2nd International Symposium on Triglycerides and HDL

Lipoprotein subclasses

Robert S. Rosenson (Chicago IL) discussed lipoprotein subclasses, inflammation, and cardiovascular disease (CVD) risk in the metabolic syndrome. Insulin resistance impairs VLDL particle clearance, leading to greater interchange of core triglyceride from VLDL with LDL and HDL, with LDL and HDL triglyceride enrichment leading both to become substrates for hepatic lipase, resulting in smaller, denser particles. Insulin resistance also is associated with decreased levels of apolipoprotein (apo)A1, and elevated free fatty acid (FFA) levels downregulate the ABCA1 transporter, which is involved in reverse cholesterol transport. Insulin resistance then is associated with smaller HDL and LDL and with larger-sized VLDL. As the number of metabolic syndrome components increases, LDL particle number increases with increased small, dense LDL and decreased large LDL particle numbers. Persons with LDL <100, therefore, may or may not have low particle number, so that only one-quarter of persons with the metabolic syndrome in the Framingham Offspring Study who had LDL <100 had optimal LDL particle distribution (1). In the Women’s Health Study, LDL particle number was associated with risk, particularly if small and large particle numbers were included; the only additional lipid variable adding to risk in this analysis is HDL cholesterol. In the AFCAPS/TexCAPS (Air Force/Texas Coronary Atherosclerosis Prevention Study), low HDL was an important risk marker, with risk particularly related to apoB level. Rosenson noted that this again supports the “need to pay attention to atherogenic lipoproteins.”

Lipoprotein subclasses are related to inflammation, with smaller, usually negatively charged, particles more likely to pass through the extracellular matrix, enter the vascular wall, and interact with monocyte receptors, initiating an inflammatory cascade. Lipoprotein-associated phospholipase …