Sex Differences in the Associations of HDL Particle Concentration and Cholesterol Efflux Capacity with Incident Coronary Artery Disease in Type 1 Diabetes: the RETRO HDLc Cohort Study.

Background: In type 1 diabetes, women lose their relative protection (compared to men) against coronary artery disease (CAD), while high-density lipoprotein cholesterol (HDL-C) is less strongly associated with lower CAD risk in women. Objective: We aimed to assess whether sex differences in the HDL particle concentration (HDL-P) and cholesterol efflux capacity (CEC) association with CAD may explain these findings. Methods: HDL-P (calibrated differential ion mobility analysis) and total and ATP binding cassette transporter A1 (ABCA1)-specific CEC were quantified among 279 men and 271 women with type 1 diabetes (baseline mean age 27 8 years; diabetes duration, 19 6 years). Clinical CAD was defined as Results: Women had higher large HDL-P levels and marginally lower concentrations of small HDLP and ABCA1-specific CEC than men. No sex differences were observed in extra-small HDL-P, medium HDL-P and total CEC. During a median follow-up of 26 years, 37 6 % of men and 35 8 % of women developed CAD ( p = 0 72). In multivariable Cox models stratified by sex (pTotal HDL-P x sex interaction = 0 01), HDL-P was negatively associated with CAD incidence in both sexes. However, associations were stronger in men, particularly for extra-small HDL-P (hazard ratio (HR)men = 0 11, 95 % confidence interval (CI): 0 04-0 30; HRwomen = 0 68, 95 % CI: 0 28-1 66; pinteraction = 0 001). CEC did not independently predict CAD in either sex.