In defense of alternative antihypertensive therapy.

HE standard step-care approach to the treat- ment of patients with mild hypertension, as outlined in reports of the Joint National Committee for the Detection, Evaluation, and Treat- ment of Hypertension 1 prior to 1988, has served both the hypertensive patient population and the practicing physician well over the past 10 to 20 years. By bringing to the attention of the patient population the advantages of antihypertensive ther- apy with regard to a reduction in overall mortality, this approach has increased public awareness and encouraged hypertension-screening programs at worksites, community health fairs, and health care facilities. Concurrently, physicians have proceeded to treat hypertensive patients in an organized fash- ion, with the result that high blood pressure is controlled in virtually all patients who maintain contact with a physician and who are compliant with their antihypertensive regimen. As Dr. Marvin .Moser points out in the preceding article, 2 step-care therapy is an effective treatment for patients with mild forms of hypertension. We differ in our approach to the treatment of hypertensive patients because, in my opinion, the principal argument in favor of step-care therapy is simply the fact that it has been used successfully for many years. The principal components of step-care therapy, diuretics and /3-adrenergic receptor block- ers, were among the first agents developed for the treatment of hypertension, and we have the greatest experience with them. The question I would pose is Can we do better? Is there reason to believe that newer antihypertensive agents, if evaluated in prop- erly designed clinical trials, would demonstrate greater efficacy in the reduction of cardiovascular morbidity? At least four factors suggest that vasodilating agents confer an advantage over diuretics or /3- adrenergic blockers (or both) as the initial therapeu- tic regimen for patients with hypertension. First, most hypertensive patients manifest an increase in systemic vascular resistance, which leads to com- pensatory changes in cardiovascular performance. These changes include left ventricular hypertrophy and, sometimes, an increase in left ventricular end- diastolic volume with associated abnormalities of diastolic ventricular filling. 3 Diuretics and p- adrenergic blockers do little to reverse this under- lying physiological abnormality. Indeed, many /3- adrenergic blocking agents increase systemic vas- cular resistance and decrease cardiac output ini- tially, if not chronically. They thus reduce blood pressure through a cardiosuppressive physiological response. 4 In contrast, a-adrenergic antagonists, angiotensin converting enzyme inhibitors, and cal- cium channel blockers lower blood pressure by decreasing systemic vascular resistance and improv- ing or maintaining cardiac output. Further, cal- cium channel blockers improve ventricular diastolic function. 5 Second, many questions remain regarding the management of hypercholesterolemia in patients with hypertension. The deleterious effects of anti- hypertensive therapy on plasma lipoprotein levels are not uniformly accepted. It is clear that diuretic agents have no beneficial effect on lipoprotein metab- olism. Although Dr. Moser cites a number of clini- cal trials in which diuretic therapy produced insig- nificant changes in total cholesterol levels, other investigators have reported significant increases in total cholesterol levels and decreases in the high density lipoprotein fraction of cholesterol in patients treated with thiazide-type diuretics or /3-adrenergic blockers (or both). 6 The adverse effects of these agents have not been investigated adequately. Dra- matic changes can occur in serum cholesterol con- centrations in individual patients. Patients receiving diuretic therapy must be carefully monitored for this adverse metabolic side effect. None of the trials cited by Dr. Moser were designed to measure changes in lipoprotein frac- tions in response to antihypertensive therapy. Patients were not randomized to therapeutic groups based on lipid variables, nor was any uniform effort made to modify dietary practices, physical activity, or other factors that might lead to changes in cholesterol concentrations in cholesterol concentra- tions. No trial evaluating patients according to