Effects of statins on coronary and peripheral endothelial function in humans: A systematic review and metaanalysis of randomized controlled trials

Martin K. Reriani, Shannon M Dunlay, Bhanu Gupta, Colin Patrick West, Charanjit S. Rihal, Lilach O Lerman, Amir Lerman

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64 Citations (Scopus)

Abstract

Objective: The purpose of this study was to quantify the effect of statins on peripheral and coronary endothelial function in patients with and without established cardiovascular disease. Background: Early atherosclerosis is characterized by endothelial dysfunction, a known prognostic factor for cardiovascular disease. Methods and results: The search included MEDLINE, Cochrane Library, Scopus, and EMBASE to identify studies up to 1 December 2009. Eligible studies were randomized controlled trials on the effects of statins compared with placebo on endothelial function. Two reviewers extracted data on study characteristics, methods, and outcomes. Forty-six eligible trials enrolled a total of 2706 patients: 866 (32%) were women and 432 (16%) had established cardiovascular disease. Meta-analysis using random-effects models showed treatment with statins significantly improved endothelial function [standardized mean difference (SMD) 0.66, 95% CI 0.46-0.85, p<0.001]. Subgroup analyses demonstrated statistically significant improvement in endothelial function assessed both peripherally by flow-mediated dilatation (SMD 0.68, 95% CI 0.46-0.90, p<0.001) and venous occlusion plethysmography (SMD 0.59, 95% CI 0.06-1.13, p=0.03) and centrally in the coronary circulation by infusion of acetylcholine (SMD 1.58, 95% CI 0.31-2.84, p=0.01). Significant heterogeneity observed across studies was explained in part by the type of endothelial function measurement, statin type and dose, and study population differences. Exclusion of outlier studies did not significantly alter the results. Conclusion: Statin therapy is associated with significant improvement in both peripheral and coronary endothelial function. The current study supports a role for statin therapy in patients with endothelial dysfunction.

Original languageEnglish (US)
Pages (from-to)704-716
Number of pages13
JournalEuropean Journal of Cardiovascular Prevention and Rehabilitation
Volume18
Issue number5
DOIs
StatePublished - Oct 2011

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Randomized Controlled Trials
Cardiovascular Diseases
Coronary Circulation
Plethysmography
MEDLINE
Libraries
Acetylcholine
Meta-Analysis
Dilatation
Atherosclerosis
Therapeutics
Placebos
Population

Keywords

  • Endothelial function
  • Meta-analysis
  • Statins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Epidemiology

Cite this

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title = "Effects of statins on coronary and peripheral endothelial function in humans: A systematic review and metaanalysis of randomized controlled trials",
abstract = "Objective: The purpose of this study was to quantify the effect of statins on peripheral and coronary endothelial function in patients with and without established cardiovascular disease. Background: Early atherosclerosis is characterized by endothelial dysfunction, a known prognostic factor for cardiovascular disease. Methods and results: The search included MEDLINE, Cochrane Library, Scopus, and EMBASE to identify studies up to 1 December 2009. Eligible studies were randomized controlled trials on the effects of statins compared with placebo on endothelial function. Two reviewers extracted data on study characteristics, methods, and outcomes. Forty-six eligible trials enrolled a total of 2706 patients: 866 (32{\%}) were women and 432 (16{\%}) had established cardiovascular disease. Meta-analysis using random-effects models showed treatment with statins significantly improved endothelial function [standardized mean difference (SMD) 0.66, 95{\%} CI 0.46-0.85, p<0.001]. Subgroup analyses demonstrated statistically significant improvement in endothelial function assessed both peripherally by flow-mediated dilatation (SMD 0.68, 95{\%} CI 0.46-0.90, p<0.001) and venous occlusion plethysmography (SMD 0.59, 95{\%} CI 0.06-1.13, p=0.03) and centrally in the coronary circulation by infusion of acetylcholine (SMD 1.58, 95{\%} CI 0.31-2.84, p=0.01). Significant heterogeneity observed across studies was explained in part by the type of endothelial function measurement, statin type and dose, and study population differences. Exclusion of outlier studies did not significantly alter the results. Conclusion: Statin therapy is associated with significant improvement in both peripheral and coronary endothelial function. The current study supports a role for statin therapy in patients with endothelial dysfunction.",
keywords = "Endothelial function, Meta-analysis, Statins",
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T2 - A systematic review and metaanalysis of randomized controlled trials

AU - Reriani, Martin K.

AU - Dunlay, Shannon M

AU - Gupta, Bhanu

AU - West, Colin Patrick

AU - Rihal, Charanjit S.

AU - Lerman, Lilach O

AU - Lerman, Amir

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N2 - Objective: The purpose of this study was to quantify the effect of statins on peripheral and coronary endothelial function in patients with and without established cardiovascular disease. Background: Early atherosclerosis is characterized by endothelial dysfunction, a known prognostic factor for cardiovascular disease. Methods and results: The search included MEDLINE, Cochrane Library, Scopus, and EMBASE to identify studies up to 1 December 2009. Eligible studies were randomized controlled trials on the effects of statins compared with placebo on endothelial function. Two reviewers extracted data on study characteristics, methods, and outcomes. Forty-six eligible trials enrolled a total of 2706 patients: 866 (32%) were women and 432 (16%) had established cardiovascular disease. Meta-analysis using random-effects models showed treatment with statins significantly improved endothelial function [standardized mean difference (SMD) 0.66, 95% CI 0.46-0.85, p<0.001]. Subgroup analyses demonstrated statistically significant improvement in endothelial function assessed both peripherally by flow-mediated dilatation (SMD 0.68, 95% CI 0.46-0.90, p<0.001) and venous occlusion plethysmography (SMD 0.59, 95% CI 0.06-1.13, p=0.03) and centrally in the coronary circulation by infusion of acetylcholine (SMD 1.58, 95% CI 0.31-2.84, p=0.01). Significant heterogeneity observed across studies was explained in part by the type of endothelial function measurement, statin type and dose, and study population differences. Exclusion of outlier studies did not significantly alter the results. Conclusion: Statin therapy is associated with significant improvement in both peripheral and coronary endothelial function. The current study supports a role for statin therapy in patients with endothelial dysfunction.

AB - Objective: The purpose of this study was to quantify the effect of statins on peripheral and coronary endothelial function in patients with and without established cardiovascular disease. Background: Early atherosclerosis is characterized by endothelial dysfunction, a known prognostic factor for cardiovascular disease. Methods and results: The search included MEDLINE, Cochrane Library, Scopus, and EMBASE to identify studies up to 1 December 2009. Eligible studies were randomized controlled trials on the effects of statins compared with placebo on endothelial function. Two reviewers extracted data on study characteristics, methods, and outcomes. Forty-six eligible trials enrolled a total of 2706 patients: 866 (32%) were women and 432 (16%) had established cardiovascular disease. Meta-analysis using random-effects models showed treatment with statins significantly improved endothelial function [standardized mean difference (SMD) 0.66, 95% CI 0.46-0.85, p<0.001]. Subgroup analyses demonstrated statistically significant improvement in endothelial function assessed both peripherally by flow-mediated dilatation (SMD 0.68, 95% CI 0.46-0.90, p<0.001) and venous occlusion plethysmography (SMD 0.59, 95% CI 0.06-1.13, p=0.03) and centrally in the coronary circulation by infusion of acetylcholine (SMD 1.58, 95% CI 0.31-2.84, p=0.01). Significant heterogeneity observed across studies was explained in part by the type of endothelial function measurement, statin type and dose, and study population differences. Exclusion of outlier studies did not significantly alter the results. Conclusion: Statin therapy is associated with significant improvement in both peripheral and coronary endothelial function. The current study supports a role for statin therapy in patients with endothelial dysfunction.

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KW - Meta-analysis

KW - Statins

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