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.