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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 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 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 CAD death, myocardial infarction and/or coronary revascularization.

RESULTS: Women had higher large HDL-P levels and marginally lower concentrations of small HDL-P 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 (HRmen =0·11, 95 % 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.

CONCLUSION: Despite few absolute differences in HDL-P concentrations by sex, the HDL-P - CAD association was weaker in women, particularly for extra-small HDL-P, suggesting that HDL-P may be less efficient in providing atheroprotection in women and perhaps explaining the lack of a sex difference in CAD in type 1 diabetes.

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