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

Abstract

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 A(2) (HDL-LpPLA(2)), 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 PLA(2) 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 PLA(2) 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(2) enzyme activity in all patient subgroups compared to controls. Measurement of total HDL-C level only may not be sufficient to predict CAD risk.