Early Menopause Linked to Increased ASCVD Risk

Early onset of menopause is an important risk factor for atherosclerotic cardiovascular disease (ASCVD), according to an analysis of women enrolled in numerous population-based studies.

“To me, what it says is that we need to start even earlier with prevention measures,” senior author Sadiya S. Khan, MD, MS (Northwestern University Feinberg School of Medicine, Chicago, IL), told TCTMD. “If somebody goes through menopause early, we need to be paying extra close attention to blood pressure, cholesterol, diabetes, and other risk factors for heart disease.”

Premature menopause—defined as natural or surgical menopause before age 40—was associated with ASCVD, independent of traditional risk factors, with an HR 1.24 (95% CI 1.03-1.49) in Black women and 1.28 (95% CI 1.13-1.45) in white women.

Adding premature menopause status to the pooled cohort equations used to predict 10-year risk, however, did not result in any incremental benefit in terms of prediction ability. While the study doesn’t directly address how well the American College of Cardiology/American Heart Association practice guidelines for reducing ASCVD are working in women, the implication from this study is that the pooled cohort equations for risk assessment are adequate, Khan said.

For the study, published this week as a research letter in JAMA Cardiology, Khan and colleagues, including lead author Priya M. Freaney, MD (Northwestern University Feinberg School of Medicine), analyzed data from the Framingham Heart Study, the Framingham Offspring Study, the Atherosclerosis Risk in Communities study, the Coronary Artery Risk Development in Young Adults study, the Cardiovascular Health Study, the Multi-Ethnic Study of Atherosclerosis, and the Women’s Health Initiative. Participants were ages 40 to 79 years and had no history of ASCVD.

Enhanced Risk in Black Women

Three sensitivity analyses of women with natural menopause, surgical menopause, and those ages 40 to 54 years showed similar levels of increased ASCVD risk when early menopausal transition occurred. “I think the finding that that was consistent is reemphasizing that the risk-factor levels are still the most prominent part of the risk-prediction model,” Khan noted.

In the paper, the researchers say premature menopause “may be a marker of underlying risk rather than a contributor to ASCVD development, because studies have reported a positive association between premenopausal cardiovascular health (eg, body mass index, systolic blood pressure, physical activity) and early age at menopause.”

While there were fewer Black women (n = 5,466) than white women (n = 10,584) overall in the cohorts, Black women were much more likely to experience premature menopause (17.4% vs 9.8%), confirming data from several prior studies. Additionally, Black women were more likely than white women to have high blood pressure, high cholesterol, and diabetes.

“In this relatively young group of Black women, half of them were on treatment for hypertension, and that's irrespective of menopausal status,” Khan observed. “We need to work on implementing evidence-based therapies for risk-factor control, or preventing the risk factors from developing in the first place.”

She added that looking at what happens to women’s health in midlife and how that can differ by race and ethnicity is increasingly important given the known influence of social determinants of health.

“I think future research should investigate whether adverse social factors play a role in early menopause, and whether they may also be contributing to risk for ASCVD in midlife for Black women compared with white women,” Khan added.