Effects of renin-angiotensin-aldosterone system inhibitors and beta-blockers on markers of arterial stiffness

doi:10.1016/j.jash.2013.09.001

Journal of the American Society of Hypertension

Volume 8, Issue 2, February 2014, Pages 74-82

https://doi.org/10.1016/j.jash.2013.09.001 Get rights and content

Abstract

Antihypertensive agents may, even within the same class, exert variable effects on arterial stiffness variables. Nebivolol could have a better impact than atenolol on arterial stiffness, by increasing the bioavailability of endothelium-derived nitric oxide. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) increase plasma renin activity (enhancing the production of angiotensin II via non-ACE-related pathways) whereas aliskiren does not, potentially affecting central hemodynamics differently. We compared the effects of two renin-angiotensin-aldosterone system (RAAS) inhibitors (quinapril and aliskiren) and 2 beta-blockers (atenolol and nebivolol) on arterial stiffness variables. Treatment-naïve patients (n = 72; 68.1% males; age, 47.6 ± 10.6 years) with uncomplicated stage I-II essential hypertension were randomly assigned to quinapril, aliskiren, atenolol, or nebivolol for 10 weeks. Central systolic and diastolic blood pressure (BP), central pulse pressure (PP), augmentation index (AIx), and pulse wave velocity (PWV) were measured at baseline, 2, and 10 weeks. The same measurements were performed in 20 normotensive subjects (65.0% males; age, 40.0 ± 8.9 years). Peripheral and central systolic and diastolic BP, peripheral PP, and PWV were significantly and similarly reduced by all agents. However, PWV continued to decline between the second and last visit in patients on quinapril and aliskiren but did not change in those on nebivolol or atenolol. Central PP and AIx decreased in patients on quinapril, aliskiren, and nebivolol but did not change in those taking atenolol. The decrease in central PP and AIx did not differ between patients on quinapril, aliskiren, and nebivolol. Despite similar reductions in peripheral BP, atenolol is less effective than nebivolol and RAAS inhibitors in improving central pulsatile hemodynamics. Aliskiren exerts similar effects on markers of arterial stiffness as quinapril. The clinical relevance of these differences remains to be established.

Introduction

Central blood pressure (BP) measurements and arterial stiffness are associated with higher risk for cardiovascular events1, 2, 3, 4, 5, 6 and appear to be stronger predictors of cardiovascular risk than peripheral BP.⁵ Arterial stiffness has emerged as a potential treatment target, and several studies evaluated the effects of antihypertensive drugs on arterial stiffness variables.2, 7, 8, 9, 10, 11 It appears that differences exist regarding the effects on arterial stiffness variables not only among antihypertensive drug classes, but also between agents of the same class, even when comparable changes in peripheral BP are achieved.9, 10, 11

Inhibition of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) appears to reduce arterial stiffness more than other classes of antihypertensive drugs, despite similar lowering of peripheral BP.10, 11, 12, 13, 14 In contrast, the effect on arterial stiffness of aliskiren, which directly inhibits renin, is less clear.15, 16, 17, 18 Even though both ACEIs and ARBs appear to be more effective than the classic cardioselective beta-blockers (eg, atenolol) in reducing markers of arterial stiffness,10, 11, 19, 20, 21, 22, 23, 24, 25 it is unclear whether newer beta-blockers with vasodilating properties (ie, nebivolol and carvedilol) differ from other members of their class in their effect on arterial stiffness.23, 24, 25, 26

The aim of the present study was to compare the effects of an ACEI (quinapril), aliskiren, a conventional cardioselective beta-blocker (atenolol), and a vasodilating beta-blocker (nebivolol) on markers of arterial stiffness in treatment-naïve patients with uncomplicated, stage I-II essential hypertension.

Section snippets

Methods

Treatment-naïve, adult patients (n = 72; 68.1% males; age, 47.6 ± 10.6 years) with uncomplicated, stage I-II, essential hypertension (mean sitting systolic BP, 140–180 mm Hg and/or mean sitting diastolic BP 90–110 mm Hg, confirmed on at least three occasions separated by a month) and 20 normotensive (systolic BP <140 mm Hg and diastolic BP <90 mm Hg) adults (65.0% males; age, 40.0 ± 8.9 years) were recruited from the Second Propedeutic Department of Internal Medicine of Aristotle University, at

Results

Baseline characteristics of the study population are shown in Table 1. The four groups of hypertensive patients did not differ in any characteristic, except for the marginally higher AIx in patients assigned to aliskiren than in those assigned to atenolol (P = .015). Controls had lower central systolic BP, central diastolic BP, and PWV than all groups of hypertensive patients. Central pulse pressure (PP) was lower in controls than in patients assigned to aliskiren (P = .004) but did not differ

Discussion

The present study suggests that the effects of atenolol on central pulsatile hemodynamics are less favorable than the vasodilating beta-blocker nebivolol and the two RAAS inhibitors despite similar reductions in both peripheral BP and PWV. This differentiation might be attributed to the HR deceleration observed only in the atenolol group, which allows the reflected wave to return to the ascending aorta earlier in the cardiac cycle, during systole, augmenting both central BP and AIx. In

References (32)

G.M. London et al.
Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol
J Am Coll Cardiol
(2004)
G. Mancia et al.
2013 ESH/ESCGuidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)
J Hypertens
(2013)
S. Laurent et al.
European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications
EurHeart J
(2006)
N. Katsiki et al.
Thinking beyond traditional cardiovascular risk factors: The role of arterial stiffness in targeting residual risk
Angiology
(2012)
S. Laurent et al.
Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients
Hypertension
(2001)
M.J. Roman et al.
Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the Strong Heart Study
Hypertension
(2007)
C. Koumaras et al.
Metabolic syndrome and arterial stiffness: the past, the present and the future
J Cardiovasc Med
(2013)
E. Agabiti-Rosei et al.
Central blood pressure measurements and antihypertensive therapy: a consensus document
Hypertension
(2007)
L. Ghiadoni et al.
Central blood pressure, arterial stiffness, and wave reflection: new targets of treatment in essential hypertension
Curr Hypertens Rep
(2009)
K.T. Ong et al.
Aortic stiffness is reduced beyond blood pressure lowering by short-term and long-term antihypertensive treatment: a meta-analysis of individual data in 294 patients
J Hypertens
(2011)

A.D. Protogerou et al.

The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part II: evidence for specific class-effects of antihypertensive drugs on pressure amplification

Curr Pharm Des

(2009)

C. Koumaras et al.

Role of antihypertensive drugs in arterial ‘de-stiffening’ and central pulsatile hemodynamics

Am J Cardiovasc Drugs

(2012)

A. Mahmud et al.

Arterial stiffness and the renin-angiotensin-aldosterone system

J Renin Angiotensin Aldosterone Syst

(2004)

P. Jankowski et al.

Pleiotropic effects of drugs inhibiting the renin-angiotensin-aldosterone system

Curr Pharm Des

(2009)

A.D. Protogerou et al.

The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part I: (patho)-physiology, rationale and perspective on pulse pressure amplification

Curr Pharm Des

(2009)

J.Q. Guo et al.

Effect of aliskiren on arterial stiffness, compared with ramipril in patients with mild to moderate essential hypertension

Chin Med J (Engl)

(2013)

Cited by (77)

Regional and Global Aortic Pulse Wave Velocity in Patients with Abdominal Aortic Aneurysm
2024, European Journal of Vascular and Endovascular Surgery
Abdominal aortic aneurysm (AAA) is commonly defined as localised aortic dilatation with a diameter > 30 mm. The pathophysiology of AAA includes chronic inflammation and enzymatic degradation of elastin, possibly increasing aortic wall stiffness and pulse wave velocity (PWV). Whether aortic stiffness is more prominent in the abdominal aorta at the aneurysm site is not elucidated. The aim of this study was to evaluate global and regional aortic PWV in patients with AAA.
Experimental study of local PWV in the thoracic descending and abdominal aorta in patients with AAA and matched controls. The study cohort comprised 25 patients with an AAA > 30 mm (range 36 – 70 mm, all male, age range 65 – 76 years) and 27 age and sex matched controls free of AAA. PWV was measured with applanation tonometry (carotid-femoral PWV, cfPWV) as well as a 4D flow MRI technique, assessing regional aortic PWV. Blood pressure and anthropometrics were measured.
Global aortic PWV was greater in men with an AAA than controls, both by MRI (AAA 8.9 ± 2.4 m/s vs. controls 7.1 ± 1.5 m/s; p = .007) and cfPWV (AAA 11.0 ± 2.1 m/s vs. controls 9.3 ± 2.3 m/s; p = .007). Regionally, PWV was greater in the abdominal aorta in the AAA group (AAA 7.0 ± 1.8 m/s vs. controls 5.8 ± 1.0 m/s; p = .022), but similar in the thoracic descending aorta (AAA 8.7 ± 3.2 m/s vs. controls 8.2 ± 2.4 m/s; p = .59). Furthermore, PWV was positively associated with indices of central adiposity both in men with AAA and controls.
PWV is higher in men with AAA compared with matched controls in the abdominal but not the thoracic descending aorta. Furthermore, aortic stiffness was linked with central fat deposition. It remains to be seen whether there is a causal link between AAA and increased regional aortic stiffness.
Effects of common antihypertensive treatments on pulsatile arterial hemodynamics
2022, Textbook of Arterial Stiffness and Pulsatile Hemodynamics in Health and Disease
Antihypertensive treatments may have different effects on central arterial hemodynamics. We reviewed randomized controlled clinical trials that tested efficacy of pharmaceutical- or device-based treatments in reducing central blood pressure (BP) and augmentation index (AI). In parallel-group comparison studies, antihypertensive drug treatment was efficacious in reducing central systolic BP and AI. The effect was more evident for renin-angiotensin-aldosterone inhibitors and calcium-channel blockers, but not for diuretics, β-blockers, or α-blockers. Both renal sympathetic denervation and continuous positive airway pressure showed significant effects on central BP. Whether the changes in central pulsatile hemodynamics are clinically relevant for cardiovascular protection and prevention remains to be investigated.
Impact of antihypertensive agents on arterial stiffness in hypertensive patients
2018, International Journal of Cardiology
The present network meta-analysis was performed to comprehensively compare the ability of different types of antihypertensive agents to ameliorate arterial stiffness in hypertensive patients.
To conduct this network meta-analysis, we searched PubMed, the Embase database, and the https://clinicaltrials.gov/ website for all relevant articles concerning clinical trials on hypertension therapy. The last search date was 10 August 2017. As a result, 28 eligible articles were enrolled in our meta-analysis. According to the included studies, there was no significant difference in pulse wave velocity (PWV) between these treatments. The eight types of antihypertension agents outperformed placebo in controlling systolic blood pressure (SBP). Angiotensin-converting enzyme inhibitor (ACEI) outperformed angiotensin II receptor blocker (ARB) in SBP; and angiotensin receptor-neprilysin inhibitor (ARNI) outperformed diuretic (D) in SBP.
This study found that the eight antihypertensive agents show obvious effect on reducing SBP other than arterial stiffness.
Nanocomposite Hydrogels and Extracellular Matrix—Advantages and Associated Risks
2023, Gels
Fructose-induced salt-sensitive blood pressure differentially affects sympathetically mediated aortic stiffness in male and female Sprague-Dawley rats
2023, Physiological Reports
Vascular Aging: Assessment and Intervention
2023, Clinical Interventions in Aging

View all citing articles on Scopus

: Conflict of interest: This study was conducted independently; no company or institution supported it financially. Some of the authors have attended conferences, given lectures, and participated in advisory boards or trials sponsored by various pharmaceutical companies.

: Dr Koumaras was supported by an educational grant from the Hellenic Atherosclerosis Society.

View full text

Research ArticleEffects of renin-angiotensin-aldosterone system inhibitors and beta-blockers on markers of arterial stiffness

Abstract

Introduction

Section snippets

Methods

Results

Discussion

J Am Coll Cardiol

2013 ESH/ESCGuidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)

J Hypertens

European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications

EurHeart J

Thinking beyond traditional cardiovascular risk factors: The role of arterial stiffness in targeting residual risk

Angiology

Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients

Hypertension

Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the Strong Heart Study

Hypertension

Metabolic syndrome and arterial stiffness: the past, the present and the future

J Cardiovasc Med

Central blood pressure measurements and antihypertensive therapy: a consensus document

Hypertension

Central blood pressure, arterial stiffness, and wave reflection: new targets of treatment in essential hypertension

Curr Hypertens Rep

Aortic stiffness is reduced beyond blood pressure lowering by short-term and long-term antihypertensive treatment: a meta-analysis of individual data in 294 patients

J Hypertens

The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part II: evidence for specific class-effects of antihypertensive drugs on pressure amplification

Curr Pharm Des

Role of antihypertensive drugs in arterial ‘de-stiffening’ and central pulsatile hemodynamics

Am J Cardiovasc Drugs

Arterial stiffness and the renin-angiotensin-aldosterone system

J Renin Angiotensin Aldosterone Syst

Pleiotropic effects of drugs inhibiting the renin-angiotensin-aldosterone system

Curr Pharm Des

The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part I: (patho)-physiology, rationale and perspective on pulse pressure amplification

Curr Pharm Des

Effect of aliskiren on arterial stiffness, compared with ramipril in patients with mild to moderate essential hypertension

Chin Med J (Engl)

Research Article
Effects of renin-angiotensin-aldosterone system inhibitors and beta-blockers on markers of arterial stiffness