High plasma phospholipid transfer protein levels as a risk factor for coronary artery disease

Objective - Plasma phospholipid transfer protein (PLTP) mediates both net transfer and exchange of phospholipids between different lipoproteins. Animal studies have shown that it is closely related to the development of atherosclerosis. PLTP-deficient mice have demonstrated increased antioxidation potential as well as a decrease in apolipoprotein B secretion and atherosclerotic lesions. In humans, high PLTP is associated with type II diabetes and obesity. Methods and Results - To assess the relationship between PLTP activity and coronary artery disease (CAD), a novel, high-throughput method to measure plasma PLTP activity was used, relating it to CAD in 1102 cases and 444 controls. This demonstrated that PLTP activity in patients with CAD was significantly higher than in controls (25.5 versus 22.4 pmol/μL per h; P<0.0001). Using multivariate logistic regression analysis, PLTP activity was found to have independent predictive value for CAD. Patients within the highest quintile of PLTP activity revealed a 1.9-fold increase in risk for CAD compared with patients within the lowest quintile. Conclusions - These findings indicate that PLTP activity is positively and independently related to CAD and suggest that (1) prospective studies to evaluate this relationship are warranted and (2) PLTP should be considered a therapeutic target.