Effects of Various Antihypertensive Drugs on Arterial Stiffness and Wave Reflections

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Abstract

We reviewed trials that tested the efficacy of antihypertensive drugs in reducing arterial stiffness and wave reflections as assessed by pulse wave velocity and augmentation index, respectively. Regardless of cross-over or parallel-group comparison design, placebo-controlled trials demonstrated that antihypertensive drugs were effective in reducing pulse wave velocity. In actively-controlled parallel-group comparison studies, this effect on arterial stiffness was more evident for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers than other classes of antihypertensive drugs, particularly when brachial-ankle pulse wave velocity was measured. Regardless of cross-over or parallel-group comparison or placebo- or actively-controlled design, the reviewed trials showed that β-blockers were inferior to all the other classes of antihypertensive drugs in reducing augmentation index. However, these studies had a small sample size and a short follow-up time and did not link the changes in measurements of arterial function with cardiovascular events. Whether the superiority or inferiority is clinically relevant for cardiovascular protection and prevention remains to be investigated.

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Most cited references 67

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Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial.

Nicola C. Edwards, Richard Steeds, Paul Stewart … (2009)

We sought to determine whether the addition of spironolactone to angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) improves left ventricular mass and arterial stiffness in early-stage chronic kidney disease (CKD). Chronic kidney disease is associated with a high risk of cardiovascular disease and a high prevalence of left ventricular hypertrophy and arterial stiffness that confer an adverse prognosis. It is believed that these abnormalities are in part a result of activation of the renin-angiotensin-aldosterone system. After an active run-in phase with spironolactone 25 mg once daily, 112 patients with stage 2 and 3 CKD with good blood pressure control (mean daytime ambulatory blood pressure <130/85 mm Hg) on established treatment with ACE inhibitors or ARBs were randomized to continue spironolactone or to receive a matching placebo. Left ventricular mass (cardiac magnetic resonance) and arterial stiffness (pulse wave velocity/analysis, aortic distensibility) were measured before run in and after 40 weeks of treatment. Compared with placebo, the use of spironolactone resulted in significant improvements in left ventricular mass (-14 +/- 13 g vs. +3 +/- 11 g, p < 0.01), pulse wave velocity (-0.8 +/- 1.0 m/s vs. -0.1 +/- 0.9 m/s, p < 0.01), augmentation index (-5.2 +/- 6.1% vs. -1.4 +/- 5.9%, p < 0.05), and aortic distensibility (0.69 +/- 0.86 x 10(-3) mm Hg vs. 0.04 +/- 1.04 x 10(-3) mm Hg, p < 0.01). The use of spironolactone reduces left ventricular mass and improves arterial stiffness in early-stage CKD. These effects suggest that aldosterone exerts adverse cardiovascular effects in CKD and that spironolactone is worthy of further study as a treatment that could reduce adverse cardiovascular events. (Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure; NCT00291720).

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Effect of different antihypertensive drug classes on central aortic pressure.

Trefor Morgan, Jann Lauri, Denise Bertram … (2004)

Central aortic systolic blood pressure (BP) is an important determinant of cardiac workload and cardiac hypertrophy. The relationship of central aortic systolic BP and brachial BP varies depending on the stiffness of blood vessels. It is not certain whether the different drug classes affect the brachial and aortic systolic BP in a similar manner. In a double-blind crossover study, we measured the effects of the four major drug classes compared with placebo on central aortic pressure. Central aortic pressure and various indices were determined using the Sphygmo Cor apparatus. The study was undertaken in patients aged 65 to 85 years with systolic BP >150 mm Hg at study entry. Results are reported for 32 patients who had satisfactory applanation tonometry in all five periods. Calcium channel blockers and diuretics caused a greater fall in brachial artery systolic BP than angiotensin-converting enzyme (ACE) inhibitors or beta-blocking drugs. On placebo, central aorta augmentation pressure and index were 23 mm Hg and 33.3%; on ACE inhibitors the values were 18 mm Hg and 30%; on beta-blockers, 26 mm Hg and 38.5%; on calcium channel blockers, 16 mm Hg and 28%; and on diuretics, 17 mm Hg and 28.8%. The augmentation pressure on beta-blocking drugs was greater than on the other three drug classes (P <.05), and augmentation pressures on ACE inhibitors, calcium channel blockers, and diuretics were less than on placebo (P <.05). The lowest central aortic pressures were achieved with calcium blocking drugs and diuretics. Therapy based on brachial artery recordings may thus overestimate the effect of beta-blocking drugs on central aortic systolic BP and underestimate the effectiveness of ACE inhibitors and calcium blocking drugs. The clinical importance of this discrepancy needs to be evaluated.

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Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension.

Barbara Roniker, Daniela Krause, Krystal St. Julien … (2003)

Eplerenone is a highly selective aldosterone blocker, which is under development for the treatment of hypertension and heart failure. To assess its usefulness in older patients with systolic hypertension and widened pulse pressure, we compared the effects of eplerenone with amlodipine, on clinic blood pressure (BP) and pulse pressure and in a subset of the patients, ambulatory BP, vascular compliance, and urinary albumin excretion. The study involved 269 patients > or =50 years of age who were randomly assigned to either eplerenone (50 to 200 mg daily) or amlodipine (2.5 to 10 mg daily) in a double-blind titration to effect design. After 24 weeks of therapy, reductions in clinic systolic BP were similar for both treatments (eplerenone, -20.5+/-1.1 mm Hg; amlodipine, -20.1+/-1.1 mm Hg). Reductions in clinic diastolic BP were modestly larger on amlodipine (-6.9+/-0.7 mm Hg) compared with eplerenone (-4.5+/-0.7 mm Hg) (P=0.014). Pulse pressure was also reduced similarly from baseline by the 2 treatment groups (eplerenone, -15.9 mm Hg versus amlodipine, -13.4 mm Hg, P=0.07). Changes from baseline in pulse wave velocity after 24 weeks of therapy were statistically similar for eplerenone and amlodipine. In patients with microalbuminuria at baseline (>30 mg albumin/g creatinine), eplerenone reduced the urinary albumin/creatinine ratio by 52% compared with a reduction of 10% by amlodipine (P=0.04). Thus, eplerenone was as effective as amlodipine in lowering systolic BP and pulse pressure as well as pulse wave velocity in older patients with widened pulse pressure hypertension. Furthermore, eplerenone reduced microalbuminuria to a greater extent than amlodipine in this older patient group.

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Journal ID (nlm-ta): Pulse

Journal ID (iso-abbrev): Pulse

Journal ID (publisher-id): PLS

Title: Pulse

Publisher: S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.ch )

ISSN (Print): 2235-8676

ISSN (Electronic): 2235-8668

Publication date (Print): October 2013

Publication date (Electronic): 10 September 2013

Publication date PMC-release: 10 September 2013

Volume: 1

Issue: 2

Pages: 97-107

Affiliations

Centre for Epidemiological Studies and Clinical Trials, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

Author notes

*Ji-Guang Wang, MD, PhD, The Shanghai Institute of Hypertension, Ruijin 2nd Road 197, Shanghai 200025 (China), E-Mail jiguangwang@ 123456aim.com

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Publisher ID: pls-0001-0097

DOI: 10.1159/000354108

PMC ID: 4315340

SO-VID: bf1238d2-1280-4204-89b0-f5f787dbed35

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This is an open access article distributed under the terms of Karger's Author's Choice™ licensing agreement, adapted from the Creative Commons Attribution Non-Commercial 2.5 license. This license allows authors to re-use their articles for educational and research purposes as long as the author and the journal are fully acknowledged.

Effects of Various Antihypertensive Drugs on Arterial Stiffness and Wave Reflections

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Most cited references 67

Effect of spironolactone on left ventricular mass and aortic stiffness in early-stage chronic kidney disease: a randomized controlled trial.

Effect of different antihypertensive drug classes on central aortic pressure.

Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension.

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