Objective-The risk of cardiovascular disease increases after menopause. Recent evidence suggests that it is possible for HDL to become proatherogenic or dysfunctional in certain situations. Our objective was to evaluate whether the relationship of 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 the Study of Women's Health Across the Nation (SWAN Heart). Women, not using hormone therapy, were stratified into premenopausal or earlyperimenopausal (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, SBP, glucose, BMI, smoking, menopausal status and LDL-C. Specifically: Multivariable modeling demonstrated an inverse association between HDL-C 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 triglycerides and more total LDL particles compared to Pre/EP women (p<0.05).Conclusion-These results suggest that the protective effect of HDL may be diminished as women transition the menopause. Future studies should examine whether this may be due to changes in HDL size, functionality, or related changes in other lipids or lipoproteins.
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