Angiotensin receptor blockade in the challenging era of systolic hypertension

Abstract

Systolic blood pressure is a major cardiovascular risk factor which is often associated with arterial stiffness. Markers of arterial stiffness, such as pulse pressure and carotid-femoral pulse wave velocity, have been proved independent predictors of cardiovascular risk. Recent evidence suggests that the renin-angiotensin system is involved in the pathogenesis of systolic hypertension and arterial stiffness. Outcome trials have shown impressive cardiovascular protection by reducing systolic blood pressure (BP) with drug treatment. However, in clinical practice systolic hypertension remains largely uncontrolled, first, because systolic BP goal is more difficult to be reached than diastolic and, second, because physicians are often reluctant to intensify treatment in patients with systolic BP close to 150 mmHg. Recent trials have focused on the effects of antihypertensive drugs not only on blood pressure, but also on pulse pressure and pulse-wave velocity. Blockade of the renin-angiotensin-aldosterone system, using angiotensin-converting enzyme inhibitors and more recently angiotensin receptor blockers, has been shown to provide beneficial effects on arterial stiffness that appear to be independent of their antihypertensive effects. Recent outcome trials have shown significant cardiovascular protection with angiotensin receptor blockers. These drugs have an excellent placebolike profile of adverse effects which is maintained when these drugs are combined with low-dose diuretics. Therefore, an angiotensin receptor blocker-based treatment strategy appears to be an attractive and evidencebased approach for the management of systolic hypertension, the reduction of arterial stiffness and the prevention of cardiovascular disease.

Comparison of antihypertensive effects of an angiotensin-converting enzyme inhibitor, a calcium antagonist and a diuretic in patients with hypertension not controlled by angiotensin receptor blocker monotherapy

“…The co-administration of agents from different classes results in multidimensional mechanisms of action that provide complementary cardiovascular effects [1,2]. Unfortunately, the evidence from randomized clinical trials that might guide the selection of optimal combinations of antihypertensive drugs remains limited [1,4].…”

Evaluation of arterial stiffness in morning hypertension under high-dose valsartan compared to valsartan plus low-dose diuretic

“…20 Angiotensin II promotes arterial stiffness by inducing fibrosis, collagen synthesis, smooth muscle cell proliferation and calcification in the arteries. 21,22 The finding that the differences in baPWV between the measured and estimated value were smaller in the high-dose valsartan group may also indicate that high-dose valsartan exerts a greater beneficial effect on arterial stiffness. These results lend support to the contention that high-dose valsartan has a direct beneficial effect on arterial stiffness, in addition to that exerted through its antihypertensive effect.…”

Combination pharmacotherapy in hypertension

“…Several studies suggested that physicians might not be aggressive enough in treating hypertension, particularly regarding the systolic blood pressure [20][21][22][23][24][25]. It seems that there is still some uncertainty among primary care physicians about the importance of reducing elevated blood pressure, particularly systolic, which may explain, at least in part, the poor levels of hypertension control in the population [18].…”