Cystatin C identifies patients with stable chronic heart failure at increased risk for adverse cardiovascular events

Abstract

Background: Renal function is a strong predictor of adverse events in heart failure. Current renal function measures are imperfect, and cystatin C (CysC) is promoted as a better marker of glomerular filtration rate. This study compares the prognostic use of CysC and derived glomerular filtration rate estimates with other measures of renal function in patients with chronic heart failure.

Methods and results: We measured serum CysC levels in 823 patients with heart failure undergoing coronary angiography with follow-up of major adverse cardiovascular events (death, myocardial infarction, stroke). CysC levels strongly correlated with creatinine (r=0.73), blood urea nitrogen (r=0.70), and estimated glomerular filtration rate by the 4-variable modification of diet in renal disease equation (r=-0.62) (all P<0.001). However, the correlation was lower in estimated glomerular filtration rate ≥60 mL/min per 1.73 m(2). CysC-based measures significantly improved areas under the receiver operating characteristic curve for the prediction of major adverse cardiovascular events, especially in estimated glomerular filtration rate ≥60 mL/min per 1.73 m(2) (P<0.01). Net reclassification improvement was 22.2% (P<0.001) in this group. CysC remained an independent predictor of major adverse cardiovascular events (P<0.001) after adjustment for traditional risk factors and brain natriuretic peptide.

Conclusions: CysC is an independent predictor of adverse events in chronic heart failure. It adds prognostic value to creatinine, particularly in patients with preserved renal function.

Trial registration: ClinicalTrials.gov NCT00590200.

Figures

Figure 1. Histogram of serum Cystatin C Concentrations

Patients with eGFRMDRD < 60ml/min/1.73m2 are projected in darker shade.

Figure 2. Forrest Plots (unadjusted) For Quartiles of Different Measures of Renal Function

Hazards ratio compared to reference for quartiles of urea, cystatin, creatinine (all in mg/dL) as well as estimated glomerular filtration rate equations (all in ml/min/1.73m2).

Figure 3

Kaplan-Meier curves for Death/MI/Stroke according to Quartiles of Cystatin C (A) and eGFRCysC (B).

Figure 4. Risk Stratification in Patients with Heart Failure According to Tertiles of Cystatin C and BNP

The risk of the combined outcome (death, myocardial infarction, stroke) increases from 12.3% in patients with both biomarkers in the lowest tertile to 44.8% in patients with both biomarkers in the highest tertile (p