The role of non-LDL:non-HDL particles in atherosclerosis

Elevated concentrations of circulating apolipoprotein B (apoB)-containing lipoproteins, other than low-density lipoprotein (LDL), have been implicated as causative agents for the development of atherosclerosis. A form of dyslipidemia, the atherogenic lipoprotein profile, that consists of elevated intermediate-density lipoprotein (IDL), triglycerides (TGs), dense LDL and dense very low density lipoprotein (VLDL), and low high density lipoprotein-2, occurs in 40% to 50% of patients with coronary artery disease (CAD). The recently released Adult Treatment Panel III guidelines suggest that because elevated TGs are an independent CAD risk factor, some TG-rich lipoproteins, commonly called remnant lipoproteins, must be atherogenic. Relevant to this series on diabetes, a number of studies have shown that in type 2 diabetes, the severity of CAD is positively related to the numbers of TG-rich particles in the plasma. Although less clear, other studies in type 2 diabetes suggest that elevated levels of lipoprotein (a) Lp(a)] may also be independently associated with CAD. In this article, we summarize evidence for the role of apoB-containing lipoprotein particles other than LDL in the development of atherosclerosis and discuss methods of quantification and possible pharmacologic interventions for lowering their plasma concentrations. The particles reviewed include the TG-rich lipoproteins: VLDL and its remnants, chylomicron remnants and IDL, and the C-rich lipoprotein: Lp(a).