SERUM-CHOLESTEROL LEVELS AND MORTALITY

Mortality rates vary with serum cholesterol levels: the causal nature of this relationship is studied by prospective studies (analysis of associations) and unifactorial primary prevention trials (experimentation to determine causality). In prospective studies all cause mortality is often increased at low and high cholesterol levels because of the inverse relationships of this factor with cardiovascular mortality (positive) and non-cardiovascular mortality (negative). Coronary death increases proportionally to serum cholesterol levels in all populations, including those with low cholesterol levels, in both sexes and at all ages. The relationship with cerebrovascular mortality seems to depend on the clinical feature: increased mortality rate due to cerebral haemorrhage in patients with low serum cholesterol and a positive correlation with cerebral thrombosis. Mortality due to cancers is generally negatively correlated to serum cholesterol levels with a significant increase in mortality in patients with a low serum cholesterol. This relationship often becomes less significant as the time between measurement and death increases. Mortality due to violent causes is not usually related to serum cholesterol. The multitude of possible causes of confusion makes any causal interpretation of data illusory. Experimentation by unifactorial primary prevention trials is essential for any etiological research but none of the trials performed to date was designed to analyse the effect of lowering serum cholesterol on global or coronary mortality. The results of 4 trials with acceptable methodologies show, however, that lowering the serum cholesterol by diet and/or lipid lowering drugs in subjects with high serum cholesterol levels: a) reduces the incidence of hard coronary disease, b) probably reduces coronary mortality, c) probably does not increase other causes of death , with perhaps the exception of the increased number of violent deaths in the treatment groups and also the increased mortality probably related to the drug used in one particular trial. The data presently available is not complete. Further advances are awaited from the results of on-going trials but they will certainly not answer all the questions. However, in the present state of our knowledge, measures of prevention cannot reasonably be queried: maintaining throughout life serum cholesterol levels within the limits of low coronary risk and reducing the serum cholesterol levels of hypercholesterolaemic middle-aged men.