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CLINICAL RESEARCH

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

Noyan Gokce, MD, FACC^*, John F. Keaney, Jr, MD, FACC^*, Liza M. Hunter, ANP^*, Michael T. Watkins, MD, Zoran S. Nedeljkovic, MD^*, James O. Menzoian, MD and Joseph A. Vita, MD, FACC^*,*

^* Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, USA
Surgical Service, Massachusetts General Hospital, Boston, Massachusetts, USA
Department of Surgery, Boston University School of Medicine, Boston, Massachusetts, USA

Manuscript received October 22, 2002; revised manuscript received January 2, 2003, accepted February 13, 2003.

^* Reprint requests and correspondence: Dr. Joseph A. Vita, Section of Cardiology, Boston Medical Center, 88 East Newton Street, Boston, Massachusetts 02118, USA.
jvita{at}bu.edu

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

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