Review: Promise of prevention and reversal of target organ involvement in hypertension

JRAAS 2001;2 (suppl 1):S4-S9 Introduction The benefits derived from antihypertensive therapy over the past four decades have been substantial. Clinical outcome studies in the US have demonstrated a progressive reduction of death and morbidity from strokes as well as from coronary heart disease (CHD) in the order of approximately 70% and 55%, respectively. Reduction in deaths from stroke has been demonstrated consistently in most prospective double-blind, placebocontrolled studies, probably because the cerebral circulation seems to be responsive to therapy that reduces arterial pressure. However, the initial review of the earlier multicentre trials demonstrated a significant reduction in deaths from CHD, but this was not as great as had been predicted. This led some observers to ascribe this finding to an atherogenic effect of diuretics mediated by elevated blood lipid levels. However, when the recommended doses of the thiazide diuretics were reduced drastically from those used in the earlier trials (e.g., from 100–150 mg hydrochlorothiazide to 12.5–25 mg daily) the same initially-projected reduction in deaths from CHD was confirmed. A subsequent meta-analysis involving elderly hypertensive patients with systolic and diastolic pressure elevation showed a 26% reduction in CHD deaths. Thus, reports from many national and international hypertension advisory panels continue to extol the benefits of the initial antihypertensive therapy in its ability to prevent strokes and CHD. Unfortunately, this confidence has been challenged over recent years. Worldwide efforts to treat patients with hypertension have become less successful. In many countries, the numbers of patients with hypertension detected, evaluated, treated and controlled are significantly less today than in the early 1970s when the national education and control efforts in the US were begun. Secondly, despite the continued reduction in stroke and CHD mortality, there has been a continuous and steady increase in the numbers of patients with hypertension who have progressed to end-stage renal disease (ESRD) or congestive heart failure (CHF). Further,although the greatest numbers of patients with ESRD have diabetes mellitus, patients with hypertension are the second most common group. Many of those patients with diabetes mellitus also have co-existent hypertension. Furthermore, as will be discussed below, while hypertension was the most common diagnostic group of patients with CHF in the pre-antihypertensive drug therapy era, its nature is very different today although continues to be the most common cause of CHF. This paper summarises studies from our laboratory in rats with CHD, ESRD in elderly spontaneously hypertensive rats (SHR) and young adult SHRs with exacerbated ESRD resulting from induced endothelial dysfunction. The beneficial effects on SHR target organs of antihypertensive therapy will be highlighted. These observations in the SHR will be supported by recent clinical experiences in patients with essential hypertension that underscore our present thesis that there is a real potential for prevention and reversal of target organ involvement in hypertension.