title: Serum complement C3/C4 ratio, a novel marker for recurrent cardiovascular events.
abstract: Acute coronary syndrome is an inflammatory disease, during which the complement cascade is activated. We assessed the complement C3 and C4 concentration ratio (C3/C4 ratio) in serum as a potential measurement to predict cardiovascular attacks. Patients with acute coronary syndrome (n=148) were followed after an initial attack for subsequent ischemic cardiovascular events (composite end point of death, myocardial infarction, recurrent unstable angina, or stroke). During the follow-up period (average 555 days), 44 patients met an end point. Blood samples were taken at hospitalization, 1 week, 3 months, and 1 year after hospital admission. Serum complement C3 and C4 concentrations and the C3/C4 ratio were analyzed. Patients with an end point had, throughout the follow-up period, a higher C3/C4 ratio than patients without these end points (repeated measures analysis of variance, p=0.007). When all traditional cardiovascular risk factors and other potential confounding factors were included in a Cox multivariate logistic regression survival analysis, the C3/C4 ratio emerged as the novel risk factor for any new cardiovascular event (odds ratio 1.33, 95% confidence interval 1.08 to 1.63, p=0.007). When the C3/C4 ratio was divided into 4 quartiles, 24% in quartiles 1 and 2 (lowest) and 48% in quartile 4 (highest) had end points during follow-up (odds ratio 3.04, 95% confidence interval 1.27 to 7.29, p=0.01). In conclusion, increased serum C3/C4 ratio is a readily available and novel marker for recurrent cardiovascular events in acute coronary syndrome. The relative increase in serum C3 protein and decrease in C4 protein could explain changes in the C3/C4 ratio.
authors.affiliation: Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Anil
authors.initials: A
authors.lastname: Palikhe
authors.forename: Juha
authors.initials: J
authors.lastname: Sinisalo
authors.forename: Mikko
authors.initials: M
authors.lastname: Seppänen
authors.forename: Heikki
authors.initials: H
authors.lastname: Haario
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
authors.forename: Ville
authors.initials: V
authors.lastname: Valtonen
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: Marja-Liisa
authors.initials: ML
authors.lastname: Lokki
mesh_terms: D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D000789:Angina, Unstable / Q000097:blood / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D002544:Cerebral Infarction / Q000097:blood / Q000401:mortality; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism*; D003181:Complement C4 / Q000235:genetics / Q000378:metabolism*; D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000401:mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013577:Syndrome
chemical_list: D015415:Biomarkers; D003176:Complement C3; D003181:Complement C4; D018836:Inflammation Mediators; D020097:Natriuretic Peptide, Brain