Large HDL₂ combined with inflammatory factors as superior predictors for coronary artery disease than small HDL₃

This study investigated whether combinations of high-density lipoprotein (HDL) subfractions and inflammatory markers would add value to coronary artery disease (CAD) prediction.

Non-CAD subjects (n=245) were stratified into low/moderate/high-Framingham risk (L/M/H-FR) groups and 180 CAD patients were enrolled. Levels of HDL-C, HDL₂, HDL₃, monocyte chemoattractant protein-1 (MCP-1), and high-sensitivity C-reactive protein (hsCRP) were measured. Multivariable logistic models for CAD were estimated with a single parameter or all parameters together after adjustment for conventional risk factors (CRFs), and Z statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to compare discrimination among different models.

The results show that HDL-C, HDL_2, and HDL₃ gradually decreased, while MCP-1 and hsCRP gradually increased from L/M/H-FR to the CAD group. When applying a single factor in the CRFs-adjusted models, HDL-C (OR 0.011, 95% CI, 0.002-0.071, P<0.05) and HDL₂ (OR 0.000072, 95% CI, 0.000001-0.004, P<0.05), but not HDL₃, were significantly related to CAD risk. Only HDL₂ (OR 0.000072, 95% CI, 0.000001-0.004, P<0.001) remained significant when applying all HDL parameters. In the model including all HDL and inflammatory parameters, HDL₂ (OR 0.001, 95% CI, 0.000027-0.051), MCP-1 (OR 1.066, 95% CI, 1.039-1.094), and hsCRP (OR 1.130, 95% CI, 1.041-1.227) showed significant differences (all P<0.05). This combined model showed improved discrimination over the models with a single factor (P<0.05) or all HDL parameters (Z=3.299, NRI =0.179, IDI =0.081, P<0.001).

Large HDL₂ is superior to small HDL₃ in the inverse association with CAD. The combination of HDL₂, MCP-1, and hsCRP with CRFs provides an optimal prediction for CAD.