Triglycerides are more important in atherosclerosis than epidemiology has suggested

Epidemiology call be a useful guide to risk prediction. If, for example, the value of serum cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides as predictors of future CHD events is considered, then generally the triglyceride level measured on a single occasion will add little to the prognostic information contained in cholesterol and HDL cholesterol. The serum triglyceride concentration is, however, often more strongly correlated with future CHD incidence in univariate analysis than is serum cholesterol. However, in multiple logistic regression analysis, particularly when HDL cholesterol is included, the strength of the apparent independent relationship between triglycerides and CHD incidence is weakened often to the point of insignificance in individual trials, although it is still evident on meta-analysis of all the epidemiological trials in which both HDL cholesterol and triglyceride levels were measured. The erosion of the relationship between triglycerides and CHD incidence when HDL is included in multiple logistic regression analysis is to some extent is an artefact of the greater biological variation of triglyceride concentrations compared with HDL cholesterol. When allowance is made for this triglycerides can have more predictive power than HDL. Important clinical decisions are generally not based on single measurements, but on a series which reduces the effect of biological variation. However, even more importantly epidemiology cannot tell us that lowering cholesterol or raising HDL cholesterol levels will have more therapeutic benefit than decreasing triglyceride levels. That can only be established in clinical trials. An overview of trials involving drugs, which have as their principal action triglyceride-lowering, revealed them to decrease CHD incidence as much as statins. In the trials the drugs, which principally lowered triglycerides, also produced small decreases in serum cholesterol. The decrease in CHD incidence was, however, more than would be predicted from a similar reduction in cholesterol achieved with statins. Epidemiology can thus be a poor guide to clinical decisions. Furthermore the epidemiological relationship between cholesterol, triglycerides, HDL and CHD gives us only limited insight into the mechanisms by which these lipids and lipoproteins are involved in atherogenesis and their relative importance in this process. Thus evidence from clinical studies linking hypertriglyceridaemia with potentially important atherogenic factors such as intermediate density lipoproteins, small dense LDL and increased cholesteryl ester exchange may provide a greater understanding of atherogenesis and potential sites of therapeutic intervention than epidemiology. There is thus evidence for the therapeutic value of lowering triglycerides and an emerging view that triglyceride-rich lipoproteins are frequently crucial in atherogenesis.