Troponin I and NT-proBNP and the association of systolic blood pressure with outcomes in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study

Abstract

Background: There is uncertainty regarding treatment of hypertension in hemodialysis patients due to the observed J-shaped association between blood pressure (BP) and death. We hypothesized that this association reflects confounding by cardiovascular disease (CVD) and that stratification by CVD biomarkers, cardiac troponin I (cTnI) and N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP), might change this association.

Study design: National prospective cohort study.

Setting & participants: 446 incident hemodialysis patients.

Predictor: Predialysis systolic BP.

Outcomes: Mortality (all-cause and CVD) and first CVD event assessed using Cox regression adjusted for demographics, comorbid conditions, and clinical factors.

Measurements: Participants with cTnI level ≥0.1 ng/mL or NT-proBNP level ≥9,252 pg/mL were classified as the high-biomarker group; remaining participants were included in the low-biomarker group.

Results: Participants in the high-biomarker group (n=138 [31%]) were older (61 vs. 57 years) and had a higher prevalence of CVD (67% vs. 23%), but similar baseline BPs (152 vs. 153 mm Hg). There were 323 deaths (143 from CVD) and 271 CVD events. The high-biomarker group had a higher risk of mortality than the low-biomarker group (HR, 1.75; 95% CI, 1.37-2.24). The association between BP and outcomes differed between the 2 biomarker groups (P for interaction=0.01, 0.2, and 0.07 for all-cause mortality, CVD mortality, and first CVD event, respectively). In the low-biomarker group, BP was associated with greater risk of outcomes: HR per 10 mm Hg higher BP was 1.07 (95% CI, 1.01-1.14), 1.10 (95% CI, 0.96-1.25), and 1.04 (95% CI, 0.96-1.13) for all-cause mortality, CVD mortality, and first CVD event, respectively. Importantly, lower BP was not associated with increased risk of outcomes in stratified models, including for those in high biomarker group.

Limitations: BP measurements not standardized.

Conclusions: The observed J-shaped association between BP and outcomes in hemodialysis patients is due to confounding by subclinical CVD. A stratification approach based on cTnI and NT-proBNP levels has the potential to inform BP treatment in hemodialysis patients.

Keywords: End-stage renal disease (ESRD); N-terminal pro–brain natriuretic peptide (NT-proBNP); dialysis; epidemiology; hemodialysis; hypertension; mortality; outcomes; systolic blood pressure; troponin I.

Figure 1

Distribution of predialysis systolic blood pressure (BP) in 446 CHOICE Study participants stratified by cardiac troponin I (cTnI) and N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP). Lines represent the kernel density estimates. Broken line shows the distribution of predialysis systolic BP in 138 participants with cTnI ≥ 0.1 ng/mL or NT-proBNP ≥ 9,252 pg/mL. Solid line shows the distribution of predialysis systolic BP in 308 participants with cTnI below 0.1 ng/mL and NT-proBNP below 9,252 pg/mL.

Figure 2

Adjusted relative hazards of all-cause mortality associated with predialysis systolic blood pressure in 446 incident hemodialysis participants of the CHOICE Study. Those with cardiac troponin I (cTnI) ≥ 0.1 ng/mL or N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) ≥ 9,252 pg/mL are classified as high biomarker group and the remaining participants as low biomarker group. Figure 2a presents the relative hazard of all-cause mortality, Figure 2b presents the relative hazard of cardiovascular mortality and Figure 2c presents the relative hazard of first cardiovascular disease event. Top panel for each figure presents the unadjusted and adjusted results for the full cohort, the middle panel for those in the low biomarker group and the lower panel for those in the high biomarker groups. Model adjusted for demographics (age, sex and race) comorbidities [baseline Index of Coexistent Disease (ICED) score, CVD and diabetes], body mass index, baseline antihypertensive medication use and serum albumin. Overall model also includes an interaction between blood pressure and biomarker group. Relative hazard predicted using Cox proportional hazards regression. Predialysis systolic blood pressure is modeled as a restricted cubic spline with knots at 10^th, 50^th and 90^th percentile. The solid line is the adjusted hazard ratio of mortality; systolic blood pressure = 140 mm Hg was used as the reference (hazard ratio =1). The shaded area represents the 95% confidence interval. Red color represents the hazard before adjustment and blue color represents the hazard after adjustment.