Clinical research
Predictive value of noninvasivelydetermined endothelial dysfunction for long-term cardiovascular events inpatients with peripheral vascular disease

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Abstract

Objectives

The goal of this study was to prospectively examine the long-term predictive value of brachial-artery endothelial dysfunction for future cardiovascular events.

Background

Brachial-artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors. The prospective relation between endothelial function determined by brachial-artery ultrasound and long-term cardiovascular risk is unknown.

Methods

We examined brachial-artery endothelial function using ultrasound in 199 patients with peripheral arterial disease before elective vascular surgery. Patients were prospectively followed with an average follow-up of 1.2 years after surgery.

Results

Thirty-five patients had an event during follow-up, including cardiac death (5 patients), myocardial infarction (17 patients), unstable angina (10 patients), or stroke (3 patients). Preoperative endothelium-dependent flow-mediated dilation (FMD) was significantly lower in patients with an event (4.4 ± 2.8%) compared with those without an event (7.0 ± 4.9%, p < 0.001), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. In a Cox proportional-hazards model, independent predictors of events included age (p = 0.003), more invasive surgery (surgery other than carotid endarterectomy, p = 0.02), and impaired brachial-artery endothelial function (p = 0.002). Risk was approximately nine-fold higher in patients with FMD <8.1% (lower two tertiles) compared with those in the upper tertile (odds ratio 9.5; 95% confidence interval 2.3 to 40).

Conclusions

Impaired brachial-artery endothelial function independently predicts long-term cardiovascular events in patients with peripheral arterial disease. The findings suggest that noninvasive assessment of endothelial function using brachial-artery FMD may serve as a surrogate end point for cardiovascular risk.

Abbreviations

CAD
coronary artery disease
FMD
flow-mediated dilation
MI
myocardial infarction
NTG
nitroglycerin

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Supported by a Specialized Center of Research in Ischemic Heart Disease grant from the NIH (HL55993) and NIH grants HL60886 and HL52936. Dr. Gokce is the recipient of a Mentored Patient-Oriented Research Career Transition Award from the National Institutes of Health (K23 HL04425). Dr. Watkins is supported by NIH grant HL48152 and a grant from the Research Administration of the Department of Veterans Affairs. Dr. Keaney is an Established Investigator of the American Heart Association.