Cited by 1,961Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionAntioxidant Activity and Oxidative Stress

Endothelial Dysfunction, Oxidative Stress, and Risk of Cardiovascular Events in Patients With Coronary Artery Disease

Heitzer, Thomas, Schlinzig, Titus, Krohn, Karoline, Meinertz, Thomas, Münzel, Thomas·2001·Circulation

Abstract

Background Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations. Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events. This study was designed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease. Methods and Results Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography. The effect of the coadministration of vitamin C (24 mg/min) was assessed in a subgroup of 179 patients. Cardiovascular events, including death from cardiovascular causes, myocardial infarction, ischemic stroke, coronary angioplasty, and coronary or peripheral bypass operation, were studied during a mean follow-up period of 4.5 years. Patients experiencing cardiovascular events (n=91) had lower vasodilator responses to acetylcholine ( P <0.001) and sodium nitroprusside ( P <0.05), but greater benefit from vitamin C ( P <0.01). The Cox proportional regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation ( P =0.001), the effect of vitamin C ( P =0.001), and age ( P =0.016) remained independent predictors of cardiovascular events. Conclusions Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease. These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity.

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Crossref · 10.1161/hc4601.099485

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  • Endothelial dysfunction occurs early in the pathogenesis of atherosclerosis, and predicts future cardiovascular events.

    “Endothelial dysfunction occurs early in the pathogenesis of atherosclerosis, and predicts future cardiovascular events.”

    From The Vasculature in Prediabetes (2018) · cites this paper as [31]

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Authors
Heitzer, T., Schlinzig, T., Krohn, K., Meinertz, T., & Münzel, T.
Affiliations
  • University Medical Center Hamburg-Eppendorf (DE)
  • From the Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Innere Medizin, Abteilung Kardiologie, Hamburg, Germany.
Venue
Circulation
Published
2001-11-27
Volume
104
Issue
22
Pages
2673-2678
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
OpenAlex
W2083481797
Cited by
1,961
References
35
Citations by year
2026: 24 · 2025: 35 · 2024: 53 · 2023: 41 · 2022: 42 · 2021: 77 · 2020: 83 · 2019: 82 · 2018: 83 · 2017: 71 · 2016: 83 · 2015: 104 · 2014: 95 · 2013: 77 · 2012: 102
FWCI
46.23
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
endothelial dysfunction, oxidative stress, coronary artery disease, cardiovascular events, acetylcholine-induced vasodilation, sodium nitroprusside, vitamin C, forearm blood flow, venous occlusion plethysmography, cardiovascular risk prediction, myocardial infarction, ischemic stroke, atherosclerosis
MeSH terms
Antioxidants, Ascorbic Acid, Cardiovascular Diseases, Coronary Artery Disease, Dose-Response Relationship, Drug, Endothelium, Vascular, Female, Follow-Up Studies, Forearm, Humans, Male, Middle Aged, Plethysmography, Predictive Value of Tests, Prognosis, Prospective Studies, Regional Blood Flow, Vasodilation, Vasodilator Agents, Survival Rate, Proportional Hazards Models, Oxidative Stress, Disease Progression, Risk Assessment

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