Cystatin C identifies cardiovascular risk better than creatinine-based estimates of glomerular filtration in middle-aged individuals without a history of cardiovascular disease

ObjectivesCreatinine- and cystatin C-based estimates of renal function are considered to be cardiovascular disease (CVD) risk factors, but the clinical utility in middle-aged subjects without a history of CVD is controversial. DesignWe related plasma cystatin C and creatinine-based glomerular filtration rate (GFR) [MDRD, CKD-EPI-2009, and CKD-EPI-comb (a combination of creatinine and cystatin C)] to incident CVD, CVD mortality, all-cause mortality, and heart failure in 4650 middle-aged subjects without CVD. ResultsThe hazard ratio (HR) per standard deviation increment (95% CI) of cystatin C predicted incident CVD (1.22, 1.11-1.33; P<0.0001), CVD mortality (1.44, 1.24-1.66; P<0.0001), all-cause mortality (1.15, 1.05-1.26; P=0.002), and heart failure (1.27, 1.05-1.55; P=0.02), whereas MDRD and CKD-EPI-2009 only predicted CVD mortality (0.79, 0.66-0.93; P=0.006 and 0.78, 0.66-0.92; P=0.003, respectively). Cystatin C led to a significant increase in the net reclassification improvement for all endpoints, except heart failure. Only within the quartile with the worst renal function were all measures related to all-cause and CVD mortality. The top 25% of cystatin C in the population significantly predicted risk of incident CVD and CVD mortality, whereas MDRD and CKD-EPI-2009 were predictors of CVD mortality only at a GFR<60mL/min/1.73m(2) (11-13% of the population) and of incident CVD only at a GFR<45mL/min/1.73m(2) (<1% of the population). ConclusionCystatin C is a better risk marker for CVD morbidity and mortality than creatinine-based GFR. Whether this is explained by cystatin C being a better marker for true GFR or through other effects of cystatin C remains to be shown.