The complement system has been proposed to play a role in the development of cardiovascular disease (CVD). The aim of this study was to investigate the association of complement C3a, an anaphylatoxin generated upon complement C3 activation, with prevalent CVD and markers of subclinical atherosclerosis [i.e. carotid intima-media thickness (cIMT) and ankle-arm blood-pressure index (AAIx)]. We conducted cross-sectional analyses among 521 participants (61% men, aged 59.5 ± 6.9 years, 23% with impaired glucose metabolism/23% with type 2 diabetes, and 27% with CVD) of the Cohort on Diabetes and Atherosclerosis Maastricht Study (CODAM) population. Data were analysed with multiple logistic and linear regression analyses, adjusted for age and sex, and further for glucose metabolism, lipids, waist, renal function, blood pressure, smoking, physical activity and use of medication. Plasma C3a (per doubling) was positively associated with CVD [age and sex-adjusted odds ratio (OR) = 1.55; 95% confidence interval (95%CI): 0.99; 2.40 and p-value = 0.053] but this association was not independent of other covariates [OR = 1.05 (95%CI: 0.62; 1.78), p-value = 0.862]. In contrast, in fully adjusted models, higher levels of C3a were independently associated with higher cIMT [regression coefficient = 0.031 (95%CI: 0.002; 0.059), p-value = 0.037] and lower AAIx [regression coefficient = -0.029 (95%CI: -0.051; -0.007), p-value = 0.011], both consistent with more atherosclerosis. These associations were also independent of C3, the precursor of C3a. The independent adverse associations of higher C3a with higher cIMT and lower AAIx support the concept that activated complement is involved in atherosclerosis. The independent association with markers of subclinical atherosclerosis but not with CVD suggests that C3a may be primarily involved in atherogenesis, and to a lesser extent in processes that favour plaque rupture and atherothrombotic events.
|Title of host publication||XXIV International Complement Workshop, Chania, 10-15 October 2012|
|Place of Publication||2012|
|Publication status||Published - 2012|
|Event||XXIV International Complement Workshop - |
Duration: 10 Oct 2012 → 15 Oct 2012
|Workshop||XXIV International Complement Workshop|
|Period||10/10/12 → 15/10/12|