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.

Background-Brachial artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors and improves with risk reduction therapy. However, the predictive value of brachial artery endothelial dysfunction for future cardiovascular events is unknown. Methods and Results-We preoperatively examined brachial artery vasodilation using ultrasound in 187 patients undergoing vascular surgery. Patients were prospectively followed for 30 days after surgery. Forty-five patients had a postoperative event, including cardiac death (3), myocardial infarction (12), unstable angina/ischemic ventricular fibrillation (2), stroke (3), or elevated troponin I, reflecting myocardial necrosis (25). Preoperative endotheliumdependent flow-mediated dilation was significantly lower in patients with an event (4.9Ϯ3.1%) than in those without an event (7.3Ϯ5%; PϽ0.001), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. In a Cox proportional-hazards model, the independent predictors of events were age (Pϭ0.001), renal insufficiency (Pϭ0.03), noncarotid surgery (Pϭ0.05), and lower brachial artery flow-mediated dilation (Pϭ0.007). If troponin I elevation was not considered an event, low flow-mediated dilation remained an independent predictor of risk (odds ratio 9.0, 95% CI 1.2 to 68; Pϭ0.03). When a flow-mediated dilation cutpoint of 8.1% was used, endothelial function had a sensitivity of 95%, specificity of 37%, and negative predictive value of 98% for events. Conclusions-Impaired brachial artery endothelial function independently predicts postoperative cardiac events, which supports a role for endothelial dysfunction in the pathogenesis of cardiovascular disease. The strong negative predictive value of preserved endothelial function raises the possibility that assessment of brachial artery flow-mediated dilation will be useful in the management of patients undergoing vascular surgery.

Objective-Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. Key Words: endothelium Ⅲ cardiovascular risk Ⅲ surrogate markers Ⅲ reactive hyperemia Ⅲ flow-mediated dilation R eactive hyperemia is a complex response that occurs after a period of tissue ischemia and primarily depends on local production of adenosine and other non-endothelium-dependent vasodilators that dilate tissue microvessels. 1 Studies in humans have shown that endothelium-derived nitric oxide also contributes to reactive hyperemia. 2,3 Peak brachial artery hyperemic flow velocity after 5-minute cuff occlusion of the arm relates inversely to traditional cardiovascular disease risk factors 4 and to markers of inflammation 5 in the Framingham Heart Study. Smaller scale mechanistic studies suggest that the nitric oxide-dependent component of reactive hyperemia may be particularly affected by risk factors. 3 The relation of reactive hyperemia to the incidence of cardiovascular disease events in atherosclerosis has not been previously studied.