Increase HDL-C level over the menopausal transition is associated with greater atherosclerotic progression

Background Experimental and observational evidence demonstrates that high-density lipoprotein (HDL) can lose its well-documented atheroprotective functions and even adopt a paradoxically proinflammatory nature in certain conditions. Hormonal alterations, especially estradiol reduction, influence the accumulation of risk factors that could potentially impair the quality of HDL during the menopausal transition (MT). Limited data exist to evaluate the relationship between changes in HDL-cholesterol (HDL-C) and its main carried protein, apolipoprotein A (apoA), over the MT, and atherosclerosis development. Objective To evaluate the associations of changes in HDL-C and apoA with progression of carotid intima-media thickness (cIMT), carotid adventitial diameter (cAD), and presence of carotid plaque relative to the onset of the postmenopause. Methods A total of 213 participants (age [mean (SD)]: 45.7 [2.5] years at baseline; 70% white) from the Study of Women's Health Across the Nation Pittsburgh site were included. Participants had up to 5 measures of cIMT, cAD, and carotid plaque over a maximum of 9 years of follow-up. Results Adjusting for sociodemographic, cardiovascular disease risk factors, cardiovascular disease medication use, and C-reactive protein, a larger increase in HDL-C since baseline was significantly associated with a greater cIMT progression (P = .008). Additionally, a higher apoA level at baseline was significantly associated with a lower cIMT progression (P = .03). No significant associations were found with cAD or plaque presence. Conclusions As women transition through menopause, increases in HDL-C levels are independently associated with greater cIMT progression. Thus, the quality of HDL may be altered over the MT rendering HDL dysfunctional and not providing the expected cardioprotective effect.