High-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and risk of incident heart failure in patients with CKD: the Chronic Renal Insufficiency Cohort (CRIC) Study

Abstract

High-sensitivity troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) strongly predict heart failure (HF) in the general population. However, the interpretation of levels of these biomarkers as predictors of HF is uncertain among patients with CKD. Here, we investigated whether hsTnT and NT-proBNP are associated with incident HF among patients with CKD. In a prospective cohort analysis, we studied 3483 people with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study recruited from June of 2003 to August of 2008 who were free of HF at baseline. We used Cox regression to examine the association of baseline levels of hsTnT and NT-proBNP with incident HF after adjustment for demographic factors, traditional cardiovascular risk factors, markers of kidney disease, pertinent medication use, and mineral metabolism markers. At baseline, hsTnT levels ranged from ≤5.0 to 738.7 pg/ml, and NT-proBNP levels ranged from ≤5 to 35,000 pg/ml. Compared with those who had undetectable hsTnT, participants in the highest quartile (>26.5 pg/ml) had a significantly higher rate of HF (hazard ratio, 4.77; 95% confidence interval, 2.49 to 9.14). Similarly, compared with those in the lowest NT-proBNP quintile (<47.6 pg/ml), participants in the highest quintile (>433.0 pg/ml) experienced a substantially higher rate of HF (hazard ratio, 9.57; 95% confidence interval, 4.40 to 20.83) [corrected]. In conclusion, hsTnT and NT-proBNP were strongly associated with incident HF among a diverse cohort of individuals with mild to severe CKD. Elevations in these biomarkers may indicate subclinical changes in volume and myocardial stress that subsequently contribute to clinical HF.

Keywords: cardiovascular disease; heart failure; kidney disease.

Figure 1.

Distributions of cardiac biomarkers among participants without HF in the CRIC Study. (A) Distribution of hsTnT. (B) Distribution of NT-proBNP.

Figure 2.

Crude rates of incident HF per 1000 person-years of follow-up in the CRIC Study across categories of hsTnT and NT-proBNP. Events rates for hsTnT are shown for those with undetectable levels (≤5) and then by quartile among detectable levels; event rates for NT-proBNP are shown by quintile. LLD, lower limit of detection; Q, quartile.

Figure 3.

Multivariable-adjusted association of hsTnT (per 1 SD increase) and incident HF in specific subgroups. Adjusted for age, sex, race/ethnicity, clinical center, diabetes status, self-reported cardiovascular disease at baseline, current smoking, alcohol use, log(urine total protein excretion), eGFR, systolic BP, body mass index, LDL, HDL, hemoglobin, angiotensin-converting enzyme/angiotensin receptor blocker use, diuretic use, β-blocker use, serum phosphorus, log(PTH), and log(FGF23).

Figure 4.

Multivariable-adjusted association of NT-proBNP (per 1 SD increase) and incident HF in specific subgroups. Adjusted for age, sex, race/ethnicity, clinical center, diabetes status, self-reported cardiovascular disease at baseline, current smoking, alcohol use, log(urine total protein excretion), eGFR, systolic BP, body mass index, LDL, HDL, hemoglobin, angiotensin-converting enzyme/angiotensin receptor blocker use, diuretic use, β-blocker use, serum phosphorus, log(PTH), and log(FGF23).