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


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.


CONCLUSIONS
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.
Speidl
Walter S
WS
Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Exner
Markus
M
Amighi
Jasmin
J
Kastl
Stefan P
SP
Zorn
Gerlinde
G
Maurer
Gerald
G
Wagner
Oswald
O
Huber
Kurt
K
Minar
Erich
E
Wojta
Johann
J
Schillinger
Martin
M
D000368:Aged; D050197:Atherosclerosis / Q000150:complications / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D003167:Complement Activation / Q000276:immunology; D015936:Complement C5a / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D016491:Peripheral Vascular Diseases / Q000209:etiology / Q000276:immunology*; D011446:Prospective Studies; D012307:Risk Factors
D015415:Biomarkers; D015936:Complement C5a