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. 2024 Mar-Apr;18(2):e218-e229.
doi: 10.1016/j.jacl.2024.01.004. Epub 2024 Jan 29.

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

Tina Costacou  1 , Rachel G Miller  2 , Karin E Bornfeldt  3 , Jay W Heinecke  3 , Trevor J Orchard  2 , Tomas Vaisar  3
Affiliations

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

Tina Costacou et al. J Clin Lipidol. 2024 Mar-Apr.

Abstract

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 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 (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.

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.

Keywords: Cholesterol efflux capacity; Coronary artery disease; HDL particles; Incidence; Risk; Sex differences; Type 1 diabetes.

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Conflict of interest statement

Declaration of competing interest T.C., R.G.M., J.W.H., T.J.O. and T.V. have no relevant conflicts of interest to disclose. K.E.B. serves on the Scientific Advisory Board of Esperion Therapeutics.

Figures

Figure 1.
Figure 1.
Hazard ratios for the prediction of incident CAD by sex Models allowed for diabetes duration, BMI, smoking, HbA1c, HDL-C (in models where HDL-C was not the main predictor), non-HDL-C, hypertension, WBC count, AER and eGFR. For total and ABCA1-specific CEC, hazard ratios are per SD (0·44 for total CEC and 0·31 for ABCA1 CEC).
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