Close relation of endothelial function in the human coronary and peripheral circulations

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Objectives.

The relation between endothelium-dependent vasodilator function in the brachial and coronary arteries was determined in the same subjects.

Background.

Coronary artery endothelial dysfunction precedes the development of overt atherosclerosis and is important in its pathogenesis. A noninvasive assessment of endothelial function in a peripheral conduit vessel, the brachial artery, was recently described, but the relation between brachial artery function and coronary artery vasodilator function has not been explored.

Methods.

In 50 patients referred to the catheterization laboratory for the evaluation of coronary artery disease (mean age ± SD 56 ± 10 years), the coronary vasomotor response to serial intracoronary infusions of the endothelium-dependent agonist acetylcholine (10−8to 10−6mol/liter), was studied. Endotheliumdependent vasodilation was also assessed in the brachial artery by measuring the change in brachial artery diameter in response to reactive hyperemia.

Results.

Patients with coronary artery endothelial dysfunction manifested as vasoconstriction in response to acetylcholine had significantly impaired flow-mediated vasodilation in the brachial artery compared with that of patients with normal coronary endothelial function (4.8 ± 5.5% vs. 10.8 ± 7.6%, p < 0.01). Patients with coronary artery disease also had an attenuated brachial artery vasodilator response compared with that of patients with angiographically smooth coronary arteries (4.5 ± 4.6% vs. 9.7 ± 8.1%, p < 0.02). By multivariate analysis, the strongest predictors of reduced brachial dilator responses to flow were baseline brachial artery diameter (p < 0.001), coronary endothelial dysfunction (p = 0.003), the presence of coronary artery disease (p = 0.007) and cigarette smoking (p = 0.016). The brachial artery vasodilator response to sublingual nitroglycerin was independent of coronary endothelial responses or the presence of coronary artery disease. The positive predictive value of abnormal brachial dilation (<3%) in predicting coronary endothelial dysfunction is 95%.

Conclusions.

This study demonstrated a close relation between coronary artery endothelium-dependent vasomotor responses to acetylcholine and flow-mediated vasodilation in the brachial artery. This noninvasive method may become a useful surrogate in assessing the predisposition to atherosclerosis in patients with cardiac risk factors.

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This study was supported by a Clinical Fellowship of the Alberta Heritage Foundation for Medical Research, Edmonton, Canada (Dr. Anderson); the National Defense Medical College of Japan, Tokyo, Japan (Dr. Uehata); a National Heart Foundation of Australia Ralph Reader Overseas Research Fellowship, Melbourne, Australia (Dr. Meredith); and the following awards from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland: Academic Award in Systemic and Pulmonary Vascular Medicine HL-02663 (Dr. Creager), Clinician-Investigator Development Award I K08 HL-02787 (Dr. Yeung), Research Career Development Award 1 K04 HL-02566 and N1H 5P01 HL 48743 (Dr. Ganz) and R01 HL-38780-05 (Dr. Selwyn).

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Present address and address for correspondence:Dr. Todd J. Anderson, 8th Floor, Foothills Hospital, 1403-29th Street NW, Calgary, Alberta. Canada T2N-2T9.