Metabolic disturbances increasing the risk of coronary heart disease during diuretic-based antihypertensive therapy: lipid alterations and glucose intolerance.

The treatment of hypertension reduces the incidence of stroke and congestive heart failure. Surprisingly, however, no reduction in morbidity from coronary heart disease (CHD) has been found in any of the placebo-controlled trials of hypertension treatment. This observation is unexpected because hypertension is a major risk factor for CHD. The one clinical trial demonstrating reduction of CHD with treatment of hypertension was not placebo controlled, thus provoking uncertainty about the cause of improvement. This article is a summary of the evidence that modest increases of 5% to 7% in serum total cholesterol during diuretic-based antihypertensive therapy offset, in part, the benefit expected from the lowering of blood pressure. Correlative data suggest a link between the lipid disturbance and the long-known glucose intolerance caused by diuretic drugs. The findings raise the possibility that treatment regimens free of these metabolic disturbances may provide the means for greater gains against CHD in patients with hypertension.