Lipids, menopause, and early atherosclerosis in Study of Women's Health Across the Nation Heart women

Objective: The risk of cardiovascular disease increases after menopause. Recent evidence suggests that it is possible for high-density lipoprotein (HDL) to become proatherogenic or dysfunctional in certain situations. Our objective was to evaluate whether the relationship of HDL cholesterol (HDL-C) to subclinical cardiovascular disease differed across the menopausal transition, which would provide insight for this increased risk. Methods: Aortic calcification (AC), coronary artery calcification (CAC), carotid plaque, and intima media thickness (IMT) were measured in an ancillary study of the Study of Women's Health Across the Nation. Women not using hormone therapy were stratified into premenopausal or early perimenopausal (Pre/EP, n = 316) and late perimenopausal or postmenopausal (LP/Post, n = 224). Results: The inverse relationship of HDL-C to subclinical atherosclerosis measures among Pre/EP women was weaker or reversed among LP/Post women, adjusted for age, site, race, systolic blood pressure, glucose, body mass index, smoking, menopause status, and low-density lipoprotein cholesterol. Specifically, multivariable modeling demonstrated an inverse association between HDL-C level and AC and IMT among Pre/EP women; however, the protective effect of HDL-C for AC, left main CAC, carotid plaque, and IMT was not seen in LP/Post women. In a small subset (n = 53), LP/Post women had more total and small HDL particles, higher triglyceride levels, and more total low-density lipoprotein particles compared with Pre/EP women (P < 0.05). Conclusions: These results suggest that the protective effect of HDL may be diminished as women transition in menopause. Future studies should examine whether this may be due to changes in HDL size, functionality, or related changes in other lipids or lipoproteins.