Pleiotropic effects of HDL subfractions and HDL-associated enzymes on protection against coronary artery disease.

Objective: High-density lipoprotein cholesterol (HDL-C) levels are inversely related to the risk of coronary artery disease (CAD). Alterations in HDL-C subclass distribution and HDL-associated enzyme activities may be more important than total HDL levels for the progression of CAD. We intended to investigate the relationship of HDL-C subclass distribution and HDL-associated enzyme activities with CAD.

Method And Results: Our study included 101 patients with stable coronary artery disease, and 64 healthy subjects. Serum levels of HDL lipoprotein-associated-phospholipase A2 (HDL-LpPLA2), paraoxonase 1 (PON1), and HDL subfraction distribution were measured. We found increased small HDL (sHDL) subfractions in patients with one-vessel disease (P < 0.001). We also found a reverse correlation between total HDL-C levels and affected vessel number (P < 0.05). Plasma HDL-Lp PLA2 enzyme level was higher in each vessel disease category compared to the control group (P < 0.001). However, PON1 enzyme activity in patients with CAD was not statically significant. Plasma sHDL, HDL-Lp PLA2 enzyme and Lp(a) were significantly different between subjects with CAD and control participants.

Conclusions: We demonstrated decreased sHDL particles and a lower cardioprotective HDL-LpPLA, enzyme activity in all patient subgroups compared to controls. Measurement of total HDL-C level only may not be sufficient to predict CAD risk.