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J Am Coll Cardiol, 2001; 38:1843-1849
© 2001 by the American College of Cardiology Foundation
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CLINICAL STUDY: ENDOTHELIAL FUNCTION

Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease

Jeffrey T. Kuvin, MD, FACCa, Ayan R. Patel, MD, FACCa, Kathleen A. Sliney, RNa, Natesa G. Pandian, MD, FACCa, William M. Rand, PhDa, James E. Udelson, MD, FACCa and Richard H. Karas, MD, PhD, FACC*,a

a Department of Medicine/Division of Cardiology, New England Medical Center Hospitals, Tufts University School of Medicine, Boston, Massachusetts, USA

Manuscript received May 9, 2001; revised manuscript received August 6, 2001, accepted August 24, 2001.

* Reprint requests and correspondence: Dr. Richard H. Karas, Molecular Cardiology Research Institute, New England Medical Center, 750 Washington Street, Box 80, Boston, Massachusetts 02111 USA.
rkaras{at}lifespan.org

OBJECTIVES

We studied whether assessment of endothelium-dependent vasomotion (EDV) with brachial artery ultrasound (BAUS) imaging predicts the presence or absence of coronary artery disease (CAD) as defined by exercise myocardial perfusion imaging (ExMPI).

BACKGROUND

Abnormalities in EDV can be detected in arteries before the development of overt atherosclerosis, and its presence may predict poor long-term prognosis. Brachial artery ultrasound during reactive hyperemia is a noninvasive method of assessing peripheral EDV.

METHODS

Clinically-indicated ExMPI along with BAUS were performed in 94 subjects (43 women, 51 men). Coronary artery disease was defined by myocardial ischemia or infarction on single photon emission computed tomography images. Flow-mediated dilation (FMD) after upper arm occlusion was defined as the percent change in arterial diameter during reactive hyperemia relative to the baseline.

RESULTS

Subjects with CAD by ExMPI (n = 23) had a lower FMD (6.3 ± 0.7%) than those without CAD by ExMPI (n = 71) (10.5 ± 0.6%; p = 0.0004). Flow-mediated dilation was highly predictive for CAD with an odds ratio of 1.32 for each percent decrease in FMD (p = 0.001). Based on a receiver-operator analysis, an FMD of 10% was used as a cut-point for further analysis. Twenty-one of 23 subjects who were positive for ExMPI had an FMD <10% (sensitivity 91%), whereas only two of 40 subjects with an FMD ≥10% were ExMPI-positive (negative predictive value: 95%). There was a correlation between the number of cardiac risk factors and FMD. Individuals with an FMD <10% exercised for a shorter duration than those with an FMD ≥10% (456 ± 24 vs. 544 ± 31 s, respectively; p = 0.02).

CONCLUSIONS

Assessment of EDV with BAUS has a high sensitivity and an excellent negative predictive value for CAD and, thus, has the potential for use as a screening tool to exclude CAD in low-risk subjects. Further standardization of BAUS is required, however, before specific cut-points for excluding CAD can be established.

Abbreviations and Acronyms
  CAD = coronary artery disease
  BAUS = brachial artery ultrasound
  EDV = endothelium-dependent vasomotion
  ExMPI = exercise myocardial perfusion imaging
  FMD = flow-mediated dilation
  LVEF = left ventricular ejection fraction
  NMD = nitroglycerin-mediated vasodilation
  ROC = receiver operator characteristic
  SPECT = single photon emission computed tomography




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