Published Online
on August 16, 2004

A more recent version of this article appeared on August 31, 2004

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Submitted on February 11, 2004
Revised on April 20, 2004
Accepted on May 20, 2004

Chronic Inflammation and Impaired Coronary Vasoreactivity in Patients With Coronary Risk Factors

Thomas H. Schindler MD^*, Egbert U. Nitzsche MD, Manfred Olschewski MSc, Nobuhisa Magosaki MD, Michael Mix PhD, John O. Prior MD, PhD, Alvaro D. Facta MD, Ulrich Solzbach MD, Hanjoerg Just MD, and Heinrich R. Schelbert MD, PhD

From the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, Calif (T.H.S., E.U.N., J.O.P., A.D.F., H.R.S.), and Division of Cardiology and Nuclear Medicine (T.H.S., E.U.N., M.M., U.S., H.J.) and Department for Medical Statistics (M.O.), University Freiburg, Freiburg, Germany.

^* To whom correspondence should be addressed. E-mail: tschindler{at}mednet.ucla.edu.

Background--The goal of this study was to examine a possible association between systemic microinflammation, as reflected by C-reactive protein (CRP) serum levels, and coronary vasomotion in patients with coronary risk factors but with angiographically normal coronary arteries.

Methods and Results--Coronary vasomotor function was studied in response to cold pressor testing (CPT) in 71 patients with normal angiograms. In all patients, CPT-induced changes in epicardial luminal area (LA; mm²) were assessed with quantitative angiography. Within 20 days, myocardial blood flow (MBF) responses to CPT were measured (mL · g^-1 · min^-1) noninvasively with ¹³N-ammonia and PET imaging. The CPT-induced mean changes in LA and in MBF in patients with elevated CRP (0.5 mg/dL) were significantly impaired compared with patients presenting with CRP levels within normal range (<0.5 mg/dL) (LA, -1.09±0.86 versus 0.45±0.63 mm²; MBF, 0.06±0.18 versus 0.44±0.31 mL · g^-1 · min^-1; P<0.0001, respectively). Coronary LA changes and MBF responses to CPT were inversely correlated with CRP serum levels (r=-0.84 and r=-0.63; P<0.0001). Lastly, regression analysis revealed a significant correlation between the changes in LA and MBF during CPT for patients with elevated CRP levels and those for patients with normal CRP levels (r=0.56 and r=0.66; P<0.001).

Conclusions--These findings suggest a direct association between systemic microinflammation and altered coronary vasomotor function of both the epicardial conductance and the arteriolar resistance vessels.

Key words: blood flow • C-reactive protein • coronary disease • endothelium • inflammation

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