Cardiovascular prevention: relationships between arterial aging and chronic drug treatment

Abstract

In hypertension, structural and functional properties of the arterial wall are altered, and morbidity and mortality associated with hypertension are related to the vascular damage affecting several organs.Going from central to peripheral arteries, the diameter and the composition of the vessel wall vary in important ways. In addition, the aorta and its main branches are highly sensitive to aging and changes in blood pressure while the more distal compartment is the major source of wave reflections and highly sensitive to vasoactive substances.Indeed, blood pressure propagation within the arterial tree is based on arterial stiffness, wave reflections and pulse pressure (PP). 1 Of note, arterial stiffness is an independent predictor for cardiovascular mortality and morbidity, and pulse wave velocity is currently accepted as the gold standard measure of arterial stiffness. [2][3][4] Early wave reflections, as evaluated by pulse wave analysis, are also an independent predictor of cardiovascular risk. 5 In the treatment of hypertension there is evidence by large randomized controlled trials and meta-analyses for a beneficial effect on hard endpoints (cardiovascular morbidity and mortality, stroke, kidney disease) for b-blockers, diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor blockers. 6 In the first (but small) prospective randomised study, for example, Mackenzie et al. 7 investigated the effects of four major antihypertensive classes (atenolol, bendrofluazide, lercarnidipine, perindopril) on both central and peripheral blood pressures, PP amplification and aortic pulse wave velocity (PWV) in isolated systolic hypertension patients. They found that aortic PWV was not changed by any of the investigated drugs, and that despite similar reductions in peripheral systolic and pulse pressures with the four drugs, the changes in central pressure and augmentation index varied.Therapies combating arterial stiffness, reducing PP and reducing early wave reflections are believed to further reduce cardiovascular mortality. These treatments include exercise, nitrates, renin-angiotensin-aldosterone inhibitors, drugs acting on collagen cross-linking and vasopeptidase inhibitors. 8 Large scale, long term randomised controlled are necessary to prove that these agents effectively and safely diminish arterial stiffness and by this reduce cardiovascular morbidity and mortality.In the current issue of the Journal of Human Hypertension, Lieber et al. 9 report the results of a rather small cross-sectional analysis determining statistical associations between chronic drug treatment acting on cardiovascular prevention (antihypertensives, statins and oral antidiabetics and/or insulin) and age-induced changes in arterial stiffness and wave reflections. They conclude that calcium channel blockers and statins do not show any statistical association with PWV or wave reflection (augmentation index); that b-blockers are significantly associated with increased wave reflections and central PP; and that diuretics, angiotens...