Glomerular Filtration Rate-Specific Cutoffs Can Refine the Prognostic Value of Circulating Cardiac Biomarkers in Advanced Chronic Kidney Disease.

Background: Using standard cutoffs derived from healthy adults, high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are frequently elevated in patients with reduced glomerular filtration rate (GFR), with unclear implications. We sought to compare GFR-specific cutoffs of each biomarker with standard cutoffs for discrimination of cardiovascular risk in asymptomatic patients with chronic kidney disease.
Methods: We investigated a prospective cohort of 1956 participants with median GFR of 27 mL/min/1.73 m ² . Cox proportional hazards models were used to examine the association between each biomarker and first adjudicated cardiovascular event (unstable angina, myocardial infarction, heart failure, stroke, cardiovascular death). We used an outcome-based approach to identify optimal risk-based cutoffs for each biomarker within GFR strata (< 20, 20-29, 30-44 mL/min/1.73 m ² ). We evaluated the added prognostic value of each biomarker to a multivariable base model, comparing GFR-specific with standard cutoffs.
Results: Hs-cTnT and NT-proBNP were elevated in 76% and 82% of participants, respectively. A total of 401 events were recorded during 6772 person-years at risk. Both biomarkers were independent predictors of cardiovascular events. Optimal cutoffs for each biomarker were higher than standard thresholds, being highest at GFR values < 20 mL/min/1.73 m ² . Addition of hs-cTnT to the base model using GFR-specific cutoffs significantly improved reclassification for events (52%) and nonevents (21%). Similar findings were observed for NT-proBNP. In contrast, use of standard cutoffs failed to reclassify patients who had no event as lower risk.
Conclusions: Among asymptomatic patients with advanced chronic kidney disease, optimal cutoffs for hs-cTnT and NT-proBNP differed according to GFR level and outperformed standard cutoffs for discrimination of cardiovascular risk.
(Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)