Elsevier

Atherosclerosis

Volume 129, Issue 1, 28 February 1997, Pages 111-118
Atherosclerosis

Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease

https://doi.org/10.1016/S0021-9150(96)06018-2Get rights and content

Abstract

Flow-mediated vasodilation (FMD) of systemic arteries, a non-invasive parameter of endothelial function, is correlated with cardiovascular risk factors. The relationship between FMD and morphologically and clinically evident coronary artery disease has not been described. This study was performed to test the hypothesis that an impairment of FMD in the brachial artery is related to the presence and/or extent and severity of coronary artery disease (CAD). We examined 74 patients with angina pectoris and 14 control subjects (age 17–36 years). Angiography revealed coronary artery disease (≥30% diameter stenosis) in 44 patients (CAD, age 32–67 years) and smooth coronary arteries in 30 patients (non-CAD, age 22–73 years). Vasodilation following reactive hyperemia and after sublingual nitroglycerin (NTG) was assessed in the brachial artery using B-mode high resolution ultrasound. CAD patients showed markedly impaired FMD compared to the non-CAD group (5.7±4.8 versus 12.6±6.7%, P<0.0001) and to controls (5.7±4.8 versus 15.7±3.9%, P<0.00001). NTG induced similar degrees of vasodilation in the CAD and non-CAD groups but less vasodilation in the CAD patients compared to controls (12.2±6.3 versus 20.4±6.9%, P<0.01). On univariate analysis, impaired FMD in CAD patients and non-CAD patients was related to the extent of coronary disease (1-, 2- or 3-vessel disease; r=−0.67, P<0.0001), to the maximum percent diameter stenosis in one of the major coronary vessels (r=−0.52, P<0.0001), brachial artery diameter (r=−0.46, P<0.0001) and plasma cholesterol level (r=−0.34, P<0.001). On multiple stepwise regression analysis the extent of coronary disease (r=−0.51, P<0.0001) and the baseline brachial artery diameter (r=−0.37, P<0.0001) were independently associated with FMD in CAD and non-CAD patients. The present findings suggest that the impairment of FMD in the brachial artery, a marker of systemic endothelial function, is closely related to the angiographic extent of CAD.

Introduction

Endothelial function is increasingly recognized as a sensitive indicator of the integrity of the arterial wall 1, 2, 3, 4. In several stages of coronary atherosclerosis, disturbed endothelial function has been revealed clinically by documenting impaired vasodilation to acetylcholine, indicating an altered activity of the endothelium-derived relaxing factor (EDRF) 5, 6, 7, 8. Although attractive as an early functional sign of atherosclerosis, assessment of this response is invasive and is usually performed on the occasion of coronary arteriography, whenever the latter is clinically indicated. Therefore, recent efforts have focused on the feasibility of non-invasive tests of endothelial function. These approaches, first described by Celermajer et al. [9], utilize high resolution ultrasound to assess flow-mediated vasodilation (FMD), an endothelium-dependent response 10, 11, 12, of large peripheral arteries which is largely mediated by nitric oxide 13, 14. Using this method, these authors have demonstrated impaired FMD in the systemic arteries of children and adults with hypercholesterolemia, children with homozygous homocystinuria, adult smokers and patients with coronary artery disease (CAD) 9, 15. Furthermore, the same group has found that coronary risk factors in asymptomatic subjects interact to produce this endothelial dysfunction, which may serve as an early sign in the preclinical phase of vascular disease [16]. These data not only demonstrate a close relationship between established risk factors for cardiovascular disease and endothelial dysfunction, but also suggest a possible systemic endothelial defect in subjects with risk factors but without overt disease. This defect may extend to the microvasculature, as previous studies have documented impaired acetylcholine-induced vasodilation of forearm [17]and coronary resistance arteries [18]in CAD patients. Less is known, however, about the relationship between FMD of the brachial artery, a non-invasive parameter of endothelial function, and morphologically and clinically evident CAD.

Therefore, this study was performed to test the hypothesis that the impairment of FMD in the brachial artery is related to the presence and/or extent and severity of CAD in patients with angina pectoris.

Section snippets

Subjects

Seventy-four patients who were admitted for invasive evaluation of their coronary anatomy and 14 healthy subjects with no or maximally one risk factor for vascular disease were enrolled into the study. Twenty-one patients were considered unstable on admission, 23 patients had a history of exercise-induced angina pectoris and 27 patients had atypical chest pain. Three patients were asymptomatic. Among these, 2 had severe hypercholesterolemia and underwent angiography before the initiation of

Angiographic results and risk factor profile

Coronary arteriography revealed 1-VD in 19 patients, 2-VD in 15 patients and 3-VD in 10 patients. A maximum coronary diameter stenosis of 30–50% in the left main coronary artery (LM), left anterior descending (LAD), left circumflex (CX) or right coronary artery (RCA) was found in 11 patients, 50–70% in 7 patients, 70–90% in 16 patients and 99% in 3 patients. Totally occluded vessels were present in 7 patients. CAD patients showed a tendency toward a higher risk factor profile compared to

Discussion

This study shows that FMD of the brachial artery, reflecting systemic endothelial function, is significantly related to angiographically evident CAD. Among patients with a history of typical or atypical angina pectoris, FMD of the brachial artery was significantly impaired in patients with CAD, defined as luminal narrowings ≥30% in at least one coronary vessel, compared to patients with chest pain but smooth coronary arteries. This impairment of FMD was independently associated with the

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