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.
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.


METHODS
National prospective cohort study.


METHODS
446 incident hemodialysis patients.


METHODS
Predialysis systolic BP.


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


METHODS
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.


CONCLUSIONS
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.
Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD. Electronic address: tshafi@jhmi.edu.
Tariq
T
Shafi
Division of Nephrology, University of New Mexico, Albuquerque, NM.
Philip G
PG
Zager
Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD.
Stephen M
SM
Sozio
Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD.
Morgan E
ME
Grams
Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD; Nephrology Center of Maryland, Baltimore, MD.
Bernard G
BG
Jaar
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD.
Robert H
RH
Christenson
Division of General Internal Medicine, Duke University School of Medicine, Chapel Hill, NC.
L Ebony
LE
Boulware
Department of Pediatrics, Hospital for Sick Children and Medicine, University Health Network, and University of Toronto, Toronto, Ontario, Canada.
Rulan S
RS
Parekh
Department of Medicine, San Francisco General Hospital and University of California, San Francisco, CA.
Neil R
NR
Powe
Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Epidemiology and Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Josef
J
Coresh
D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D006435:Renal Dialysis; D019210:Troponin I / Q000097:blood*
D015415:Biomarkers; D010446:Peptide Fragments; D019210:Troponin I; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
End-stage renal disease (ESRD); N-terminal pro–brain natriuretic peptide (NT-proBNP); dialysis; epidemiology; hemodialysis; hypertension; mortality; outcomes; systolic blood pressure; troponin I