High-sensitivity C-reactive protein and cystatin C independently and jointly predict all-cause mortality among the middle-aged and elderly Chinese population

Studies investigating the relationship between high-sensitivity C-reactive protein (hs-CRP), cystatin C, and all-cause mortality yielded inconsistent results. Moreover, the joint effect of hs-CRP and cystatin C on mortality risk is largely unknown for the general population. In this study, we examined the associations between hs-CRP, cystatin C, and all-cause mortality using data from the China Health and Retirement Longitudinal Study (CHARLS). Middle-aged and elderly participants with complete data were enrolled for a 4-year follow-up of total mortality and plasma levels of hs-CRP (n = 11,409) and cystatin C (n = 8680). In study population, the highest quartiles of hs-CRP and cystatin C were significantly associated with increased total mortality risk compared with the lowest quartile, and adjusted hazard ratios (95% confidence intervals) were 2.08 (1.49-2.91) and 1.97 (1.33-2.94) for hs-CRP and cystatin C, respectively. Remarkably, the adjusted hazard ratio (95% confidence interval) of the co-occurrence of elevated hs-CRP and increased cystatin C was 4.17 (2.94-5.92), in contrast to each elevation alone: 1.89 (1.45-2.47) for hs-CRP and 2.08 (1.46-2.97) for cystatin C. Moreover, a subgroup analysis by gender yielded similar associations. Lastly, the addition of hs-CRP and cystatin C to conventional factors significantly improved risk prediction of total mortality (net reclassification index 0.3622, P < 0.0001; integrated discrimination improvement 0.0354, P < 0.0001). Taken together, findings suggest that plasma hs-CRP and cystatin C serve as independent predictors of all-cause mortality among the middle-aged and elderly Chinese population. Furthermore, the combination of hs-CRP and cystatin C could predict overall mortality better than each component individually.