Association of cardiac biomarkers, kidney function, and mortality among adults with chronic kidney disease

Abstract

Background and aims: The performance of high sensitivity troponin T (hs-cTnT), hs-cTnI, and N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) in patients with chronic kidney disease (CKD) is poorly understood.

Methods: We included adults with CKD (eGFR<60 ml/min/1.73m²) in the 1999-2004 NHANES. We calculated the 99^th percentile of hs-cTnT, hs-cTnI (Abbott, Ortho, and Siemens assays), and NT-proBNP, measured the association between eGFR and cardiac biomarker concentration, and used Cox regression models to assess the relationship between cardiac biomarkers and CVD mortality.

Results: Across 1,068 adults with CKD, the mean [SD] age was 71.9[12.7] years and 61.2% were female; 78.8% had elevated NT-proBNP and 42.6% had elevated hs-cTnT based on traditional clinical reference limits. The 99^th percentile of hs-cTnT was 122 ng/L (95% confidence interval (CI) 101-143), hs-cTnI_Abbott was 69 ng/L (95% CI 38-99), and NT-proBNP was 8952 pg/mL (95% CI 7506-10,399). A 10 ml/min decrease in eGFR was associated with greater increases in hs-cTnT and NT-proBNP than hs-cTnI (hs-cTnT: 27.5% increase (β=27.5, 95% CI 28.2-43.3)), NT-proBNP 46.0% increase (β=46.0, 95% CI 36.0-56.8), hs-cTnI_Siemens 17.9% (β=17.9, 95% CI 9.7-26.7). Each doubling of hs-cTnT, hs-cTnI, and NT-proBNP were associated with CVD mortality (hs-cTnT HR 1.62 [95% CI 1.32-1.98], p<0.0001; hs-cTnI_Siemens HR 1.40 [95% CI 1.26-1.55], p<0.0001; NT-proBNP HR 1.29 [95% CI 1.19-1.41], p<0.0001).

Conclusions and relevance: Community dwelling adults with CKD have elevated concentrations of cardiac biomarkers, above established reference ranges. Of the troponin assays, hs-cTnI concentration appears to be most stable across eGFR categories and is associated with CVD mortality.

Keywords: NHANES; NT-proBNP; cardiovascular disease; chronic kidney disease; estimated glomerular filtration rate; mortality; troponin.