HDL FUNCTIONALITY AND CARDIOVASCULAR DISEASE

Several prospective epidemiological studies have shown that there is a clear inverse relationship between serum high-density lipoprotein (HDL) cholesterol concentrations and risk for coronary heart disease (CHD), even at low-density lipoprotein (LDL) cholesterol levels below 70 mg/dL. HDL plays a critical role in reverse cholesterol transport (RCT) but also exhibits anti-inflammatory, antioxidant, anti-aggregating, anticoagulant, antithrombotic, endothelial/vasodilatory, and cytoprotective functions, which enhance its protective effect against cardiovascular disease (CVD). However, the function of HDL is dependent upon genetic, environmental, and lifestyle factors. Modification of the protein or lipid components of HDL in certain conditions may convert the HDL particles from antiinflammatory to pro-inflammatory and pro-atherogenic by limiting their ability to promote RCT and to prevent LDL modification. Indeed, more recent evidence from genetic studies and clinical research has come to challenge the long-standing notion that higher HDL levels are always beneficial, while lower HDL levels are always detrimental. Thus, it has become apparent that HDL functionality plays a much more significant role in atheroprotection than circulating HDL cholesterol (HDL-C) levels. This review aims to present and discuss the current clinical and scientific evidence regarding the significance of HDL functionality over the actual HDL concentration in mediating the favorable effects on the cardiovascular system. Furthermore, we will present the clinical and scientific data pertaining to the factors and conditions that impair HDL functionality and we will discuss the effects of dysfunctional HDL on CVD.