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

J Am Heart Assoc. 2018 Oct 16;7(20):e009077. doi: 10.1161/JAHA.118.009077.


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; , 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.

Keywords: acute coronary syndrome; biomarker; cystatin C; prognosis.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / drug therapy
  • Analysis of Variance
  • Benzaldehydes / therapeutic use
  • Biomarkers / metabolism*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality
  • Creatinine / metabolism
  • Cystatin C / metabolism*
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate / drug effects
  • Heart Failure / etiology
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / drug therapy
  • Oximes / therapeutic use
  • Percutaneous Coronary Intervention / statistics & numerical data
  • Phospholipase A2 Inhibitors / therapeutic use
  • Risk Assessment / methods


  • Benzaldehydes
  • Biomarkers
  • Cystatin C
  • Oximes
  • Phospholipase A2 Inhibitors
  • Creatinine
  • darapladib

Associated data