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High-density Lipoprotein-cholesterol Subfractions and Coronary Artery Calcium: The ELSA-Brasil Study
Giuliano Generoso1, Isabela M Bensenor2, Raul D Santos3
1Instituto do Coracao, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil; Center for Clinical and Epidemiological Research, University Hospital, University of Sao Paulo, Sao Paulo, SP, Brazil.
Insights
Elevated high-density lipoprotein cholesterol (HDL-C) and its subfractions are not independently associated with coronary artery calcification. This finding suggests that HDL-C levels alone may not be a reliable predictor of atherosclerosis extent.
Area of Science:
- Cardiovascular Research
- Lipid Metabolism
- Atherosclerosis
Background:
- High-density lipoprotein cholesterol (HDL-C) is traditionally viewed as protective against cardiovascular disease, but a causal link remains unproven.
- HDL-C is heterogeneous, consisting of various subfractions (e.g., HDL2-C, HDL3-C) with potentially differential impacts on atherosclerosis.
- The association between specific HDL-C subfractions and coronary artery calcification (CAC) requires further investigation.
Purpose of the Study:
- To investigate the independent association between HDL-C subfractions and coronary artery calcium (CAC) scores.
- To determine if HDL2-C, HDL3-C, or the HDL2-C/HDL3-C ratio predict coronary calcification in individuals without prior cardiovascular disease.
Main Methods:
- Analysis of 3,674 participants from the ELSA-Brasil study, excluding those with prior cardiovascular disease or on lipid-lowering medication.
- Measurement of fasting lipoprotein cholesterol fractions, including total HDL-C, HDL2-C, and HDL3-C, using zonal ultracentrifugation (VAP method).
- Statistical analysis using linear and logistic regression to assess the predictive value of HDL-C subfractions for CAC, adjusting for multiple cardiovascular risk factors.
Main Results:
- A significant inverse association was observed between total HDL-C, its subfractions, and CAC when adjusted for traditional risk factors.
- However, upon further adjustment for triglycerides, neither total HDL-C nor its subfractions (HDL2-C, HDL3-C, HDL2-C/HDL3-C ratio) remained independently associated with the presence or extent of CAC.
- Individuals with CAC > 0 exhibited lower levels of total HDL-C and its subfractions.
Conclusions:
- In this cross-sectional study, total HDL-C and its subfractions (HDL2-C, HDL3-C) are not independently associated with coronary calcification.
- The findings indicate that HDL-C subfractions, as measured by VAP, may not be direct independent predictors of coronary artery calcification when triglyceride levels are considered.
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.
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