The variation in the size and atherogenicity of the low density lipoprotein (LDL) particles has attracted a great deal of recent attention. In particular, attention has focused on the role of plasma triglyceride concentrations in driving the lipoprotein exchange that determines the concentration of the smaller, denser, more atherogenic LDL fraction. In a study at Glasgow University, researchers analysed the distribution of LDL subfractions among normocholesterolaemic men, with or without coronary artery disease, survivors of myocardial infarction, and normal controls. The results showed that the risk of coronary artery disease or myocardial infarction is considerably greater in those groups with higher plasma concentrations of small, dense LDL. In a second study, eight patients with hypercholesterolaemia were treated with fenofibrate. Radioisotope tracers showed that fenofibrate shifts the distribution of LDL subfractions from small, dense, atherogenic particles towards larger, lighter, less atherogenic ones. The efficacy of fenofibrate derives from its hypotriglyceridaemic activity. Triglycerides may have further atherogenic and thrombogenic effects: they may cause endothelial cell dysfunction in the artery wall, stimulating the recruitment of macrophages into the endothelium. They may also promote the synthesis of thrombogenic mediators, suppressing local plasmin synthesis and accelerating intra-arterial fibrin deposition. This evidence has led to an increasing recognition of the central role of triglycerides in the process of atherogenesis.

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There has been much debate over the past three decades concerning the role of hyperlipidaemia in coronary heart disease (CHD) and the efficacy of reducing plasma lipids levels. Although reduction in plasma cholesterol has been associated with a favourable effect on both primary and secondary CHD, there is a growing feeling that cholesterol may not be the only significant lipoprotein risk factor to be involved. Only relatively recently has the true role of triglycerides become apparent. Studies have indicated that the greatest reduction in CHD with some treatments has been found in those patients in whom high triglyceride levels accompany hypercholesterolaemia. In particular, in younger patients who have suffered a myocardial infarction, hypertriglyceridaemia is more common than hypercholesterolaemia. Nevertheless, recent large studies have shown that reduction of low-density lipoprotein (LDL) is beneficial, even in post-infarction patients with a relatively normal total cholesterol level. Furthermore, studies with fibrates and with HMG Co-A reductase inhibitors have indicated that progression of atheromatous lesions can be halted and in may cases there is evidence of regression. Continuing research on the pathophysiology of atherosclerosis, including the role of macrophages and thrombotic involvement, will further define the role of hypolipidaemics in the prevention and management of coronary heart disease.

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