CLINICAL RESEARCH: CORONARY ARTERY DISEASE
The prognostic importance of endothelial dysfunction and carotid atheromaburden in patients with coronary artery disease
Sammy Y. Chan, MD, FRCP(C)*,
G. B. John Mancini, MD, FRCP(C), FACC*,*,
Lisa Kuramoto, BSc ,
Michael Schulzer, MD, PhD,
Jiri Frohlich, MD, FRCP(C) and
Andrew Ignaszewski, MD, FRCP(C)*
* Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada
Department of Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
* Reprint requests and correspondence: Dr. G. B. John Mancini, Vancouver Hospital, 3300-950 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 4E3.
mancini{at}interchange.ubc.ca
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.
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Abbreviations and Acronyms
| | 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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