Complement C3 and C4 in plasma and incidence of myocardial infarction and stroke: a population-based cohort study.

BACKGROUND: Complement factor C3 and C4 have been associated with atherosclerosis and cardiovascular risk factors. This study explored whether plasma levels of C3 and C4 are risk factors for the incidence of cardiovascular disease (CVD). DESIGN: A population-based prospective study of 5850 initially healthy men, 28-61 years old at baseline. METHODS: Plasma levels of C3 and C4 were analysed at the baseline examination. The incidence of coronary events (i.e. fatal or non-fatal myocardial infarction), ischaemic stroke and cardiovascular events (i.e. myocardial infarction, ischaemic stroke or cardiovascular death) was studied over 18 years of follow-up. RESULTS: Adjusted for age, C3 in the fourth quartile (versus the first quartile) was associated with an increased incidence of coronary events relative risk (RR) 1.54, 95% confidence interval (CI) 1.2-1.9], cardiovascular events (RR 1.56, 95% CI 1.3-1.9), and non-significantly with the incidence of ischaemic stroke (RR 1.31, 95% CI 0.89-1.8). However, after adjustments for smoking, body mass index (BMI), cholesterol, diabetes and systolic blood pressure, these relationships were completely attenuated and non-significant. The relationships were similar for C4 concentrations within the normal range. However, for men with C4 in the top 10% of the distribution (>0.34 g/l), a significantly increased incidence of coronary events was found, which persisted after adjustments for risk factors. CONCLUSION: C3 and C4 show substantial correlations with cardiovascular risk factors, including blood pressure, BMI, and lipids. This relationship accounts for the increased incidence of CVD in men with high C3 levels. However, very high C4 levels may be associated with the incidence of CVD, independently of traditional cardiovascular risk factors.