Impact of Elevated Cystatin C Level on Cardiovascular Disease Risk in Predominantly High Cardiovascular Risk Populations: A Meta-Analysis

Background—Chronic kidney disease is a growing public health problem that carries substantial risk for cardiovascular disease (CVD). Single studies have differentially examined the role of cystatin C, a novel renal index, with varying cut-point use. We undertook a meta-analysis of prospective studies to properly assess the link between cystatin C (dichotomized and continuous) versus CVD. Methods and Results—Systematic literature search for studies reporting a multivariate-adjusted estimate, represented as relative risk (RR) with 95% confidence interval (CI), of the association between cystatin C and subsequent risk of (1) any CVD event and (2) specific CVD events. Data were collated from 14 studies, with 13 high cardiovascular risk population cohorts and 1 general population cohort, involving 22 509 subjects with 2321 CVD events, 741 coronary heart disease events, and 828 stroke events. Highest cystatin C category versus lowest was associated with greater risk of CVD (RR, 2.62; 95% CI, 2.05 to 3.37, P<0.001), coronary heart disease (RR, 1.72; 95% CI, 1.27 to 2.34; P<0.001), and stroke (RR, 1.83; 95% CI, 1.12 to 3.00; P=0.02) after adjustment for established cardiovascular risk factors. Each standard deviation rise in cystatin C concentration boosted CVD risk (RR, 1.34; 95% CI, 1.18 to 1.51; P<0.001). Highest cystatin C category was also independently linked to greater risk of all-cause mortality and heart failure. Conclusions—The meta-analysis, mostly derived from high cardiovascular populations, showed that cystatin C is strongly and independently associated with subsequent CVD risk. Further investigation is warranted to clarify whether measurement of cystatin C can usefully enhance CVD stratification beyond established predictors already in clinical use.