Long-term potential of angiotensin receptor blockade for cardiovascular protection in hypertension: The VALUE trial

The recent decrease of cardiovascular mortality in the USA is less pronounc ed than it has been in the preceding three decades. Elsewhere, cardiovascul ar mortality decreased and in some countries it increased. Cerebrovascular disease and ischemic heart disease were responsible for 21% of deaths recor ded by the World Health Organization in 1990 and 1997, of which hypertensio n was estimated to be directly responsible for half of these deaths. Apart from blood pressure (BP) elevation, essential hypertension is frequently as sociated with factors that increase the risk of poor cardiovascular outcome s: insulin resistance/dyslipidemia, elevated angiotensin and norepinephrine , a tendency for hypercoagulability, platelet overactivity, tachycardia, vu lnerability to arrhythmias, vascular hypertrophy, endothelial dysfunction, and left ventricular hypertrophy. Excess activation of the renin-angiotensi n system, independent of BP elevation, contributes to these abnormalities. To achieve better results in the future, focus must be shifted from BP lowe ring to recognition of specific effects of drugs on these diverse pathophys iologic aspects of hypertension. The Valsartan Antihypertensive Long-term U se Evaluation (VALUE) trial, which is evaluating the effect of valsartan (D iovan(R))vs. amlodipine, is a milestone in the effort to test whether newer compounds offer a better reduction of the cardiovascular consequences of h ypertension, as well as good BP control. The hypothesis is that valsartan b y antagonizing the negative effects of angiotensin on smooth muscle cell gr owth, endothelial function, sympathetic overactivity, and coagulation, may have for the same degree of BP lowering, better protective effects than the leading calcium antagonist amlodipine.