Cholesterol efflux capacity and subclasses of HDL particles in healthy women transitioning through menopause

Abstract

Context: Growing evidence challenges the concept that high-density lipoprotein-cholesterol (HDL-C) is cardioprotective after menopause. HDL particle concentration (HDL-P) and cholesterol efflux capacity (CEC) might be better predictors of cardiovascular risk. Objective: Quantify alterations in HDL-P and CEC during menopause, correlating those changes with alterations in estradiol (E2) and FSH. Design: Longitudinal study of HDL metrics before and after menopause as indexed by the final menstrual period (FMP). Participants: Forty-six women, mean baseline age 47.1 years, 33% black, 67% white. Main Outcomes and Measures: HDL-P concentration (HDL-PIMA) by calibrated ion mobility analysis (IMA); macrophage CEC with cAMP-stimulated macrophages; ATP-binding cassette transporter A1 (ABCA1)-specific CEC with BHK cells expressing human ABCA1. Results: After a median of 2.1 years since FMP, both HDL-C (P = .03) and HDL-PIMA (P = .01) increased, with a selective increase in large HDL-PIMA (P=.01), whereas sizes of medium and small HDL-PIMA were decreased (P < .001). Greater declines in E2 correlated with larger increases in small HDL-PIMA (P=.01), whereas greater increases in FSH associated with greater reductions in the size of medium HDL-PIMA (P = .04). Macrophage CEC and ABCA1-specific CEC correlated positively with E2 levels only before menopause (P = .04 and .009, respectively). Conclusions: Large HDL-PIMA and CEC increased significantly in the early phase of the menopausal transition. Whether patterns of these alterations differ in late postmenopause is unknown. Further exploration is needed to assess that and to determine whether the reported changes in HDL metrics associate with increased cardiovascular risk after menopause.