Low serum complement C3 levels are associated with all-cause mortality in Chinese centenarians: a prospective cohort study.

BACKGROUND

The complement system plays an important role in innate immunity and age-related inflammation, but its prognostic value in centenarians remains unclear. This study aimed to examine the associations between serum complement C3 and C4 levels and all-cause mortality among centenarians.

METHODS

We studied centenarians in Hainan Island, China. We used multivariable-adjusted restricted cubic splines, Cox proportional hazards models, and Kaplan-Meier survival analysis to assess the relationships between serum C3 and C4 levels and all-cause mortality.

RESULTS

A total of 906 centenarians were included in the final analysis. During a median follow-up of 30.1 months, 838 (92.5%) participants died. There was a significant inverse linear relationship between serum C3 levels and all-cause mortality (P = 0.031). Compared with the highest C3 quartile (Q4), individuals in the lowest quartile (Q1) had an increased risk of all-cause mortality (hazard ratio = 1.337; 95% confidence interval: 1.092-1.635; P = 0.005), whereas C4 levels showed no significant relationship with mortality (P > 0.05). When we used Q1 (0.86 g/L) as a cut-off, centenarians with C3 levels below this threshold also showed a higher mortality risk than those above this threshold (hazard ratio = 1.250; 95% confidence interval: 1.063-1.470; P = 0.007). A Kaplan-Meier analysis further indicated a shorter survival time in the lowest C3 quartile (Q1 vs. Q4: 26 vs. 34 months, P = 0.002). In contrast, C4 levels were not significantly associated with survival.

CONCLUSION

Serum complement C3 levels, but not C4 levels, might be associated with the risk of all-cause mortality in centenarians. However, because all centenarians were recruited from Hainan Island, external validation in other regions and ethnic populations is warranted.