HDL3-C is a Marker of Coronary Artery Disease Severity and Inflammation in Patients on Statin Therapy.

Introduction: Low high-density lipoprotein (HDL-C) and inflammation are risk factors for coronary artery disease (CAD). However, limited data are available determining the role of HDL-C sub-particles HDL2-C and HDL3-C for assessing CAD severity in patients on statin therapy.

Methods: Blood samples were obtained prior to cardiac catheterization in 304 consecutive patients with suspected CAD on statin therapy in this sub-analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678) study. Detailed lipid profiling and oxidized LDL (ox-LDL) were analyzed. CAD severity was angiographically defined as severe CAD (>75% luminal diameter stenosis [LDS]) and non-severe CAD (≤75% LDS). Multi-regression analysis was performed to test for statistical significance. Receiver operator curve (ROC) analysis was performed to determine cut-point for predicting severe CAD.

Results: Patients with severe CAD had a significantly lower total-HDL-C, lower HDL3-C and higher lipoprotein(a) levels. HDL3-C and lipoprotein(a) cholesterol [Lp(a)-C] retained statistical significance on multiple regression analysis. ROC analysis showed HDL3-C to have a C-statistic of 0.60 (p = 0.003) and Lp(a)-C to have a C-statistic of 0.61 (p = 0.0007). Patients with HDL3-C ≤ 33 mg/dL and Lp(a)-C > 7 mg/dL were found to have significantly elevated ox-LDL levels.

Conclusion: In patients on statin therapy, HDL3-C and Lp(a)-C improve prediction of severe CAD compared to a traditional lipid panel. In addition, patients with HDL3-C ≤ 33 mg/dL and Lp(a)-C > 7 mg/dL have greater inflammation marked by ox-LDL. Further studies are needed to evaluate the utility of these novel biomarkers in predicting CAD severity.