Renin-angiotensin system blockade and exercise-induced increase in aortic stiffness.

Abstract

In physiological conditions, the cushioning function of central conduit arteries transforms the cyclic high-flow and pressure oscillations in the ascending aorta into continuous and low-pressure blood flow at the level of microcirculation. Aging and elevated blood pressure (BP) induces structural and functional changes in arterial wall viscoelastic properties, resulting in arterial stiffening. The latter is reflected in progressive impairment of the cushioning function of central arteries and is typically associated with the development of isolated systolic hypertension and left ventricular hypertrophy. Importantly, prospective cohort studies have demonstrated that arterial hardening represents a strong and independent predictor of all-cause and cardiovascular mortality in various diseased populations, including patients with essential hypertension. Current guidelines on the management of arterial hypertension recommend regular physical activity as a major nonpharmacologic treatment approach towards BP lowering and cardiovascular risk reduction. In contrast, several lines of evidence from clinical studies suggest that acute high-intensity exercise can transiently elevate the risk of fatal and nonfatal cardiovascular events, mainly in prediposed individuals with substrate of structural cardiovascular disease. The mechanistic background of this deleterious impact of acute exercise on the cardiovascular system remains largely unclear. Activation of the sympathetic nervous system, aggravation of oxidative stress, platelet activation, impaired coagulation and fibrinolysis, and acute deterioration of large artery elasticity represent some of the mechanisms that have been proposed to be involved. It has to be noted that the type, frequency, duration, and intensity of physical exercise, play an important role in the exercise-induced alterations on the cardiovascular system. In this regard, previous clinical studies that investigated the effects of acute exercise on arterial elasticity, provide variable results. Some studies have shown high-intensity exercise to be associated with an acute increase in stiffness of central conduit arteries in healthy individuals. In other clinical studies, maximal aerobic exercise was found not to acutely affect large artery elasticity in young healthy patients. In contrast to the above, other investigators observed a sustained and prolonged improvement in compliance of peripheral muscular-type arteries and no change in elasticity of central conduit arteries after submaximal acute exercise in healthy patients. In this issue of The Journal of Clinical Hypertension, Gkaliagkousi and coworkers add important information to our knowledge, in this area, by reporting the results of a clinical study that explored acute changes in aortic stiffness after a high-intensity aerobic exercise test: (1) in untreated hypertensive compared with normotensive individuals, and (2) in hypertensive patients after 3 months of treatment with the angiotensin receptor blocker (ARB), valsartan. The study included 25 young patients with never-treated, newly diagnosed, stage I hypertension and 15 ageand sexmatched healthy volunteers. The investigators performed a careful workup of patients prior to study enrollment, excluding patients with secondary causes of hypertension and patients with white-coat or masked hypertension by performing 24-hour ambulatory BP monitoring. Arterial stiffness was assessed by measuring carotid to femoral pulse wave velocity (cf-PWV) with the use of the Sphygmocor device (AtCor Medical, West Ryde, Australia) at maximal exercise and at 10, 30, and 60 minutes after the completion of a treadmill exercise test. At baseline exercise test, significant elevations in systolic BP were noted at maximal exercise in both, hypertensive patients and healthy controls, which returned to pre-exercise levels after 10 and 30 minutes of recovery, respectively. In contrast, diastolic BP was not significantly different during acute high-intensity exercise, in both study groups. With regards to exercised-induced changes in aortic stiffness, cf-PWV was significantly elevated at maximal exercise in the group of hypertensive patients but not in the group of healthy controls. Of importance, despite the post-exercise reduction in systolic BP levels, the increase in cf-PWV persisted, even after 30 minutes of recovery in hypertensive patients. As expected, systolic BP and cf-PWV levels at all 5 timepoints of the baseline exercise test were significantly higher in hypertensive patients than in controls. After completion of the baseline test, 15 hypertensive participants who had indications to receive BP-lowering therapy according to guidelines were included in a subsequent interventional phase of the study to receive treatment with valsartan 160 mg daily for 3 months. Valsartan treatment resulted in significant reductions in both office and ambulatory BP and all treated hypertensive patients achieved adequate BP control at study Address for correspondence: Pantelis E. Zebekakis, MD, PhD, Section of Nephrology and Hypertension, 1st Department of Medicine, AHEPA University Hospital, St. Kiriakidi 1, GR54636, Thessaloniki, Greece E-mail: pzebeka@med.auth.gr