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European Heart Journal Advance Access published online on June 16, 2005

European Heart Journal, doi:10.1093/eurheartj/ehi356
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European Heart Journal © The European Society of Cardiology 2005; All rights reserved
Received January 12, 2005
Revised April 4, 2005
Accepted May 10, 2005

Clinical research

Elevated C-reactive protein levels and coronary microvascular dysfunction in patients with coronary artery disease

Fabrizio Tomai 1*, Flavio Ribichini 2, Anna S. Ghini 3, Valeria Ferrero 2, Giuseppe Andò 3, Corrado Vassanelli 2, Francesco Romeo 3, Filippo Crea 4, and Luigi Chiariello 3

1 Division of Cardiology and Cardiac Surgery, Università di Roma Tor Vergata, European Hospital, via Portuense 700, 00149 Rome, Italy
2 Division of Cardiology, Università del Piemonte Orientale, Novara, Italy
3 Division of Cardiology and Cardiac Surgery, Università di Roma Tor Vergata, European Hospital, via Portuense 700, 00149 Rome, Italy
4 Institute of Cardiology, Università Cattolica del Sacro Cuore, Rome, Italy

* To whom correspondence should be addressed.
Fabrizio Tomai, E-mail: f.tomai{at}tiscali.it


   Abstract

Aims It is still unknown whether elevated C-reactive protein levels are responsible for coronary microcirculatory dysfunction in patients with coronary artery disease (CAD). This study was aimed at evaluating the association between C-reactive protein levels and endothelium-dependent and endothelium-independent coronary blood flow (CBF) responses in non-culprit arteries of patients with CAD.

Methods and results We studied 28 patients (14 with normal and 14 with elevated C-reactive protein levels, >5 mg/L) with single-vessel disease and otherwise angiographically normal coronary arteries undergoing percutaneous transluminal coronary angioplasty (PTCA). CBF was measured in the non-PTCA vessel using an intracoronary Doppler guide wire and quantitative coronary angiography at baseline, after intracoronary infusion of substance P and of adenosine, and expressed as per cent change from baseline. The increases in CBF during infusion of substance P and of adenosine were lesser in patients with elevated than in those with normal C-reactive protein levels (34±22 vs. 61±34%, P=0.04 and 131±53 vs. 189±89%, P=0.03, respectively). Multivariable analysis identified elevated C-reactive protein level as the only independent predictor of reduced response to substance P (P=0.01) and adenosine (P=0.02).

Conclusion In patients with CAD, evidence of systemic inflammation is independently associated with endothelium-dependent and endothelium-independent coronary microvascular dysfunction, which, in turn, may be critical to precipitate myocardial ischaemia, in particular, in unstable patients.

Keywords: Adenosine; Coronary disease; Endothelium; Inflammation; Microcirculation.
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