Association of NTproBNP and cTnI with outpatient sudden cardiac death in hemodialysis patients: the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study

Abstract

BackgroundSudden cardiac death (SCD) is the most common etiology of death in hemodialysis patients but not much is known about its risk factors. The goal of our study was to determine the association and risk prediction of SCD by serum N-terminal prohormone of brain natriuretic peptide (NTproBNP) troponin I (cTnI) in hemodialysis patients.MethodsWe measured NTproBNP and cTnI in 503 hemodialysis patients of a national prospective cohort study. We determined their association with SCD using Cox regression, adjusting for demographics, co-morbidities, and clinical factors and risk prediction using C-statistic and Net Reclassification Improvement (NRI).ResultsPatients’ mean age was 58 years and 54 % were male. During follow-up (median 3.5 years), there were 75 outpatient SCD events. In unadjusted and fully-adjusted models, NTproBNP had a significant association with the risk of SCD. Analyzed as a continuous variable, the risk of SCD increased 27 % with each 2-fold increase in NTproBNP (HR, 1.27 per doubling; 95 % CI, 1.13–1.43; p < 0.001). In categorical models, the risk of SCD was 3-fold higher in the highest tertile of NTproBNP (>7,350 pg/mL) compared with the lowest tertile (<1,710 pg/mL; HR for the highest tertile, 3.03; 95 % CI, 1.56–5.89; p = 0.001). Higher cTnI showed a trend towards increased risk of SCD in fully adjusted models, but was not statistically significant (HR, 1.17 per doubling; 95 % CI, 0.98–1.40; p = 0.08). Sensitivity analyses using competing risk models showed similar results. Improvement in risk prediction by adding cardiac biomarkers to conventional risk factors was greater with NTproBNP (C-statistic for 3-year risk: 0.810; 95 % CI, 0.757 to 0.864; and continuous NRI: 0.270; 95 % CI, 0.046 to 0.495) than with cTnI.ConclusionsNTproBNP is associated with the risk of SCD in hemodialysis patients. Further research is needed to determine if biomarkers measurement can guide SCD risk prevention strategies in dialysis patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0230-x) contains supplementary material, which is available to authorized users.

Classic and Novel Biomarkers as Potential Predictors of Ventricular Arrhythmias and Sudden Cardiac Death

“…The authors speculated that volume overload with consequent ventricular stretching, may drive NT-proBNP elevation. Nevertheless, they did not exclude decreased renal clearance as a potential reason for the NT-proBNP elevation in this patient group [71]. On the other hand, when measuring levels of NT-proBNP during a four-year follow-up in dialysis patients with type 2 diabetes mellitus, Winkler et al were able to identify subgroups of patients with increased risk of SCD.…”

“…However, different cut-off serum levels were suggested. Winkler et al concluded serum levels over 9252 pg/mL being predictive of SCD (two-fold increased risk) [72], while Kruzan et al proposed a cut-off > 7350 pg/mL (three-fold higher risk of SCD) [71]. Of note, this group also observed a higher predictive value for NT-proBNP than for cTnI.…”

“…Therefore, several studies focused on NT-proBNP in patients with kidney disease. An association was found between SCD and elevated NT-proBNP, but also cTnI levels, in hemodialysis patients [70][71][72]. However, different cut-off serum levels were suggested.…”

Sympathetic Activation in Hypertensive Chronic Kidney Disease – A Stimulus for Cardiac Arrhythmias and Sudden Cardiac Death?

“…Moreover, natriuretic peptides exert a key function in regulating blood pressure and extracellular fluid volume (Volpe et al, 2016). In non-adjusted and completely adjusted analyses, N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) correlated strongly with SCD hazard (Kruzan et al, 2016). When assessed as a continuous parameter, SCD hazard rose by 27% at every 2-fold NT-proBNP growth.…”

Chronic Kidney Disease and Arrhythmias: Conclusions From a Kidney Disease: Improving Global Outcomes (Kdigo) Controversies Conference

“…149 Troponins and brain natriuretic peptides could have an additive value and should be further explored to assess their role in a comprehensive risk assessment for SCD. [150][151][152][153] There are very limited data regarding the prognostic significance of incidentally detected arrhythmias in CKD and ESKD. Identification of episodes of non-sustained ventricular tachycardia, frequent premature ventricular complexes, bradyarrhythmias and pauses may be useful in identifying patients at risk of SCD.…”