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

Arch Med Res. 2019 Aug;50(6):362-367. doi: 10.1016/j.arcmed.2019.10.006. Epub 2019 Oct 31.


Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: CAC; Coronary calcification; HDL-C; Subclasses; Subclinical atherosclerosis; Subfractions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atherosclerosis / blood
  • Atherosclerosis / pathology*
  • Brazil
  • Calcium / analysis*
  • Cholesterol / blood*
  • Cholesterol, HDL / blood*
  • Coronary Vessels / pathology*
  • Cross-Sectional Studies
  • Fasting
  • Female
  • Humans
  • Lipoproteins / blood*
  • Logistic Models
  • Male
  • Middle Aged
  • Triglycerides / blood
  • Vascular Calcification / pathology*


  • Cholesterol, HDL
  • Lipoproteins
  • Triglycerides
  • lipoprotein cholesterol
  • Cholesterol
  • Calcium