Postmenopausal factors may negatively affect the heart-protective qualities of high-density lipoproteins (HDL), according to new findings from the Study of Women’s Health Across the Nation (SWAN) Heart and HDL ancillary studies. The research was presented in a poster session at the 2022 North American Menopause Society (NAMS) Annual Meeting held October 12 to 15 in Atlanta, Georgia.

Large HDL particles were found to become dysfunctional during the menopause transition. Higher levels of these particles may detrimentally modify the expected cardioprotective association of HDL function with aortic artery calcification, lead author Samar El Khoudary, PhD, MPH, FAHA, said in an interview. Dr El Khoudary is vice chair for education and associate professor in the Department of Epidemiology at the University of Pittsburgh School of Public Health.

The findings call into question the current use of HDL cholesterol into calculations of heart disease risk among women in menopause. Previous research by Dr El Khoudary and colleagues found that women with a high number of large HDL particles had an increased risk of cardiovascular disease close to menopause, while postmenopausal women with a high number of small HDL particles showed a lower risk regardless of the duration of time in menopause.

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“The ability of HDL subclasses, mainly large HDL particles, to promote cholesterol efflux capacity (CEC) from macrophages is weaker after than before menopause,” the study authors explained. “This suggests that CEC associations with cardiovascular risk may vary by HDL subclasses in pre vs postmenopausal stages.”

To assess the association between CEC and aortic artery calcification and whether this association varies by level of large HDL subclasses among premenopausal and postmenopausal women, the researchers analyzed data from the SWAN ancillary studies. The data included measurements of aortic artery calcification, CEC, and nuclear magnetic resonance spectroscopy of HDL subclasses (total, large, medium and small HDL particles) at the same time point.

The study included 262 women (mean age, 50.9 years); 163 were in pre/early perimenopause stages and 99 were in late peri/postmenopause stages.

Effect of Large HDL Subclasses Among Women in Menopause

A significant 3-way interaction of CEC, HDL subclasses, and menopause stage was found after adjusting for age, study site, race, body mass index, systolic blood pressure, smoking status, physical activity, anti-lipid medication use, and hormone therapy use. Among women in late perimenopause or postmenopause, CEC was more strongly positively associated with a higher prevalence of artery calcification at higher levels of large HDL particles. Among women who were premenopausal or in early perimenopause, CEC was more strongly positively associated with higher prevalence of artery calcification at lower levels of large HDL particles.

“In late peri/postmenopause stages, higher levels of large HDL subclasses may detrimentally modify the expected cardioprotective associations of CEC with aortic calcification,” they study authors concluded.

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El Khoudary, Chen X, Crawford S, et al. The contribution of HDL subclasses to the associations of HDL function with aortic calcification in pre- vs postmenopausal women: the SWAN Heart and HDL Ancillary Studies. Poster presented at: 2022 NAMS Annual Meeting; October 12-15, 2022; Atlanta, GA.