for age, cardiovascular risk factors, and some forms of hormone therapy. The increased risk from natural premature menopause, on the other hand, was lower – a 36% increased risk of heart disease – compared with those producing endogenous hormones. Although randomized controlled trials are unavailable and unlikely to be done, the Nurses’ Health Study and the Danish Nurses Cohort Study, both observational studies, found that heart disease risk was diminished in those taking hormone therapy after surgical premature menopause.

Recommendations for premature or early menopause, from a wide range of different medical societies including NAMS, are that women without contraindications be given estrogen-based hormone therapy until the average age of natural menopause. Though not included in the same guidance, research has also shown that estrogen after oophorectomy does not increase the risk of breast cancer in women with a BRCA1 mutation, Dr. Shufelt said. Hormone therapy for premature or early menopause should adequately replace the levels women have lost and that means younger menopausal women often need higher doses than what older women receive, such as 2 mg/day of oral estradiol rather than the standard doses of 0.5 or 1 mg/day.
 

Functional hypothalamic amenorrhea and cardiovascular risk

Dr. Shufelt then discussed functional hypothalamic amenorrhea (hypogonadotropic hypogonadism), a common type of secondary amenorrhea that affects at least 1.4 million U.S. women. Diagnosis includes lack of a period for at least 3 months in someone who previously menstruated plus lab values below 50 pg/mL for estradiol, below 10 mIU/L for follicle stimulating hormone, and below 10 mIU/L for luteinizing hormone. Causes of this reversible form of infertility can include stress, overexercising, undereating, or some combination of these, plus an underlying genetic predisposition.

“After ruling out polycystic ovary syndrome, prolactinoma, and thyroid dysfunction, clinicians need to consider the diagnosis of hypothalamic amenorrhea,” Dr. Shufelt said. This condition goes beyond low estrogen levels: Women have elevated cortisol, low thyroid levels, low leptin levels, and increased ghrelin.

”This is not going away,” Dr. Shufelt said, sharing data on stress levels among U.S. adults, particularly Gen Z and millennial adults, noting that the ongoing “national mental health crisis” may be contributing to functional hypothalamic amenorrhea.

A 2020 substudy from the Nurses’ Health Study II found an increased risk of premature death in those who didn’t have a period or always had irregular periods starting as early as 14-17 years old. The increased risk of premature death rose with age in those with irregular or absent cycles – a 37% higher risk in 18- to 22-year-olds and a 39% increased risk in 29- to 46-year-olds.

But clinicians aren’t adequately identifying the “phenotype of the hypothalamic women,” Dr. Shufelt said, despite research showing overlap between hypothalamic amenorrhea and a higher risk of cardiovascular disease. Hypothalamic amenorrhea is so understudied that the last original research on the topic was in 2008, Dr. Shufelt said in an interview. ”No research except mine has been done to evaluate heart health in these young women,” she said.

Dr. Shufelt described a study she led involving 30 women with functional hypothalamic amenorrhea, 29 women with normal menstrual cycles, and 30 women who were recently menopausal and not on hormone therapy. The women with hypothalamic amenorrhea had average stress levels but their depression scores were higher than those of the other two groups.

The results showed that women with hypothalamic amenorrhea had lower estradiol and leptin levels and higher testosterone levels compared with the control group, and they had higher cortisol levels than those of both groups. Despite having similar body mass indexes as the control and menopausal groups, women with hypothalamic amenorrhea had lower blood pressure than that of the other two groups, yet they had higher cholesterol levels than those of the control group. EndoPAT^© (Itamar Medical) testing showed that they had poor vascular function.

“In fact, one-third of the women [with hypothalamic amenorrhea] entered the trial with a diagnosis of what would be considered endothelial dysfunction,” Dr. Shufelt said. “Our results demonstrated significantly higher circulating levels of serum proinflammatory cytokines in the women with hypothalamic amenorrhea compared to eumenorrheic controls.”

Dr. Shufelt’s team then tested whether giving estradiol to the women with hypothalamic amenorrhea for 12 weeks would improve their vascular health, but they saw no significant differences between the women who received estrogen and those who received placebo.

“Endothelial function is partly mediated by estrogen, and it was expected that giving back estrogen would ‘fix’ the endothelium, but that is not what happened,” Nanette Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado at Denver, Aurora, said in interview. “The mechanisms that maintain vascular function in women are not limited to hormones,” said Dr. Santoro, who was not involved in Dr. Shufelt’s study but attended her lecture. “We need to think beyond the simple model of estrogen-good, no-estrogen-bad.”

Dr. Santoro noted how easy it is to overlook the women who may have cardiovascular risk because of hypothalamic amenorrhea.

“Because many women with functional hypothalamic amenorrhea are super athletic and do not have the typical features of people with cardiometabolic disease – such as glucose intolerance, obesity, abnormal cholesterol or triglycerides, or high blood pressure – clinicians tend to think of them as healthy and to think that simply giving back hormones will fix the problems with bone density and vascular function, but that is not enough,” Dr. Santoro said. “The cognitive-behavioral therapy model for treatment of women with functional hypothalamic amenorrhea addresses the stress-related factors that drive the disorder, and this needs to be considered the standard of care for treatment.”

Stephanie S. Faubion, MD, professor of medicine and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Fla., who was not involved in Dr. Shufelt’s presentation, also emphasized the importance of recognizing functional hypothalamic amenorrhea.

“This is an underrecognized entity to begin with, and the fact that these women appear to be at increased risk for vascular dysfunction and potentially increased risk for cardiovascular disease down the road makes it even more important for clinicians to identify them and provide interventions early on,” Dr. Faubion said in an interview. “These women need to be identified and the etiology of the amenorrhea addressed, whether it relates to overexercising, being underweight, or experiencing significant stressors that have led to the loss of menstrual cycles.”

Dr. Shufelt’s research was funded by the National Institutes of Health. She had no disclosures. Dr. Santoro is a member of the scientific advisory board for Astellas, Menogenix, Amazon Ember, and Que Oncology, and she consults for Ansh Labs. Dr. Faubion had no disclosures.

Results from an observational study exploring the link between dairy intake and risk of cardiovascular disease events in patients with stable angina pectoris suggest different dairy products may have different health effects.

The study, which analyzed a cohort from the Western Norway B-vitamin Intervention Trial (WENBIT), showed that higher dairy and milk consumption were associated with increased risk of mortality and stroke and butter was associated with an increased risk of acute myocardial infarction (AMI), but that cheese was associated with a decreased risk of AMI.

The findings are published in the European Journal of Preventive Cardiology.

“Dairy is a diverse food group, and different dairy products should be considered individually and not only in combination,” senior author Vegard Lysne, MSc, of the Centre for Nutrition, University of Bergen and the department of heart disease, Haukeland University Hospital, Bergen, Norway, said in an interview.

“Today’s dietary recommendations regarding dairy products are mainly based on the nutrient contents, with a focus on calcium, iodine, and saturated fat,” Dr. Lysne said.

Previous studies have indicated that different dairy products may influence cardiovascular health differently, even in opposite directions, but this has primarily been investigated in healthy populations, he noted.

“Data on CVD patients are scarce, and therefore, we wanted to investigate this in a population of patients with established CVD. Our primary aim in this study was to explore how the intake of different dairy products might be linked to cardiovascular outcomes and mortality in such a population,” he said.

The researchers analyzed 1,929 patients who had stable angina pectoris and were participants in WENBIT, a randomized, double-blind, placebo-controlled prospective secondary prevention study investigating the effect of vitamin B treatment on mortality and cardiovascular outcomes.

The majority, 80%, of the cohort were men, and the mean age of the patients was 61.8 years. In addition to stable angina pectoris, 47% of the cohort had hypertension, 31% had diabetes, and 29% were smokers. Most (90%) of the patients were taking acetylsalicylic acid, 90% were taking statins, and 77% were on beta-blockers.

Dietary data were obtained by a food frequency questionnaire that was given to patients at their first visit and returned either by mail or at a follow-up visit 1 month after the initial visit.

Frequency of consumption was given as times per day, week, month, or never consumed. Quantity was estimated using units such as slices, pieces, etc., or household measures.

The milk variable included high-fat, low-fat, skimmed, or unspecified milk. Cheese included brown cheese, which is a Norwegian caramel-like cheese made from whey, milk, and cream; white cheese; cream cheeses; cooked or processed cheeses; and boxed cheeses.

Total dairy was calculated as the sum, in grams, of milk, cheese, yogurt, cream, sour cream, ice cream, and butter.

Median follow-up times were 5.2 years for stroke, 7.8 years for AMI, and 14.1 years for mortality.

Patients who reported a higher intake of total dairy and milk had a higher risk of stroke and mortality.

Among those who reported a higher intake of total dairy, the hazard ratio for stroke was 1.4 (95% confidence interval [CI], 1.02-1.27).

Among those who reported a higher intake of milk, the HR for stroke was 1.13 (95% CI, 1.02-1.27).

Cardiovascular mortality appeared heightened in those who reported a higher intake of total dairy (HR, 1.06; 95% CI, 1.00-1.12) and in those who reported a higher intake of milk (HR, 1.07; 95% CI, 1.01-1.13).

Similarly, all-cause mortality was greater in those who reported higher total dairy consumption (HR, 1.07; 95% CI, 1.03-1.11) and in those who reported higher milk consumption (HR, 1.06; 95% CI, 1.03-1.10).

Higher cheese intake was inversely associated with AMI risk (HR, 0.92; 95% CI, 0.83-1.02).

Butter was associated with increased AMI risk (HR, 1.10; 95% CI, 0.97-1.24), as well as all-cause mortality (HR, 1.10; 95% CI, 1.00-1.20).

Dr. Lysne stressed that the results are from an observational study, and that doctors should not change what they tell their patients based on the results alone.

“There is a growing literature indicating that cheese might be linked to reduced cardiovascular risk, but if this is a causal effect, or if cheese is a marker of higher socioeconomic status and a healthier overall lifestyle remains unknown,” he said.

“I would like for future studies to evaluate dairy products on an individual basis, rather than a collective one. If the data suggest that different dairy products have distinct health effects, this should be implemented in dietary recommendations,” Dr. Lysne added.
 

Dairy a heterogeneous food group

“These results are not really surprising, because we have been hearing advice to consume low-fat milk, avoid whole milk, and so on, for a long time, so this study confirms what we already know,” Qi Sun, MD, ScD, associate professor in the departments of nutrition and epidemiology, Harvard T.H. Chan School of Public Health, Boston, told this news organization.

“However, I would be more specific about milk, and I don’t see any data regarding the fat content of the different types of milk. Their data only show the association for total milk. I would like to see data for low-fat milk versus high-fat milk in relation to heart disease,” Dr. Sun said.

“They also say in their conclusion that cheese was associated with a decreased risk of acute myocardial infarction, but as the hazard ratio shows, this is a nonsignificant association,” he said.

Dr. Sun agrees that dairy is a heterogeneous group of foods and that it is best to consider each type separately with regard to cardiovascular health.

“For example, heavy cream contains tons of saturated fat, butter contains a lot of saturated fat. Then there is yogurt, which also comes in regular, reduced-fat and low-fat varieties, which is a fantastic food. I would say it’s very healthy and is associated with a lower risk of heart disease and diabetes, so a good type of dairy. Yogurt and fermented dairy products should be beneficial, at least more so than full-fat milk or butter. I think butter and full-fat milk are still the primary dairy foods for people to avoid to reduce risk for cardiovascular disease,” he said.

Dr. Lysne and Dr. Sun have disclosed no relevant financial relationships.

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

Results from an observational study exploring the link between dairy intake and risk of cardiovascular disease events in patients with stable angina pectoris suggest different dairy products may have different health effects.

The study, which analyzed a cohort from the Western Norway B-vitamin Intervention Trial (WENBIT), showed that higher dairy and milk consumption were associated with increased risk of mortality and stroke and butter was associated with an increased risk of acute myocardial infarction (AMI), but that cheese was associated with a decreased risk of AMI.

The findings are published in the European Journal of Preventive Cardiology.

“Dairy is a diverse food group, and different dairy products should be considered individually and not only in combination,” senior author Vegard Lysne, MSc, of the Centre for Nutrition, University of Bergen and the department of heart disease, Haukeland University Hospital, Bergen, Norway, said in an interview.

“Today’s dietary recommendations regarding dairy products are mainly based on the nutrient contents, with a focus on calcium, iodine, and saturated fat,” Dr. Lysne said.

Previous studies have indicated that different dairy products may influence cardiovascular health differently, even in opposite directions, but this has primarily been investigated in healthy populations, he noted.

“Data on CVD patients are scarce, and therefore, we wanted to investigate this in a population of patients with established CVD. Our primary aim in this study was to explore how the intake of different dairy products might be linked to cardiovascular outcomes and mortality in such a population,” he said.

The researchers analyzed 1,929 patients who had stable angina pectoris and were participants in WENBIT, a randomized, double-blind, placebo-controlled prospective secondary prevention study investigating the effect of vitamin B treatment on mortality and cardiovascular outcomes.

The majority, 80%, of the cohort were men, and the mean age of the patients was 61.8 years. In addition to stable angina pectoris, 47% of the cohort had hypertension, 31% had diabetes, and 29% were smokers. Most (90%) of the patients were taking acetylsalicylic acid, 90% were taking statins, and 77% were on beta-blockers.

Dietary data were obtained by a food frequency questionnaire that was given to patients at their first visit and returned either by mail or at a follow-up visit 1 month after the initial visit.

Frequency of consumption was given as times per day, week, month, or never consumed. Quantity was estimated using units such as slices, pieces, etc., or household measures.

The milk variable included high-fat, low-fat, skimmed, or unspecified milk. Cheese included brown cheese, which is a Norwegian caramel-like cheese made from whey, milk, and cream; white cheese; cream cheeses; cooked or processed cheeses; and boxed cheeses.

Total dairy was calculated as the sum, in grams, of milk, cheese, yogurt, cream, sour cream, ice cream, and butter.

Median follow-up times were 5.2 years for stroke, 7.8 years for AMI, and 14.1 years for mortality.

Patients who reported a higher intake of total dairy and milk had a higher risk of stroke and mortality.

Among those who reported a higher intake of total dairy, the hazard ratio for stroke was 1.4 (95% confidence interval [CI], 1.02-1.27).

Among those who reported a higher intake of milk, the HR for stroke was 1.13 (95% CI, 1.02-1.27).

Cardiovascular mortality appeared heightened in those who reported a higher intake of total dairy (HR, 1.06; 95% CI, 1.00-1.12) and in those who reported a higher intake of milk (HR, 1.07; 95% CI, 1.01-1.13).

Similarly, all-cause mortality was greater in those who reported higher total dairy consumption (HR, 1.07; 95% CI, 1.03-1.11) and in those who reported higher milk consumption (HR, 1.06; 95% CI, 1.03-1.10).

Higher cheese intake was inversely associated with AMI risk (HR, 0.92; 95% CI, 0.83-1.02).

Butter was associated with increased AMI risk (HR, 1.10; 95% CI, 0.97-1.24), as well as all-cause mortality (HR, 1.10; 95% CI, 1.00-1.20).

Dr. Lysne stressed that the results are from an observational study, and that doctors should not change what they tell their patients based on the results alone.

“There is a growing literature indicating that cheese might be linked to reduced cardiovascular risk, but if this is a causal effect, or if cheese is a marker of higher socioeconomic status and a healthier overall lifestyle remains unknown,” he said.

“I would like for future studies to evaluate dairy products on an individual basis, rather than a collective one. If the data suggest that different dairy products have distinct health effects, this should be implemented in dietary recommendations,” Dr. Lysne added.
 

Dairy a heterogeneous food group

“These results are not really surprising, because we have been hearing advice to consume low-fat milk, avoid whole milk, and so on, for a long time, so this study confirms what we already know,” Qi Sun, MD, ScD, associate professor in the departments of nutrition and epidemiology, Harvard T.H. Chan School of Public Health, Boston, told this news organization.

“However, I would be more specific about milk, and I don’t see any data regarding the fat content of the different types of milk. Their data only show the association for total milk. I would like to see data for low-fat milk versus high-fat milk in relation to heart disease,” Dr. Sun said.

“They also say in their conclusion that cheese was associated with a decreased risk of acute myocardial infarction, but as the hazard ratio shows, this is a nonsignificant association,” he said.

Dr. Sun agrees that dairy is a heterogeneous group of foods and that it is best to consider each type separately with regard to cardiovascular health.

“For example, heavy cream contains tons of saturated fat, butter contains a lot of saturated fat. Then there is yogurt, which also comes in regular, reduced-fat and low-fat varieties, which is a fantastic food. I would say it’s very healthy and is associated with a lower risk of heart disease and diabetes, so a good type of dairy. Yogurt and fermented dairy products should be beneficial, at least more so than full-fat milk or butter. I think butter and full-fat milk are still the primary dairy foods for people to avoid to reduce risk for cardiovascular disease,” he said.

Dr. Lysne and Dr. Sun have disclosed no relevant financial relationships.

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

Results from an observational study exploring the link between dairy intake and risk of cardiovascular disease events in patients with stable angina pectoris suggest different dairy products may have different health effects.

The study, which analyzed a cohort from the Western Norway B-vitamin Intervention Trial (WENBIT), showed that higher dairy and milk consumption were associated with increased risk of mortality and stroke and butter was associated with an increased risk of acute myocardial infarction (AMI), but that cheese was associated with a decreased risk of AMI.

The findings are published in the European Journal of Preventive Cardiology.

“Dairy is a diverse food group, and different dairy products should be considered individually and not only in combination,” senior author Vegard Lysne, MSc, of the Centre for Nutrition, University of Bergen and the department of heart disease, Haukeland University Hospital, Bergen, Norway, said in an interview.

“Today’s dietary recommendations regarding dairy products are mainly based on the nutrient contents, with a focus on calcium, iodine, and saturated fat,” Dr. Lysne said.

Previous studies have indicated that different dairy products may influence cardiovascular health differently, even in opposite directions, but this has primarily been investigated in healthy populations, he noted.

“Data on CVD patients are scarce, and therefore, we wanted to investigate this in a population of patients with established CVD. Our primary aim in this study was to explore how the intake of different dairy products might be linked to cardiovascular outcomes and mortality in such a population,” he said.

The researchers analyzed 1,929 patients who had stable angina pectoris and were participants in WENBIT, a randomized, double-blind, placebo-controlled prospective secondary prevention study investigating the effect of vitamin B treatment on mortality and cardiovascular outcomes.

The majority, 80%, of the cohort were men, and the mean age of the patients was 61.8 years. In addition to stable angina pectoris, 47% of the cohort had hypertension, 31% had diabetes, and 29% were smokers. Most (90%) of the patients were taking acetylsalicylic acid, 90% were taking statins, and 77% were on beta-blockers.

Dietary data were obtained by a food frequency questionnaire that was given to patients at their first visit and returned either by mail or at a follow-up visit 1 month after the initial visit.

Frequency of consumption was given as times per day, week, month, or never consumed. Quantity was estimated using units such as slices, pieces, etc., or household measures.

The milk variable included high-fat, low-fat, skimmed, or unspecified milk. Cheese included brown cheese, which is a Norwegian caramel-like cheese made from whey, milk, and cream; white cheese; cream cheeses; cooked or processed cheeses; and boxed cheeses.

Total dairy was calculated as the sum, in grams, of milk, cheese, yogurt, cream, sour cream, ice cream, and butter.

Median follow-up times were 5.2 years for stroke, 7.8 years for AMI, and 14.1 years for mortality.

Patients who reported a higher intake of total dairy and milk had a higher risk of stroke and mortality.

Among those who reported a higher intake of total dairy, the hazard ratio for stroke was 1.4 (95% confidence interval [CI], 1.02-1.27).

Among those who reported a higher intake of milk, the HR for stroke was 1.13 (95% CI, 1.02-1.27).

Cardiovascular mortality appeared heightened in those who reported a higher intake of total dairy (HR, 1.06; 95% CI, 1.00-1.12) and in those who reported a higher intake of milk (HR, 1.07; 95% CI, 1.01-1.13).

Similarly, all-cause mortality was greater in those who reported higher total dairy consumption (HR, 1.07; 95% CI, 1.03-1.11) and in those who reported higher milk consumption (HR, 1.06; 95% CI, 1.03-1.10).

Higher cheese intake was inversely associated with AMI risk (HR, 0.92; 95% CI, 0.83-1.02).

Butter was associated with increased AMI risk (HR, 1.10; 95% CI, 0.97-1.24), as well as all-cause mortality (HR, 1.10; 95% CI, 1.00-1.20).

Dr. Lysne stressed that the results are from an observational study, and that doctors should not change what they tell their patients based on the results alone.

“There is a growing literature indicating that cheese might be linked to reduced cardiovascular risk, but if this is a causal effect, or if cheese is a marker of higher socioeconomic status and a healthier overall lifestyle remains unknown,” he said.

“I would like for future studies to evaluate dairy products on an individual basis, rather than a collective one. If the data suggest that different dairy products have distinct health effects, this should be implemented in dietary recommendations,” Dr. Lysne added.
 

Dairy a heterogeneous food group

“These results are not really surprising, because we have been hearing advice to consume low-fat milk, avoid whole milk, and so on, for a long time, so this study confirms what we already know,” Qi Sun, MD, ScD, associate professor in the departments of nutrition and epidemiology, Harvard T.H. Chan School of Public Health, Boston, told this news organization.

“However, I would be more specific about milk, and I don’t see any data regarding the fat content of the different types of milk. Their data only show the association for total milk. I would like to see data for low-fat milk versus high-fat milk in relation to heart disease,” Dr. Sun said.

“They also say in their conclusion that cheese was associated with a decreased risk of acute myocardial infarction, but as the hazard ratio shows, this is a nonsignificant association,” he said.

Dr. Sun agrees that dairy is a heterogeneous group of foods and that it is best to consider each type separately with regard to cardiovascular health.

“For example, heavy cream contains tons of saturated fat, butter contains a lot of saturated fat. Then there is yogurt, which also comes in regular, reduced-fat and low-fat varieties, which is a fantastic food. I would say it’s very healthy and is associated with a lower risk of heart disease and diabetes, so a good type of dairy. Yogurt and fermented dairy products should be beneficial, at least more so than full-fat milk or butter. I think butter and full-fat milk are still the primary dairy foods for people to avoid to reduce risk for cardiovascular disease,” he said.

Dr. Lysne and Dr. Sun have disclosed no relevant financial relationships.

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

Cardiovascular health (CVH) scores that include sleep predicted CV disease risk among older U.S. adults, supporting the American Heart Association’s recent inclusion of sleep in its own checklist.

Sleep duration is now considered “an essential component for ideal heart and brain health,” according to the AHA’s updated checklist, now called Life’s Essential 8. “Our study is the first to show that sleep metrics add independent predictive value for CVD events over and above the original seven cardiovascular health metrics, providing support for updating the guidelines from Life’s Simple 7 (LS7) to Life’s Essential 8,” lead author Nour Makarem, PhD, of the Mailman School of Public Health at Columbia University Irving Medical Center, New York, said in an interview.

For the study, her team compared four versions of LS7 checklists that included sleep in relation to cardiovascular disease (CVD) risk.

“CVH scores that included sleep duration alone as a measure of overall sleep health, as well as scores that included multiple dimensions of sleep health (that is, sleep duration, efficiency, and regularity, daytime sleepiness, and sleep disorders), were both predictive of future CVD,” she said.

Study participants scoring in the highest tertile of the CVH checklists that included sleep had up to a 47% lower CVD risk.

Sleeping 7 hours or more but less than 9 hours nightly was considered “ideal,” according to the study, which was published online  in the Journal of the American Heart Association.
 

Lower the odds

Dr. Makarem and colleagues analyzed data from participants in the Multi-Ethnic Study of Atherosclerosis (MESA) sleep study using overnight polysomnography, 7-day wrist actigraphy, validated questionnaires, and outcomes. They used the data to evaluate the four iterations of an expanded LS7 score:

• Score 1 included sleep duration;
• Score 2 included sleep characteristics linked to CVD in the literature (sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnea [OSA]);
• Score 3 included sleep characteristics associated with CVD in MESA (sleep duration and efficiency, daytime sleepiness, and OSA); and
• Score 4, also based on CVD in MESA, included sleep regularity.

Among 1,920 participants (mean age 69 years; 54% women; 40%, White individuals), the mean LS7 score was 7.3, and the means of the alternate CVH scores that included sleep ranged from 7.4 to 7.8 (scores range from 0 to 14, with higher scores indicating better CVH).

On actigraphy, 63% of participants slept less than 7 hours; 30% slept less than 6 hours; 39% had high night-to-night variability in sleep duration; and 25% had high variability in sleep onset timing.

Overall, 10% had sleep efficiency less than 85%; 14% had excessive daytime sleepiness; 36% had high insomnia symptoms; and 47% had moderate to severe OSA. Short-duration sleepers also had a higher prevalence of overweight/obesity, diabetes, and hypertension and had lower mean LS7 scores.

During a mean follow-up of 4.4 years, 95 prevalent CVD events and 93 incident cases occurred.

Higher scores on all four expanded versions were related to lower odds of having CVD. Participants in the highest versus the lowest tertile of the LS7 score had 75% lower CVD odds (odds ratio, 0.25). Similarly, those in the highest versus the lowest tertile of CVH scores 1 and 2 had 71% and 80% lower odds of prevalent CVD (OR, 0.29 and OR, 0.20), respectively.

Overall, participants in the highest versus lowest tertile of the LS7 score and all CVH scores had up to 80% lower odds of prevalent CVD; those in the highest versus lowest tertile of CVH score 1, which included sleep duration, and CVH score 4, which included multidimensional sleep health, had 43% and 47% lower incident CVD risk (hazard ratios, 0.57 and 0.53), respectively.

The LS7 score alone was not significantly associated with CVD incidence (HR, 0.62).

“Clinicians should ask patients about their sleep health and emphasize the importance of prioritizing sleep for heart disease prevention,” Dr. Makarem said.
 

Sleep ‘devalued’

“The sleep field has been fighting to get more sleep education into medical education for decades,” AHA volunteer expert Michael A. Grandner, PhD, Director of the Sleep & Health Research Program and of the Behavioral Sleep Medicine Clinic at the University of Arizona College of Medicine, Tucson, said in an interview.

“To my knowledge, there still is not a lot of attention given to it, partly because the culture in medical school and among residents is one of not sleeping,” said Dr. Grandner, who was not involved in the study. “The culture among physicians is ‘Who needs sleep? I function fine without it.’ ”

“Sleep made it to the checklist because it is a biological requirement for human life,” he noted. “We sleep for the same reason we breathe and drink. It’s an imperative. Yet we live in a society that devalues sleep.”

It’s “extremely unusual” for a doctor to ask a patient how they’re sleeping, he said. “It’s also pretty unusual to have sleep-related conversations between doctors and patients, especially in the context of health, not just, ‘Hey, doc, I can’t sleep, throw me a pill.’”

Clinicians should be asking every patient about how they’re sleeping at every visit, Dr. Grandner said. “It’s now part of the official definition of heart health. Just like you would be remiss if you didn’t ask about smoking or test blood pressure, you’d be missing something important by not asking about sleep – something that has similar billing to diet, exercise, blood pressure, and all the other ‘essentials.’ ”

No commercial funding or conflicts of interest were declared.

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

Cardiovascular health (CVH) scores that include sleep predicted CV disease risk among older U.S. adults, supporting the American Heart Association’s recent inclusion of sleep in its own checklist.

Sleep duration is now considered “an essential component for ideal heart and brain health,” according to the AHA’s updated checklist, now called Life’s Essential 8. “Our study is the first to show that sleep metrics add independent predictive value for CVD events over and above the original seven cardiovascular health metrics, providing support for updating the guidelines from Life’s Simple 7 (LS7) to Life’s Essential 8,” lead author Nour Makarem, PhD, of the Mailman School of Public Health at Columbia University Irving Medical Center, New York, said in an interview.

For the study, her team compared four versions of LS7 checklists that included sleep in relation to cardiovascular disease (CVD) risk.

“CVH scores that included sleep duration alone as a measure of overall sleep health, as well as scores that included multiple dimensions of sleep health (that is, sleep duration, efficiency, and regularity, daytime sleepiness, and sleep disorders), were both predictive of future CVD,” she said.

Study participants scoring in the highest tertile of the CVH checklists that included sleep had up to a 47% lower CVD risk.

Sleeping 7 hours or more but less than 9 hours nightly was considered “ideal,” according to the study, which was published online  in the Journal of the American Heart Association.
 

Lower the odds

Dr. Makarem and colleagues analyzed data from participants in the Multi-Ethnic Study of Atherosclerosis (MESA) sleep study using overnight polysomnography, 7-day wrist actigraphy, validated questionnaires, and outcomes. They used the data to evaluate the four iterations of an expanded LS7 score:

• Score 1 included sleep duration;
• Score 2 included sleep characteristics linked to CVD in the literature (sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnea [OSA]);
• Score 3 included sleep characteristics associated with CVD in MESA (sleep duration and efficiency, daytime sleepiness, and OSA); and
• Score 4, also based on CVD in MESA, included sleep regularity.

Among 1,920 participants (mean age 69 years; 54% women; 40%, White individuals), the mean LS7 score was 7.3, and the means of the alternate CVH scores that included sleep ranged from 7.4 to 7.8 (scores range from 0 to 14, with higher scores indicating better CVH).

On actigraphy, 63% of participants slept less than 7 hours; 30% slept less than 6 hours; 39% had high night-to-night variability in sleep duration; and 25% had high variability in sleep onset timing.

Overall, 10% had sleep efficiency less than 85%; 14% had excessive daytime sleepiness; 36% had high insomnia symptoms; and 47% had moderate to severe OSA. Short-duration sleepers also had a higher prevalence of overweight/obesity, diabetes, and hypertension and had lower mean LS7 scores.

During a mean follow-up of 4.4 years, 95 prevalent CVD events and 93 incident cases occurred.

Higher scores on all four expanded versions were related to lower odds of having CVD. Participants in the highest versus the lowest tertile of the LS7 score had 75% lower CVD odds (odds ratio, 0.25). Similarly, those in the highest versus the lowest tertile of CVH scores 1 and 2 had 71% and 80% lower odds of prevalent CVD (OR, 0.29 and OR, 0.20), respectively.

Overall, participants in the highest versus lowest tertile of the LS7 score and all CVH scores had up to 80% lower odds of prevalent CVD; those in the highest versus lowest tertile of CVH score 1, which included sleep duration, and CVH score 4, which included multidimensional sleep health, had 43% and 47% lower incident CVD risk (hazard ratios, 0.57 and 0.53), respectively.

The LS7 score alone was not significantly associated with CVD incidence (HR, 0.62).

“Clinicians should ask patients about their sleep health and emphasize the importance of prioritizing sleep for heart disease prevention,” Dr. Makarem said.
 

Sleep ‘devalued’

“The sleep field has been fighting to get more sleep education into medical education for decades,” AHA volunteer expert Michael A. Grandner, PhD, Director of the Sleep & Health Research Program and of the Behavioral Sleep Medicine Clinic at the University of Arizona College of Medicine, Tucson, said in an interview.

“To my knowledge, there still is not a lot of attention given to it, partly because the culture in medical school and among residents is one of not sleeping,” said Dr. Grandner, who was not involved in the study. “The culture among physicians is ‘Who needs sleep? I function fine without it.’ ”

“Sleep made it to the checklist because it is a biological requirement for human life,” he noted. “We sleep for the same reason we breathe and drink. It’s an imperative. Yet we live in a society that devalues sleep.”

It’s “extremely unusual” for a doctor to ask a patient how they’re sleeping, he said. “It’s also pretty unusual to have sleep-related conversations between doctors and patients, especially in the context of health, not just, ‘Hey, doc, I can’t sleep, throw me a pill.’”

Clinicians should be asking every patient about how they’re sleeping at every visit, Dr. Grandner said. “It’s now part of the official definition of heart health. Just like you would be remiss if you didn’t ask about smoking or test blood pressure, you’d be missing something important by not asking about sleep – something that has similar billing to diet, exercise, blood pressure, and all the other ‘essentials.’ ”

No commercial funding or conflicts of interest were declared.

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

Cardiovascular health (CVH) scores that include sleep predicted CV disease risk among older U.S. adults, supporting the American Heart Association’s recent inclusion of sleep in its own checklist.

Sleep duration is now considered “an essential component for ideal heart and brain health,” according to the AHA’s updated checklist, now called Life’s Essential 8. “Our study is the first to show that sleep metrics add independent predictive value for CVD events over and above the original seven cardiovascular health metrics, providing support for updating the guidelines from Life’s Simple 7 (LS7) to Life’s Essential 8,” lead author Nour Makarem, PhD, of the Mailman School of Public Health at Columbia University Irving Medical Center, New York, said in an interview.

For the study, her team compared four versions of LS7 checklists that included sleep in relation to cardiovascular disease (CVD) risk.

“CVH scores that included sleep duration alone as a measure of overall sleep health, as well as scores that included multiple dimensions of sleep health (that is, sleep duration, efficiency, and regularity, daytime sleepiness, and sleep disorders), were both predictive of future CVD,” she said.

Study participants scoring in the highest tertile of the CVH checklists that included sleep had up to a 47% lower CVD risk.

Sleeping 7 hours or more but less than 9 hours nightly was considered “ideal,” according to the study, which was published online  in the Journal of the American Heart Association.
 

Lower the odds

Dr. Makarem and colleagues analyzed data from participants in the Multi-Ethnic Study of Atherosclerosis (MESA) sleep study using overnight polysomnography, 7-day wrist actigraphy, validated questionnaires, and outcomes. They used the data to evaluate the four iterations of an expanded LS7 score:

• Score 1 included sleep duration;
• Score 2 included sleep characteristics linked to CVD in the literature (sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnea [OSA]);
• Score 3 included sleep characteristics associated with CVD in MESA (sleep duration and efficiency, daytime sleepiness, and OSA); and
• Score 4, also based on CVD in MESA, included sleep regularity.

Among 1,920 participants (mean age 69 years; 54% women; 40%, White individuals), the mean LS7 score was 7.3, and the means of the alternate CVH scores that included sleep ranged from 7.4 to 7.8 (scores range from 0 to 14, with higher scores indicating better CVH).

On actigraphy, 63% of participants slept less than 7 hours; 30% slept less than 6 hours; 39% had high night-to-night variability in sleep duration; and 25% had high variability in sleep onset timing.

Overall, 10% had sleep efficiency less than 85%; 14% had excessive daytime sleepiness; 36% had high insomnia symptoms; and 47% had moderate to severe OSA. Short-duration sleepers also had a higher prevalence of overweight/obesity, diabetes, and hypertension and had lower mean LS7 scores.

During a mean follow-up of 4.4 years, 95 prevalent CVD events and 93 incident cases occurred.

Higher scores on all four expanded versions were related to lower odds of having CVD. Participants in the highest versus the lowest tertile of the LS7 score had 75% lower CVD odds (odds ratio, 0.25). Similarly, those in the highest versus the lowest tertile of CVH scores 1 and 2 had 71% and 80% lower odds of prevalent CVD (OR, 0.29 and OR, 0.20), respectively.

Overall, participants in the highest versus lowest tertile of the LS7 score and all CVH scores had up to 80% lower odds of prevalent CVD; those in the highest versus lowest tertile of CVH score 1, which included sleep duration, and CVH score 4, which included multidimensional sleep health, had 43% and 47% lower incident CVD risk (hazard ratios, 0.57 and 0.53), respectively.

The LS7 score alone was not significantly associated with CVD incidence (HR, 0.62).

“Clinicians should ask patients about their sleep health and emphasize the importance of prioritizing sleep for heart disease prevention,” Dr. Makarem said.
 

Sleep ‘devalued’

“The sleep field has been fighting to get more sleep education into medical education for decades,” AHA volunteer expert Michael A. Grandner, PhD, Director of the Sleep & Health Research Program and of the Behavioral Sleep Medicine Clinic at the University of Arizona College of Medicine, Tucson, said in an interview.

“To my knowledge, there still is not a lot of attention given to it, partly because the culture in medical school and among residents is one of not sleeping,” said Dr. Grandner, who was not involved in the study. “The culture among physicians is ‘Who needs sleep? I function fine without it.’ ”

“Sleep made it to the checklist because it is a biological requirement for human life,” he noted. “We sleep for the same reason we breathe and drink. It’s an imperative. Yet we live in a society that devalues sleep.”

It’s “extremely unusual” for a doctor to ask a patient how they’re sleeping, he said. “It’s also pretty unusual to have sleep-related conversations between doctors and patients, especially in the context of health, not just, ‘Hey, doc, I can’t sleep, throw me a pill.’”

Clinicians should be asking every patient about how they’re sleeping at every visit, Dr. Grandner said. “It’s now part of the official definition of heart health. Just like you would be remiss if you didn’t ask about smoking or test blood pressure, you’d be missing something important by not asking about sleep – something that has similar billing to diet, exercise, blood pressure, and all the other ‘essentials.’ ”

No commercial funding or conflicts of interest were declared.

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

MONTREAL – Amid common patient concerns about weight gain in the treatment of hyperthyroidism, findings from a large study suggest the therapy with the most favorable survival rate – radioiodine – is not associated with an increased risk of weight gain or obesity.

“EGRET is the first large study using population-based linked community and hospital data to elucidate the long-term consequences of treatment modalities for hyperthyroidism,” said co-author Kristien Boelaert, MD, PhD, while presenting the research at the American Thyroid Association annual meeting.

“The administration of [radioiodine] for hyperthyroidism is associated with a survival benefit for patients with hyperthyroidism and is not associated with increased risks of becoming obese,” Dr. Boelaert, a professor of endocrinology and consultant endocrinologist with the Institute of Applied Health Research, University of Birmingham, England, told this news organization.

However, “overall, there was a nearly 10% risk of major adverse cardiac events [MACE] in patients with hyperthyroidism regardless of the treatment modality used,” she noted.

Commenting on the findings, Jonathon O. Russell, MD, said the study offers surprising – but encouraging – results.

The discovery that radioiodine shows no increase in weight gain “contradicts numerous previous studies which have consistently demonstrated weight gain following definitive radioiodine,” Dr. Russell told this news organization.

Overall, however, “these findings reinforce our knowledge that definitive treatment of an overactive thyroid leads to a longer life – even if there is some weight gain,” added Dr. Russell, who is chief of the Division of Head and Neck Endocrine Surgery at Johns Hopkins, Baltimore.
 

Hyperthyroidism associated with serious long-term cardiometabolic issues

Hyperthyroidism is associated with serious long-term cardiovascular and metabolic morbidity and mortality, and treatment is therefore essential. However, the swing to hypothyroidism that often occurs afterward commonly results in regaining the weight lost due to the hyperthyroidism, if not more, potentially leading to obesity and its attendant health risks.

To investigate those risks in relation to the three key hyperthyroidism treatments, the authors conducted the EGRET trial. They identified 62,474 patients in the United Kingdom population-based electronic health record database who had newly diagnosed hyperthyroidism and were treated with antithyroid drugs (73.4%), radioiodine (19.5%), or thyroidectomy (7.1%) between April 1997 and December 2015.

Exclusion criteria included those with less than 6 months of antithyroid drugs as the only form of treatment, thyroid cancer, or pregnancy during the first episode.

With a median follow-up of about 8 years, those who were treated with thyroidectomy had a significantly increased risk of gaining weight, compared with the general population (P < .001), and of developing obesity (body mass index > 30 kg/m2; P = .003), while the corresponding increases with antithyroid drugs and radioiodine were not significantly different, compared with the general population over the same period.

In terms of survival, with an average follow-up of about 11 years per person, about 14% of the cohort died, with rates of 14.4% in the antithyroid drug group, 15.8% in the radioiodine group, and 9.2% in the thyroidectomy group.

Mortality rates were further assessed based on an average treatment effects analysis in which the average change was estimated, compared with the index of antithyroid drugs – for instance, if all were treated instead with radioiodine. In that extension of life analysis, those treated with radioiodine could be expected to die, on average, 1.2 years later than those taking antithyroid drugs (P < .001), while those treated with thyroidectomy would be expected to die 0.6 years later, which was not statistically significant.

Using the same average treatment effects analysis, Dr. Boelaert noted, “we found a slightly increased risk of major adverse cardiovascular events following radioiodine, compared with antithyroid drugs; [however], the risk was very small and may not be clinically relevant.”

“Previous data from our and other groups have shown reduced risks of mortality and cardiovascular death following radioiodine-induced hypothyroidism, although this is not confirmed in all studies.”
 

Weight gain after hyperthyroid treatment drives concerns

The findings are important because weight gain associated with hyperthyroidism treatment is no small matter for many patients, even prompting a lack of adherence to therapy for some, despite its importance, Dr. Boelaert noted.

“Since the majority of patients lose weight as a consequence of being hyperthyroid, it can be expected that they will at least regain the lost weight and possibly even have a weight overshoot,” she explained. “Indeed, many patients are reluctant to accept definitive treatment with surgery or radioiodine out of fear of weight gain.”

“This may cause difficulties to some patients who occasionally may even stop taking antithyroid drugs to prevent this weight regain. Such lack of adherence may have dire consequences and is likely a contributing factor to the increased mortality in these patients,” she observed.

In a previous study of 1,373 patients, Dr. Boelaert and colleagues found that men treated for hyperthyroidism gained an average of 8.0 kg (17.6 lb), and women gained an average of 5.5 kg (12.1 lb).

Compared with the background population, men were significantly more likely to gain weight over the study period (odds ratio, 1.7; P < .001) as were women (OR, 1.3; P < .001). Also in that study, radioiodine was associated with greater weight gain (0.6 kg; P < .001), compared with antithyroid drug treatment alone.

Dr. Russell added that even when weight gain does occur, the payoff of having treated the potentially serious state of hyperthyroidism is a highly beneficial trade-off.

Ultimately, “the goal of treating any patient with Graves’ should be to get them to become hypothyroid as quickly as possible,” he said. “Patients have options, and all of these options can be safe in the right situation.”

“It is unrealistic to think that going from a hyperthyroid state to a low thyroid state will not result in weight gain for many patients,” Dr. Russell added. “But the key point is that overall health is better despite this weight gain.”

Dr. Boelaert has disclosed consulting fees paid to the University of Birmingham by Lilly and Eisai. Dr. Russell has reported no relevant financial relationships.

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

MONTREAL – Amid common patient concerns about weight gain in the treatment of hyperthyroidism, findings from a large study suggest the therapy with the most favorable survival rate – radioiodine – is not associated with an increased risk of weight gain or obesity.

“EGRET is the first large study using population-based linked community and hospital data to elucidate the long-term consequences of treatment modalities for hyperthyroidism,” said co-author Kristien Boelaert, MD, PhD, while presenting the research at the American Thyroid Association annual meeting.

“The administration of [radioiodine] for hyperthyroidism is associated with a survival benefit for patients with hyperthyroidism and is not associated with increased risks of becoming obese,” Dr. Boelaert, a professor of endocrinology and consultant endocrinologist with the Institute of Applied Health Research, University of Birmingham, England, told this news organization.

However, “overall, there was a nearly 10% risk of major adverse cardiac events [MACE] in patients with hyperthyroidism regardless of the treatment modality used,” she noted.

Commenting on the findings, Jonathon O. Russell, MD, said the study offers surprising – but encouraging – results.

The discovery that radioiodine shows no increase in weight gain “contradicts numerous previous studies which have consistently demonstrated weight gain following definitive radioiodine,” Dr. Russell told this news organization.

Overall, however, “these findings reinforce our knowledge that definitive treatment of an overactive thyroid leads to a longer life – even if there is some weight gain,” added Dr. Russell, who is chief of the Division of Head and Neck Endocrine Surgery at Johns Hopkins, Baltimore.
 

Hyperthyroidism associated with serious long-term cardiometabolic issues

Hyperthyroidism is associated with serious long-term cardiovascular and metabolic morbidity and mortality, and treatment is therefore essential. However, the swing to hypothyroidism that often occurs afterward commonly results in regaining the weight lost due to the hyperthyroidism, if not more, potentially leading to obesity and its attendant health risks.

To investigate those risks in relation to the three key hyperthyroidism treatments, the authors conducted the EGRET trial. They identified 62,474 patients in the United Kingdom population-based electronic health record database who had newly diagnosed hyperthyroidism and were treated with antithyroid drugs (73.4%), radioiodine (19.5%), or thyroidectomy (7.1%) between April 1997 and December 2015.

Exclusion criteria included those with less than 6 months of antithyroid drugs as the only form of treatment, thyroid cancer, or pregnancy during the first episode.

With a median follow-up of about 8 years, those who were treated with thyroidectomy had a significantly increased risk of gaining weight, compared with the general population (P < .001), and of developing obesity (body mass index > 30 kg/m2; P = .003), while the corresponding increases with antithyroid drugs and radioiodine were not significantly different, compared with the general population over the same period.

In terms of survival, with an average follow-up of about 11 years per person, about 14% of the cohort died, with rates of 14.4% in the antithyroid drug group, 15.8% in the radioiodine group, and 9.2% in the thyroidectomy group.

Mortality rates were further assessed based on an average treatment effects analysis in which the average change was estimated, compared with the index of antithyroid drugs – for instance, if all were treated instead with radioiodine. In that extension of life analysis, those treated with radioiodine could be expected to die, on average, 1.2 years later than those taking antithyroid drugs (P < .001), while those treated with thyroidectomy would be expected to die 0.6 years later, which was not statistically significant.

Using the same average treatment effects analysis, Dr. Boelaert noted, “we found a slightly increased risk of major adverse cardiovascular events following radioiodine, compared with antithyroid drugs; [however], the risk was very small and may not be clinically relevant.”

“Previous data from our and other groups have shown reduced risks of mortality and cardiovascular death following radioiodine-induced hypothyroidism, although this is not confirmed in all studies.”
 

Weight gain after hyperthyroid treatment drives concerns

The findings are important because weight gain associated with hyperthyroidism treatment is no small matter for many patients, even prompting a lack of adherence to therapy for some, despite its importance, Dr. Boelaert noted.

“Since the majority of patients lose weight as a consequence of being hyperthyroid, it can be expected that they will at least regain the lost weight and possibly even have a weight overshoot,” she explained. “Indeed, many patients are reluctant to accept definitive treatment with surgery or radioiodine out of fear of weight gain.”

“This may cause difficulties to some patients who occasionally may even stop taking antithyroid drugs to prevent this weight regain. Such lack of adherence may have dire consequences and is likely a contributing factor to the increased mortality in these patients,” she observed.

In a previous study of 1,373 patients, Dr. Boelaert and colleagues found that men treated for hyperthyroidism gained an average of 8.0 kg (17.6 lb), and women gained an average of 5.5 kg (12.1 lb).

Compared with the background population, men were significantly more likely to gain weight over the study period (odds ratio, 1.7; P < .001) as were women (OR, 1.3; P < .001). Also in that study, radioiodine was associated with greater weight gain (0.6 kg; P < .001), compared with antithyroid drug treatment alone.

Dr. Russell added that even when weight gain does occur, the payoff of having treated the potentially serious state of hyperthyroidism is a highly beneficial trade-off.

Ultimately, “the goal of treating any patient with Graves’ should be to get them to become hypothyroid as quickly as possible,” he said. “Patients have options, and all of these options can be safe in the right situation.”

“It is unrealistic to think that going from a hyperthyroid state to a low thyroid state will not result in weight gain for many patients,” Dr. Russell added. “But the key point is that overall health is better despite this weight gain.”

Dr. Boelaert has disclosed consulting fees paid to the University of Birmingham by Lilly and Eisai. Dr. Russell has reported no relevant financial relationships.

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

MONTREAL – Amid common patient concerns about weight gain in the treatment of hyperthyroidism, findings from a large study suggest the therapy with the most favorable survival rate – radioiodine – is not associated with an increased risk of weight gain or obesity.

“EGRET is the first large study using population-based linked community and hospital data to elucidate the long-term consequences of treatment modalities for hyperthyroidism,” said co-author Kristien Boelaert, MD, PhD, while presenting the research at the American Thyroid Association annual meeting.

“The administration of [radioiodine] for hyperthyroidism is associated with a survival benefit for patients with hyperthyroidism and is not associated with increased risks of becoming obese,” Dr. Boelaert, a professor of endocrinology and consultant endocrinologist with the Institute of Applied Health Research, University of Birmingham, England, told this news organization.

However, “overall, there was a nearly 10% risk of major adverse cardiac events [MACE] in patients with hyperthyroidism regardless of the treatment modality used,” she noted.

Commenting on the findings, Jonathon O. Russell, MD, said the study offers surprising – but encouraging – results.

The discovery that radioiodine shows no increase in weight gain “contradicts numerous previous studies which have consistently demonstrated weight gain following definitive radioiodine,” Dr. Russell told this news organization.

Overall, however, “these findings reinforce our knowledge that definitive treatment of an overactive thyroid leads to a longer life – even if there is some weight gain,” added Dr. Russell, who is chief of the Division of Head and Neck Endocrine Surgery at Johns Hopkins, Baltimore.
 

Hyperthyroidism associated with serious long-term cardiometabolic issues

Hyperthyroidism is associated with serious long-term cardiovascular and metabolic morbidity and mortality, and treatment is therefore essential. However, the swing to hypothyroidism that often occurs afterward commonly results in regaining the weight lost due to the hyperthyroidism, if not more, potentially leading to obesity and its attendant health risks.

To investigate those risks in relation to the three key hyperthyroidism treatments, the authors conducted the EGRET trial. They identified 62,474 patients in the United Kingdom population-based electronic health record database who had newly diagnosed hyperthyroidism and were treated with antithyroid drugs (73.4%), radioiodine (19.5%), or thyroidectomy (7.1%) between April 1997 and December 2015.

Exclusion criteria included those with less than 6 months of antithyroid drugs as the only form of treatment, thyroid cancer, or pregnancy during the first episode.

With a median follow-up of about 8 years, those who were treated with thyroidectomy had a significantly increased risk of gaining weight, compared with the general population (P < .001), and of developing obesity (body mass index > 30 kg/m2; P = .003), while the corresponding increases with antithyroid drugs and radioiodine were not significantly different, compared with the general population over the same period.

In terms of survival, with an average follow-up of about 11 years per person, about 14% of the cohort died, with rates of 14.4% in the antithyroid drug group, 15.8% in the radioiodine group, and 9.2% in the thyroidectomy group.

Mortality rates were further assessed based on an average treatment effects analysis in which the average change was estimated, compared with the index of antithyroid drugs – for instance, if all were treated instead with radioiodine. In that extension of life analysis, those treated with radioiodine could be expected to die, on average, 1.2 years later than those taking antithyroid drugs (P < .001), while those treated with thyroidectomy would be expected to die 0.6 years later, which was not statistically significant.

Using the same average treatment effects analysis, Dr. Boelaert noted, “we found a slightly increased risk of major adverse cardiovascular events following radioiodine, compared with antithyroid drugs; [however], the risk was very small and may not be clinically relevant.”

“Previous data from our and other groups have shown reduced risks of mortality and cardiovascular death following radioiodine-induced hypothyroidism, although this is not confirmed in all studies.”
 

Weight gain after hyperthyroid treatment drives concerns

The findings are important because weight gain associated with hyperthyroidism treatment is no small matter for many patients, even prompting a lack of adherence to therapy for some, despite its importance, Dr. Boelaert noted.

“Since the majority of patients lose weight as a consequence of being hyperthyroid, it can be expected that they will at least regain the lost weight and possibly even have a weight overshoot,” she explained. “Indeed, many patients are reluctant to accept definitive treatment with surgery or radioiodine out of fear of weight gain.”

“This may cause difficulties to some patients who occasionally may even stop taking antithyroid drugs to prevent this weight regain. Such lack of adherence may have dire consequences and is likely a contributing factor to the increased mortality in these patients,” she observed.

In a previous study of 1,373 patients, Dr. Boelaert and colleagues found that men treated for hyperthyroidism gained an average of 8.0 kg (17.6 lb), and women gained an average of 5.5 kg (12.1 lb).

Compared with the background population, men were significantly more likely to gain weight over the study period (odds ratio, 1.7; P < .001) as were women (OR, 1.3; P < .001). Also in that study, radioiodine was associated with greater weight gain (0.6 kg; P < .001), compared with antithyroid drug treatment alone.

Dr. Russell added that even when weight gain does occur, the payoff of having treated the potentially serious state of hyperthyroidism is a highly beneficial trade-off.

Ultimately, “the goal of treating any patient with Graves’ should be to get them to become hypothyroid as quickly as possible,” he said. “Patients have options, and all of these options can be safe in the right situation.”

“It is unrealistic to think that going from a hyperthyroid state to a low thyroid state will not result in weight gain for many patients,” Dr. Russell added. “But the key point is that overall health is better despite this weight gain.”

Dr. Boelaert has disclosed consulting fees paid to the University of Birmingham by Lilly and Eisai. Dr. Russell has reported no relevant financial relationships.

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

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

Diabetes persists as a risk factor for cardiovascular events, but where it once meant the same risk of heart attack or stroke as cardiovascular disease itself, a large Canadian population study reports that’s no longer the case. Thanks to advances in diabetes management over the past quarter century, diabetes is no longer considered equivalent to CVD as a risk factor for cardiovascular events, researchers from the University of Toronto reported.

The retrospective, population-based study used administrative data from Ontario’s provincial universal health care system. The researchers created five population-based cohorts of adults at 5-year intervals from 1994 to 2014, consisting of 1.87 million adults in the first cohort and 1.5 million in the last. In that 20-year span, the prevalence of diabetes in this population tripled, from 3.1% to 9%.

“In the last 25 years we’ve seen wholesale changes in the way people approach diabetes,” lead study author Calvin Ke, MD, PhD, an endocrinologist and assistant professor at the University of Toronto, said in an interview. “Part of the findings show that diabetes and cardiovascular disease were equivalent for risk of cardiovascular events in 1994, but by 2014 that was not the case.”

However, Dr. Ke added, “Diabetes is still a very strong cardiovascular risk factor.”

The investigators for the study, reported as a research letter in JAMA, analyzed the risk of cardiovascular events in four subgroups: those who had both diabetes and CVD, CVD only, diabetes only, and no CVD or diabetes.

Between 1994 and 2014, the cardiovascular event rates declined significantly among people with diabetes alone, compared with people with no disease: from 28.4 to 12.7 per 1,000 person-years, or an absolute risk increase (ARI) of 4.4% and a relative risk (RR) more than double (2.06), in 1994 to 14 vs. 8 per 1,000 person-years, and an ARI of 2% and RR less than double (1.58) 20 years later.

Among people with CVD only, those values shifted from 36.1 per 1,000 person-years, ARI of 5.1% and RR of 2.16 in 1994 to 23.9, ARI of 3.7% and RR still more than double (2.06) in 2014.

People with both CVD and diabetes had the highest CVD event rates across all 5-year cohorts: 74 per 1,000 person-years, ARI of 12% and RR almost four times greater (3.81) in 1994 than people with no disease. By 2014, the ARI in this group was 7.6% and the RR 3.10.

The investigators calculated that event rates from 1994 to 2014 declined across all four subgroups, with rate ratios of 0.49 for diabetes only, 0.66 for CVD only, 0.60 for both diabetes and CVD, and 0.63 for neither disease.

Shift in practice

The study noted that the shift in diabetes as a risk factor for heart attack and stroke is “a change that likely reflects the use of modern, multifactorial approaches to diabetes.”

“A number of changes have occurred in practice that really focus on this idea of a multifactorial approach to diabetes: more aggressive management of blood sugar, blood pressure, and lipids,” Dr. Ke said. “We know from the statin trials that statins can reduce the risk of heart disease significantly, and the use of statins increased from 28.4% in 1999 to 56.3% in 2018 in the United States,” Dr. Ke said. He added that statin use in Canada in adults ages 40 and older went from 1.2% in 1994 to 58.4% in 2010-2015. Use of ACE inhibitors and angiotensin receptor blockers for hypertension followed similar trends, contributing further to reducing risks for heart attack and stroke, Dr. Ke said.

Dr. Ke also noted that the evolution of guidelines and advances in treatments for both CVD and diabetes since 1994 have contributed to improving risks for people with diabetes. SGLT2 inhibitors have been linked to a 2%-6% reduction in hemoglobin A1c, he said. “All of these factors combined have had a major effect on the reduced risk of cardiovascular events.”

Prakash Deedwania, MD, professor at the University of California, San Francisco, Fresno, said that this study confirms a trend that others have reported regarding the risk of CVD in diabetes. The large database covering millions of adults is a study strength, he said.

And the findings, Dr. Deedwania added, underscore what’s been published in clinical guidelines, notably the American Heart Association scientific statement for managing CVD risk in patients with diabetes. “This means that, from observations made 20-plus years ago, when most people were not being treated for diabetes or heart disease, the pendulum has swung,” he said.

However, he added, “The authors state clearly that it does not mean that diabetes is not associated with a higher risk of cardiovascular events; it just means it is no longer equivalent to CVD.”

Managing diabetes continues to be “particularly important,” Dr. Deedwania said, because the prevalence of diabetes continues to rise. “This is a phenomenal risk, and it emphasizes that, to really conquer or control diabetes, we should make every effort to prevent diabetes,” he said.

Dr. Ke and Dr. Deedwania have no relevant financial relationships to disclose.

People with a rare genetic condition that causes extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) may miss out on decades of treatment because of a lack of lipid screening in childhood, researchers reported at the annual meeting of the American Academy of Pediatrics.

The condition, homozygous familial hypercholesterolemia (FH), raises the risk for atherosclerotic cardiovascular disease (ASCVD) as early as the first decade of life.

Routine screening for FH is uncommon, however, the researchers said. Lack of familiarity with guidelines and limited access to lipid specialists have been cited as possible reasons for inconsistent screening practices.

“These findings and recent improvement in lipid lowering therapies make a compelling case for rigorous compliance with AAP’s guidelines on lipid screening for children with a family history of FH or ASCVD at age 2,” study coauthor Mary P. McGowan, MD, chief medical officer of the Family Heart Foundation, said in a statement about the new study.
 

Early consequences

To characterize patients with homozygous FH, Dr. McGowan and her colleagues examined data from 67 participants in the CASCADE-FH registry. The Family Heart Foundation created the registry in 2013, and 40 medical centers in the United States contribute data to the repository. The researchers had access to data about patients with homozygous FH from 20 centers in the registry.

Dr. McGowan’s group compared 16 patients with homozygous FH who enrolled in the registry when they were children and 51 patients who were adults at the time of their enrollment.

Patients enrolled as children had a median age at diagnosis of 2 years (interquartile range [IQR], 2-3.5), whereas patients enrolled as adults had a median age at diagnosis of 12.6 years (IQR, 4.1-26.5).

The median untreated level of LDL-C in those enrolled as children was 776 mg/dL (IQR, 704-892). Among those enrolled as adults, it was 533 mg/dL (IQR, 467-702).

Approximately 19% of those enrolled as children had evidence of aortic valve stenosis, and 43.8% had evidence of ASCVD. The median age at onset of ASCVD was 8.9 years. One child was diagnosed with ASCVD at age 2 years and underwent liver transplant at age 4 years. Another was diagnosed with the condition at age 3 years and underwent liver transplant at age 8 years. Two children underwent coronary artery bypass grafting at ages 6 years and 14 years. Five participants underwent liver transplant before age 18 years.

About 56% of participants who enrolled as children had xanthomas, or fat deposits in tendons, and none had corneal arcus — a gray-white line of fat deposits around the edge of the cornea, both of which can indicate homozygous FH in children.

Treatment reduced LDL-C substantially, but only 25% of children achieved goal levels of cholesterol, the researchers reported. Patients who received more lipid-lowering therapies had a better chance of reaching their target levels, they found.

The data raise “the possibility that only children with the most severe phenotypes are diagnosed before adulthood,” the researchers said.

Clinical diagnosis of homozygous FH can be based on LDL-C levels, family history, and the presence of xanthomas, the researchers noted. Many children do not have physical findings, however, and a lipid panel or genetic testing may be necessary.

“There is a clear need to implement universal screening” to identify all children with homozygous FH and heterozygous FH, a less severe and more common form of FH, Dr. McGowan said.
 

Possible missed cases

As many as 1 in 250 people may have heterozygous FH, and 1 in 300,000 people may have homozygous FH, according to estimates. Patients with homozygous FH have two FH genes, one from each parent. In patients with homozygous FH, levels of LDL-C levels typically range between 400 and 1,000 mg/dL without treatment, which is four to 10 times higher than normal concentrations of the blood fat, according to the Family Heart Foundation.

“This study adds to a growing body of literature – including our own work – demonstrating that recommended universal screening occurs in barely 1 in 5 children. This means some patients are not being recognized as having treatable diseases,” said Justin H. Berger, MD, PhD, a pediatric cardiologist at Children’s Hospital of Philadelphia.

Even among children who are at the highest risk for early onset adult-type heart disease, only a quarter to two-thirds receive recommended screening, said Dr. Berger, who was not a member of the study team.

While Dr. Berger advocates universal lipid screening, improving screening rates in practice probably isn’t as simple as telling clinicians to screen more, he said. “Increasing testing will increase health care spending and the burden on busy primary care providers without addressing who will subsequently evaluate and manage children with abnormal lipid screening results,” Dr. Berger said.

Instead, clinicians may want to focus on screening patients who are at risk, which “could have dramatic benefits for their life-long cardiovascular health,” he said.

Dr. McGowan disclosed ties to Abbott and Regeneron, and her coauthors disclosed ties to Esperion Therapeutics and research funding from Regeneron and REGENXBIO. Dr. Berger disclosed no relevant financial relationships.

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

People with a rare genetic condition that causes extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) may miss out on decades of treatment because of a lack of lipid screening in childhood, researchers reported at the annual meeting of the American Academy of Pediatrics.

The condition, homozygous familial hypercholesterolemia (FH), raises the risk for atherosclerotic cardiovascular disease (ASCVD) as early as the first decade of life.

Routine screening for FH is uncommon, however, the researchers said. Lack of familiarity with guidelines and limited access to lipid specialists have been cited as possible reasons for inconsistent screening practices.

“These findings and recent improvement in lipid lowering therapies make a compelling case for rigorous compliance with AAP’s guidelines on lipid screening for children with a family history of FH or ASCVD at age 2,” study coauthor Mary P. McGowan, MD, chief medical officer of the Family Heart Foundation, said in a statement about the new study.
 

Early consequences

To characterize patients with homozygous FH, Dr. McGowan and her colleagues examined data from 67 participants in the CASCADE-FH registry. The Family Heart Foundation created the registry in 2013, and 40 medical centers in the United States contribute data to the repository. The researchers had access to data about patients with homozygous FH from 20 centers in the registry.

Dr. McGowan’s group compared 16 patients with homozygous FH who enrolled in the registry when they were children and 51 patients who were adults at the time of their enrollment.

Patients enrolled as children had a median age at diagnosis of 2 years (interquartile range [IQR], 2-3.5), whereas patients enrolled as adults had a median age at diagnosis of 12.6 years (IQR, 4.1-26.5).

The median untreated level of LDL-C in those enrolled as children was 776 mg/dL (IQR, 704-892). Among those enrolled as adults, it was 533 mg/dL (IQR, 467-702).

Approximately 19% of those enrolled as children had evidence of aortic valve stenosis, and 43.8% had evidence of ASCVD. The median age at onset of ASCVD was 8.9 years. One child was diagnosed with ASCVD at age 2 years and underwent liver transplant at age 4 years. Another was diagnosed with the condition at age 3 years and underwent liver transplant at age 8 years. Two children underwent coronary artery bypass grafting at ages 6 years and 14 years. Five participants underwent liver transplant before age 18 years.

About 56% of participants who enrolled as children had xanthomas, or fat deposits in tendons, and none had corneal arcus — a gray-white line of fat deposits around the edge of the cornea, both of which can indicate homozygous FH in children.

Treatment reduced LDL-C substantially, but only 25% of children achieved goal levels of cholesterol, the researchers reported. Patients who received more lipid-lowering therapies had a better chance of reaching their target levels, they found.

The data raise “the possibility that only children with the most severe phenotypes are diagnosed before adulthood,” the researchers said.

Clinical diagnosis of homozygous FH can be based on LDL-C levels, family history, and the presence of xanthomas, the researchers noted. Many children do not have physical findings, however, and a lipid panel or genetic testing may be necessary.

“There is a clear need to implement universal screening” to identify all children with homozygous FH and heterozygous FH, a less severe and more common form of FH, Dr. McGowan said.
 

Possible missed cases

As many as 1 in 250 people may have heterozygous FH, and 1 in 300,000 people may have homozygous FH, according to estimates. Patients with homozygous FH have two FH genes, one from each parent. In patients with homozygous FH, levels of LDL-C levels typically range between 400 and 1,000 mg/dL without treatment, which is four to 10 times higher than normal concentrations of the blood fat, according to the Family Heart Foundation.

“This study adds to a growing body of literature – including our own work – demonstrating that recommended universal screening occurs in barely 1 in 5 children. This means some patients are not being recognized as having treatable diseases,” said Justin H. Berger, MD, PhD, a pediatric cardiologist at Children’s Hospital of Philadelphia.

Even among children who are at the highest risk for early onset adult-type heart disease, only a quarter to two-thirds receive recommended screening, said Dr. Berger, who was not a member of the study team.

While Dr. Berger advocates universal lipid screening, improving screening rates in practice probably isn’t as simple as telling clinicians to screen more, he said. “Increasing testing will increase health care spending and the burden on busy primary care providers without addressing who will subsequently evaluate and manage children with abnormal lipid screening results,” Dr. Berger said.

Instead, clinicians may want to focus on screening patients who are at risk, which “could have dramatic benefits for their life-long cardiovascular health,” he said.

Dr. McGowan disclosed ties to Abbott and Regeneron, and her coauthors disclosed ties to Esperion Therapeutics and research funding from Regeneron and REGENXBIO. Dr. Berger disclosed no relevant financial relationships.

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

People with a rare genetic condition that causes extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) may miss out on decades of treatment because of a lack of lipid screening in childhood, researchers reported at the annual meeting of the American Academy of Pediatrics.

The condition, homozygous familial hypercholesterolemia (FH), raises the risk for atherosclerotic cardiovascular disease (ASCVD) as early as the first decade of life.

Routine screening for FH is uncommon, however, the researchers said. Lack of familiarity with guidelines and limited access to lipid specialists have been cited as possible reasons for inconsistent screening practices.

“These findings and recent improvement in lipid lowering therapies make a compelling case for rigorous compliance with AAP’s guidelines on lipid screening for children with a family history of FH or ASCVD at age 2,” study coauthor Mary P. McGowan, MD, chief medical officer of the Family Heart Foundation, said in a statement about the new study.
 

Early consequences

To characterize patients with homozygous FH, Dr. McGowan and her colleagues examined data from 67 participants in the CASCADE-FH registry. The Family Heart Foundation created the registry in 2013, and 40 medical centers in the United States contribute data to the repository. The researchers had access to data about patients with homozygous FH from 20 centers in the registry.

Dr. McGowan’s group compared 16 patients with homozygous FH who enrolled in the registry when they were children and 51 patients who were adults at the time of their enrollment.

Patients enrolled as children had a median age at diagnosis of 2 years (interquartile range [IQR], 2-3.5), whereas patients enrolled as adults had a median age at diagnosis of 12.6 years (IQR, 4.1-26.5).

The median untreated level of LDL-C in those enrolled as children was 776 mg/dL (IQR, 704-892). Among those enrolled as adults, it was 533 mg/dL (IQR, 467-702).

Approximately 19% of those enrolled as children had evidence of aortic valve stenosis, and 43.8% had evidence of ASCVD. The median age at onset of ASCVD was 8.9 years. One child was diagnosed with ASCVD at age 2 years and underwent liver transplant at age 4 years. Another was diagnosed with the condition at age 3 years and underwent liver transplant at age 8 years. Two children underwent coronary artery bypass grafting at ages 6 years and 14 years. Five participants underwent liver transplant before age 18 years.

About 56% of participants who enrolled as children had xanthomas, or fat deposits in tendons, and none had corneal arcus — a gray-white line of fat deposits around the edge of the cornea, both of which can indicate homozygous FH in children.

Treatment reduced LDL-C substantially, but only 25% of children achieved goal levels of cholesterol, the researchers reported. Patients who received more lipid-lowering therapies had a better chance of reaching their target levels, they found.

The data raise “the possibility that only children with the most severe phenotypes are diagnosed before adulthood,” the researchers said.

Clinical diagnosis of homozygous FH can be based on LDL-C levels, family history, and the presence of xanthomas, the researchers noted. Many children do not have physical findings, however, and a lipid panel or genetic testing may be necessary.

“There is a clear need to implement universal screening” to identify all children with homozygous FH and heterozygous FH, a less severe and more common form of FH, Dr. McGowan said.
 

Possible missed cases

As many as 1 in 250 people may have heterozygous FH, and 1 in 300,000 people may have homozygous FH, according to estimates. Patients with homozygous FH have two FH genes, one from each parent. In patients with homozygous FH, levels of LDL-C levels typically range between 400 and 1,000 mg/dL without treatment, which is four to 10 times higher than normal concentrations of the blood fat, according to the Family Heart Foundation.

“This study adds to a growing body of literature – including our own work – demonstrating that recommended universal screening occurs in barely 1 in 5 children. This means some patients are not being recognized as having treatable diseases,” said Justin H. Berger, MD, PhD, a pediatric cardiologist at Children’s Hospital of Philadelphia.

Even among children who are at the highest risk for early onset adult-type heart disease, only a quarter to two-thirds receive recommended screening, said Dr. Berger, who was not a member of the study team.

While Dr. Berger advocates universal lipid screening, improving screening rates in practice probably isn’t as simple as telling clinicians to screen more, he said. “Increasing testing will increase health care spending and the burden on busy primary care providers without addressing who will subsequently evaluate and manage children with abnormal lipid screening results,” Dr. Berger said.

Instead, clinicians may want to focus on screening patients who are at risk, which “could have dramatic benefits for their life-long cardiovascular health,” he said.

Dr. McGowan disclosed ties to Abbott and Regeneron, and her coauthors disclosed ties to Esperion Therapeutics and research funding from Regeneron and REGENXBIO. Dr. Berger disclosed no relevant financial relationships.

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

Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.

COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.

ClaudioVentrella/Thinkstock

“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.

“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”

The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.

It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.

Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.

“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.

When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.

For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.

Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.

Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.

While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.

“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”

Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.

The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.

Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.

“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.

“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”

The authors reported no relevant financial relationships.

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

Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.

COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.

ClaudioVentrella/Thinkstock

“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.

“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”

The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.

It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.

Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.

“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.

When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.

For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.

Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.

Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.

While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.

“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”

Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.

The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.

Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.

“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.

“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”

The authors reported no relevant financial relationships.

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

Nirmatrelvir/ritonavir (Paxlovid) has been a game changer for high-risk patients with early COVID-19 symptoms but has significant interactions with commonly used cardiovascular medications, a new paper cautions.

COVID-19 patients with cardiovascular disease (CVD) or risk factors such as diabetes, hypertension, and chronic kidney disease are at high risk of severe disease and account for the lion’s share of those receiving Paxlovid. Data from the initial EPIC-HR trial and recent real-world data also suggest they’re among the most likely to benefit from the oral antiviral, regardless of their COVID-19 vaccination status.

ClaudioVentrella/Thinkstock

“But at the same time, it unfortunately interacts with many very commonly prescribed cardiovascular medications and with many of them in a very clinically meaningful way, which may lead to serious adverse consequences,” senior author Sarju Ganatra, MD, said in an interview. “So, while it’s being prescribed with a good intention to help these people, we may actually end up doing more harm than good.

“We don’t want to deter people from getting their necessary COVID-19 treatment, which is excellent for the most part these days as an outpatient,” he added. “So, we felt the need to make a comprehensive list of cardiac medications and level of interactions with Paxlovid and also to help the clinicians and prescribers at the point of care to make the clinical decision of what modifications they may need to do.”

The paper, published online in the Journal of the American College of Cardiology, details drug-drug interactions with some 80 CV medications including statins, antihypertensive agents, heart failure therapies, and antiplatelet/anticoagulants.

It also includes a color-coded figure denoting whether a drug is safe to coadminister with Paxlovid, may potentially interact and require a dose adjustment or temporary discontinuation, or is contraindicated.

Among the commonly used blood thinners, for example, the paper notes that Paxlovid significantly increases drug levels of the direct oral anticoagulants (DOACs) apixaban, rivaroxaban, edoxaban, and dabigatran and, thus, increases the risk of bleeding.

“It can still be administered, if it’s necessary, but the dose of the DOAC either needs to be reduced or held depending on what they are getting it for, whether they’re getting it for pulmonary embolism or atrial fibrillation, and we adjust for all those things in the table in the paper,” said Dr. Ganatra, from Lahey Hospital and Medical Center, Burlington, Mass.

When the DOAC can’t be interrupted or dose adjusted, however, Paxlovid should not be given, the experts said. The antiviral is safe to use with enoxaparin, a low-molecular-weight heparin, but can increase or decrease levels of warfarin and should be used with close international normalized ratio monitoring.

For patients on antiplatelet agents, clinicians are advised to avoid prescribing nirmatrelvir/ritonavir to those on ticagrelor or clopidogrel unless the agents can be replaced by prasugrel.

Ritonavir – an inhibitor of cytochrome P 450 enzymes, particularly CYP3A4 – poses an increased risk of bleeding when given with ticagrelor, a CYP3A4 substrate, and decreases the active metabolite of clopidogrel, cutting its platelet inhibition by 20%. Although there’s a twofold decrease in the maximum concentration of prasugrel in patients on ritonavir, this does not affect its antiplatelet activity, the paper explains.

Among the lipid-lowering agents, experts suggested temporarily withholding atorvastatin, rosuvastatin, simvastatin, and lovastatin because of an increased risk for myopathy and liver toxicity but say that other statins, fibrates, ezetimibe, and the proprotein convertase subtilisin/kexin type 9 inhibitors evolocumab and alirocumab are safe to coadminister with Paxlovid.

While statins typically leave the body within hours, most of the antiarrhythmic drugs, except for sotalol, are not safe to give with Paxlovid, Dr. Ganatra said. It’s technically not feasible to hold these drugs because most have long half-lives, reaching about 100 days, for example, for amiodarone.

“It’s going to hang around in your system for a long time, so you don’t want to be falsely reassured that you’re holding the drug and it’s going to be fine to go back slowly,” he said. “You need to look for alternative therapies in those scenarios for COVID-19 treatment, which could be other antivirals, or a monoclonal antibody individualized to the patient’s risk.”

Although there’s limited clinical information regarding interaction-related adverse events with Paxlovid, the team used pharmacokinetics and pharmacodynamics data to provide the guidance. Serious adverse events are also well documented for ritonavir, which has been prescribed for years to treat HIV, Dr. Ganatra noted.

The Infectious Disease Society of America also published guidance on the management of potential drug interactions with Paxlovid in May and, earlier in October, the Food and Drug Administration updated its Paxlovid patient eligibility screening checklist.

Still, most prescribers are actually primary care physicians and even pharmacists, who may not be completely attuned, said Dr. Ganatra, who noted that some centers have started programs to help connect primary care physicians with their cardiology colleagues to check on CV drugs in their COVID-19 patients.

“We need to be thinking more broadly and at a system level where the hospital or health care system leverages the electronic health record systems,” he said. “Most of them are sophisticated enough to incorporate simple drug-drug interaction information, so if you try to prescribe someone Paxlovid and it’s a heart transplant patient who is on immunosuppressive therapy or a patient on a blood thinner, then it should give you a warning ... or at least give them a link to our paper or other valuable resources.

“If someone is on a blood thinner and the blood thinner level goes up by ninefold, we can only imagine what we would be dealing with,” Dr. Ganatra said. “So, these interactions should be taken very seriously and I think it’s worth the time and investment.”

The authors reported no relevant financial relationships.

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

Cardiac biomarkers vary according to sex hormones in healthy transgender adults, just as in cisgender individuals, a new cross-sectional study suggests.

Previous research in the general population has shown that females have a lower 99th percentile upper reference limit for high-sensitivity cardiac troponin (hs-cTn) than males, whereas N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentrations are higher in females than males across all ages after puberty.

“That trend is similar for people that have been on gender-affirming hormones, saying that sex hormones are playing a role in how cardiac turnover happens in a healthy state,” study author Dina M. Greene, PhD, University of Washington, Seattle, said in an interview.

Although the number of transgender people seeking gender-affirming care is increasing, studies are limited and largely retrospective cohorts, she noted. The scientific literature evaluating and defining cardiac biomarker concentrations is “currently absent.”

The American Heart Association’s recent scientific statement on the cardiovascular health of transgender and gender diverse (TGD) people says mounting evidence points to worse CV health in TGD people and that part of this excess risk is driven by significant psychosocial stressors across the lifespan. “In addition, the use of gender-affirming hormone therapy may be associated with cardiometabolic changes, but health research in this area remains limited and, at times, contradictory.”

For the present study, Dr. Greene and colleagues reached out to LGBTQ-oriented primary care and internal medicine clinics in Seattle and Iowa City to recruit 79 transgender men prescribed testosterone (mean age, 28.8 years) and 93 transgender women (mean age, 35.1 years) prescribed estradiol for at least 12 months. The mean duration of hormone therapy was 4.8 and 3.5 years, respectively.

The median estradiol concentration was 51 pg/mL in transgender men and 207 pg/mL in transgender women. Median testosterone concentrations were 4.6 ng/mL and 0.4 ng/mL, respectively.

The cardiac biomarkers were measured with the ARCHITECT STAT (Abbott Diagnostics) and ACCESS (Beckman Coulter) high-sensitivity troponin I assays, the Elecsys Troponin T Gen 5 STAT assay (Roche Diagnostics), and the Elecsys ProBNP II immunoassay (Roche Diagnostics).

As reported in JAMA Cardiology, the median hs-cTnI level on the ARCHITECT STAT assay was 0.9 ng/L (range, 0.6-1.7) in transgender men and 0.6 ng/L (range, 0.3-1.0) in transgender women. The pattern was consistent across the two other assays.

In contrast, the median NT-proBNP level was 17 ng/L (range, 13-27) in transgender men and 49 ng/L (range, 32-86) in transgender women.

“It seems that sex hormone concentration is a stronger driver of baseline cardiac troponin and NT-proBNP concentrations relative to sex assigned at birth,” Dr. Greene said.

The observed differences in hs-cTn concentrations “are likely physiological and not pathological,” given that concentrations between healthy cisgender people are also apparent and not thought to portend adverse events, the authors noted.

Teasing out the clinical implications of sex-specific hs-cTn upper reference limits for ruling in acute myocardial infarction (MI), however, is complicated by biological and social factors that contribute to poorer outcomes in women, despite lower baseline levels, they added. “Ultimately, the psychosocial benefits of gender-affirming hormones are substantial, and informed consent is likely the ideal method to balance the undetermined risks.”

Dr. Greene pointed out that the study wasn’t powered to accurately calculate gender-specific hs-cTn 99th percentiles or reference intervals for NT-proBNP and assessed the biomarkers at a single time point.

For the transgender person presenting with chest pain, she said, the clinical implications are not yet known, but the data suggest that when sex-specific 99th percentiles for hs-cTn are used, the numeric value associated with the affirmed gender, rather than the sex assigned at birth, may be the appropriate URL.

“It really depends on what the triage pathway is and if that pathway has differences for people of different sexes and how often people get serial measurements,” Dr. Greene said. “Within this population, it’s very important to look at those serial measurements because for people that are not cismen, those 99th percentiles when they’re non–sex specific, are going to favor in detection of a heart attack. So, you need to look at the second value to make sure there hasn’t been a change over time.”

The observed differences in the distribution of NT-proBNP concentrations is similar to that in the cisgender population, Dr. Greene noted. But these differences do not lead to sex-specific diagnostic thresholds because of the significant elevations present in overt heart failure and cardiovascular disease. “For NT-proBNP, it’s not as important. People don’t usually have a little bit of heart failure, they have heart failure, where people have small MIs.”

Dr. Greene said she would like to see larger trials looking at biomarker measurements and cardiac imaging before hormone therapy but that the biggest issue is the need for inclusion of transgender people in all cardiovascular trials.

“The sample sizes are never going to be as big as we get for cisgender people for a number of reasons but ensuring that it’s something that’s being asked on intake and monitored over time so we can understand how transgender people fit into the general population for cardiac disease,” Dr. Greene said. “And so, we can normalize that they exist. I keep driving this point home, but this is the biggest thing right now when it’s such a political issue.”

The study was supported in part by the department of laboratory medicine at the University of Washington, the department of pathology at the University of Iowa, and a grant from Abbott Diagnostics for in-kind high-sensitivity cardiac troponin I reagent. One coauthor reported financial relationships with Siemens Healthineers, Roche Diagnostics, Beckman Coulter, Becton, Dickinson, Abbott Diagnostics, Quidel Diagnostics, Sphingotech, and PixCell Medical. No other disclosures were reported.

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

Cardiac biomarkers vary according to sex hormones in healthy transgender adults, just as in cisgender individuals, a new cross-sectional study suggests.

Previous research in the general population has shown that females have a lower 99th percentile upper reference limit for high-sensitivity cardiac troponin (hs-cTn) than males, whereas N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentrations are higher in females than males across all ages after puberty.

“That trend is similar for people that have been on gender-affirming hormones, saying that sex hormones are playing a role in how cardiac turnover happens in a healthy state,” study author Dina M. Greene, PhD, University of Washington, Seattle, said in an interview.

Although the number of transgender people seeking gender-affirming care is increasing, studies are limited and largely retrospective cohorts, she noted. The scientific literature evaluating and defining cardiac biomarker concentrations is “currently absent.”

The American Heart Association’s recent scientific statement on the cardiovascular health of transgender and gender diverse (TGD) people says mounting evidence points to worse CV health in TGD people and that part of this excess risk is driven by significant psychosocial stressors across the lifespan. “In addition, the use of gender-affirming hormone therapy may be associated with cardiometabolic changes, but health research in this area remains limited and, at times, contradictory.”

For the present study, Dr. Greene and colleagues reached out to LGBTQ-oriented primary care and internal medicine clinics in Seattle and Iowa City to recruit 79 transgender men prescribed testosterone (mean age, 28.8 years) and 93 transgender women (mean age, 35.1 years) prescribed estradiol for at least 12 months. The mean duration of hormone therapy was 4.8 and 3.5 years, respectively.

The median estradiol concentration was 51 pg/mL in transgender men and 207 pg/mL in transgender women. Median testosterone concentrations were 4.6 ng/mL and 0.4 ng/mL, respectively.

The cardiac biomarkers were measured with the ARCHITECT STAT (Abbott Diagnostics) and ACCESS (Beckman Coulter) high-sensitivity troponin I assays, the Elecsys Troponin T Gen 5 STAT assay (Roche Diagnostics), and the Elecsys ProBNP II immunoassay (Roche Diagnostics).

As reported in JAMA Cardiology, the median hs-cTnI level on the ARCHITECT STAT assay was 0.9 ng/L (range, 0.6-1.7) in transgender men and 0.6 ng/L (range, 0.3-1.0) in transgender women. The pattern was consistent across the two other assays.

In contrast, the median NT-proBNP level was 17 ng/L (range, 13-27) in transgender men and 49 ng/L (range, 32-86) in transgender women.

“It seems that sex hormone concentration is a stronger driver of baseline cardiac troponin and NT-proBNP concentrations relative to sex assigned at birth,” Dr. Greene said.

The observed differences in hs-cTn concentrations “are likely physiological and not pathological,” given that concentrations between healthy cisgender people are also apparent and not thought to portend adverse events, the authors noted.

Teasing out the clinical implications of sex-specific hs-cTn upper reference limits for ruling in acute myocardial infarction (MI), however, is complicated by biological and social factors that contribute to poorer outcomes in women, despite lower baseline levels, they added. “Ultimately, the psychosocial benefits of gender-affirming hormones are substantial, and informed consent is likely the ideal method to balance the undetermined risks.”

Dr. Greene pointed out that the study wasn’t powered to accurately calculate gender-specific hs-cTn 99th percentiles or reference intervals for NT-proBNP and assessed the biomarkers at a single time point.

For the transgender person presenting with chest pain, she said, the clinical implications are not yet known, but the data suggest that when sex-specific 99th percentiles for hs-cTn are used, the numeric value associated with the affirmed gender, rather than the sex assigned at birth, may be the appropriate URL.

“It really depends on what the triage pathway is and if that pathway has differences for people of different sexes and how often people get serial measurements,” Dr. Greene said. “Within this population, it’s very important to look at those serial measurements because for people that are not cismen, those 99th percentiles when they’re non–sex specific, are going to favor in detection of a heart attack. So, you need to look at the second value to make sure there hasn’t been a change over time.”

The observed differences in the distribution of NT-proBNP concentrations is similar to that in the cisgender population, Dr. Greene noted. But these differences do not lead to sex-specific diagnostic thresholds because of the significant elevations present in overt heart failure and cardiovascular disease. “For NT-proBNP, it’s not as important. People don’t usually have a little bit of heart failure, they have heart failure, where people have small MIs.”

Dr. Greene said she would like to see larger trials looking at biomarker measurements and cardiac imaging before hormone therapy but that the biggest issue is the need for inclusion of transgender people in all cardiovascular trials.

“The sample sizes are never going to be as big as we get for cisgender people for a number of reasons but ensuring that it’s something that’s being asked on intake and monitored over time so we can understand how transgender people fit into the general population for cardiac disease,” Dr. Greene said. “And so, we can normalize that they exist. I keep driving this point home, but this is the biggest thing right now when it’s such a political issue.”

The study was supported in part by the department of laboratory medicine at the University of Washington, the department of pathology at the University of Iowa, and a grant from Abbott Diagnostics for in-kind high-sensitivity cardiac troponin I reagent. One coauthor reported financial relationships with Siemens Healthineers, Roche Diagnostics, Beckman Coulter, Becton, Dickinson, Abbott Diagnostics, Quidel Diagnostics, Sphingotech, and PixCell Medical. No other disclosures were reported.

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

Cardiac biomarkers vary according to sex hormones in healthy transgender adults, just as in cisgender individuals, a new cross-sectional study suggests.

Previous research in the general population has shown that females have a lower 99th percentile upper reference limit for high-sensitivity cardiac troponin (hs-cTn) than males, whereas N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentrations are higher in females than males across all ages after puberty.

“That trend is similar for people that have been on gender-affirming hormones, saying that sex hormones are playing a role in how cardiac turnover happens in a healthy state,” study author Dina M. Greene, PhD, University of Washington, Seattle, said in an interview.

Although the number of transgender people seeking gender-affirming care is increasing, studies are limited and largely retrospective cohorts, she noted. The scientific literature evaluating and defining cardiac biomarker concentrations is “currently absent.”

The American Heart Association’s recent scientific statement on the cardiovascular health of transgender and gender diverse (TGD) people says mounting evidence points to worse CV health in TGD people and that part of this excess risk is driven by significant psychosocial stressors across the lifespan. “In addition, the use of gender-affirming hormone therapy may be associated with cardiometabolic changes, but health research in this area remains limited and, at times, contradictory.”

For the present study, Dr. Greene and colleagues reached out to LGBTQ-oriented primary care and internal medicine clinics in Seattle and Iowa City to recruit 79 transgender men prescribed testosterone (mean age, 28.8 years) and 93 transgender women (mean age, 35.1 years) prescribed estradiol for at least 12 months. The mean duration of hormone therapy was 4.8 and 3.5 years, respectively.

The median estradiol concentration was 51 pg/mL in transgender men and 207 pg/mL in transgender women. Median testosterone concentrations were 4.6 ng/mL and 0.4 ng/mL, respectively.

The cardiac biomarkers were measured with the ARCHITECT STAT (Abbott Diagnostics) and ACCESS (Beckman Coulter) high-sensitivity troponin I assays, the Elecsys Troponin T Gen 5 STAT assay (Roche Diagnostics), and the Elecsys ProBNP II immunoassay (Roche Diagnostics).

As reported in JAMA Cardiology, the median hs-cTnI level on the ARCHITECT STAT assay was 0.9 ng/L (range, 0.6-1.7) in transgender men and 0.6 ng/L (range, 0.3-1.0) in transgender women. The pattern was consistent across the two other assays.

In contrast, the median NT-proBNP level was 17 ng/L (range, 13-27) in transgender men and 49 ng/L (range, 32-86) in transgender women.

“It seems that sex hormone concentration is a stronger driver of baseline cardiac troponin and NT-proBNP concentrations relative to sex assigned at birth,” Dr. Greene said.

The observed differences in hs-cTn concentrations “are likely physiological and not pathological,” given that concentrations between healthy cisgender people are also apparent and not thought to portend adverse events, the authors noted.

Teasing out the clinical implications of sex-specific hs-cTn upper reference limits for ruling in acute myocardial infarction (MI), however, is complicated by biological and social factors that contribute to poorer outcomes in women, despite lower baseline levels, they added. “Ultimately, the psychosocial benefits of gender-affirming hormones are substantial, and informed consent is likely the ideal method to balance the undetermined risks.”

Dr. Greene pointed out that the study wasn’t powered to accurately calculate gender-specific hs-cTn 99th percentiles or reference intervals for NT-proBNP and assessed the biomarkers at a single time point.

For the transgender person presenting with chest pain, she said, the clinical implications are not yet known, but the data suggest that when sex-specific 99th percentiles for hs-cTn are used, the numeric value associated with the affirmed gender, rather than the sex assigned at birth, may be the appropriate URL.

“It really depends on what the triage pathway is and if that pathway has differences for people of different sexes and how often people get serial measurements,” Dr. Greene said. “Within this population, it’s very important to look at those serial measurements because for people that are not cismen, those 99th percentiles when they’re non–sex specific, are going to favor in detection of a heart attack. So, you need to look at the second value to make sure there hasn’t been a change over time.”

The observed differences in the distribution of NT-proBNP concentrations is similar to that in the cisgender population, Dr. Greene noted. But these differences do not lead to sex-specific diagnostic thresholds because of the significant elevations present in overt heart failure and cardiovascular disease. “For NT-proBNP, it’s not as important. People don’t usually have a little bit of heart failure, they have heart failure, where people have small MIs.”

Dr. Greene said she would like to see larger trials looking at biomarker measurements and cardiac imaging before hormone therapy but that the biggest issue is the need for inclusion of transgender people in all cardiovascular trials.

“The sample sizes are never going to be as big as we get for cisgender people for a number of reasons but ensuring that it’s something that’s being asked on intake and monitored over time so we can understand how transgender people fit into the general population for cardiac disease,” Dr. Greene said. “And so, we can normalize that they exist. I keep driving this point home, but this is the biggest thing right now when it’s such a political issue.”

The study was supported in part by the department of laboratory medicine at the University of Washington, the department of pathology at the University of Iowa, and a grant from Abbott Diagnostics for in-kind high-sensitivity cardiac troponin I reagent. One coauthor reported financial relationships with Siemens Healthineers, Roche Diagnostics, Beckman Coulter, Becton, Dickinson, Abbott Diagnostics, Quidel Diagnostics, Sphingotech, and PixCell Medical. No other disclosures were reported.

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

Women with repeated attempts at weight loss, even if the weight is regained, have modestly greater weight loss at an obesity management clinic than women without such a history, data suggest.

In a retrospective study of data for more than 11,000 participants in a weight-management program, the frequency of weight loss was significantly correlated with the total lifetime weight loss in men (r = 0.61, P < .0001) and women (r = 0.60, P < .0001).

“It should be harder for you to lose weight when you’re older, as opposed to younger. That’s just biology,” study author Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic, Burlington, Ont., told this news organization. But older people “have practiced a whole lot more than younger people. That’s probably one of the big things” in their favor, he added.

Dr. Wharton also is a clinical adjunct professor at York University, Toronto, and the lead author of 2020 Canadian clinical practice guidelines on obesity.

The current data were published in Obesity.
 

Practice makes perfect?

The prevalence of obesity is increasing. It is uncertain whether frequent weight losses help or hinder future weight-loss attempts. The effect of age at overweight on future weight loss attempts is also unclear.

To examine these questions, the current researchers analyzed the experiences of patients with obesity treated at the Wharton Medical Clinic Weight Management Program, Hamilton, Ont. At enrollment, participants responded to a questionnaire that elicited information about basic demographics, past weight loss and health practices, medical history, and family medical history. Patients did not receive any stipend for their participation and consented to the use of their medical data for research purposes. The investigators assessed weight change through a retrospective review of electronic medical records.

The study examined a data set that included 36,124 patients who were predominantly White, middle-aged women. “Although this is reflective of the demographic that is most commonly seeking obesity management in North America, the applicability of these findings to other groups is unclear,” wrote the investigators.

As a group, women under age 40 lost 1.7 kg, while those from ages 40 to 60 lost 3.2 kg, and women older than 60 lost 4.2 kg. Weight loss among men was greater and followed a similar pattern. Men under age 40 lost 3.0 kg, those between ages 40 and 60 lost 4.2 kg, and those older than 60 lost 5.2 kg.

To examine how long participants had been trying to lose weight, the investigators analyzed their age of overweight onset. Most participants reported having become overweight before age 40 and having lost at least 4.5 kg at least once in their lifetime. Older women with a longer history of losing weight had better results during the study.

In middle-aged and older women, but not men or younger women, earlier age of overweight onset and lifetime weight loss were associated with modestly greater weight loss at the clinic. When the researchers assessed women age 60 and older, they found that those who had an age of overweight onset before age 10 lost 4.9 kg on average, while those whose age of overweight onset was between ages 20 and 39 lost 4.3 kg. Women with an age of overweight onset above 40 had a weight loss of 3.5 kg.

The finding of greater weight loss in older women who were experienced in dieting was surprising, said Dr. Wharton. It may reflect the effects of perseverance and lifestyle changes. “The other thing is that [older women] also have more time. They have more availability. They make more appointments. They have the ability to be more focused,” said Dr. Wharton.

The Wharton Medical Clinic operates within the Ontario Health Insurance Plan, and all services are provided at no charge to the patient, which may reduce the selection bias against patients with low socioeconomic status, wrote the investigators.
 

Inclusive population

Lesley D. Lutes, PhD, director of the Center for Obesity and Well-Being Research Excellence (CORE) at the University of British Columbia, Vancouver, said that one of its strengths was its reflection of real-world experience.

Too often, study populations do not reflect well the experiences of people battling obesity, she added. Many potential participants are excluded because of common medical comorbidities such as heart conditions. “So, you don’t see the real-world outcomes for the majority of people” from these studies, said Dr. Lutes.

Furthermore, researchers sometimes draw conclusions about obesity based on data that draws from only a “tiny slice” of the group of patients who can qualify for studies, she added. The resulting recommendations may not suit most patients.

In contrast, the current research was based on a more inclusive set of patient data. “That was an incredible strength of this study, that there [were] no exclusionary criteria” in terms of medical conditions, she said.

No outside funding for the study was reported. Dr. Wharton is the medical director of the Wharton Medical Clinic.

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

Women with repeated attempts at weight loss, even if the weight is regained, have modestly greater weight loss at an obesity management clinic than women without such a history, data suggest.

In a retrospective study of data for more than 11,000 participants in a weight-management program, the frequency of weight loss was significantly correlated with the total lifetime weight loss in men (r = 0.61, P < .0001) and women (r = 0.60, P < .0001).

“It should be harder for you to lose weight when you’re older, as opposed to younger. That’s just biology,” study author Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic, Burlington, Ont., told this news organization. But older people “have practiced a whole lot more than younger people. That’s probably one of the big things” in their favor, he added.

Dr. Wharton also is a clinical adjunct professor at York University, Toronto, and the lead author of 2020 Canadian clinical practice guidelines on obesity.

The current data were published in Obesity.
 

Practice makes perfect?

The prevalence of obesity is increasing. It is uncertain whether frequent weight losses help or hinder future weight-loss attempts. The effect of age at overweight on future weight loss attempts is also unclear.

To examine these questions, the current researchers analyzed the experiences of patients with obesity treated at the Wharton Medical Clinic Weight Management Program, Hamilton, Ont. At enrollment, participants responded to a questionnaire that elicited information about basic demographics, past weight loss and health practices, medical history, and family medical history. Patients did not receive any stipend for their participation and consented to the use of their medical data for research purposes. The investigators assessed weight change through a retrospective review of electronic medical records.

The study examined a data set that included 36,124 patients who were predominantly White, middle-aged women. “Although this is reflective of the demographic that is most commonly seeking obesity management in North America, the applicability of these findings to other groups is unclear,” wrote the investigators.

As a group, women under age 40 lost 1.7 kg, while those from ages 40 to 60 lost 3.2 kg, and women older than 60 lost 4.2 kg. Weight loss among men was greater and followed a similar pattern. Men under age 40 lost 3.0 kg, those between ages 40 and 60 lost 4.2 kg, and those older than 60 lost 5.2 kg.

To examine how long participants had been trying to lose weight, the investigators analyzed their age of overweight onset. Most participants reported having become overweight before age 40 and having lost at least 4.5 kg at least once in their lifetime. Older women with a longer history of losing weight had better results during the study.

In middle-aged and older women, but not men or younger women, earlier age of overweight onset and lifetime weight loss were associated with modestly greater weight loss at the clinic. When the researchers assessed women age 60 and older, they found that those who had an age of overweight onset before age 10 lost 4.9 kg on average, while those whose age of overweight onset was between ages 20 and 39 lost 4.3 kg. Women with an age of overweight onset above 40 had a weight loss of 3.5 kg.

The finding of greater weight loss in older women who were experienced in dieting was surprising, said Dr. Wharton. It may reflect the effects of perseverance and lifestyle changes. “The other thing is that [older women] also have more time. They have more availability. They make more appointments. They have the ability to be more focused,” said Dr. Wharton.

The Wharton Medical Clinic operates within the Ontario Health Insurance Plan, and all services are provided at no charge to the patient, which may reduce the selection bias against patients with low socioeconomic status, wrote the investigators.
 

Inclusive population

Lesley D. Lutes, PhD, director of the Center for Obesity and Well-Being Research Excellence (CORE) at the University of British Columbia, Vancouver, said that one of its strengths was its reflection of real-world experience.

Too often, study populations do not reflect well the experiences of people battling obesity, she added. Many potential participants are excluded because of common medical comorbidities such as heart conditions. “So, you don’t see the real-world outcomes for the majority of people” from these studies, said Dr. Lutes.

Furthermore, researchers sometimes draw conclusions about obesity based on data that draws from only a “tiny slice” of the group of patients who can qualify for studies, she added. The resulting recommendations may not suit most patients.

In contrast, the current research was based on a more inclusive set of patient data. “That was an incredible strength of this study, that there [were] no exclusionary criteria” in terms of medical conditions, she said.

No outside funding for the study was reported. Dr. Wharton is the medical director of the Wharton Medical Clinic.

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

Women with repeated attempts at weight loss, even if the weight is regained, have modestly greater weight loss at an obesity management clinic than women without such a history, data suggest.

In a retrospective study of data for more than 11,000 participants in a weight-management program, the frequency of weight loss was significantly correlated with the total lifetime weight loss in men (r = 0.61, P < .0001) and women (r = 0.60, P < .0001).

“It should be harder for you to lose weight when you’re older, as opposed to younger. That’s just biology,” study author Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic, Burlington, Ont., told this news organization. But older people “have practiced a whole lot more than younger people. That’s probably one of the big things” in their favor, he added.

Dr. Wharton also is a clinical adjunct professor at York University, Toronto, and the lead author of 2020 Canadian clinical practice guidelines on obesity.

The current data were published in Obesity.
 

Practice makes perfect?

The prevalence of obesity is increasing. It is uncertain whether frequent weight losses help or hinder future weight-loss attempts. The effect of age at overweight on future weight loss attempts is also unclear.

To examine these questions, the current researchers analyzed the experiences of patients with obesity treated at the Wharton Medical Clinic Weight Management Program, Hamilton, Ont. At enrollment, participants responded to a questionnaire that elicited information about basic demographics, past weight loss and health practices, medical history, and family medical history. Patients did not receive any stipend for their participation and consented to the use of their medical data for research purposes. The investigators assessed weight change through a retrospective review of electronic medical records.

The study examined a data set that included 36,124 patients who were predominantly White, middle-aged women. “Although this is reflective of the demographic that is most commonly seeking obesity management in North America, the applicability of these findings to other groups is unclear,” wrote the investigators.

As a group, women under age 40 lost 1.7 kg, while those from ages 40 to 60 lost 3.2 kg, and women older than 60 lost 4.2 kg. Weight loss among men was greater and followed a similar pattern. Men under age 40 lost 3.0 kg, those between ages 40 and 60 lost 4.2 kg, and those older than 60 lost 5.2 kg.

To examine how long participants had been trying to lose weight, the investigators analyzed their age of overweight onset. Most participants reported having become overweight before age 40 and having lost at least 4.5 kg at least once in their lifetime. Older women with a longer history of losing weight had better results during the study.

In middle-aged and older women, but not men or younger women, earlier age of overweight onset and lifetime weight loss were associated with modestly greater weight loss at the clinic. When the researchers assessed women age 60 and older, they found that those who had an age of overweight onset before age 10 lost 4.9 kg on average, while those whose age of overweight onset was between ages 20 and 39 lost 4.3 kg. Women with an age of overweight onset above 40 had a weight loss of 3.5 kg.

The finding of greater weight loss in older women who were experienced in dieting was surprising, said Dr. Wharton. It may reflect the effects of perseverance and lifestyle changes. “The other thing is that [older women] also have more time. They have more availability. They make more appointments. They have the ability to be more focused,” said Dr. Wharton.

The Wharton Medical Clinic operates within the Ontario Health Insurance Plan, and all services are provided at no charge to the patient, which may reduce the selection bias against patients with low socioeconomic status, wrote the investigators.
 

Inclusive population

Lesley D. Lutes, PhD, director of the Center for Obesity and Well-Being Research Excellence (CORE) at the University of British Columbia, Vancouver, said that one of its strengths was its reflection of real-world experience.

Too often, study populations do not reflect well the experiences of people battling obesity, she added. Many potential participants are excluded because of common medical comorbidities such as heart conditions. “So, you don’t see the real-world outcomes for the majority of people” from these studies, said Dr. Lutes.

Furthermore, researchers sometimes draw conclusions about obesity based on data that draws from only a “tiny slice” of the group of patients who can qualify for studies, she added. The resulting recommendations may not suit most patients.

In contrast, the current research was based on a more inclusive set of patient data. “That was an incredible strength of this study, that there [were] no exclusionary criteria” in terms of medical conditions, she said.

No outside funding for the study was reported. Dr. Wharton is the medical director of the Wharton Medical Clinic.

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

STOCKHOLM – New insights into the benefits of treatment with the “twincretin” tirzepatide for people with overweight or obesity – with or without diabetes – come from new findings reported at the annual meeting of the European Association for the Study of Diabetes.

Additional results from the SURMOUNT-1 trial, which matched tirzepatide against placebo in people with overweight or obesity, provide further details on the favorable changes produced by 72 weeks of tirzepatide treatment on outcomes that included fat and lean mass, insulin sensitivity, and patient-reported outcomes related to functional health and well being, reported Ania M. Jastreboff, MD, PhD.

Mitchel L. Zoler/MDedge News

And results from a meta-analysis of six trials that compared tirzepatide (Mounjaro) against several different comparators in patients with type 2 diabetes further confirm the drug’s ability to reliably produce positive changes in blood lipids, especially by significantly lowering levels of triglycerides, LDL cholesterol, and very LDL (VLDL) cholesterol, said Thomas Karagiannis, MD, PhD, in a separate report at the meeting.

Tirzepatide works as an agonist on receptors for both the glucagonlike peptide–1 (GLP-1), and for the glucose-dependent insulinotropic polypeptide, and received Food and Drug Administration approval for treating people with type 2 diabetes in May 2022. On the basis of results from SURMOUNT-1, the FDA on Oct. 6 granted tirzepatide fast-track designation for a proposed labeling of the agent for treating people with overweight or obesity. This FDA decision will likely remain pending at least until results from a second trial in people with overweight or obesity but without diabetes, SURMOUNT-2, become available in 2023.

SURMOUNT-1 randomized 2,539 people with obesity or overweight and at least one weight-related complication to a weekly injection of tirzepatide or placebo for 72 weeks. The study’s primary efficacy endpoints were the average reduction in weight from baseline, and the percentage of people in each treatment arm achieving weight loss of at least 5% from baseline.

For both endpoints, the outcomes with tirzepatide significantly surpassed placebo effects. Average weight loss ranged from 15%-21% from baseline, depending on dose, compared with 3% on placebo. The rate of participants with at least a 5% weight loss ranged from 85% to 91%, compared with 35% with placebo, as reported in July 2022 in the New England Journal of Medicine.

Cutting fat mass, boosting lean mass

New results from the trial reported by Dr. Jastreboff included a cut in fat mass from 46.2% of total body mass at baseline to 38.5% after 72 weeks, compared with a change from 46.8% at baseline to 44.7% after 72 weeks in the placebo group. Concurrently, lean mass increased with tirzepatide treatment from 51.0% at baseline to 58.1% after 72 weeks.

Participants who received tirzepatide, compared with those who received placebo, had “proportionately greater decrease in fat mass and proportionately greater increase in lean mass” compared with those who received placebo, said Dr. Jastreboff, an endocrinologist and obesity medicine specialist with Yale Medicine in New Haven, Conn. “I was impressed by the amount of visceral fat lost.”

These effects translated into a significant reduction in fat mass-to-lean mass ratio among the people treated with tirzepatide, with the greatest reduction in those who lost at least 15% of their starting weight. In that subgroup the fat-to-lean mass ratio dropped from 0.94 at baseline to 0.64 after 72 weeks of treatment, she said.
 

Focus on diet quality

People treated with tirzepatide “eat so little food that we need to improve the quality of what they eat to protect their muscle,” commented Carel le Roux, MBChB, PhD, a professor in the Diabetes Complications Research Centre of University College Dublin. “You no longer need a dietitian to help people lose weight, because the drug does that. You need dietitians to look after the nutritional health of patients while they lose weight,” Dr. le Roux said in a separate session at the meeting.

Mitchel L. Zoler/MDedge News

Additional tests showed that blood glucose and insulin levels were all significantly lower among trial participants on all three doses of tirzepatide compared with those on placebo, and the tirzepatide-treated subjects also had significant, roughly twofold elevations in their insulin sensitivity measured by the Matsuda Index.

The impact of tirzepatide on glucose and insulin levels and on insulin sensitivity was similar regardless of whether study participants had normoglycemia or prediabetes at entry. By design, no study participants had diabetes.

The trial assessed patient-reported quality-of-life outcomes using the 36-Item Short Form Survey (SF-36). Participants had significant increases in all eight domains within the SF-36 at all three tirzepatide doses, compared with placebo, at 72 weeks, Dr. Jastreboff reported. Improvements in the physical function domain increased most notably among study participants on tirzepatide who had functional limitations at baseline. Heart rate rose among participants who received either of the two highest tirzepatide doses by 2.3-2.5 beats/min, comparable with the effect of other injected incretin-based treatments.

Lipids improve in those with type 2 diabetes

Tirzepatide treatment also results in a “secondary effect” of improving levels of several lipids in people with type 2 diabetes, according to a meta-analysis of findings from six randomized trials. The meta-analysis collectively involved 4,502 participants treated for numerous weeks with one of three doses of tirzepatide and 2,144 people in comparator groups, reported Dr. Karagiannis, a diabetes researcher at Aristotle University of Thessaloniki (Greece).

Among the significant lipid changes linked with tirzepatide treatment, compared with placebo, were an average 13 mg/dL decrease in LDL cholesterol, an average 6 mg/dL decrease in VLDL cholesterol, and an average 50 mg/dL decrease in triglycerides. In comparison to a GLP-1 receptor agonist, an average 25 mg/dL decrease in triglycerides and an average 4 mg/dL reduction in VLDL cholesterol were seen. And trials comparing tirzepatide with basal insulin saw average reductions of 7% in LDL cholesterol, 15% in VLDL cholesterol, 15% in triglycerides, and an 8% increase in HDL cholesterol.

Dr. Karagiannis highlighted that the clinical impact of these effects is unclear, although he noted that the average reduction in LDL cholesterol relative to placebo is of a magnitude that could have a modest effect on long-term outcomes.

These lipid effects of tirzepatide “should be considered alongside” tirzepatide’s “key metabolic effects” on weight and hemoglobin A1c as well as the drug’s safety, concluded Dr. Karagiannis.

The tirzepatide trials were all funded by Eli Lilly, which markets tirzepatide (Mounjaro). Dr. Jastreboff has been an adviser and consultant to Eli Lilly, as well as to Intellihealth, Novo Nordisk, Pfizer, Rhythm Scholars, Roche, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Karagiannis had no disclosures. Dr. le Roux has had financial relationships with Eli Lilly, as well as with Boehringer Ingelheim, Consilient Health, Covidion, Fractyl, GL Dynamics, Herbalife, Johnson & Johnson, Keyron, and Novo Nordisk.

STOCKHOLM – New insights into the benefits of treatment with the “twincretin” tirzepatide for people with overweight or obesity – with or without diabetes – come from new findings reported at the annual meeting of the European Association for the Study of Diabetes.

Additional results from the SURMOUNT-1 trial, which matched tirzepatide against placebo in people with overweight or obesity, provide further details on the favorable changes produced by 72 weeks of tirzepatide treatment on outcomes that included fat and lean mass, insulin sensitivity, and patient-reported outcomes related to functional health and well being, reported Ania M. Jastreboff, MD, PhD.

Mitchel L. Zoler/MDedge News

And results from a meta-analysis of six trials that compared tirzepatide (Mounjaro) against several different comparators in patients with type 2 diabetes further confirm the drug’s ability to reliably produce positive changes in blood lipids, especially by significantly lowering levels of triglycerides, LDL cholesterol, and very LDL (VLDL) cholesterol, said Thomas Karagiannis, MD, PhD, in a separate report at the meeting.

Tirzepatide works as an agonist on receptors for both the glucagonlike peptide–1 (GLP-1), and for the glucose-dependent insulinotropic polypeptide, and received Food and Drug Administration approval for treating people with type 2 diabetes in May 2022. On the basis of results from SURMOUNT-1, the FDA on Oct. 6 granted tirzepatide fast-track designation for a proposed labeling of the agent for treating people with overweight or obesity. This FDA decision will likely remain pending at least until results from a second trial in people with overweight or obesity but without diabetes, SURMOUNT-2, become available in 2023.

SURMOUNT-1 randomized 2,539 people with obesity or overweight and at least one weight-related complication to a weekly injection of tirzepatide or placebo for 72 weeks. The study’s primary efficacy endpoints were the average reduction in weight from baseline, and the percentage of people in each treatment arm achieving weight loss of at least 5% from baseline.

For both endpoints, the outcomes with tirzepatide significantly surpassed placebo effects. Average weight loss ranged from 15%-21% from baseline, depending on dose, compared with 3% on placebo. The rate of participants with at least a 5% weight loss ranged from 85% to 91%, compared with 35% with placebo, as reported in July 2022 in the New England Journal of Medicine.

Cutting fat mass, boosting lean mass

New results from the trial reported by Dr. Jastreboff included a cut in fat mass from 46.2% of total body mass at baseline to 38.5% after 72 weeks, compared with a change from 46.8% at baseline to 44.7% after 72 weeks in the placebo group. Concurrently, lean mass increased with tirzepatide treatment from 51.0% at baseline to 58.1% after 72 weeks.

Participants who received tirzepatide, compared with those who received placebo, had “proportionately greater decrease in fat mass and proportionately greater increase in lean mass” compared with those who received placebo, said Dr. Jastreboff, an endocrinologist and obesity medicine specialist with Yale Medicine in New Haven, Conn. “I was impressed by the amount of visceral fat lost.”

These effects translated into a significant reduction in fat mass-to-lean mass ratio among the people treated with tirzepatide, with the greatest reduction in those who lost at least 15% of their starting weight. In that subgroup the fat-to-lean mass ratio dropped from 0.94 at baseline to 0.64 after 72 weeks of treatment, she said.
 

Focus on diet quality

People treated with tirzepatide “eat so little food that we need to improve the quality of what they eat to protect their muscle,” commented Carel le Roux, MBChB, PhD, a professor in the Diabetes Complications Research Centre of University College Dublin. “You no longer need a dietitian to help people lose weight, because the drug does that. You need dietitians to look after the nutritional health of patients while they lose weight,” Dr. le Roux said in a separate session at the meeting.

Mitchel L. Zoler/MDedge News

Additional tests showed that blood glucose and insulin levels were all significantly lower among trial participants on all three doses of tirzepatide compared with those on placebo, and the tirzepatide-treated subjects also had significant, roughly twofold elevations in their insulin sensitivity measured by the Matsuda Index.

The impact of tirzepatide on glucose and insulin levels and on insulin sensitivity was similar regardless of whether study participants had normoglycemia or prediabetes at entry. By design, no study participants had diabetes.

The trial assessed patient-reported quality-of-life outcomes using the 36-Item Short Form Survey (SF-36). Participants had significant increases in all eight domains within the SF-36 at all three tirzepatide doses, compared with placebo, at 72 weeks, Dr. Jastreboff reported. Improvements in the physical function domain increased most notably among study participants on tirzepatide who had functional limitations at baseline. Heart rate rose among participants who received either of the two highest tirzepatide doses by 2.3-2.5 beats/min, comparable with the effect of other injected incretin-based treatments.

Lipids improve in those with type 2 diabetes

Tirzepatide treatment also results in a “secondary effect” of improving levels of several lipids in people with type 2 diabetes, according to a meta-analysis of findings from six randomized trials. The meta-analysis collectively involved 4,502 participants treated for numerous weeks with one of three doses of tirzepatide and 2,144 people in comparator groups, reported Dr. Karagiannis, a diabetes researcher at Aristotle University of Thessaloniki (Greece).

Among the significant lipid changes linked with tirzepatide treatment, compared with placebo, were an average 13 mg/dL decrease in LDL cholesterol, an average 6 mg/dL decrease in VLDL cholesterol, and an average 50 mg/dL decrease in triglycerides. In comparison to a GLP-1 receptor agonist, an average 25 mg/dL decrease in triglycerides and an average 4 mg/dL reduction in VLDL cholesterol were seen. And trials comparing tirzepatide with basal insulin saw average reductions of 7% in LDL cholesterol, 15% in VLDL cholesterol, 15% in triglycerides, and an 8% increase in HDL cholesterol.

Dr. Karagiannis highlighted that the clinical impact of these effects is unclear, although he noted that the average reduction in LDL cholesterol relative to placebo is of a magnitude that could have a modest effect on long-term outcomes.

These lipid effects of tirzepatide “should be considered alongside” tirzepatide’s “key metabolic effects” on weight and hemoglobin A1c as well as the drug’s safety, concluded Dr. Karagiannis.

The tirzepatide trials were all funded by Eli Lilly, which markets tirzepatide (Mounjaro). Dr. Jastreboff has been an adviser and consultant to Eli Lilly, as well as to Intellihealth, Novo Nordisk, Pfizer, Rhythm Scholars, Roche, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Karagiannis had no disclosures. Dr. le Roux has had financial relationships with Eli Lilly, as well as with Boehringer Ingelheim, Consilient Health, Covidion, Fractyl, GL Dynamics, Herbalife, Johnson & Johnson, Keyron, and Novo Nordisk.

STOCKHOLM – New insights into the benefits of treatment with the “twincretin” tirzepatide for people with overweight or obesity – with or without diabetes – come from new findings reported at the annual meeting of the European Association for the Study of Diabetes.

Additional results from the SURMOUNT-1 trial, which matched tirzepatide against placebo in people with overweight or obesity, provide further details on the favorable changes produced by 72 weeks of tirzepatide treatment on outcomes that included fat and lean mass, insulin sensitivity, and patient-reported outcomes related to functional health and well being, reported Ania M. Jastreboff, MD, PhD.

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And results from a meta-analysis of six trials that compared tirzepatide (Mounjaro) against several different comparators in patients with type 2 diabetes further confirm the drug’s ability to reliably produce positive changes in blood lipids, especially by significantly lowering levels of triglycerides, LDL cholesterol, and very LDL (VLDL) cholesterol, said Thomas Karagiannis, MD, PhD, in a separate report at the meeting.

Tirzepatide works as an agonist on receptors for both the glucagonlike peptide–1 (GLP-1), and for the glucose-dependent insulinotropic polypeptide, and received Food and Drug Administration approval for treating people with type 2 diabetes in May 2022. On the basis of results from SURMOUNT-1, the FDA on Oct. 6 granted tirzepatide fast-track designation for a proposed labeling of the agent for treating people with overweight or obesity. This FDA decision will likely remain pending at least until results from a second trial in people with overweight or obesity but without diabetes, SURMOUNT-2, become available in 2023.

SURMOUNT-1 randomized 2,539 people with obesity or overweight and at least one weight-related complication to a weekly injection of tirzepatide or placebo for 72 weeks. The study’s primary efficacy endpoints were the average reduction in weight from baseline, and the percentage of people in each treatment arm achieving weight loss of at least 5% from baseline.

For both endpoints, the outcomes with tirzepatide significantly surpassed placebo effects. Average weight loss ranged from 15%-21% from baseline, depending on dose, compared with 3% on placebo. The rate of participants with at least a 5% weight loss ranged from 85% to 91%, compared with 35% with placebo, as reported in July 2022 in the New England Journal of Medicine.

Cutting fat mass, boosting lean mass

New results from the trial reported by Dr. Jastreboff included a cut in fat mass from 46.2% of total body mass at baseline to 38.5% after 72 weeks, compared with a change from 46.8% at baseline to 44.7% after 72 weeks in the placebo group. Concurrently, lean mass increased with tirzepatide treatment from 51.0% at baseline to 58.1% after 72 weeks.

Participants who received tirzepatide, compared with those who received placebo, had “proportionately greater decrease in fat mass and proportionately greater increase in lean mass” compared with those who received placebo, said Dr. Jastreboff, an endocrinologist and obesity medicine specialist with Yale Medicine in New Haven, Conn. “I was impressed by the amount of visceral fat lost.”

These effects translated into a significant reduction in fat mass-to-lean mass ratio among the people treated with tirzepatide, with the greatest reduction in those who lost at least 15% of their starting weight. In that subgroup the fat-to-lean mass ratio dropped from 0.94 at baseline to 0.64 after 72 weeks of treatment, she said.
 

Focus on diet quality

People treated with tirzepatide “eat so little food that we need to improve the quality of what they eat to protect their muscle,” commented Carel le Roux, MBChB, PhD, a professor in the Diabetes Complications Research Centre of University College Dublin. “You no longer need a dietitian to help people lose weight, because the drug does that. You need dietitians to look after the nutritional health of patients while they lose weight,” Dr. le Roux said in a separate session at the meeting.

Mitchel L. Zoler/MDedge News

Additional tests showed that blood glucose and insulin levels were all significantly lower among trial participants on all three doses of tirzepatide compared with those on placebo, and the tirzepatide-treated subjects also had significant, roughly twofold elevations in their insulin sensitivity measured by the Matsuda Index.

The impact of tirzepatide on glucose and insulin levels and on insulin sensitivity was similar regardless of whether study participants had normoglycemia or prediabetes at entry. By design, no study participants had diabetes.

The trial assessed patient-reported quality-of-life outcomes using the 36-Item Short Form Survey (SF-36). Participants had significant increases in all eight domains within the SF-36 at all three tirzepatide doses, compared with placebo, at 72 weeks, Dr. Jastreboff reported. Improvements in the physical function domain increased most notably among study participants on tirzepatide who had functional limitations at baseline. Heart rate rose among participants who received either of the two highest tirzepatide doses by 2.3-2.5 beats/min, comparable with the effect of other injected incretin-based treatments.

Lipids improve in those with type 2 diabetes

Tirzepatide treatment also results in a “secondary effect” of improving levels of several lipids in people with type 2 diabetes, according to a meta-analysis of findings from six randomized trials. The meta-analysis collectively involved 4,502 participants treated for numerous weeks with one of three doses of tirzepatide and 2,144 people in comparator groups, reported Dr. Karagiannis, a diabetes researcher at Aristotle University of Thessaloniki (Greece).

Among the significant lipid changes linked with tirzepatide treatment, compared with placebo, were an average 13 mg/dL decrease in LDL cholesterol, an average 6 mg/dL decrease in VLDL cholesterol, and an average 50 mg/dL decrease in triglycerides. In comparison to a GLP-1 receptor agonist, an average 25 mg/dL decrease in triglycerides and an average 4 mg/dL reduction in VLDL cholesterol were seen. And trials comparing tirzepatide with basal insulin saw average reductions of 7% in LDL cholesterol, 15% in VLDL cholesterol, 15% in triglycerides, and an 8% increase in HDL cholesterol.

Dr. Karagiannis highlighted that the clinical impact of these effects is unclear, although he noted that the average reduction in LDL cholesterol relative to placebo is of a magnitude that could have a modest effect on long-term outcomes.

These lipid effects of tirzepatide “should be considered alongside” tirzepatide’s “key metabolic effects” on weight and hemoglobin A1c as well as the drug’s safety, concluded Dr. Karagiannis.

The tirzepatide trials were all funded by Eli Lilly, which markets tirzepatide (Mounjaro). Dr. Jastreboff has been an adviser and consultant to Eli Lilly, as well as to Intellihealth, Novo Nordisk, Pfizer, Rhythm Scholars, Roche, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Karagiannis had no disclosures. Dr. le Roux has had financial relationships with Eli Lilly, as well as with Boehringer Ingelheim, Consilient Health, Covidion, Fractyl, GL Dynamics, Herbalife, Johnson & Johnson, Keyron, and Novo Nordisk.