The clinical significance of the size of low-density-lipoproteins and the modulation of subclasses by fibrates.

Beyond total low-density-lipoproteins (LDL) levels, increasing evidence suggests that the 'quality' of LDL exerts a great influence on the cardiovascular risk. Several studies have also shown that the therapeutic modulation of LDL size is of benefit in reducing the risk of cardiovascular events. Hypolipidaemic treatment is able to alter LDL subclass distribution but strong variations have been noticed among different agents. Fibrates have a major impact on triglyceride metabolism and in modulating LDL size and subclasses, but variations exist among the different molecules. A literature search (by Medline and Scopus) was performed using the following headings: 'small dense LDL', 'LDL size', 'LDL subfractions', 'LDL subclasses', 'LDL distribution' and 'fenofibrate', 'bezafibrate', 'ciprofibrate' and 'gemfibrozil' up to 20 January 2007. The authors also manually reviewed the references of selected articles for any pertinent material. Analysis of all published studies revealed that treatment with fenofibrate, ciprofibrate, bezafibrate and gemfibrozil is usually beneficial, and fenofibrate may be more efficacious than the other molecules. This is supported by using all the available techniques in subjects with a very wide range of lipid alterations. Among the different agents, fenofibrate has been found to be particularly effective in modulating LDL size and subclasses in patients at higher cardiovascular risk, such as those with type 2 diabetes or the metabolic syndrome.