Clinical research: coronary artery disease
The prognostic importance of endothelial dysfunction and carotid atheromaburden in patients with coronary artery disease

https://doi.org/10.1016/S0735-1097(03)00927-6Get rights and content
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Abstract

Objectives

The goal of this study was to determine the relative prognostic importance of noninvasive measures of endothelial function and atheroma burden in patients with coronary artery disease (CAD).

Background

Direct measurement of atherosclerosis by carotid ultrasound and endothelial function assessment by brachial artery flow-mediated dilation (FMD) have both been shown to predict vascular events. The combined prognostic utility of carotid ultrasound and FMD relative to traditional risk markers and cardiovascular fitness has not been evaluated.

Methods

A total of 152 patients with CAD underwent metabolic testing, exercise stress tests, carotid ultrasound, and endothelial function measurements.

Results

Patients were followed for 34 ± 10 months during which 22 vascular events occurred. Peak FMD (p = 0.012) and FMD/nitroglycerin-mediated dilation (NMD) ratio (p = 0.008) were lower in subjects with events. Univariate analysis with Cox proportional hazards modeling identified plaque area (p = 0.0047), total area (p = 0.0085), peak FMD (p = 0.01), FMD/NMD ratio (p = 0.008), stress test workload (p = 0.027), long-acting nitroglycerin (NTG) (p = 0.0071), and calcium blockers (p = 0.0057) as predictors of adverse events. Multivariate analysis showed that FMD/NMD ratio (p < 0.0001), carotid plaque area (p = 0.06), and NTG (p = 0.005) were independent predictors. Based on median values, subjects were divided into high and low “plaque burden” groups and into high and low FMD/NMD subgroups. Patients with high FMD/NMD had low event rates irrespective of the degree of carotid atheroma. Patients with low FMD/NMD and high “plaque burden” had the highest event rate (p < 0.05).

Conclusions

The structural and functional status of the vasculature are independent predictors of coronary events as shown by noninvasive measurement of endothelial function and carotid atheroma burden in patients with CAD. Preserved endothelial function attenuates the risk of future events associated with a high plaque burden.

Abbreviations

CABG
coronary artery bypass grafting
CAD
coronary artery disease
EST
exercise stress test
FMD
flow-mediated dilation
HDL
high-density lipoprotein
IMT
intima medial thickness
LDL
low-density lipoprotein
MI
myocardial infarction
NMD
nitroglycerin-mediated dilation
NTG
nitroglycerin
PTCA
percutaneous coronary angioplasty

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Supported, in part, by an unrestricted educational grant by Merck Frosst Canada.