Critical appraisal of the differential effects of antihypertensive agents on arterial stiffness

Integrated Blood Pressure Control Dovepress open access to scientific and medical research Review Integrated Blood Pressure Control downloaded from https://www.dovepress.com/ by 37.59.46.207 on 13-Jul-2018 For personal use only. Open Access Full Text Article Critical appraisal of the differential effects of antihypertensive agents on arterial stiffness This article was published in the following Dove Press journal: Integrated Blood Pressure Control 3 June 2010 Number of times this article has been viewed Francesca Kum Janaka Karalliedde Unit for Metabolic Medicine, Cardiovascular Division, Kings College-Waterloo Campus, King’s College London, United Kingdom Introduction Correspondence: Janaka Karalliedde Unit for Metabolic Medicine, Cardiovascular Division, 3rd Floor, Franklin-Wilkins Building, King’s College London, London SE1 9NH, United Kingdom Tel +44 (0) 207 848 4464 Fax +44 (0) 207 848 4567 Email submit your manuscript | www.dovepress.com Dovepress 6651 Powered by TCPDF (www.tcpdf.org) Abstract: Increased central arterial stiffness, involving accelerated vascular ageing of the aorta, is a powerful and independent risk factor for early mortality and provides prognostic information above and beyond traditional risk factors for cardiovascular disease (CVD). Central arterial stiffness is an important determinant of pulse pressure; therefore, any pathological increase may result in left ventricular hypertrophy and impaired coronary perfusion. Central artery stiffness can be assessed noninvasively by measurement of aortic pulse wave velocity, which is the gold standard for measurement of arterial stiffness. Earlier, it was believed that changes in arterial stiffness, which are primarily influenced by long-term pressure-dependent structural changes, may be slowed but not reversed by pharmacotherapy. Recent studies with drugs that inhibit the renin–angiotensin–aldosterone system, advanced glycation end products crosslink breakers, and endothelin antagonists suggest that blood pressure (BP)-independent reduction and reversal of arterial stiffness are feasible. We review the recent literature on the differential effect of antihypertensive agents either as monotherapy or combination therapy on arterial stiffness. Arterial stiffness is an emerging therapeutic target for CVD risk reduction; however, further clinical trials are required to confirm whether BP-independent changes in arterial stiffness directly translate to a reduction in CVD events. Keywords: aortic pulse wave velocity, augmentation index, blood pressure, renin–angiotensin– aldosterone system Hypertension is an increasingly prevalent condition, managed with a combination of lifestyle changes and increasingly by various pharmacological agents. These agents include the β-blockers, diuretics, calcium channel blockers (CCB), and drugs that interfere with the renin–angiotensin–aldosterone system (RAAS) pathway such as angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), and aldosterone antagonists. Currently, blood pressure (BP) is routinely measured in the clinical setting by brachial sphygmomanometry. However, prior to the routine use of the sphygmomanometer, the importance of arterial aging and the characteristics of the arterial pressure pulse wave as a bedside index of arterial aging were well documented.1 Abnormalities in the pulse wave shape were in fact used more than 100 years ago to diagnose hypertension and to demonstrate effects of drugs such as nitrates.1 Systolic pressure waves are augmented during transmission to the periphery; therefore, emerging evidence suggests that peripheral BP is only an indirect correlate of central aortic pressures. Importantly, the magnitude of such augmentation is dependent on stiffness of conduit vasculature, Integrated Blood Pressure Control 2010:3 63–71 63 © 2010 Kum and Karalliedde, publisher and licensee Dove Medical Press Ltd.This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Dovepress Integrated Blood Pressure Control downloaded from https://www.dovepress.com/ by 37.59.46.207 on 13-Jul-2018 For personal use only. Kum and Karalliedde described as central arterial stiffness. Central hemodynamic parameters, such as central systolic BP, pulse pressure (PP), and the augmentation index (AIx), are important determinants of cardiac workload. These can be measured noninvasively at the radial artery using sensitive methods.1,2–6 AIx is calculated as the ratio of the augmentation pressure (AP), the amplification of peak systolic BP, which is in turn due to the reflected systolic wave, to the PP (AIx = AP/PP), Figure 1.2 Aortic pulse wave velocity (Ao-PWV) is recognized as the current gold-standard measure of arterial stiffness.2 Ao-PWV can be determined from carotid and femoral pressure waveforms obtained noninvasively by applanation tonometry. Pressure waveforms are referenced to a concurrently recorded electrocardiography (ECG), and carotid to femoral transit time (∆T) is calculated from the foot-to-foot time difference between carotid and femoral waveforms. The distance between the surface markings of the sternal notch and the femoral artery is used to estimate the path length between the carotid and femoral arteries (L) and Ao-PWV is computed as L/∆T. This technique is a reproducible and noninvasive method validated in a range of clinical settings and trials.2 Arterial stiffness, as evaluated by Ao-PWV, has been extensively studied in recent years and is an established A independent predictor of cardiovascular risk; both fatal and nonfatal cardiovascular events and all cause mortality in hypertensive patients, in addition to an independent predictor of coronary heart disease and stroke in the healthy population.2,5 It is important to note the differences between AIx and Ao-PWV both of which are markers of arterial stiffness. AIx is known to be influenced by gender, heart rate, and body habitus in addition to BP and age.7,8 A transfer function derived from invasive studies is used to estimate central aortic pressure, APs, and AIx. Often there is poor correlation between Ao-PWV and AIx and some drugs can influence 1 parameter independently of the other. In fact, AIx and Ao-PWV may not reflect the same arterial wall properties with AIx being a surrogate index for the stiffness of resistance vessels (arterioles), whereas Ao-PWV is an indicator of aortic stiffness. Indeed, AIx and Ao-PWV can change independently of each other due to the elastic properties of the aorta and the adaptive responses of the endothelium.7–9 Furthermore, the age-related changes in AIx and Ao-PWV are nonlinear. Some suggest that AIx is a more sensitive marker of central arterial stiffness in younger adults as compared with Ao-PWV, an index that changes B S AP D PP D Healthy / Normotensive / Young Diabetes / Hypertensive / Elderly Forward systolic wave. Reflected wave, from p (...truncated)