Cystatin C and Estimated Glomerular Filtration Rate as Predictors for Adverse Outcome in Patients With ST-Elevation and non-ST-Elevation Acute Coronary Syndromes: Results From the Platelet Inhibition and Patient Outcomes (PLATO) Study

Study Questions:

What measurement of renal function is the best predictor of long-term death or myocardial infarction (MI) in patients with acute coronary syndrome (ACS)?

Methods:

The authors measured cystatin C and creatinine in 16,401 patients in the PLATO (Platelet Inhibition and Patient Outcomes) study. The predictive ability of cystatin C and equations used to estimate glomerular filtration rate (eGFR), including Cockcroft-Gault, MDRD, and the new Chronic Kidney Disease–Epidemiology (CKD-EPI) equation, were evaluated for their ability to predict the composite endpoint of cardiovascular death or MI within 1 year. Two Cox proportional hazards models were used, the first adjusting for clinical characteristics and the second for clinical characteristics plus the biomarkers N-terminal pro–B-type natriuretic peptide, troponin I, and C-reactive protein.

Results:

The median cystatin C value was 0.83 mg/L. Increasing quartiles of cystatin C were strongly associated with death and MI (6.9%, 7.1%, 9.5%, and 16.2%). The fully adjusted hazard ratios per standard deviation of cystatin C in the non–ST-segment elevation (NSTE)-ACS and STE-ACS populations were 1.12 (95% confidence interval [CI], 1.04-1.20) (n = 8,053) and 1.06 (95% CI, 0.97-1.17) (n = 5,278), respectively. However, the overall C-statistics for the different renal function measurements were minimally different, ranging from 0.6923 (cystatin C) to 0.6941 (CKD-EPI). Neither cystatin C nor other creatinine-based equations increased the area under the curve compared to a model that did not include a renal marker. The benefit of ticagrelor tended to be greater with higher levels of cystatin C.

Conclusions:

The authors concluded that cystatin C concentration contributed independently in predicting the risk of cardiovascular death or MI in NSTE-ACS. The CKD-EPI equation exhibited the largest predictive value of all renal markers. Nevertheless, the additive predictive value of cystatin C or creatinine-based eGFR measures in these ACS patients was small.

Perspective:

This is a large analysis from the recent PLATO trial substantiating prior information indicating that measures of renal function are important prognostic factors in ACS patients. In this analysis, the effects shown were more modest than previous effects, and in contrast to prior studies, measures of GFR were equivalent to the use of cystatin C in the evaluation. In fact, the EPI formula for GFR was the most predictive, although none of the measures altered the area under the curve.

Clinical Topics: Acute Coronary Syndromes, ACS and Cardiac Biomarkers

Keywords: Natriuretic Peptides, Myocardial Infarction, Acute Coronary Syndrome, C-Reactive Protein, Biological Markers, Troponin I, Glomerular Filtration Rate, Creatinine, Cystatin C


< Back to Listings