Increasing High-Density Lipoprotein as a Therapeutic Target in Atherothrombotic Disease

Atherothrombosis, atherosclerosis and their thrombotic complications have become epidemic. Both an elevated low-density lipoprotein (LDL) cholesterol level and a decreased high-density lipoprotein (HDL) cholesterol level are associated with the increased incidence of atherothrombosis. Reducing LDL using statins has been shown to provide very effective therapy for both primary and secondary prevention. Nevertheless, despite statin treatment, a large percentage of patients continues to experience cardiovascular events. Therapies aimed at increasing HDL have been investigated for several decades, with promising results. However, because statin treatment was not standardized in earlier trials, it has been difficult to draw clear conclusions. Recent advances in both animal studies and clinical trials indicate that increasing the HDL level could result in additional benefits to those achieved by reducing LDL levels using statins. Intravenous infusion of various HDL preparations appears to lead to the accelerated regression and stabilization of atheromatous plaque, and could provide a novel approach to treatment in high-risk patients. This review describes the biological rationale underlying the use of treatments that increase HDL and discusses the potential benefits of such treatment.