Menopause may play role in CVD risk in older women
LAS VEGAS — Menopause may play a significant role in the increased risk for CVD in older women, according to a presentation at the National Lipid Association Scientific Sessions.
For years, CVD was known as a condition affecting men, which led to a major focus on CVD prevention efforts on men, Samar R. El Khoudary, PhD, MPH, FAHA, associate professor of epidemiology at University of Pittsburgh Graduate School of Public Health, said during the presentation. This resulted in a mortality gap between men and women, with an elevated mortality rate in women.
Although CVD remains the leading cause of death in women in the United States, there is a slow increase in awareness among women, according to the presentation.
“This issue is not just at the level of women, but also at the level of health care providers,” El Khoudary said.
In a study published in the Journal of the American College of Cardiology in 2017, only 40% of routine care in women included a heart risk check, according to the presentation. In addition, only 22% of primary care physicians and 42% of cardiologists said they felt that they were well-prepared to assess patients for CVD risk.
Age has been shown to be an important confounder for CVD, and the incidence of CVD increases as men and women age, according to the presentation. Sex differences also decreased with age.
“This is probably due to the increase of cardiovascular prevalence in women that happens at the age of 40 to 59, in which occurs the menopausal transition,” El Khoudary said.
Men develop CVD at double the rate compared with women when they are younger than 60 years, according to the presentation.
The Framingham study was one of the earliest studies that established the link between menopause and CVD risk. Compared with age-matched men, women who were premenopausal had decreased risk for CVD. The incidence of CVD in women who were postmenopausal was more than double that in age-matched women who were premenopausal. Menopause’s effect was greater in women aged 40 to 44 years compared with aged 45 to 49 years.
“This longstanding observation led to hypothesizing that ovarian hormone, in particular estrogen, is cardioprotective, a hypothesis that has been supported through observational and experimental studies, but we are really not able to prove this through clinical trials,” El Khoudary said. “This is one of the hottest topic areas in women’s health.”
Another challenge to this hypothesis is that age-specific CHD mortality does not show a bend around menopause, according to the presentation. The steep increase in CHD mortality after age 60 years is most likely related to changes at least 10 to 20 years before, which coincides with menopause.
Menopause is not an event, but rather a health transition that occurs over several years and varies in length, onset and manifestation through symptoms, El Khoudary said.
“When defining menopause dichotomously in a study as a pre- or post- or even by age, we are overseeing many changes that women experience during this stage,” El Khoudary said. “If we want to understand the contribution of menopause to cardiovascular health and other health issues, we need to track risk factor changes by menopausal stage and ovarian aging. This is something that can only be done by following women over time.”
Aspects of CV health that are mostly affected by menopause include body composition and fat distribution, incidence of metabolic syndrome, progression of carotid intima-media thickness and accelerated lipid changes.
Postmenopausal women are more likely to have higher levels of total cholesterol, LDL, apolipoprotein B and triglycerides, according to the presentation. The increase in LDL within 1 year of the final menstrual period was associated with an increased risk for the presence of carotid plaque after menopause, which was independent of all potential confounders. In addition, women with obesity with the greatest LDL increases within 1 year of the final menstrual period had the greatest increase in carotid intima-media thickness.
“[This is] suggesting that increases in LDL-C and body weight synergize each other at midlife,” El Khoudary said.
The relationship between HDL and menopause is currently unclear, as studies have suggested increases, decreases and no changes in HDL. In the SWAN study, women had an increase in HDL within 1 year of the final menstrual period, however apolipoprotein A-I continued to increase.
Recent studies have challenged the link between HDL and CV risk in postmenopausal women, and there are data showing that HDL may not always be cardioprotective in these women. Several studies have shown that higher HDL increases the risk for stroke, carotid intima-media thickness progression and calcification in the left main coronary artery.
“These results highlight that something could happen during the menopausal transition,” El Khoudary said.
A study published in the Journal of Clinical Lipidology in 2016 found that an increase in HDL before menopause is associated with a lower risk for carotid intima-media thickness, and an increase in HDL after menopause increased the risk for carotid intima-media thickness.
Preliminary data from a study published in Current Opinion in Lipidology in 2017 found that menopause may indirectly affect HDL efflux capacity.
Several guidelines have been written by the American Heart Association on preventing CVD in women. They do not recommend the use of hormone therapy in these women, but rather healthy lifestyle measures, according to the presentation.
The most recent guidelines published in 2011 suggest preventive drug interventions, major risk factor interventions and lifestyle interventions for CVD prevention. Since these have been published, researchers have learned a lot about CVD risk in menopausal women, according to the presentation.
Although a healthy lifestyle has been shown to prevent CVD in women, in 2007-2008 and 2011-2012 National Health and Examination Survey data, only 21% of women had more than five health lifestyle metrics.
“Definitely there’s still a lot we can do to encourage healthy lifestyle and reduce cardiovascular disease in women,” El Khoudary said.
The guidelines also addressed major risk factor interventions in women.
“If we want to reduce cardiovascular risk in older women, prevention strategies should not await the substantial risk factor changes that occur during and after the menopausal transition,” El Khoudary said. “We need to think about ultimate timing of early intervention for midlife women. Hopefully this is something that can be applied in the guidelines once they get updated.” – by Darlene Dobkowski
El Khoudary SR. Session III – Underserved Issues and Gender. Presented at: National Lipid Association Scientific Sessions; April 26-29, 2018; Las Vegas.
Disclosure: El Khoudary reports no relevant financial disclosures.