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European Heart Journal Advance Access originally published online on May 25, 2005
European Heart Journal 2005 26(21):2294-2299; doi:10.1093/eurheartj/ehi339
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Complement component C5a predicts future cardiovascular events in patients with advanced atherosclerosis

Walter S. Speidl1,2, Markus Exner3, Jasmin Amighi1, Stefan P. Kastl1,2, Gerlinde Zorn1,2, Gerald Maurer1,2, Oswald Wagner3, Kurt Huber4, Erich Minar1, Johann Wojta1,2 and Martin Schillinger1,*

1Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18–20, A-1090 Vienna, Austria
2Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria
3Department of Laboratory Medicine, Medical University of Vienna, Austria
4Third Medical Department, Wilhelminenhospital, Vienna, Austria

Received 10 February 2005; revised 9 April 2005; accepted 28 April 2005; online publish-ahead-of-print 25 May 2005.

* Corresponding author. Tel: +43 1 40400 4670; fax: +43 1 40400 4665. E-mail address: martin.schillinger{at}meduniwien.ac.at

Aims Complement activation occurs in atherosclerotic lesions, and particularly complement component C5a exerts potent chemotactic and proinflammatory effects. However, it is yet unknown, whether plasma levels of C5a may predict cardiovascular risk. The aim of this study was to examine whether plasma levels of the complement component C5a may predict cardiovascular risk in patients with advanced atherosclerosis.

Methods and results We studied 173 patients with symptomatic peripheral artery disease (median age 72, 82 male). Cardiovascular risk profile, levels of the complement factor C5a, and other non-specific inflammatory parameters [high sensitivity C-reactive protein, serum amyloid A (SAA), and fibrinogen] were obtained at baseline, and patients were followed for median 22 months [interquartile range (IQR) 13–27] for the occurrence of major adverse cardiovascular events (MACE: myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, carotid revascularization, stroke, and death). We observed 65 MACE in 49 patients (28%). Cumulative event rates (95% confidence interval (CI)) within quartiles of C5a at 24 months were 16 (5–27), 26 (13-39), 36 (21–51), and 37% (23–51), respectively (P=0.0077). Adjusted hazard ratios for the occurrence of a first MACE according to increasing quartiles of C5a were 1.81, 2.23, and 2.66, respectively, as compared to the lowest quartile (P=0.038), irrespective of the level of other inflammatory parameters.

Conclusion Complement activation, indicated by the elevation of C5a, seems to be associated with increased cardiovascular risk in patients with advanced atherosclerosis. Clinically, determination of C5a may add to the predictive value of other non-specific inflammatory parameters.

Key Words: Atherosclerosis • Complications • Complement factor • Inflammation


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