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Vitamin D deficiency linked to death, new study finds
Vitamin D deficiency increases mortality risk and raising levels even slightly could decrease the risk, researchers examining data from the UK Biobank have found.
They used a Mendelian randomization approach, which uses genetic variants as “proxy indicators” for external factors that affect vitamin D levels, such as sun exposure or dietary intake. It allows for analysis of the relationship between deficiency and outcomes including mortality, which can’t be done in randomized clinical trials for ethical reasons.
Using this method, nutritionist Joshua P. Sutherland, PhD, of the Australian Centre for Precision Health, Adelaide, and colleagues found an association between genetically predicted vitamin D levels [25-(OH)D] and mortality from several major causes, with evidence of causality among people with measured concentrations below, but not above, 50 nmol/L. The findings were published online in Annals of Internal Medicine.
“Unlike other types of observational studies, we have overcome some of the methodological obstacles. What is special about this new study is we were able to look at people with very low vitamin D concentrations and what would happen if their concentrations were a little bit higher. Most randomized controlled trials don’t show much of an effect. That’s because most people have sufficient concentrations. Ethically you can’t do a trial of people with very low levels without treating them,” senior author Elina Hypp
The data support the 50 nmol/L cut-off endorsed by the United States National Academy of Medicine and align with previous data suggesting the benefit of vitamin D supplementation is largely seen in people with deficiency.
“Everybody with vitamin D levels less than 50 nmol/L is recommended to increase their levels. Our results suggest there’s no need to go very high. The positive message is that if we are able to raise levels to just the current U.S. recommendations, that’s fine. There’s no need to use large supplement doses,” Dr. Hyppönen explained.
Thus, she advised, “Supplementation will clearly help, especially during wintertime or if a person isn’t getting enough vitamin D from the sun or in places where food isn’t fortified with vitamin D.”
But the data don’t support the approach of using large intermittent doses, she added.
“Sometimes doctors want to fix the deficiency quickly with a large ‘bolus’ dose, then continue with a maintenance dose. Increasing evidence suggests that’s not beneficial and might disturb the body’s metabolism so that it can’t get the amount it needs. It’s safe overall but might not work the way we want it to work.”
Rather, Dr. Hyppönen said, “My sense is that daily modest vitamin D dose supplementation when it’s needed is the best way forward.”
Genetic approach reveals causal relationship
The investigators analyzed data from 307,601 individuals in the UK Biobank, a prospective cohort of people recruited from England, Scotland, and Wales during March 2006 and July 2010. Most were of White European ancestry and were aged 37-73 years at baseline.
Genetically predicted vitamin D levels were estimated using 35 confirmed 25-(OH)D variants. Participants were followed for outcomes up to June 2020.
The average baseline measured 25-(OH)D concentration was 45.2 nmol/L, and 11.7% (n = 36,009) of participants had levels between 10.0 and 24.9 nmol/L. Higher levels were seen in people living in southern areas and nonsmokers as well as those with a higher level of physical activity, less socioeconomic deprivation, and lower body mass index.
During follow-up, 6.1% of participants died (n = 18,700). After adjustment for variables, odds ratios for all causes of mortality were highest among people with 25-(OH)D levels below 25 nmol/L and appeared to plateau between 50 and 75 nmol/L, with no further reduction in mortality at values of 75-125 nmol/L.
Mortality 36% higher in those deficient in vitamin D
The risk for mortality was a significant 36% higher for participants with 25-(OH)D 25 nmol/L compared with 50 nmol/L.
With the Mendelian randomization, there was an L-shaped association between genetically predicted 25-(OH)D level and all-cause mortality (P for nonlinearity < .001) and for mortality because of cancer and cardiovascular disease (P for nonlinearity ≤ .033).
Again, the strongest association with those outcomes and genetically predicted 25-(OH)D was found at levels below 25 nmol/L and a plateau was seen by 50 nmol/L.
Compared with a measured 25-(OH)D concentration of 50 nmol/L, investigators estimated that the genetically predicted odds of all-cause mortality would increase sixfold (odds ratio, 6.00) for participants at 10 nmol/L and by 25% (OR, 1.25) for those at 25 nmol/L.
And, compared with a measured 25-(OH)D concentration of 50 nmol/L, those with 10 nmol/L had genetically predicted odds ratios of 5.98 for cardiovascular mortality, 3.37 for cancer mortality, and 12.44 for respiratory mortality.
Comparing measured 25-(OH)D concentrations of 25 nmol/L versus 50 nmol/L, odds ratios for those outcomes were 1.25, 1.16, and 1.96 (95% confidence interval, 1.88-4.67), respectively. All were statistically significant.
Consistent results supportive of a causal effect of genetically predicted 25-(OH)D on all-cause mortality in those with low measured vitamin D concentrations were also found in a sensitivity analysis of 20,837 people of non-White ethnic origin.
The study was funded by the Australian National Health and Medical Research Council. Dr. Sutherland’s studentship is funded by an Australian Research Training Program Scholarship.
A version of this article first appeared on Medscape.com.
Vitamin D deficiency increases mortality risk and raising levels even slightly could decrease the risk, researchers examining data from the UK Biobank have found.
They used a Mendelian randomization approach, which uses genetic variants as “proxy indicators” for external factors that affect vitamin D levels, such as sun exposure or dietary intake. It allows for analysis of the relationship between deficiency and outcomes including mortality, which can’t be done in randomized clinical trials for ethical reasons.
Using this method, nutritionist Joshua P. Sutherland, PhD, of the Australian Centre for Precision Health, Adelaide, and colleagues found an association between genetically predicted vitamin D levels [25-(OH)D] and mortality from several major causes, with evidence of causality among people with measured concentrations below, but not above, 50 nmol/L. The findings were published online in Annals of Internal Medicine.
“Unlike other types of observational studies, we have overcome some of the methodological obstacles. What is special about this new study is we were able to look at people with very low vitamin D concentrations and what would happen if their concentrations were a little bit higher. Most randomized controlled trials don’t show much of an effect. That’s because most people have sufficient concentrations. Ethically you can’t do a trial of people with very low levels without treating them,” senior author Elina Hypp
The data support the 50 nmol/L cut-off endorsed by the United States National Academy of Medicine and align with previous data suggesting the benefit of vitamin D supplementation is largely seen in people with deficiency.
“Everybody with vitamin D levels less than 50 nmol/L is recommended to increase their levels. Our results suggest there’s no need to go very high. The positive message is that if we are able to raise levels to just the current U.S. recommendations, that’s fine. There’s no need to use large supplement doses,” Dr. Hyppönen explained.
Thus, she advised, “Supplementation will clearly help, especially during wintertime or if a person isn’t getting enough vitamin D from the sun or in places where food isn’t fortified with vitamin D.”
But the data don’t support the approach of using large intermittent doses, she added.
“Sometimes doctors want to fix the deficiency quickly with a large ‘bolus’ dose, then continue with a maintenance dose. Increasing evidence suggests that’s not beneficial and might disturb the body’s metabolism so that it can’t get the amount it needs. It’s safe overall but might not work the way we want it to work.”
Rather, Dr. Hyppönen said, “My sense is that daily modest vitamin D dose supplementation when it’s needed is the best way forward.”
Genetic approach reveals causal relationship
The investigators analyzed data from 307,601 individuals in the UK Biobank, a prospective cohort of people recruited from England, Scotland, and Wales during March 2006 and July 2010. Most were of White European ancestry and were aged 37-73 years at baseline.
Genetically predicted vitamin D levels were estimated using 35 confirmed 25-(OH)D variants. Participants were followed for outcomes up to June 2020.
The average baseline measured 25-(OH)D concentration was 45.2 nmol/L, and 11.7% (n = 36,009) of participants had levels between 10.0 and 24.9 nmol/L. Higher levels were seen in people living in southern areas and nonsmokers as well as those with a higher level of physical activity, less socioeconomic deprivation, and lower body mass index.
During follow-up, 6.1% of participants died (n = 18,700). After adjustment for variables, odds ratios for all causes of mortality were highest among people with 25-(OH)D levels below 25 nmol/L and appeared to plateau between 50 and 75 nmol/L, with no further reduction in mortality at values of 75-125 nmol/L.
Mortality 36% higher in those deficient in vitamin D
The risk for mortality was a significant 36% higher for participants with 25-(OH)D 25 nmol/L compared with 50 nmol/L.
With the Mendelian randomization, there was an L-shaped association between genetically predicted 25-(OH)D level and all-cause mortality (P for nonlinearity < .001) and for mortality because of cancer and cardiovascular disease (P for nonlinearity ≤ .033).
Again, the strongest association with those outcomes and genetically predicted 25-(OH)D was found at levels below 25 nmol/L and a plateau was seen by 50 nmol/L.
Compared with a measured 25-(OH)D concentration of 50 nmol/L, investigators estimated that the genetically predicted odds of all-cause mortality would increase sixfold (odds ratio, 6.00) for participants at 10 nmol/L and by 25% (OR, 1.25) for those at 25 nmol/L.
And, compared with a measured 25-(OH)D concentration of 50 nmol/L, those with 10 nmol/L had genetically predicted odds ratios of 5.98 for cardiovascular mortality, 3.37 for cancer mortality, and 12.44 for respiratory mortality.
Comparing measured 25-(OH)D concentrations of 25 nmol/L versus 50 nmol/L, odds ratios for those outcomes were 1.25, 1.16, and 1.96 (95% confidence interval, 1.88-4.67), respectively. All were statistically significant.
Consistent results supportive of a causal effect of genetically predicted 25-(OH)D on all-cause mortality in those with low measured vitamin D concentrations were also found in a sensitivity analysis of 20,837 people of non-White ethnic origin.
The study was funded by the Australian National Health and Medical Research Council. Dr. Sutherland’s studentship is funded by an Australian Research Training Program Scholarship.
A version of this article first appeared on Medscape.com.
Vitamin D deficiency increases mortality risk and raising levels even slightly could decrease the risk, researchers examining data from the UK Biobank have found.
They used a Mendelian randomization approach, which uses genetic variants as “proxy indicators” for external factors that affect vitamin D levels, such as sun exposure or dietary intake. It allows for analysis of the relationship between deficiency and outcomes including mortality, which can’t be done in randomized clinical trials for ethical reasons.
Using this method, nutritionist Joshua P. Sutherland, PhD, of the Australian Centre for Precision Health, Adelaide, and colleagues found an association between genetically predicted vitamin D levels [25-(OH)D] and mortality from several major causes, with evidence of causality among people with measured concentrations below, but not above, 50 nmol/L. The findings were published online in Annals of Internal Medicine.
“Unlike other types of observational studies, we have overcome some of the methodological obstacles. What is special about this new study is we were able to look at people with very low vitamin D concentrations and what would happen if their concentrations were a little bit higher. Most randomized controlled trials don’t show much of an effect. That’s because most people have sufficient concentrations. Ethically you can’t do a trial of people with very low levels without treating them,” senior author Elina Hypp
The data support the 50 nmol/L cut-off endorsed by the United States National Academy of Medicine and align with previous data suggesting the benefit of vitamin D supplementation is largely seen in people with deficiency.
“Everybody with vitamin D levels less than 50 nmol/L is recommended to increase their levels. Our results suggest there’s no need to go very high. The positive message is that if we are able to raise levels to just the current U.S. recommendations, that’s fine. There’s no need to use large supplement doses,” Dr. Hyppönen explained.
Thus, she advised, “Supplementation will clearly help, especially during wintertime or if a person isn’t getting enough vitamin D from the sun or in places where food isn’t fortified with vitamin D.”
But the data don’t support the approach of using large intermittent doses, she added.
“Sometimes doctors want to fix the deficiency quickly with a large ‘bolus’ dose, then continue with a maintenance dose. Increasing evidence suggests that’s not beneficial and might disturb the body’s metabolism so that it can’t get the amount it needs. It’s safe overall but might not work the way we want it to work.”
Rather, Dr. Hyppönen said, “My sense is that daily modest vitamin D dose supplementation when it’s needed is the best way forward.”
Genetic approach reveals causal relationship
The investigators analyzed data from 307,601 individuals in the UK Biobank, a prospective cohort of people recruited from England, Scotland, and Wales during March 2006 and July 2010. Most were of White European ancestry and were aged 37-73 years at baseline.
Genetically predicted vitamin D levels were estimated using 35 confirmed 25-(OH)D variants. Participants were followed for outcomes up to June 2020.
The average baseline measured 25-(OH)D concentration was 45.2 nmol/L, and 11.7% (n = 36,009) of participants had levels between 10.0 and 24.9 nmol/L. Higher levels were seen in people living in southern areas and nonsmokers as well as those with a higher level of physical activity, less socioeconomic deprivation, and lower body mass index.
During follow-up, 6.1% of participants died (n = 18,700). After adjustment for variables, odds ratios for all causes of mortality were highest among people with 25-(OH)D levels below 25 nmol/L and appeared to plateau between 50 and 75 nmol/L, with no further reduction in mortality at values of 75-125 nmol/L.
Mortality 36% higher in those deficient in vitamin D
The risk for mortality was a significant 36% higher for participants with 25-(OH)D 25 nmol/L compared with 50 nmol/L.
With the Mendelian randomization, there was an L-shaped association between genetically predicted 25-(OH)D level and all-cause mortality (P for nonlinearity < .001) and for mortality because of cancer and cardiovascular disease (P for nonlinearity ≤ .033).
Again, the strongest association with those outcomes and genetically predicted 25-(OH)D was found at levels below 25 nmol/L and a plateau was seen by 50 nmol/L.
Compared with a measured 25-(OH)D concentration of 50 nmol/L, investigators estimated that the genetically predicted odds of all-cause mortality would increase sixfold (odds ratio, 6.00) for participants at 10 nmol/L and by 25% (OR, 1.25) for those at 25 nmol/L.
And, compared with a measured 25-(OH)D concentration of 50 nmol/L, those with 10 nmol/L had genetically predicted odds ratios of 5.98 for cardiovascular mortality, 3.37 for cancer mortality, and 12.44 for respiratory mortality.
Comparing measured 25-(OH)D concentrations of 25 nmol/L versus 50 nmol/L, odds ratios for those outcomes were 1.25, 1.16, and 1.96 (95% confidence interval, 1.88-4.67), respectively. All were statistically significant.
Consistent results supportive of a causal effect of genetically predicted 25-(OH)D on all-cause mortality in those with low measured vitamin D concentrations were also found in a sensitivity analysis of 20,837 people of non-White ethnic origin.
The study was funded by the Australian National Health and Medical Research Council. Dr. Sutherland’s studentship is funded by an Australian Research Training Program Scholarship.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Early estrogen loss increases cardiovascular risk in women
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.
FROM NAMS 2022
Study reveals racial disparities in advanced HF therapies
A new study shows that Black Americans received ventricular assist devices (VADs) and heart transplants about half as often as White Americans, even when receiving care at an advanced heart failure (HF) center.
The analysis, drawn from 377 patients treated at one of 21 VAD centers in the United States as part of the RIVIVAL study, found that 22.3% of White adults received a heart transplant or VAD, compared with 11% of Black adults.
“That’s what is so concerning to us, that we’re seeing this pattern within this select population. I think it would be too reasonable to hypothesize that it very well could be worse in the general population,” study author Thomas Cascino, MD, MSc, University of Michigan, Ann Arbor, commented.
The study was published online in Circulation: Heart Failure, and it builds on previous work by the researchers, showing that patient preference for early VAD therapy is associated with higher New York Heart Association (NYHA) class and lower income level but not race.
In the present analysis, the number of Black and White participants who said they “definitely or probably” wanted VAD therapy was similar (27% vs. 29%), as was the number wanting “any and all life-sustaining therapies” (74% vs. 65%).
Two-thirds of the cohort was NYHA class III, the average EuroQoL visual analog scale (EQ-VAS) score was 64.6 among the 100 participants who identified as Black and 62.1 in the 277 White participants, and the average age was 58 and 61 years, respectively.
Death rates were also similar during the 2-year follow-up: 18% of Black patients and 13% of White patients.
After controlling for multiple clinical and social determinants of health, including age, Interagency Registry for Mechanically Assisted Circulator Support (INTERMACS) patient profile, EQ-VAS score, and level of education, Black participants had a 55% lower rate of VAD or transplant, compared with White participants (hazard ratio, 0.45; 95% confidence interval, 0.23-0.85). Adding VAD preference to the model did not affect the association.
“Our study suggests that we as providers may be making decisions differently,” Dr. Cascino said. “We can’t say for sure what the reasons are but certainly structural racism, discrimination, and provider biases are the things I worry about.”
“There’s an absolute need for us to look inwards, reflect, and acknowledge that we are likely playing a role in this and then start to be part of the change,” he added.
“The lives disabled or lost are simply too many,” coauthor Wendy Taddei-Peters, PhD, a clinical trials project official at the National Heart, Lung, and Blood Institute, said in an NIH statement. “An immediate step could be to require implicit bias training, particularly for transplant and VAD team members.”
Other suggestions are better tracking of underserved patients and the reasons why they do not receive VAD or become listed for transplant; inclusion of psychosocial components into decision-making about advanced therapy candidacy; and having “disparity experts” join in heart team meetings to help identify biases in real time.
Commenting on the study, Khadijah Breathett, MD, HF/transplant cardiologist and tenured associate professor of medicine, Indiana University Bloomington, said, “I’m glad there’s more push for awareness, because there’s still a population of people that don’t believe this is a real problem.”
Dr. Breathett, who is also a racial equity researcher, noted that the findings are similar to those of multiple studies suggesting racial disparities in HF care. In her own 2019 study of 400 providers shown identical clinical vignettes except for race, survey results and think-aloud interviews showed that decisions about advanced HF therapies are hierarchal and not democratic, social history and adherence are the most influential factors, and Black men are seen as not trustworthy and adherent, despite identical social histories, which ultimately led to White men being offered transplantation and Black men VAD implantation. The bias was particularly evident among older providers.
“This problem is real,” Dr. Breathett said. “The process of allocating life-saving therapies is not fair, and there is some level of discrimination that’s taking place towards persons of color, particularly Black patients. It’s time that we consider how we fix these issues.”
To see whether centers can move the needle and put systemic level changes into practice, Dr. Breathett and colleagues are launching the Seeking Objectivity in Allocation of Advanced Heart Failure (SOCIAL HF) Therapies Trial at 14 sites in the United States. It will measure the number of minority and female patients receiving advanced HF therapies at centers randomized to usual care or HF training, including evidence-based bias reduction training, use of objective measures of social support, and changes to facilitate group dynamics. The trial is set to start in January and be completed in September 2026.
“The main takeaway from this study is that it highlights and re-highlights the fact that racial disparities do exist in access to advanced therapy care,” Jaimin Trivedi, MD, MPH, associate professor of cardiothoracic surgery and director of clinical research and bioinformatics, University of Louisville, Ky., said in an interview.
He also called for education and training for all professionals, not just during residency or fellowship, to specifically identify issues with Black patients and encourage Black patients and their family members to get more involved in their HF care.
Dr. Trivedi said that further studies should examine why death rates were similar in the study despite the observed disparities in VAD implantation and transplantation.
He also pointed out that while patients in the study were treated from July 2015 to June 2016, a recent analysis by his team of the United Network for Organ Sharing (UNOS) database showed that 26% of transplants in 2019 were among Black patients, up from just 5% in 1987. “So, there are some encouraging signs as well.”
The study was funded by the National Institutes of Health/National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Advancing Translational Sciences. Dr. Cascino reports having no relevant financial relationships. Four coauthors report financial relationships, including David Lanfear, who serves on the advisory board at Medscape. Dr. Breathett reported funding from multiple NHLBI grants.
A version of this article first appeared on Medscape.com.
A new study shows that Black Americans received ventricular assist devices (VADs) and heart transplants about half as often as White Americans, even when receiving care at an advanced heart failure (HF) center.
The analysis, drawn from 377 patients treated at one of 21 VAD centers in the United States as part of the RIVIVAL study, found that 22.3% of White adults received a heart transplant or VAD, compared with 11% of Black adults.
“That’s what is so concerning to us, that we’re seeing this pattern within this select population. I think it would be too reasonable to hypothesize that it very well could be worse in the general population,” study author Thomas Cascino, MD, MSc, University of Michigan, Ann Arbor, commented.
The study was published online in Circulation: Heart Failure, and it builds on previous work by the researchers, showing that patient preference for early VAD therapy is associated with higher New York Heart Association (NYHA) class and lower income level but not race.
In the present analysis, the number of Black and White participants who said they “definitely or probably” wanted VAD therapy was similar (27% vs. 29%), as was the number wanting “any and all life-sustaining therapies” (74% vs. 65%).
Two-thirds of the cohort was NYHA class III, the average EuroQoL visual analog scale (EQ-VAS) score was 64.6 among the 100 participants who identified as Black and 62.1 in the 277 White participants, and the average age was 58 and 61 years, respectively.
Death rates were also similar during the 2-year follow-up: 18% of Black patients and 13% of White patients.
After controlling for multiple clinical and social determinants of health, including age, Interagency Registry for Mechanically Assisted Circulator Support (INTERMACS) patient profile, EQ-VAS score, and level of education, Black participants had a 55% lower rate of VAD or transplant, compared with White participants (hazard ratio, 0.45; 95% confidence interval, 0.23-0.85). Adding VAD preference to the model did not affect the association.
“Our study suggests that we as providers may be making decisions differently,” Dr. Cascino said. “We can’t say for sure what the reasons are but certainly structural racism, discrimination, and provider biases are the things I worry about.”
“There’s an absolute need for us to look inwards, reflect, and acknowledge that we are likely playing a role in this and then start to be part of the change,” he added.
“The lives disabled or lost are simply too many,” coauthor Wendy Taddei-Peters, PhD, a clinical trials project official at the National Heart, Lung, and Blood Institute, said in an NIH statement. “An immediate step could be to require implicit bias training, particularly for transplant and VAD team members.”
Other suggestions are better tracking of underserved patients and the reasons why they do not receive VAD or become listed for transplant; inclusion of psychosocial components into decision-making about advanced therapy candidacy; and having “disparity experts” join in heart team meetings to help identify biases in real time.
Commenting on the study, Khadijah Breathett, MD, HF/transplant cardiologist and tenured associate professor of medicine, Indiana University Bloomington, said, “I’m glad there’s more push for awareness, because there’s still a population of people that don’t believe this is a real problem.”
Dr. Breathett, who is also a racial equity researcher, noted that the findings are similar to those of multiple studies suggesting racial disparities in HF care. In her own 2019 study of 400 providers shown identical clinical vignettes except for race, survey results and think-aloud interviews showed that decisions about advanced HF therapies are hierarchal and not democratic, social history and adherence are the most influential factors, and Black men are seen as not trustworthy and adherent, despite identical social histories, which ultimately led to White men being offered transplantation and Black men VAD implantation. The bias was particularly evident among older providers.
“This problem is real,” Dr. Breathett said. “The process of allocating life-saving therapies is not fair, and there is some level of discrimination that’s taking place towards persons of color, particularly Black patients. It’s time that we consider how we fix these issues.”
To see whether centers can move the needle and put systemic level changes into practice, Dr. Breathett and colleagues are launching the Seeking Objectivity in Allocation of Advanced Heart Failure (SOCIAL HF) Therapies Trial at 14 sites in the United States. It will measure the number of minority and female patients receiving advanced HF therapies at centers randomized to usual care or HF training, including evidence-based bias reduction training, use of objective measures of social support, and changes to facilitate group dynamics. The trial is set to start in January and be completed in September 2026.
“The main takeaway from this study is that it highlights and re-highlights the fact that racial disparities do exist in access to advanced therapy care,” Jaimin Trivedi, MD, MPH, associate professor of cardiothoracic surgery and director of clinical research and bioinformatics, University of Louisville, Ky., said in an interview.
He also called for education and training for all professionals, not just during residency or fellowship, to specifically identify issues with Black patients and encourage Black patients and their family members to get more involved in their HF care.
Dr. Trivedi said that further studies should examine why death rates were similar in the study despite the observed disparities in VAD implantation and transplantation.
He also pointed out that while patients in the study were treated from July 2015 to June 2016, a recent analysis by his team of the United Network for Organ Sharing (UNOS) database showed that 26% of transplants in 2019 were among Black patients, up from just 5% in 1987. “So, there are some encouraging signs as well.”
The study was funded by the National Institutes of Health/National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Advancing Translational Sciences. Dr. Cascino reports having no relevant financial relationships. Four coauthors report financial relationships, including David Lanfear, who serves on the advisory board at Medscape. Dr. Breathett reported funding from multiple NHLBI grants.
A version of this article first appeared on Medscape.com.
A new study shows that Black Americans received ventricular assist devices (VADs) and heart transplants about half as often as White Americans, even when receiving care at an advanced heart failure (HF) center.
The analysis, drawn from 377 patients treated at one of 21 VAD centers in the United States as part of the RIVIVAL study, found that 22.3% of White adults received a heart transplant or VAD, compared with 11% of Black adults.
“That’s what is so concerning to us, that we’re seeing this pattern within this select population. I think it would be too reasonable to hypothesize that it very well could be worse in the general population,” study author Thomas Cascino, MD, MSc, University of Michigan, Ann Arbor, commented.
The study was published online in Circulation: Heart Failure, and it builds on previous work by the researchers, showing that patient preference for early VAD therapy is associated with higher New York Heart Association (NYHA) class and lower income level but not race.
In the present analysis, the number of Black and White participants who said they “definitely or probably” wanted VAD therapy was similar (27% vs. 29%), as was the number wanting “any and all life-sustaining therapies” (74% vs. 65%).
Two-thirds of the cohort was NYHA class III, the average EuroQoL visual analog scale (EQ-VAS) score was 64.6 among the 100 participants who identified as Black and 62.1 in the 277 White participants, and the average age was 58 and 61 years, respectively.
Death rates were also similar during the 2-year follow-up: 18% of Black patients and 13% of White patients.
After controlling for multiple clinical and social determinants of health, including age, Interagency Registry for Mechanically Assisted Circulator Support (INTERMACS) patient profile, EQ-VAS score, and level of education, Black participants had a 55% lower rate of VAD or transplant, compared with White participants (hazard ratio, 0.45; 95% confidence interval, 0.23-0.85). Adding VAD preference to the model did not affect the association.
“Our study suggests that we as providers may be making decisions differently,” Dr. Cascino said. “We can’t say for sure what the reasons are but certainly structural racism, discrimination, and provider biases are the things I worry about.”
“There’s an absolute need for us to look inwards, reflect, and acknowledge that we are likely playing a role in this and then start to be part of the change,” he added.
“The lives disabled or lost are simply too many,” coauthor Wendy Taddei-Peters, PhD, a clinical trials project official at the National Heart, Lung, and Blood Institute, said in an NIH statement. “An immediate step could be to require implicit bias training, particularly for transplant and VAD team members.”
Other suggestions are better tracking of underserved patients and the reasons why they do not receive VAD or become listed for transplant; inclusion of psychosocial components into decision-making about advanced therapy candidacy; and having “disparity experts” join in heart team meetings to help identify biases in real time.
Commenting on the study, Khadijah Breathett, MD, HF/transplant cardiologist and tenured associate professor of medicine, Indiana University Bloomington, said, “I’m glad there’s more push for awareness, because there’s still a population of people that don’t believe this is a real problem.”
Dr. Breathett, who is also a racial equity researcher, noted that the findings are similar to those of multiple studies suggesting racial disparities in HF care. In her own 2019 study of 400 providers shown identical clinical vignettes except for race, survey results and think-aloud interviews showed that decisions about advanced HF therapies are hierarchal and not democratic, social history and adherence are the most influential factors, and Black men are seen as not trustworthy and adherent, despite identical social histories, which ultimately led to White men being offered transplantation and Black men VAD implantation. The bias was particularly evident among older providers.
“This problem is real,” Dr. Breathett said. “The process of allocating life-saving therapies is not fair, and there is some level of discrimination that’s taking place towards persons of color, particularly Black patients. It’s time that we consider how we fix these issues.”
To see whether centers can move the needle and put systemic level changes into practice, Dr. Breathett and colleagues are launching the Seeking Objectivity in Allocation of Advanced Heart Failure (SOCIAL HF) Therapies Trial at 14 sites in the United States. It will measure the number of minority and female patients receiving advanced HF therapies at centers randomized to usual care or HF training, including evidence-based bias reduction training, use of objective measures of social support, and changes to facilitate group dynamics. The trial is set to start in January and be completed in September 2026.
“The main takeaway from this study is that it highlights and re-highlights the fact that racial disparities do exist in access to advanced therapy care,” Jaimin Trivedi, MD, MPH, associate professor of cardiothoracic surgery and director of clinical research and bioinformatics, University of Louisville, Ky., said in an interview.
He also called for education and training for all professionals, not just during residency or fellowship, to specifically identify issues with Black patients and encourage Black patients and their family members to get more involved in their HF care.
Dr. Trivedi said that further studies should examine why death rates were similar in the study despite the observed disparities in VAD implantation and transplantation.
He also pointed out that while patients in the study were treated from July 2015 to June 2016, a recent analysis by his team of the United Network for Organ Sharing (UNOS) database showed that 26% of transplants in 2019 were among Black patients, up from just 5% in 1987. “So, there are some encouraging signs as well.”
The study was funded by the National Institutes of Health/National Heart, Lung, and Blood Institute (NHLBI) and the National Center for Advancing Translational Sciences. Dr. Cascino reports having no relevant financial relationships. Four coauthors report financial relationships, including David Lanfear, who serves on the advisory board at Medscape. Dr. Breathett reported funding from multiple NHLBI grants.
A version of this article first appeared on Medscape.com.
Four commonly abused drugs linked with atrial fibrillation
Cocaine, methamphetamine, opioids, and cannabis may independently increase risk of atrial fibrillation (AFib), based on data from almost 24 million people.
While more work is needed to uncover causal links, physicians should be aware that these commonly abused substances could be driving new cases of AFib, reported investigators from the University of California, San Francisco.
“Though alcohol and tobacco smoking have each been associated with a heightened risk of [AFib], relationships between other drug use and [AFib] are poorly understood,” they wrote in European Heart Journal.
Some previous studies have ventured into this terrain, but most focused on fatal arrhythmias, or offered anecdotal evidence. This knowledge gap is particularly concerning for cannabis, the researchers noted, as medical and recreational use are on the rise.
The present analysis included data from 23.5 million adults in California who received care through a hospital, emergency department, or outpatient surgery center during 2005-2015. Based on ICD-9 diagnostic codes, 132,834 of these patients used cannabis, 98,271 used methamphetamines, 48,701 used cocaine, and 10,032 used opiates. Inclusion required lack of AFib at baseline.
Reliance on ICD-9 codes makes the data “quite specific,” but lacking sensitivity, according to principal author Gregory M. Marcus, MD, cardiologist and professor of medicine at UCSF.
“If they were designated as using these drugs, that is very likely true,” Dr. Marcus said in an interview. “But certainly, the absence of any mention of use of these drugs does not exclude the possibility that some people were still using them. That would not create spurious false-positive relationships; if anything, it attenuates existing relationships.”
In other words, using ICD-9 codes reduced the power to detect an association between each drug and AFib, meaning any relationship needed to be sufficiently strong enough to generate a significant result.
At the end of the decade-long study period, 998,747 patients (4.2%) had developed incident AFib. After adjusting for potential confounders and mediators, all four drugs showed significant, independent associations with AFib. Methamphetamines presented the greatest risk (hazard ratio, 1.86%), followed by opiates (HR, 1.74), cocaine (HR, 1.61), and cannabis (HR, 1.35).
“Our findings provide the first evidence utilizing a longitudinal cohort to demonstrate that cannabis use predicts the future onset of AFib,” Dr. Marcus and colleagues wrote.
Dose-response relationships were not detected for any of the substances; however, usage levels were also derived from ICD-9 codes, which may have been insufficient for this purpose, according to the investigators.
Causal mechanisms deserve a closer look
Causal links between AFib and each of the drugs remain unclear. Citing prior research, Dr. Marcus and colleagues explained how methamphetamines are capable of “significant cardiac electrical remodeling,” while cocaine may cause sodium channel dysregulation, and opioids can render atrial myocytes more susceptible to oxidative damage. Although cannabis has previously been linked with hospitalization for arrhythmia, a pharmacologic driver of this phenomenon remains largely unexamined.
“We don’t know for sure precisely what the constituents are that are responsible for our findings,” Dr. Marcus said. “It’s possible that there are some effects that are much more generic, such as inhaling a burned substance. There is good evidence that if you inhale pretty much any sort of particulate matter, that increases inflammation in the body. Inflammation is known to be a trigger for atrial fibrillation.”
Alternatively, all four drugs – whether stimulants or depressants – cause “quite dramatic and often rapid effects on the autonomic nervous system,” Dr. Marcus said, noting that these rapid swings are a known trigger for AFib.
Brian Olshansky, MD, emeritus professor of internal medicine-cardiovascular medicine at the University of Iowa, Iowa City, suggested that nonpharmacologic factors are likely also playing a role.
“All these drugs have slightly different mechanisms of action, so there’s not one mechanism that would explain why all of them would cause atrial fibrillation,” Dr. Olshansky said in an interview. “That does suggest that there’s something else going on, besides just the drug itself. It would be potentially concerning if we were to lay the blame totally on these drugs.”
Dr. Olshansky, who recently coauthored a review of stimulant drugs and arrhythmias, suggested that lifestyle, comorbidities, and drug impurities may have added to the risk of AF.
“[The investigators] did try to correct for that kind of stuff, but it’s very hard to correct for a lot of the issues that may be ongoing with individuals who partake in these drugs,” Dr. Olshansky said in an interview. “They may not be a healthy lot, in general.”
Still, considering previous data linking drugs of abuse with arrhythmias, he said the detected risks were “intriguing,” and deserved a closer look.
“It’s a nice groundbreaking study, with regard to the fact that they showed unique relationships that we don’t completely understand,” Dr. Olshansky said. “It opens up a new opportunity for further investigation.”
The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Olshansky disclosed no relevant competing interests.
Cocaine, methamphetamine, opioids, and cannabis may independently increase risk of atrial fibrillation (AFib), based on data from almost 24 million people.
While more work is needed to uncover causal links, physicians should be aware that these commonly abused substances could be driving new cases of AFib, reported investigators from the University of California, San Francisco.
“Though alcohol and tobacco smoking have each been associated with a heightened risk of [AFib], relationships between other drug use and [AFib] are poorly understood,” they wrote in European Heart Journal.
Some previous studies have ventured into this terrain, but most focused on fatal arrhythmias, or offered anecdotal evidence. This knowledge gap is particularly concerning for cannabis, the researchers noted, as medical and recreational use are on the rise.
The present analysis included data from 23.5 million adults in California who received care through a hospital, emergency department, or outpatient surgery center during 2005-2015. Based on ICD-9 diagnostic codes, 132,834 of these patients used cannabis, 98,271 used methamphetamines, 48,701 used cocaine, and 10,032 used opiates. Inclusion required lack of AFib at baseline.
Reliance on ICD-9 codes makes the data “quite specific,” but lacking sensitivity, according to principal author Gregory M. Marcus, MD, cardiologist and professor of medicine at UCSF.
“If they were designated as using these drugs, that is very likely true,” Dr. Marcus said in an interview. “But certainly, the absence of any mention of use of these drugs does not exclude the possibility that some people were still using them. That would not create spurious false-positive relationships; if anything, it attenuates existing relationships.”
In other words, using ICD-9 codes reduced the power to detect an association between each drug and AFib, meaning any relationship needed to be sufficiently strong enough to generate a significant result.
At the end of the decade-long study period, 998,747 patients (4.2%) had developed incident AFib. After adjusting for potential confounders and mediators, all four drugs showed significant, independent associations with AFib. Methamphetamines presented the greatest risk (hazard ratio, 1.86%), followed by opiates (HR, 1.74), cocaine (HR, 1.61), and cannabis (HR, 1.35).
“Our findings provide the first evidence utilizing a longitudinal cohort to demonstrate that cannabis use predicts the future onset of AFib,” Dr. Marcus and colleagues wrote.
Dose-response relationships were not detected for any of the substances; however, usage levels were also derived from ICD-9 codes, which may have been insufficient for this purpose, according to the investigators.
Causal mechanisms deserve a closer look
Causal links between AFib and each of the drugs remain unclear. Citing prior research, Dr. Marcus and colleagues explained how methamphetamines are capable of “significant cardiac electrical remodeling,” while cocaine may cause sodium channel dysregulation, and opioids can render atrial myocytes more susceptible to oxidative damage. Although cannabis has previously been linked with hospitalization for arrhythmia, a pharmacologic driver of this phenomenon remains largely unexamined.
“We don’t know for sure precisely what the constituents are that are responsible for our findings,” Dr. Marcus said. “It’s possible that there are some effects that are much more generic, such as inhaling a burned substance. There is good evidence that if you inhale pretty much any sort of particulate matter, that increases inflammation in the body. Inflammation is known to be a trigger for atrial fibrillation.”
Alternatively, all four drugs – whether stimulants or depressants – cause “quite dramatic and often rapid effects on the autonomic nervous system,” Dr. Marcus said, noting that these rapid swings are a known trigger for AFib.
Brian Olshansky, MD, emeritus professor of internal medicine-cardiovascular medicine at the University of Iowa, Iowa City, suggested that nonpharmacologic factors are likely also playing a role.
“All these drugs have slightly different mechanisms of action, so there’s not one mechanism that would explain why all of them would cause atrial fibrillation,” Dr. Olshansky said in an interview. “That does suggest that there’s something else going on, besides just the drug itself. It would be potentially concerning if we were to lay the blame totally on these drugs.”
Dr. Olshansky, who recently coauthored a review of stimulant drugs and arrhythmias, suggested that lifestyle, comorbidities, and drug impurities may have added to the risk of AF.
“[The investigators] did try to correct for that kind of stuff, but it’s very hard to correct for a lot of the issues that may be ongoing with individuals who partake in these drugs,” Dr. Olshansky said in an interview. “They may not be a healthy lot, in general.”
Still, considering previous data linking drugs of abuse with arrhythmias, he said the detected risks were “intriguing,” and deserved a closer look.
“It’s a nice groundbreaking study, with regard to the fact that they showed unique relationships that we don’t completely understand,” Dr. Olshansky said. “It opens up a new opportunity for further investigation.”
The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Olshansky disclosed no relevant competing interests.
Cocaine, methamphetamine, opioids, and cannabis may independently increase risk of atrial fibrillation (AFib), based on data from almost 24 million people.
While more work is needed to uncover causal links, physicians should be aware that these commonly abused substances could be driving new cases of AFib, reported investigators from the University of California, San Francisco.
“Though alcohol and tobacco smoking have each been associated with a heightened risk of [AFib], relationships between other drug use and [AFib] are poorly understood,” they wrote in European Heart Journal.
Some previous studies have ventured into this terrain, but most focused on fatal arrhythmias, or offered anecdotal evidence. This knowledge gap is particularly concerning for cannabis, the researchers noted, as medical and recreational use are on the rise.
The present analysis included data from 23.5 million adults in California who received care through a hospital, emergency department, or outpatient surgery center during 2005-2015. Based on ICD-9 diagnostic codes, 132,834 of these patients used cannabis, 98,271 used methamphetamines, 48,701 used cocaine, and 10,032 used opiates. Inclusion required lack of AFib at baseline.
Reliance on ICD-9 codes makes the data “quite specific,” but lacking sensitivity, according to principal author Gregory M. Marcus, MD, cardiologist and professor of medicine at UCSF.
“If they were designated as using these drugs, that is very likely true,” Dr. Marcus said in an interview. “But certainly, the absence of any mention of use of these drugs does not exclude the possibility that some people were still using them. That would not create spurious false-positive relationships; if anything, it attenuates existing relationships.”
In other words, using ICD-9 codes reduced the power to detect an association between each drug and AFib, meaning any relationship needed to be sufficiently strong enough to generate a significant result.
At the end of the decade-long study period, 998,747 patients (4.2%) had developed incident AFib. After adjusting for potential confounders and mediators, all four drugs showed significant, independent associations with AFib. Methamphetamines presented the greatest risk (hazard ratio, 1.86%), followed by opiates (HR, 1.74), cocaine (HR, 1.61), and cannabis (HR, 1.35).
“Our findings provide the first evidence utilizing a longitudinal cohort to demonstrate that cannabis use predicts the future onset of AFib,” Dr. Marcus and colleagues wrote.
Dose-response relationships were not detected for any of the substances; however, usage levels were also derived from ICD-9 codes, which may have been insufficient for this purpose, according to the investigators.
Causal mechanisms deserve a closer look
Causal links between AFib and each of the drugs remain unclear. Citing prior research, Dr. Marcus and colleagues explained how methamphetamines are capable of “significant cardiac electrical remodeling,” while cocaine may cause sodium channel dysregulation, and opioids can render atrial myocytes more susceptible to oxidative damage. Although cannabis has previously been linked with hospitalization for arrhythmia, a pharmacologic driver of this phenomenon remains largely unexamined.
“We don’t know for sure precisely what the constituents are that are responsible for our findings,” Dr. Marcus said. “It’s possible that there are some effects that are much more generic, such as inhaling a burned substance. There is good evidence that if you inhale pretty much any sort of particulate matter, that increases inflammation in the body. Inflammation is known to be a trigger for atrial fibrillation.”
Alternatively, all four drugs – whether stimulants or depressants – cause “quite dramatic and often rapid effects on the autonomic nervous system,” Dr. Marcus said, noting that these rapid swings are a known trigger for AFib.
Brian Olshansky, MD, emeritus professor of internal medicine-cardiovascular medicine at the University of Iowa, Iowa City, suggested that nonpharmacologic factors are likely also playing a role.
“All these drugs have slightly different mechanisms of action, so there’s not one mechanism that would explain why all of them would cause atrial fibrillation,” Dr. Olshansky said in an interview. “That does suggest that there’s something else going on, besides just the drug itself. It would be potentially concerning if we were to lay the blame totally on these drugs.”
Dr. Olshansky, who recently coauthored a review of stimulant drugs and arrhythmias, suggested that lifestyle, comorbidities, and drug impurities may have added to the risk of AF.
“[The investigators] did try to correct for that kind of stuff, but it’s very hard to correct for a lot of the issues that may be ongoing with individuals who partake in these drugs,” Dr. Olshansky said in an interview. “They may not be a healthy lot, in general.”
Still, considering previous data linking drugs of abuse with arrhythmias, he said the detected risks were “intriguing,” and deserved a closer look.
“It’s a nice groundbreaking study, with regard to the fact that they showed unique relationships that we don’t completely understand,” Dr. Olshansky said. “It opens up a new opportunity for further investigation.”
The investigators disclosed relationships with InCarda, Baylis Medical, Johnson & Johnson, and others. Dr. Olshansky disclosed no relevant competing interests.
FROM EUROPEAN HEART JOURNAL
Myocarditis after COVID vax rare and mild in teens
New data from Israel provide further evidence that myocarditis is a rare adverse event of vaccination with the Pfizer/BioNTech mRNA COVID-19 vaccine in adolescents – one that predominantly occurs in males and typically after the second dose.
The new data also indicate a “mild and benign” clinical course of myocarditis after vaccination, with “favorable” long-term prognosis based on cardiac imaging findings.
Guy Witberg, MD, MPH, Rabin Medical Center, Petah Tikva, Israel, and colleagues report their latest observations in correspondence in The New England Journal of Medicine, online.
The group previously reported in December 2021 that the incidence of myocarditis in Israel after receipt of the Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine was highest among males between the ages of 16 and 29 (10.7 cases per 100,000).
The vaccine has since been approved for adolescents aged 12-15. Initial evidence for this age group, reported by Dr. Witberg and colleagues in March 2022, suggests a similar low incidence and mild course of myocarditis, although follow-up was limited to 30 days.
In their latest report, with follow-up out to 6 months, Dr. Witberg and colleagues identified nine probable or definite cases of myocarditis among 182,605 Israeli adolescents aged 12-15 who received the Pfizer/BioNTech mRNA vaccine – an incidence of 4.8 cases per 100,000.
Eight cases occurred after the second vaccine dose. All nine cases were mild.
Cardiac and inflammatory markers were elevated in all adolescent patients and electrocardiographic results were abnormal in two-thirds.
Eight patients had a normal ejection fraction, and four had a pericardial effusion. The patients spent 2-4 days hospitalized, and the in-hospital course was uneventful.
Echocardiographic findings were available a median of 10 days after discharge for eight patients. All echocardiograms showed a normal ejection fraction and resolution of pericardial effusion.
Five patients underwent cardiac MRI, including three scans performed at a median of 104 days after discharge. The scans showed “minimal evidence” of myocardial scarring or fibrosis, with evidence of late gadolinium enhancement ranging from 0% to 2%.
At a median of 206 days following discharge, all of the patients were alive, and none had been readmitted to the hospital, Dr. Witberg and colleagues report.
This research had no specific funding. Five authors have received research grants from Pfizer.
A version of this article first appeared on Medscape.com.
New data from Israel provide further evidence that myocarditis is a rare adverse event of vaccination with the Pfizer/BioNTech mRNA COVID-19 vaccine in adolescents – one that predominantly occurs in males and typically after the second dose.
The new data also indicate a “mild and benign” clinical course of myocarditis after vaccination, with “favorable” long-term prognosis based on cardiac imaging findings.
Guy Witberg, MD, MPH, Rabin Medical Center, Petah Tikva, Israel, and colleagues report their latest observations in correspondence in The New England Journal of Medicine, online.
The group previously reported in December 2021 that the incidence of myocarditis in Israel after receipt of the Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine was highest among males between the ages of 16 and 29 (10.7 cases per 100,000).
The vaccine has since been approved for adolescents aged 12-15. Initial evidence for this age group, reported by Dr. Witberg and colleagues in March 2022, suggests a similar low incidence and mild course of myocarditis, although follow-up was limited to 30 days.
In their latest report, with follow-up out to 6 months, Dr. Witberg and colleagues identified nine probable or definite cases of myocarditis among 182,605 Israeli adolescents aged 12-15 who received the Pfizer/BioNTech mRNA vaccine – an incidence of 4.8 cases per 100,000.
Eight cases occurred after the second vaccine dose. All nine cases were mild.
Cardiac and inflammatory markers were elevated in all adolescent patients and electrocardiographic results were abnormal in two-thirds.
Eight patients had a normal ejection fraction, and four had a pericardial effusion. The patients spent 2-4 days hospitalized, and the in-hospital course was uneventful.
Echocardiographic findings were available a median of 10 days after discharge for eight patients. All echocardiograms showed a normal ejection fraction and resolution of pericardial effusion.
Five patients underwent cardiac MRI, including three scans performed at a median of 104 days after discharge. The scans showed “minimal evidence” of myocardial scarring or fibrosis, with evidence of late gadolinium enhancement ranging from 0% to 2%.
At a median of 206 days following discharge, all of the patients were alive, and none had been readmitted to the hospital, Dr. Witberg and colleagues report.
This research had no specific funding. Five authors have received research grants from Pfizer.
A version of this article first appeared on Medscape.com.
New data from Israel provide further evidence that myocarditis is a rare adverse event of vaccination with the Pfizer/BioNTech mRNA COVID-19 vaccine in adolescents – one that predominantly occurs in males and typically after the second dose.
The new data also indicate a “mild and benign” clinical course of myocarditis after vaccination, with “favorable” long-term prognosis based on cardiac imaging findings.
Guy Witberg, MD, MPH, Rabin Medical Center, Petah Tikva, Israel, and colleagues report their latest observations in correspondence in The New England Journal of Medicine, online.
The group previously reported in December 2021 that the incidence of myocarditis in Israel after receipt of the Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine was highest among males between the ages of 16 and 29 (10.7 cases per 100,000).
The vaccine has since been approved for adolescents aged 12-15. Initial evidence for this age group, reported by Dr. Witberg and colleagues in March 2022, suggests a similar low incidence and mild course of myocarditis, although follow-up was limited to 30 days.
In their latest report, with follow-up out to 6 months, Dr. Witberg and colleagues identified nine probable or definite cases of myocarditis among 182,605 Israeli adolescents aged 12-15 who received the Pfizer/BioNTech mRNA vaccine – an incidence of 4.8 cases per 100,000.
Eight cases occurred after the second vaccine dose. All nine cases were mild.
Cardiac and inflammatory markers were elevated in all adolescent patients and electrocardiographic results were abnormal in two-thirds.
Eight patients had a normal ejection fraction, and four had a pericardial effusion. The patients spent 2-4 days hospitalized, and the in-hospital course was uneventful.
Echocardiographic findings were available a median of 10 days after discharge for eight patients. All echocardiograms showed a normal ejection fraction and resolution of pericardial effusion.
Five patients underwent cardiac MRI, including three scans performed at a median of 104 days after discharge. The scans showed “minimal evidence” of myocardial scarring or fibrosis, with evidence of late gadolinium enhancement ranging from 0% to 2%.
At a median of 206 days following discharge, all of the patients were alive, and none had been readmitted to the hospital, Dr. Witberg and colleagues report.
This research had no specific funding. Five authors have received research grants from Pfizer.
A version of this article first appeared on Medscape.com.
Wake-up call on sleep and cardiovascular health
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.
“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.
“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.
“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.
FROM JOURNAL OF THE AMERICAN HEART ASSOCIATION
Don’t be afraid of weight gain with hyperthyroid treatment
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.
AT ATA 2022
More data suggest preexisting statin use improves COVID outcomes
Compared with patients who didn’t take statins, statin users had better health outcomes. For those who used these medications, the researchers saw lower mortality, lower clinical severity, and shorter hospital stays, aligning with previous observational studies, said lead author Ettore Crimi, MD, of the University of Central Florida, Orlando, and colleagues in their abstract, which was part of the agenda for the Anesthesiology annual meeting.
They attributed these clinical improvements to the pleiotropic – non–cholesterol lowering – effects of statins.
“[These] benefits of statins have been reported since the 1990s,” Dr. Crimi said in an interview. “Statin treatment has been associated with a marked reduction of markers of inflammation, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), interleukin-6 (IL-6), ferritin, and white blood cell count, among others.”
He noted that these effects have been studied in an array of conditions, including cancer, autoimmune diseases, chronic inflammatory disease, and in the perioperative setting, and with infectious diseases, including COVID-19.
In those previous studies, “preexisting statin use was protective among hospitalized COVID-19 patients, but a large, multicenter cohort study has not been reported in the United States,” Dr. Crimi and his colleagues wrote in their abstract.
To address this knowledge gap, they turned to electronic medical records from 38,875 patients hospitalized with COVID-19 from January to September 2020. Almost one-third of the population (n = 11,533) were using statins prior to hospitalization, while the remainder (n = 27,342) were nonusers.
The primary outcome was all-cause mortality. Secondary outcomes included death from COVID-19, along with a variety of severe complications. While the analysis did account for a range of potentially confounding variables, the effects of different SARS-CoV-2 variants and new therapeutics were not considered. Vaccines were not yet available at the time the data were collected.
Statin users had a 31% lower rate of all-cause mortality (odds ratio, 0.69; 95% confidence interval, 0.64-0.75; P = .001) and a 37% reduced rate of death from COVID-19 (OR, 0.63; 95% CI, 0.58-0.69; P = .001).
A litany of other secondary variables also favored statin users, including reduced rates of discharge to hospice (OR, 0.79), ICU admission (OR, 0.69), severe acute respiratory distress syndrome (ARDs; OR, 0.72), critical ARDs (OR, 0.57), mechanical ventilation (OR, 0.60), severe sepsis with septic shock (OR, 0.66), and thrombosis (OR, 0.46). Statin users also had, on average, shorter hospital stays and briefer mechanical ventilation.
“Our study showed a strong association between preexisting statin use and reduced mortality and morbidity rates in hospitalized COVID-19 patients,” the investigators concluded. “Pleiotropic benefits of statins could be repurposed for COVID-19 illness.”
Prospective studies needed before practice changes
How to best use statins against COVID-19, if at all, remains unclear, Dr. Crimi said, as initiation upon infection has generated mixed results in other studies, possibly because of statin pharmacodynamics. Cholesterol normalization can take about 6 weeks, so other benefits may track a similar timeline.
“The delayed onset of statins’ pleiotropic effects may likely fail to keep pace with the rapidly progressive, devastating COVID-19 disease,” Dr. Crimi said. “Therefore, initiating statins for an acute disease may not be an ideal first-line treatment.”
Stronger data are on the horizon, he added, noting that 19 federally funded prospective trials are underway to better understand the relationship between statins and COVID-19.
Daniel Rader, MD, of the University of Pennsylvania, Philadelphia, said the present findings are “not especially notable” because they “mostly confirm previous studies, but in a large U.S. cohort.”
Dr. Rader, who wrote about the potential repurposing of statins for COVID-19 back in the first year of the pandemic (Cell Metab. 2020 Aug 4;32[2]:145-7), agreed with the investigators that recommending changes to clinical practice would be imprudent until randomized controlled data confirm the benefits of initiating statins in patients with active COVID-19.
“More research on the impact of cellular cholesterol metabolism on SARS-CoV-2 infection of cells and generation of inflammation would also be of interest,” he added.
The investigators disclosed no competing interests. Dr. Rader disclosed relationships with Novartis, Pfizer, Verve, and others.
Compared with patients who didn’t take statins, statin users had better health outcomes. For those who used these medications, the researchers saw lower mortality, lower clinical severity, and shorter hospital stays, aligning with previous observational studies, said lead author Ettore Crimi, MD, of the University of Central Florida, Orlando, and colleagues in their abstract, which was part of the agenda for the Anesthesiology annual meeting.
They attributed these clinical improvements to the pleiotropic – non–cholesterol lowering – effects of statins.
“[These] benefits of statins have been reported since the 1990s,” Dr. Crimi said in an interview. “Statin treatment has been associated with a marked reduction of markers of inflammation, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), interleukin-6 (IL-6), ferritin, and white blood cell count, among others.”
He noted that these effects have been studied in an array of conditions, including cancer, autoimmune diseases, chronic inflammatory disease, and in the perioperative setting, and with infectious diseases, including COVID-19.
In those previous studies, “preexisting statin use was protective among hospitalized COVID-19 patients, but a large, multicenter cohort study has not been reported in the United States,” Dr. Crimi and his colleagues wrote in their abstract.
To address this knowledge gap, they turned to electronic medical records from 38,875 patients hospitalized with COVID-19 from January to September 2020. Almost one-third of the population (n = 11,533) were using statins prior to hospitalization, while the remainder (n = 27,342) were nonusers.
The primary outcome was all-cause mortality. Secondary outcomes included death from COVID-19, along with a variety of severe complications. While the analysis did account for a range of potentially confounding variables, the effects of different SARS-CoV-2 variants and new therapeutics were not considered. Vaccines were not yet available at the time the data were collected.
Statin users had a 31% lower rate of all-cause mortality (odds ratio, 0.69; 95% confidence interval, 0.64-0.75; P = .001) and a 37% reduced rate of death from COVID-19 (OR, 0.63; 95% CI, 0.58-0.69; P = .001).
A litany of other secondary variables also favored statin users, including reduced rates of discharge to hospice (OR, 0.79), ICU admission (OR, 0.69), severe acute respiratory distress syndrome (ARDs; OR, 0.72), critical ARDs (OR, 0.57), mechanical ventilation (OR, 0.60), severe sepsis with septic shock (OR, 0.66), and thrombosis (OR, 0.46). Statin users also had, on average, shorter hospital stays and briefer mechanical ventilation.
“Our study showed a strong association between preexisting statin use and reduced mortality and morbidity rates in hospitalized COVID-19 patients,” the investigators concluded. “Pleiotropic benefits of statins could be repurposed for COVID-19 illness.”
Prospective studies needed before practice changes
How to best use statins against COVID-19, if at all, remains unclear, Dr. Crimi said, as initiation upon infection has generated mixed results in other studies, possibly because of statin pharmacodynamics. Cholesterol normalization can take about 6 weeks, so other benefits may track a similar timeline.
“The delayed onset of statins’ pleiotropic effects may likely fail to keep pace with the rapidly progressive, devastating COVID-19 disease,” Dr. Crimi said. “Therefore, initiating statins for an acute disease may not be an ideal first-line treatment.”
Stronger data are on the horizon, he added, noting that 19 federally funded prospective trials are underway to better understand the relationship between statins and COVID-19.
Daniel Rader, MD, of the University of Pennsylvania, Philadelphia, said the present findings are “not especially notable” because they “mostly confirm previous studies, but in a large U.S. cohort.”
Dr. Rader, who wrote about the potential repurposing of statins for COVID-19 back in the first year of the pandemic (Cell Metab. 2020 Aug 4;32[2]:145-7), agreed with the investigators that recommending changes to clinical practice would be imprudent until randomized controlled data confirm the benefits of initiating statins in patients with active COVID-19.
“More research on the impact of cellular cholesterol metabolism on SARS-CoV-2 infection of cells and generation of inflammation would also be of interest,” he added.
The investigators disclosed no competing interests. Dr. Rader disclosed relationships with Novartis, Pfizer, Verve, and others.
Compared with patients who didn’t take statins, statin users had better health outcomes. For those who used these medications, the researchers saw lower mortality, lower clinical severity, and shorter hospital stays, aligning with previous observational studies, said lead author Ettore Crimi, MD, of the University of Central Florida, Orlando, and colleagues in their abstract, which was part of the agenda for the Anesthesiology annual meeting.
They attributed these clinical improvements to the pleiotropic – non–cholesterol lowering – effects of statins.
“[These] benefits of statins have been reported since the 1990s,” Dr. Crimi said in an interview. “Statin treatment has been associated with a marked reduction of markers of inflammation, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), interleukin-6 (IL-6), ferritin, and white blood cell count, among others.”
He noted that these effects have been studied in an array of conditions, including cancer, autoimmune diseases, chronic inflammatory disease, and in the perioperative setting, and with infectious diseases, including COVID-19.
In those previous studies, “preexisting statin use was protective among hospitalized COVID-19 patients, but a large, multicenter cohort study has not been reported in the United States,” Dr. Crimi and his colleagues wrote in their abstract.
To address this knowledge gap, they turned to electronic medical records from 38,875 patients hospitalized with COVID-19 from January to September 2020. Almost one-third of the population (n = 11,533) were using statins prior to hospitalization, while the remainder (n = 27,342) were nonusers.
The primary outcome was all-cause mortality. Secondary outcomes included death from COVID-19, along with a variety of severe complications. While the analysis did account for a range of potentially confounding variables, the effects of different SARS-CoV-2 variants and new therapeutics were not considered. Vaccines were not yet available at the time the data were collected.
Statin users had a 31% lower rate of all-cause mortality (odds ratio, 0.69; 95% confidence interval, 0.64-0.75; P = .001) and a 37% reduced rate of death from COVID-19 (OR, 0.63; 95% CI, 0.58-0.69; P = .001).
A litany of other secondary variables also favored statin users, including reduced rates of discharge to hospice (OR, 0.79), ICU admission (OR, 0.69), severe acute respiratory distress syndrome (ARDs; OR, 0.72), critical ARDs (OR, 0.57), mechanical ventilation (OR, 0.60), severe sepsis with septic shock (OR, 0.66), and thrombosis (OR, 0.46). Statin users also had, on average, shorter hospital stays and briefer mechanical ventilation.
“Our study showed a strong association between preexisting statin use and reduced mortality and morbidity rates in hospitalized COVID-19 patients,” the investigators concluded. “Pleiotropic benefits of statins could be repurposed for COVID-19 illness.”
Prospective studies needed before practice changes
How to best use statins against COVID-19, if at all, remains unclear, Dr. Crimi said, as initiation upon infection has generated mixed results in other studies, possibly because of statin pharmacodynamics. Cholesterol normalization can take about 6 weeks, so other benefits may track a similar timeline.
“The delayed onset of statins’ pleiotropic effects may likely fail to keep pace with the rapidly progressive, devastating COVID-19 disease,” Dr. Crimi said. “Therefore, initiating statins for an acute disease may not be an ideal first-line treatment.”
Stronger data are on the horizon, he added, noting that 19 federally funded prospective trials are underway to better understand the relationship between statins and COVID-19.
Daniel Rader, MD, of the University of Pennsylvania, Philadelphia, said the present findings are “not especially notable” because they “mostly confirm previous studies, but in a large U.S. cohort.”
Dr. Rader, who wrote about the potential repurposing of statins for COVID-19 back in the first year of the pandemic (Cell Metab. 2020 Aug 4;32[2]:145-7), agreed with the investigators that recommending changes to clinical practice would be imprudent until randomized controlled data confirm the benefits of initiating statins in patients with active COVID-19.
“More research on the impact of cellular cholesterol metabolism on SARS-CoV-2 infection of cells and generation of inflammation would also be of interest,” he added.
The investigators disclosed no competing interests. Dr. Rader disclosed relationships with Novartis, Pfizer, Verve, and others.
FROM ANESTHESIOLOGY 2022
IM residents rate cardiology low on work-life balance
Both male and female internal medicine (IM) residents prioritized work-life balance, such as stable working hours and family friendliness, when considering career choices, and cardiology was perceived to fall short in this area, an updated survey revealed.
Originally conducted in 2010, the survey aimed to understand IM residents’ professional development preferences and perceptions of cardiology as a specialty. That survey demonstrated a discordance between what residents valued in making a career choice and their perceptions of a career in cardiology.
The discordance remained in 2020, with residents even more likely than their predecessors to report negative perceptions of cardiology.
Compared with residents surveyed in 2010, respondents in 2020 placed higher value on all aspects of work-life balance and of having role models who demonstrated a successful balance. The value change was particularly notable for men.
“While our survey does not elucidate why this is, speculation could be made that this value on work-life balance is generational and prominent in the youngest generations entering all professional fields, not just medicine,” lead author Meghan York, MD, of Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, told this news organization.
“There is also an interesting trend that dual-career couples are on the rise in the U.S.,” she said. “This may reflect that trend, [with] men in medical fields possibly taking on more domestic responsibility and requiring more work flexibility to do that.”
Regarding perceptions, she added, cardiology tends to show resident cardiologists who are working in inpatient services with “ballooning and unpredictable hours,” rather than those who are working in more time-controlled clinics. Therefore, “their prime exposure to physicians is not truly representative of the career.” The study was published online in JAMA Cardiology.
‘Lack of diversity’
The updated surveys were sent by various means to close to 30,000 residents, and were completed by 840 (mean age, 29; 50% male; 55% White). Cardiology was a favored subspecialty choice among men, with 46.5% reporting they were considering it vs. 29.7% of women. Women were more likely to report never having considered cardiology as a career choice (37.6%) compared with men (22.3%).
The survey incorporated a 5-point Likert scale of 1 (not important) to 5 (extremely important) for some of the questions.
The most important professional development preferences for respondents were positive role models (4.56), stimulating career (3.81), family friendly (3.78), patient focus (3.70), stable work hours (3.66), female or race friendly (3.33), professional challenges (3.21), and financial benefits (3.20).
The cardiology perception statements with the highest agreement were:
- Interferes with family life during training (3.93).
- Having met positive role models or having positive views of cardiovascular disease as a topic (3.85).
- Reasonable compensation (3.69).
- Adverse job conditions (3.16).
- Field lacks diversity (2.90).
Compared with the 2010 survey, the 2020 findings indicated increased importance on work-life balance components for both male and female residents, with a greater change among males.
In addition, 2020 respondents were more likely than their predecessors to report negative perceptions of cardiology, such as too much overnight or weekend call, challenging to have children during fellowship, and lack of diversity.
“The culture of the subspecialty of cardiology has not improved to become significantly more diverse or inclusive, whereas other specialties and subspecialties have, and residents interact with cardiologists frequently and can see that,” Dr. York noted.
“As women now make up greater than 50% of medical students,” she said, “it is reasonable to focus on women in medical school and residency to bring them into the field of cardiology. But as racial and ethnic minority groups are also massively underrepresented in medical school, recruitment into medicine needs to start much earlier, in high school and college.
“Creating and supporting rotations that embed residents in the outpatient cardiology setting and exposure to more longitudinal experiences will provide a more realistic picture of the career,” she concluded.
ACC ‘at the forefront’
“Work-life balance looks different for each and every individual, but there are some themes that we need to think about,” Lisa Rose-Jones, MD, chair of the American College of Cardiology’s Program Directors and Graduate Medical Educators Section, said in her comments on the study. “The ACC is really at the forefront of this. They are putting together different work groups to focus on ‘how can we have some innovations?’ ”
The ACC is seeking mentors as part of its workforce diversity efforts among African American/Black, Hispanic/LatinX and Women’s IM cardiology programs, she noted. Furthermore, on Oct. 13, the organization released its 2022 health policy statement on career flexibility in cardiology, which calls for more leeway for cardiologists to deal with common life events without jeopardizing their careers.
Dr. Rose-Jones, director of the training program in cardiovascular disease at the University of North Carolina at Chapel Hill, said that because both male and female residents placed a high value on work-life balance, “we’ve got to think about how we can have flexibility in our work hours. That is critically important. Health systems need to be able to accommodate working families that may need to alter traditional 9 to 5 work hours to meet the demands of being a successful cardiologist and also being a parent.”
In addition, she said, “We need to have very clear policies at every institution on gender-related and parent-related discrimination. Data show that many female trainees are still being questioned on their family planning. That is absolutely not appropriate. It is none of our business. While we continue to do that, we continue to create stigma in our field.”
Like Dr. York, she noted generational differences in the doctors who are coming up now. “They’ve seen burnout firsthand and want to have a well-balanced life that includes medicine, but also life outside of the hospital,” Dr. Rose-Jones said. “So, those of us in cardiology really need to look deep inside and make changes. We need to be thoughtful about how we can be innovative.”
No commercial funding or conflicts of interest were declared.
A version of this article first appeared on Medscape.com.
Both male and female internal medicine (IM) residents prioritized work-life balance, such as stable working hours and family friendliness, when considering career choices, and cardiology was perceived to fall short in this area, an updated survey revealed.
Originally conducted in 2010, the survey aimed to understand IM residents’ professional development preferences and perceptions of cardiology as a specialty. That survey demonstrated a discordance between what residents valued in making a career choice and their perceptions of a career in cardiology.
The discordance remained in 2020, with residents even more likely than their predecessors to report negative perceptions of cardiology.
Compared with residents surveyed in 2010, respondents in 2020 placed higher value on all aspects of work-life balance and of having role models who demonstrated a successful balance. The value change was particularly notable for men.
“While our survey does not elucidate why this is, speculation could be made that this value on work-life balance is generational and prominent in the youngest generations entering all professional fields, not just medicine,” lead author Meghan York, MD, of Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, told this news organization.
“There is also an interesting trend that dual-career couples are on the rise in the U.S.,” she said. “This may reflect that trend, [with] men in medical fields possibly taking on more domestic responsibility and requiring more work flexibility to do that.”
Regarding perceptions, she added, cardiology tends to show resident cardiologists who are working in inpatient services with “ballooning and unpredictable hours,” rather than those who are working in more time-controlled clinics. Therefore, “their prime exposure to physicians is not truly representative of the career.” The study was published online in JAMA Cardiology.
‘Lack of diversity’
The updated surveys were sent by various means to close to 30,000 residents, and were completed by 840 (mean age, 29; 50% male; 55% White). Cardiology was a favored subspecialty choice among men, with 46.5% reporting they were considering it vs. 29.7% of women. Women were more likely to report never having considered cardiology as a career choice (37.6%) compared with men (22.3%).
The survey incorporated a 5-point Likert scale of 1 (not important) to 5 (extremely important) for some of the questions.
The most important professional development preferences for respondents were positive role models (4.56), stimulating career (3.81), family friendly (3.78), patient focus (3.70), stable work hours (3.66), female or race friendly (3.33), professional challenges (3.21), and financial benefits (3.20).
The cardiology perception statements with the highest agreement were:
- Interferes with family life during training (3.93).
- Having met positive role models or having positive views of cardiovascular disease as a topic (3.85).
- Reasonable compensation (3.69).
- Adverse job conditions (3.16).
- Field lacks diversity (2.90).
Compared with the 2010 survey, the 2020 findings indicated increased importance on work-life balance components for both male and female residents, with a greater change among males.
In addition, 2020 respondents were more likely than their predecessors to report negative perceptions of cardiology, such as too much overnight or weekend call, challenging to have children during fellowship, and lack of diversity.
“The culture of the subspecialty of cardiology has not improved to become significantly more diverse or inclusive, whereas other specialties and subspecialties have, and residents interact with cardiologists frequently and can see that,” Dr. York noted.
“As women now make up greater than 50% of medical students,” she said, “it is reasonable to focus on women in medical school and residency to bring them into the field of cardiology. But as racial and ethnic minority groups are also massively underrepresented in medical school, recruitment into medicine needs to start much earlier, in high school and college.
“Creating and supporting rotations that embed residents in the outpatient cardiology setting and exposure to more longitudinal experiences will provide a more realistic picture of the career,” she concluded.
ACC ‘at the forefront’
“Work-life balance looks different for each and every individual, but there are some themes that we need to think about,” Lisa Rose-Jones, MD, chair of the American College of Cardiology’s Program Directors and Graduate Medical Educators Section, said in her comments on the study. “The ACC is really at the forefront of this. They are putting together different work groups to focus on ‘how can we have some innovations?’ ”
The ACC is seeking mentors as part of its workforce diversity efforts among African American/Black, Hispanic/LatinX and Women’s IM cardiology programs, she noted. Furthermore, on Oct. 13, the organization released its 2022 health policy statement on career flexibility in cardiology, which calls for more leeway for cardiologists to deal with common life events without jeopardizing their careers.
Dr. Rose-Jones, director of the training program in cardiovascular disease at the University of North Carolina at Chapel Hill, said that because both male and female residents placed a high value on work-life balance, “we’ve got to think about how we can have flexibility in our work hours. That is critically important. Health systems need to be able to accommodate working families that may need to alter traditional 9 to 5 work hours to meet the demands of being a successful cardiologist and also being a parent.”
In addition, she said, “We need to have very clear policies at every institution on gender-related and parent-related discrimination. Data show that many female trainees are still being questioned on their family planning. That is absolutely not appropriate. It is none of our business. While we continue to do that, we continue to create stigma in our field.”
Like Dr. York, she noted generational differences in the doctors who are coming up now. “They’ve seen burnout firsthand and want to have a well-balanced life that includes medicine, but also life outside of the hospital,” Dr. Rose-Jones said. “So, those of us in cardiology really need to look deep inside and make changes. We need to be thoughtful about how we can be innovative.”
No commercial funding or conflicts of interest were declared.
A version of this article first appeared on Medscape.com.
Both male and female internal medicine (IM) residents prioritized work-life balance, such as stable working hours and family friendliness, when considering career choices, and cardiology was perceived to fall short in this area, an updated survey revealed.
Originally conducted in 2010, the survey aimed to understand IM residents’ professional development preferences and perceptions of cardiology as a specialty. That survey demonstrated a discordance between what residents valued in making a career choice and their perceptions of a career in cardiology.
The discordance remained in 2020, with residents even more likely than their predecessors to report negative perceptions of cardiology.
Compared with residents surveyed in 2010, respondents in 2020 placed higher value on all aspects of work-life balance and of having role models who demonstrated a successful balance. The value change was particularly notable for men.
“While our survey does not elucidate why this is, speculation could be made that this value on work-life balance is generational and prominent in the youngest generations entering all professional fields, not just medicine,” lead author Meghan York, MD, of Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, told this news organization.
“There is also an interesting trend that dual-career couples are on the rise in the U.S.,” she said. “This may reflect that trend, [with] men in medical fields possibly taking on more domestic responsibility and requiring more work flexibility to do that.”
Regarding perceptions, she added, cardiology tends to show resident cardiologists who are working in inpatient services with “ballooning and unpredictable hours,” rather than those who are working in more time-controlled clinics. Therefore, “their prime exposure to physicians is not truly representative of the career.” The study was published online in JAMA Cardiology.
‘Lack of diversity’
The updated surveys were sent by various means to close to 30,000 residents, and were completed by 840 (mean age, 29; 50% male; 55% White). Cardiology was a favored subspecialty choice among men, with 46.5% reporting they were considering it vs. 29.7% of women. Women were more likely to report never having considered cardiology as a career choice (37.6%) compared with men (22.3%).
The survey incorporated a 5-point Likert scale of 1 (not important) to 5 (extremely important) for some of the questions.
The most important professional development preferences for respondents were positive role models (4.56), stimulating career (3.81), family friendly (3.78), patient focus (3.70), stable work hours (3.66), female or race friendly (3.33), professional challenges (3.21), and financial benefits (3.20).
The cardiology perception statements with the highest agreement were:
- Interferes with family life during training (3.93).
- Having met positive role models or having positive views of cardiovascular disease as a topic (3.85).
- Reasonable compensation (3.69).
- Adverse job conditions (3.16).
- Field lacks diversity (2.90).
Compared with the 2010 survey, the 2020 findings indicated increased importance on work-life balance components for both male and female residents, with a greater change among males.
In addition, 2020 respondents were more likely than their predecessors to report negative perceptions of cardiology, such as too much overnight or weekend call, challenging to have children during fellowship, and lack of diversity.
“The culture of the subspecialty of cardiology has not improved to become significantly more diverse or inclusive, whereas other specialties and subspecialties have, and residents interact with cardiologists frequently and can see that,” Dr. York noted.
“As women now make up greater than 50% of medical students,” she said, “it is reasonable to focus on women in medical school and residency to bring them into the field of cardiology. But as racial and ethnic minority groups are also massively underrepresented in medical school, recruitment into medicine needs to start much earlier, in high school and college.
“Creating and supporting rotations that embed residents in the outpatient cardiology setting and exposure to more longitudinal experiences will provide a more realistic picture of the career,” she concluded.
ACC ‘at the forefront’
“Work-life balance looks different for each and every individual, but there are some themes that we need to think about,” Lisa Rose-Jones, MD, chair of the American College of Cardiology’s Program Directors and Graduate Medical Educators Section, said in her comments on the study. “The ACC is really at the forefront of this. They are putting together different work groups to focus on ‘how can we have some innovations?’ ”
The ACC is seeking mentors as part of its workforce diversity efforts among African American/Black, Hispanic/LatinX and Women’s IM cardiology programs, she noted. Furthermore, on Oct. 13, the organization released its 2022 health policy statement on career flexibility in cardiology, which calls for more leeway for cardiologists to deal with common life events without jeopardizing their careers.
Dr. Rose-Jones, director of the training program in cardiovascular disease at the University of North Carolina at Chapel Hill, said that because both male and female residents placed a high value on work-life balance, “we’ve got to think about how we can have flexibility in our work hours. That is critically important. Health systems need to be able to accommodate working families that may need to alter traditional 9 to 5 work hours to meet the demands of being a successful cardiologist and also being a parent.”
In addition, she said, “We need to have very clear policies at every institution on gender-related and parent-related discrimination. Data show that many female trainees are still being questioned on their family planning. That is absolutely not appropriate. It is none of our business. While we continue to do that, we continue to create stigma in our field.”
Like Dr. York, she noted generational differences in the doctors who are coming up now. “They’ve seen burnout firsthand and want to have a well-balanced life that includes medicine, but also life outside of the hospital,” Dr. Rose-Jones said. “So, those of us in cardiology really need to look deep inside and make changes. We need to be thoughtful about how we can be innovative.”
No commercial funding or conflicts of interest were declared.
A version of this article first appeared on Medscape.com.
FROM JAMA CARDIOLOGY
VTE prophylaxis overused in low-risk hospitalized patients
A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.
Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).
However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.
Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.
“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.
Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.
In the study population, 180 patients were identified as low risk and 289 were considered high risk.
Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.
A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.
Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.
Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.
The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.
he concluded.
Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.
The study received no outside funding. The researchers had no financial conflicts to disclose.
A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.
Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).
However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.
Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.
“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.
Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.
In the study population, 180 patients were identified as low risk and 289 were considered high risk.
Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.
A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.
Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.
Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.
The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.
he concluded.
Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.
The study received no outside funding. The researchers had no financial conflicts to disclose.
A majority of hospitalized patients at low risk for venous thromboembolism were unnecessarily treated with medication, based on data from more than 400 individuals.
Prevention of venous thromboembolism (VTE) is important, and current guidelines from the American College of Chest Physicians suggest that patients with high or moderate risk for VTE be treated with mechanical prophylaxis, and that pharmacological prophylaxis is not recommended for patients at high risk for bleeding, said Hui Chong Lau, MD, in a presentation at the annual meeting of the American College of Chest Physicians (CHEST).
However, the nature of VTE prophylaxis using a risk assessment score has not been explored, said Dr. Lau, a third-year resident in internal medicine at Crozer-Chester Medical Center, Upland, Penn.
Low-molecular-weight heparin (LWMH) and intermittent pneumatic compression are often used to reduce VTE risk during hospitalization, but for patients with low VTE risk, prophylaxis is not necessarily recommended, he said. In fact, overuse of chemical prophylaxis in low-risk patients can increase bleeding risk and contribute to patient discomfort in the form of additional needle sticks while hospitalized, Dr. Lau said in the presentation.
“We wanted to see how well physicians in the hospital used a risk assessment model to stratify patients,” and how well the patients were assigned to the correct prophylaxis, he explained.
Dr. Lau and colleagues reviewed data from 469 adult patients hospitalized at a single medical center who were hospitalized between January 2021 and June 2021. The researchers retrospectively performed risk assessment using the Padua prediction score. A score of less than 4 was considered low risk for VTE, and a score of 4 or higher was considered high risk.
In the study population, 180 patients were identified as low risk and 289 were considered high risk.
Based on the Padua score, 95% of the patients at high risk were on the correct prophylaxis, Dr. Lau said.
A total of 193 high-risk patients were on heparin. However, many of these patients had good kidney function, and could have been treated with enoxaparin instead; “this would have spared them two needle sticks per day,” Dr. Lau noted.
Of the 180 low-risk patients, 168 (93.3%) were on chemical prophylaxis, and should have been on mechanical prophylaxis, he said. Only 10 patients (5%) who were considered low risk were placed on mechanical prophylaxis.
Overall, 3.6% of all patients who received chemical VTE prophylaxis developed bleeding.
The results were limited by the retrospective design and use of data from a single center. However, the findings emphasize the need for better attention to VTE risk when considering prophylaxis, said Dr. Lau. “We have to have risk assessment every day,” during a hospital stay, and adjust treatment accordingly, he said.
he concluded.
Additional research is needed to better understand the potential consequences of overusing chemical VTE, including not only bleeding risk, but also financial costs and patient discomfort, he said.
The study received no outside funding. The researchers had no financial conflicts to disclose.
FROM CHEST 2022