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

Background and AimsThe 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. MethodsWe included adults with CKD (eGFR<60 ml/min/1.73m2) in the 1999-2004 NHANES. We calculated the 99th 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. ResultsAcross 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 99th percentile of hs-cTnT was 122 ng/L (95% confidence interval (CI) 101-143), hs-cTnIAbbott 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 ({beta}=27.5, 95% CI 28.2-43.3)), NT-proBNP 46.0% increase ({beta}=46.0, 95% CI 36.0-56.8), hs-cTnISiemens 17.9% ({beta}=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-cTnISiemens 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 RelevanceCommunity 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. Clinical PerspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIThis study investigated two important questions relevant to clinical practice. First, which cardiac biomarker (hs-cTnT or hs-cTnI) and which assay is least impacted eGFR in patients with CKD. Second, whether elevated levels of cardiac biomarkers in community-dwelling patients convey prognostic information in CKD in a more representative population. C_LIO_LICommunity 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 the eGFR categories and is associated with CVD mortality in individuals with CKD. C_LI What are the clinical implications?O_LICommunity dwelling adults with CKD had elevated levels of cardiac biomarkers suggestive of subclinical myocardial injury, which were associated with increased risk of cardiovascular death. C_LIO_LIhs-cTnI was least affected by eGFR and retained prognostic significance, suggesting that it may be the superior assay for clinical use in CKD. C_LI