Serum creatinine concentration is used to estimate glomerular filtration rate (GFR), which in turn is used to identify patients with chronic kidney disease (CKD), who are at a high risk of cardiovascular morbidity and mortality. Serum cystatin C concentration is a more accurate determinant of GFR than creatinine concentration and could be used to predict cardiovascular risk in patients without clinically evident CKD as determined by creatinine level.OBJECTIVE
To assess whether elevated serum cystatin C concentration is predictive of adverse outcomes in elderly individuals (≥65 years) without CKD.DESIGN
This was a subgroup analysis of individuals enrolled in the Cardiovascular Health Study who presented for follow-up at the annual assessment in 1992-1993 and underwent creatinine and cystatin C testing. Participants in this longitudinal, community-based study were recruited from centers in four US states and were aged 65 years or older. The participants were not institutionalized, not being treated for cancer, and were expected to reside in the community for at least 3 years after enrollment.INTERVENTION
Serum cystatin C and creatinine concentrations were recorded and GFR was calculated using the 4-variable version of the Modification of Diet and Renal Disease equation. CKD was defined as estimated GFR <60 ml/min per 1.73 m2, and a serum cystatin C level of ≥1.0 mg/l was considered high. Three groups of patients were identified, those with CKD, those without CKD and a high cystatin C level, and those without CKD and a low cystatin C level.OUTCOME MEASURES
The primary outcomes were death (all-cause and cardiovascular), incident heart failure, stroke, and myocardial infarction. Incidence of progression to CKD was also evaluated.RESULTS
This cohort comprised 4,663 participants, 78% of whom did not have CKD at baseline. After a median follow-up of 9.3 years, cystatin C concentrations were found to be strongly associated with the primary outcomes; each 0.18 mg/l increase in cystatin C was associated with a marked increase in the risk of cardiovascular death (hazard ratio [HR] 1.42, 95% CI 1.30-1.54), all-cause mortality (HR 1.33, 95% CI 1.25-1.40), heart failure (HR 1.28, 95% CI 1.17-1.40), stroke (HR 1.22, 95% CI 1.08-1.38), and myocardial infarction (HR 1.20, 95% CI 1.06-1.36). Conversely, creatinine levels were less strongly associated with these outcomes. Participants with an estimated GFR of >60 ml/min per 1.73 m2 in the higher cystatin C level group experienced significantly more adverse events than those in the lower cystatin C level group (P<0.001). Among participants without CKD at baseline, 27% of 1,261 individuals with high cystatin C levels and 7.5% of 1,347 with low cystatin C levels had developed CKD after 4 years follow-up (adjusted odds ratio 4.18, 95% CI 3.25-5.38).CONCLUSION
Cystatin C concentration is a strong predictor of adverse outcomes in elderly people without CKD, and the authors postulate that this biomarker could be an indicator of preclinical kidney disease.