HDL-cholesterol as a marker of coronary heart disease risk: the Québec cardiovascular study

Background: Primary as well as secondary prevention trials have shown the relevance of lowering LDL-cholesterol to reduce coronary heart disease (CHD) risk. However, although the association between LDL-cholesterol and CHD is well recognized, there is a considerable overlap in the distribution of plasma LDL-cholesterol levels between CHD patients and healthy subjects. The objective of the present review article is to use data from the Québec cardiovascular study to demonstrate that in men, a low HDL-cholesterol may be even more of a risk factor and a target for therapy than a high LDL-cholesterol. Methods and results: Results of the Québec cardiovascular study, a prospective study of 2103 middle-aged men followed for a period of 5 years, have confirmed results of previous studies in showing that plasma HDL-cholesterol concentration was an independent predictor of a first ischemic heart disease (IHD) event which included typical effort angina, coronary insufficiency, nonfatal myocardial infarction and coronary death. In addition, a reduced plasma HDL-cholesterol concentration was found to have a greater impact than raised LDL-cholesterol on the atherogenic index (total cholesterol/HDL-cholesterol ratio), this ratio being the best variable of the traditional lipid profile for the prediction of IHD events in the Québec cardiovascular study. However, a low HDL-cholesterol concentration is not often observed as an isolated disorder but also includes hypertriglyceridemia, elevated apo B concentration, and an increased proportion of small, dense LDL particles. These abnormalities are features of an insulin resistant-hyperinsulinemic state resulting from abdominal obesity. Conclusions: It is therefore recommended that we need to go beyond LDL-cholesterol measurement lowering therapy for the optimal management of CHD risk. Raising plasma HDL-cholesterol through weight loss and a healthy diet, by an increased physical activity and, if required, by proper pharmacotherapy is therefore a legitimate therapeutic target for the optimal prevention of CHD in a large proportion of high risk patients.