Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Oct 2018)

Cystatin C for Risk Stratification in Patients After an Acute Coronary Syndrome

  • Simon Correa,
  • David A. Morrow,
  • Eugene Braunwald,
  • Richard Y. Davies,
  • Erica L. Goodrich,
  • Sabina A. Murphy,
  • Christopher P. Cannon,
  • Michelle L. O'Donoghue

DOI
https://doi.org/10.1161/JAHA.118.009077
Journal volume & issue
Vol. 7, no. 20

Abstract

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Background Cystatin C (Cys‐C) is a marker of renal function that has shown prognostic value for cardiovascular risk stratification across different patient populations. The incremental value of Cys‐C beyond established cardiac and renal biomarkers remains incompletely explored. Methods and Results SOLID‐TIMI 52 (Stabilization of Plaques Using Darapladib‐Thrombolysis in Myocardial Infarction 52; www.clinicaltrials.gov, NCT01000727) randomized patients ≤30 days post–acute coronary syndrome were treated with darapladib or placebo. The association between Cys‐C and long‐term risk (median follow‐up 2.5 years) was assessed in 4965 individuals with adjustments made for clinical variables and other risk markers (eg, estimated glomerular filtration rate, high‐sensitivity troponin I, brain‐type natriuretic peptide, and fibroblast growth factor‐23). The prespecified outcome of interest was cardiovascular death (CVD) or heart failure hospitalization. Cys‐C was strongly correlated with creatinine (r=0.60) and estimated glomerular filtration rate (r=−0.68), moderately correlated with fibroblast growth factor‐23 (r=0.39), and weakly correlated with brain‐type natriuretic peptide (r=0.28) and high‐sensitivity troponin I (r=0.06) (all P<0.0001). After multivariate adjustment, increasing concentration of Cys‐C (per SD of log‐transformed Cys‐C) was significantly associated with a 28% higher hazard of CVD or heart failure hospitalization (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.12‐1.46, P<0.001), including CVD (HR 1.24, 95% CI 1.04‐1.47, P=0.01) and heart failure hospitalization (HR 1.42, 95% CI 1.19‐1.69, P<0.001). Cys‐C was also associated with a higher hazard of CVD, myocardial infarction, or stroke (HR 1.15, 95% CI 1.04‐1.28, P<0.01), including myocardial infarction (HR 1.17, 95% CI 1.02‐1.33, P=0.02). The addition of Cys‐C to a fully adjusted model without estimated glomerular filtration rate improved the C‐statistic from 0.80 to 0.81 (P=0.03) for CVD or heart failure hospitalization. In contrast, the addition of estimated glomerular filtration rate to a fully adjusted model without Cys‐C failed to improve model discrimination (P=0.17). Conclusions Cys‐C is associated with the risk of adverse outcomes in patients after acute coronary syndrome. This relationship is independent of established and novel biomarkers of the cardiorenal axis.

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