Routinely measured cardiac troponin I and N‐terminal pro‐B‐type natriuretic peptide as predictors of mortality in haemodialysis patients

Abstract

Aims Cardiac troponin (cTn) and B-type natriuretic peptide (BNP) are elevated in haemodialysis (HD) patients, and this elevation is associated with HD-induced myocardial stunning/myocardial strain. However, studies using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS) have shown that these cardiac biomarkers are measured in <2% of HD patients in real-world practice. This study aimed to examine whether routinely measured N-terminal pro-BNP (NT-proBNP) and cTnI (contemporary assay) are more appropriate than clinical models for reclassifying the risk of HD patients who have the highest risk of death. Methods and resultsPre-dialysis levels of cTnI and NT-proBNP at study enrolment were measured in 1152 HD patients (Japan DOPPS Phase 5). The patients were prospectively followed for 3 years. Cox regression was used to test the associations of cardiac biomarkers with all-cause mortality, adjusting for potential confounders. Subgroup analyses were performed to assess potential effect modification of clinical characteristics, such as age, systolic blood pressure, HD vintage, diabetes mellitus, coronary artery disease, and a history of congestive heart failure. At baseline, 337 (29%) patients had elevated cTnI (99th percentile of a healthy population: >0.04 ng/mL) with a median (inter-quartile range) level of 0.020 (0.005-0.041) ng/mL, and 1140 (99%) patients had elevated NT-proBNP (cut-off for heart failure: >125 pg/mL) with a median level of 3658 (1689-9356) pg/mL. There were 167 deaths during a median follow-up of 2.8 (2.2-2.8) years. Higher levels of both cardiac biomarkers were incrementally associated with mortality after adjustment for potential confounders. Even after adjustment for alternative cardiac biomarkers, the overall P value for the association was <0.01 for both biomarkers. However, the prognostic significance of NT-proBNP was moderately diminished when cTnI was added to the model. The hazard ratios of mortality for cTnI > 0.04 ng/mL (vs. cTnI < 0.006 ng/mL) and NT-proBNP > 8000 pg/mL (vs. NT-proBNP < 2000 pg/mL) were 2.56 (95% confidence interval: 1.37-4.81) and 1.90 (95% confidence interval: 0.95-3.79), respectively. Subgroup analyses showed that the associations of both cardiac biomarkers with mortality were generally consistent between stratified groups. Conclusions Routinely measured NT-proBNP and cTnI levels are strongly associated with mortality among prevalent HD patients. These associations remain robust, even after adjustment for alternative biomarkers, suggesting that cTnI and NT-proBNP have identical prognostic significance and may reflect different pathological aspects of cardiac abnormalities.

Superiority of high sensitivity cardiac troponin I over NT-proBNP and adiponectin for 7-year mortality in stable patients receiving haemodialysis

“…Regarding adiponectin, only one patient had a lower level than the cut-off value for metabolic syndrome (4 μg/mL) 20 , and 184 patients (83.2%) had higher levels than the upper reference range for the healthy population (10 μg/mL) 21 . These results are similar to those of previous reports 8 , 9 , 21 – 23 . The clinical characteristics at baseline of the sub-cohorts categorised by tertiles for hs-cTnI of and NT-proBNP levels are shown in Table 1 .…”

“…Based on this analysis, the main positive independent determinant of hs-cTnI was NT-proBNP, whereas the main positive determinants of NT-proBNP were DM, CRP, and hs-cTnI. In earlier reports on dialysis patients, the NT-proBNP level was positively associated with inflammation or CRP 9 , 25 , 26 . The association between NT-proBNP and several factors may partially explain why it was not selected as an independent risk factor for mortality after adjusting for age, DM and hs-cTnI levels.…”

“…cTnI inhibits actin–myosin interaction, whereas cTnT exists on tropomyosin and mediates tropomyosin–troponin binding 7 . Compared with cTnT, cTnI is less affected by renal clearance and better reflects the cardiac pathology in patients on dialysis 8 ; increased cTnI levels are associated with all-cause and cardiovascular mortality 4 , 9 . In contrast, NT-proBNP, which is secreted by cardiomyocytes in response to left ventricular wall stress 2 , 3 , 9 and predominantly undergoes renal clearance, is used to diagnose heart failure and evaluate prognosis in the general population 10 , 11 .…”

“…Compared with cTnT, cTnI is less affected by renal clearance and better reflects the cardiac pathology in patients on dialysis 8 ; increased cTnI levels are associated with all-cause and cardiovascular mortality 4 , 9 . In contrast, NT-proBNP, which is secreted by cardiomyocytes in response to left ventricular wall stress 2 , 3 , 9 and predominantly undergoes renal clearance, is used to diagnose heart failure and evaluate prognosis in the general population 10 , 11 . In patients on dialysis, NT-proBNP has prognostic value for predicting all-cause and cardiovascular mortality 6 , 12 .…”

Predictive value of indicators for left ventricular systolic dysfunction in HD patients

“…Several studies indicated that cTnT and cardiac natriuretic hormones had good diagnostic potential for the exclusion of LVSD in ESRD patients (3,6). Although an increase in concentrations of cTnT and NT-pro-BNP were both associated with CVD, guidelines didn't provide speci c diagnostic and prognostic cut-offs of these cardiac biomarkers in HD patients (10).…”