Abstract P105: Associations Of Subclasses, Content And Function Metrics Of High-density Lipoprotein With Carotid Intima-media Thickness In Women Transitioning Through Menopause Swan Hdl And Swan Heart Studies
Authors: El Khoudary Samar R , Chen Xirun , Brooks Maria M , Billheimer Jeff , Orchard Trevor , Rader Daniel , McConnell Dan , Crawford Sybil , Janssen Imke , Everson-Rose Susan , Matthews Karen A 
Published: May 2021

Objective:
Higher levels of high-density lipoprotein cholesterol (HDL-C) may not always be cardio-protective in midlife women. Novel metrics of HDL including nuclear magnetic resonance (NMR) spectroscopy subclasses (large, medium and small HDL particles (HDL-P), and size), HDL content of phospholipids (HDL-PL) and triglycerides (HDL-Tg), and HDL function as measured by cholesterol efflux capacity (HDL-CEC) show strong associations with cardiovascular disease (CVD) risk beyond HDL-C. Women experience increases in carotid Intima-media thickness (cIMT), a subclinical measure of atherosclerosis, over the menopause transition. Associations of novel metrics of HDL with cIMT have not been well characterized in midlife women. Our objective was to assess the associations of HDL subclasses, HDL-PL, HDL-Tg, and HDL-CEC with cIMT and to determine whether these associations vary by age at menopause.

Design:
We assessed 303 women (at baseline: age 51.0 ± 2.8 years; 67.8% White and 32.2% Black; 56.6% Pre-/Early perimenopausal) who had HDL metrics and cIMT measured once (N=37 [12%]) or twice (N=266 [88%]) over the menopause transition. Age at menopause was observed prospectively among 73% of women (defined as no menses for 12 consecutive months) and imputed among the rest. Linear mixed effect models were used to individually assess the association of each HDL metric with cIMT, and to test whether the association varied by age at menopause (<50, 50-53, >53 years old). Final models were adjusted for race, education, and time varying: age, systolic blood pressure, body mass index, menopausal status, triglycerides, low density lipoprotein cholesterol and HDL-C.

Results:
In unadjusted analyses, higher concentrations of large HDL-P, medium HDL-P, HDL-PL, and HDL-CEC, and larger HDL size, and lower concentrations of small HDL-P were associated with lower cIMT; all p <0.05. In final models, only associations of medium HDL-P (p=0.008) and HDL-PL (p=0.005) with cIMT remained statistically significant. Age at menopause modified associations of HDL-Tg with cIMT in both unadjusted and final models (p=0.05 for both); in the final model, per 1 SD unit increase in HDL-Tg, women with age at menopause >53 had thicker cIMT(β(SE): 6.72(6.27) μm) than those with age at menopause <50 (β(SE): -17.88(8.48) μm), p for comparison=0.01.

Conclusions:
In midlife women, higher concentrations of medium HDL-P and greater content of HDL phospholipids were associated with thinner cIMT beyond traditional CVD risk factors including HDL-C. Associations of HDL triglycerides content with thicker cIMT was more pronounced in women who reached menopause at older ages. Findings support utilizing other metrics of HDL rather than HDL-C to better characterize CVD risk in midlife women.