Metabolic and genetic aspects of familial combined hyperlipidaemia with emphasis on low-density lipoprotein heterogeneity

The relationship between elevated plasma cholesterol and the risk of coronary artery disease is now definitively established. Accumulating evidence indicates that the total amount of triglyceride-rich lipoprotein particles, i.e. chylomicron remnants, very low-density lipoproteins (VLDLs) and intermediate-density lipoproteins (IDLs), also determines the risk of developing cardiovascular disease. This would explain the benefit of cholesterol-lowering therapy observed in the majority of patients with coronary disease who have only marginally elevated plasma cholesterol levels but may exhibit other lipid abnormalities. In patients suffering from familial combined hyperlipidaemia (FCH), elevated levels of triglyceride-rich lipoproteins mainly determine the presenting lipid phenotype. Because FCH appears to be the most common form of hyperlipidaemia in young survivors of myocardial infarction, causing an estimated 10% of all premature coronary heart disease , recent research has been focused on the pathophysiological mechanism underlying premature atherogenesis in FCH. In this review, hypotheses concerning the metabolic and genetic basis of FCH. and its related entities, as well as the origin of LDL heterogeneity associated with these lipid disorders, will be discussed.