Introduction: Low-density lipoproteins (LDL) are established risk factors for cardiovascular disease and a therapy target. Prior studies suggest that among the pool of plasma LDL, the small and dense subfractions are more strongly associated with risk. In the present study, we investigated whether LDL particle density is associated with the presence of subclinical atherosclerosis detected by coronary artery calcium score.
Methods: We included 2869 (50.3±8.5 years, 54% women) participants from the ELSA-Brasil study who had no prior history of CVD, were not currently using lipid-lowering medications, and underwent CAC evaluation. We measured the fasting lipoprotein cholesterol fractions (in mg/dL) using the vertical auto profile (VAP) ultracentrifugation method. We analyzed the independent predictive values of LDL-1, LDL-2, LDL-3 and LDL-4, as well as the ln transformed ratio of small and dense (LDL-3 and LDL-4) to larger and more buoyant LDL particles (LDL-1 and LDL-2) (LLDR (Logarithmic of LDL Density Ratio)) using logistic regression.
Results: Overall 749 (26%) of the participants had a CAC >0, and 241 (8.1%) had a CAC > 100. The mean LDL-1, LDL-2, LDL-3 and LDL-4 cholesterol were respectively (mg/dL): 22.5±9.4, 32.7±17.9, 47.1±20.4 and 10.4±10.8. Individuals with CAC>0 had higher LDL-1, LDL-3 and LDL-4, but LDL-2 was not significantly different between groups. LLDLR was also significantly higher in those with CAC>0. LLDR was associated with CAC>0 even after multivariable adjustment for age, gender, smoking, diabetes, hypertension, systolic blood pressure and Friedwald LDL-cholesterol. (p<0.01).
Conclusion: In a large cohort of asymptomatic individuals, the ratio of small and dense to larger buoyant LDL-C particles is associated with CAC score. This association is independent and complementary to the calculated LDL-cholesterol levels.