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An epidemiological design, consisting of cross-sectional (n = 2376) and cohort (n = 976) studies, was adopted to investigate the association between complement factors 3 (C3) and 4, and the metabolic syndrome (MetS) development. In the cross-sectional study, the C3 and C4 concentrations in the MetS group were higher than those in the non-MetS group (all  P  < 0.001), and the levels of immune globulin M (IgM), IgA, IgE, and IgG exhibited no significant differences between MetS and non-MetS (all  P  > 0.050). After multi-factor adjustment, the odds ratios (ORs) in the highest quartile of C3 and C4 concentrations were 7.047 (4.664, 10.648) and 1.961 (1.349, 2.849), respectively, both  P  trend  < 0.050. After a 4 years follow-up, total 166 subjects were diagnosed with MetS, and the complement baseline levels from 2009 were used to predict the MetS risk in 2013. In the adjusted model, the relative risks (RRs) in the highest quartile of C3 and C4 levels were 4.779 (2.854, 8.003) and 2.590 (1.567, 4.280), respectively, both  P  trend  < 0.001. Activation of complement factors may be an important part of inflammatory processes, and our results indicated that the elevated C3 and C4 levels were independent risk factors for MetS development.

Elevated serum complement factors 3 and 4 are strong inflammatory markers of the metabolic syndrome development: a longitudinal cohort study