Antihypertensive agents and cardiovascular risk factors.

A number of recent studies have failed to show the expected effect that aggressive antihypertensive therapy can contribute to the primary prevention of morbidity and mortality from coronary heart disease. Although antihypertensive agents effectively lower blood pressure, their ability to increase other cardiovascular risk factors may modify or even outweigh the beneficial effect gained from blood pressure control alone. In view of the vast population of patients with mild to moderate hypertension that might be treated, it is important that treatment of hypertension have as little adverse effect as possible on other risk factors. Current investigations have revealed that thiazide diuretics raise total cholesterol levels, while beta-blockers raise triglyceride and lower high-density lipoprotein levels. Thus both drugs tend to worsen the patient's serum lipid profile. Diuretics also decrease renal perfusion and increase serum glucose and uric acid concentrations. Beta-blockers have been shown to decrease exercise capacity and left ventricular performance. It is apparent, therefore, that even with a beneficial reduction of blood pressure, these drugs may have undesirable effects as well, thus tainting the expected clinical benefit. For example, data from the Framingham study indicate that a persistent increase of 10 to 20 mg/dl in total serum cholesterol largely offsets the protection from coronary heart disease afforded by a 10- to 15-mmHg reduction in blood pressure. Alpha 1-blocking agents, in contrast, appear to have desirable effects on many of the risk factors. The use of antihypertensive agents that do not adversely affect coronary heart disease risk factors, coupled with nonpharmacological measures such as diet and exercise, appears to be the best approach to therapy in hypertensive patients.