Abstract P119: Changes in Cholesterol Efflux Capacity are Associated With Greater Progression of Aortic Calcification in Women at Midlife. Effects of Estradiol, Metabolic and Inflammatory Status
Authors: El Khoudary Samar R , Heinecke Jay , Brooks Maria , Orchard Trevor , Hutchins Patrick , Matthews Karen 
Published: July 2021

Objective:
High-density lipoprotein cholesterol efflux capacity (HDL-CEC) is associated inversely with CVD events. Recently, unexpected increases inHDL-CEC have been reported early after menopause. However, associations between HDL-CEC early changes and atherosclerotic progression in midlife women are not clear. We aimed to 1) test whether HDL-CEC changes from before to after menopause are associated with coronary (CAC) and aortic calcification (AC) progression anchored to the final menstrual period (FMP) date and 2) assess whether these associations could be explained by: time-varying estradiol, insulin resistance index (HOMA-IR), or C-reactive protein (CRP).

Methods:
Participants were fromthe Pittsburgh site of the Study of Women’s Health Across the Nation (SWAN). HDL-CEC and calibrated ion mobility HDL particles (HDL-Ps) were measured at two time points: one before and one after menopause (median time difference=6 Yr) and change in each metric was calculated as the difference between the two assessments. CAC and AC Agatston scores were available at the 2
nd
time point (after menopause) and 2.08 Yr (median time difference) before that. Participants were not on lipid lowering medications or hormone therapy. Linear mixed effect models of repeated measures of log (AC+1) or log (CAC+1) as a function of within-woman change in HDL-CEC, race, time-varying BMI, time since 1
st
calcification assessment and time before/after FMP were used. Progression of calcification per 1 year increase before/after FMP for every 1 unit increase in log HDL-CEC change were estimated by adding interaction between log HDL-CEC change and time before/after FMP to the above specified model. Estradiol, HOMA-IR, or CRP was added one at a time to the final models.

Results:
We studied 33 women (66 observations) (67% White and 33% Black) aged 52±2.3 Yr who were either peri- (64%) or postmenopause (36%) at calcification 1
st
measure. At calcification 2
nd
measure, all women were postmenopausal with a median time before/after FMP = 2.81 (Q1:1.84, Q3:4.30) Yr. Higher HDL-CEC change was associated with greater AC progression per 1 year increase before/after FMP (β(SE): 2.23(0.90) for every 1 log unit higher in HDL-CEC change, P =0.02). This association remained significant after adjusting for premenopausal HDL-CEC level, or changes in HDL-C or HDL-Ps. However, adjusting for estradiol, HOMA-IR, or CRP, the positive association between HDL-CEC and AC progression was largely attenuated and no longer significant. HDL-CEC changes were not associated with CAC progression.

Conclusions:
In this pilot study, increases in HDL-CEC early after menopause were associated with greater AC progression that was largely explained by midlife hormonal, metabolic or inflammation status. The midlife is a critical period that could impact HDL function and thus its cardio-protective effects. Our results should be retested in a larger setting.