High-density Lipoprotein-cholesterol Subfractions and Coronary Artery Calcium: The ELSA-Brasil Study

Although elevated high-density lipoprotein cholesterol (HDL-C) is considered protective against atherosclerotic cardiovascular disease, no causal relationship has been demonstrated. HDL-C comprises a group of different subfractions that might have different effects on atherosclerosis. Our objective was to investigate the association between HDL-C subfractions with the coronary artery calcium (CAC) score.

We included 3,674 (49.8 ± 8.3 years, 54% women) participants from the ELSA-Brasil study who had no prior history of CVD and were not currently using lipid-lowering medications. We measured the fasting lipoprotein cholesterol fractions (in mmol/l) by a zonal ultracentrifugation method (VAP). We analyzed the independent predictive values of total HDL-C, HDL₂-C, and HDL₃-C subfractions and in the HDL₂-C/HDL₃-C ratio using linear regression to predict Ln(CAC+1) and logistic regression to predict the presence of CAC.

Overall 912 (24.8%) of the participants had CAC>0, and 294 (7.7%) had CAC>100. The mean total HDL-C, HDL₂-C, and HDL₃-C were: 1.42 ± 0.37, 0.38 ± 0.17 and 1.03 ± 0.21 mmol/l, respectively. Individuals with CAC>0 had lower levels of total HDL-C as well as of each subfraction (p < 0.001). When adjusted for age, gender, smoking, hypertension, alcohol use, physical activity, and LDL-C, we observed an inverse association between HDL-C and its subfractions and CAC (p < 0.05). However, by adding triglycerides in the adjustment, neither total HDL-C nor its subfractions remained independently associated with the presence or extent of CAC.

In this cross-sectional analysis, neither the total HDL-C nor its subfractions (HDL₂-C and HDL₃-C, as well as HDL₂-C/HDL₃-C ratio) measured by VAP are independently associated with the presence or extent of coronary calcification.