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Original Investigation
September 1, 2021

Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Outcomes After Intensive Blood Pressure Lowering: Findings From the SPRINT Randomized Clinical Trial

Author Affiliations
  • 1Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas
  • 2Michael E. DeBakey Veterans Affairs Hospital, Baylor College of Medicine, Houston, Texas
  • 3Division of Public Health Sciences, Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 4Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis
  • 5Department of Medicine, Baylor College of Medicine, Houston, Texas
  • 6Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston Salem, North Carolina
  • 7Cardiology Section, Department of Internal Medicine, Wake Forest School of Medicine, Winston Salem, North Carolina
  • 8National Institute for Prevention and Cardiovascular Health, National University of Ireland, Galway, Ireland
  • 9Department of General and Interventional Cardiology, University Heart Center Hamburg, German Center for Cardiovascular Research, partner site Hamburg/Kiel/Luebeck, Hamburg, Germany
  • 10Section on Cardiovascular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 11Section on Geriatrics, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 12Center for Cardiometabolic Disease Prevention, Department of Medicine, Baylor College of Medicine, Houston, Texas
JAMA Cardiol. Published online September 1, 2021. doi:10.1001/jamacardio.2021.3187
Key Points

Question  What is the association of intensive systolic blood pressure lowering with the risk of heart failure and mortality among individuals with elevated high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro–B-type natriuretic peptide (NTproBNP) levels?

Findings  In this nonprespecified post hoc analysis of the Systolic Blood Pressure Intervention Trial randomized clinical trial, intensive systolic blood pressure lowering was associated with an 8% absolute risk reduction in heart failure and mortality among individuals with elevation in both hscTnT and NTproBNP levels, compared with a 2% absolute risk reduction among individuals without elevated markers.

Meaning  The risk associated with elevated hscTnT and NTproBNP levels may be modifiable with intensive systolic blood pressure lowering.

Abstract

Importance  Elevated high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro–B-type natriuretic peptide (NTproBNP) levels are associated with risk of heart failure (HF) and mortality among individuals in the general population. However, it is unknown if this risk is modifiable.

Objective  To test the hypothesis that elevated hscTnT and NTproBNP levels would identify individuals with the greatest risk for mortality and HF and the largest benefit associated with intensive systolic blood pressure (SBP) lowering.

Design, Setting, and Participants  This is a nonprespecified post hoc analysis of the multicenter, prospective, randomized clinical Systolic Blood Pressure Intervention Trial (SPRINT), conducted from October 20, 2010, to August 20, 2015. A total of 9361 patients without diabetes with increased risk for cardiovascular disease were randomized to receive intensive vs standard SBP lowering. Statistical analysis was performed on an intention-to-treat basis from September 30, 2019, to July 29, 2021.

Interventions  Participants were randomized to undergo intensive (<120 mm Hg) or standard (<140 mm Hg) SBP lowering. High-sensitivity cardiac troponin T and NTproBNP levels were measured from stored specimens collected at enrollment, with elevated levels defined as 14 ng/L or more for hscTnT (to convert to micrograms per liter, multiply by 0.001) and 125 pg/mL or more for NTproBNP (to convert to nanograms per liter, multiply by 1.0).

Main Outcomes and Measures  The primary outcome of this ancillary study was HF and mortality.

Results  Of the 9361 participants enrolled in SPRINT, 8828 (5578 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured hscTnT levels and 8836 (5585 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured NTproBNP levels; 2262 of 8828 patients (25.6%) had elevated hscTnT levels, 3371 of 8836 patients (38.2%) had elevated NTproBNP, and 1411 of 8828 patients (16.0%) had both levels elevated. Randomization to the intensive SBP group led to a 4.9% (95% CI, 1.7%-7.5%) absolute risk reduction (ARR) over 4 years in death and HF (421 events) for those with elevated hscTnT and a 1.7% (95% CI, 0.7%-2.5%) ARR for those without elevated levels. Similarly, for those with elevated NTproBNP, the ARR for death and HF over 4 years was 4.6% (95% CI, 2.3%-6.5%) vs 1.8% (95% CI, 0.9%-2.5%) in those without elevated levels. For those with elevated levels of both biomarkers, the ARR for death and HF over 4 years was 7.8% (95% CI, 3.3%-11.3%) vs 1.7% (95% CI, 0.8%-2.3%) in those with neither biomarker elevated. No significant treatment group by biomarker category interactions were detected.

Conclusions and Relevance  Intensive SBP control led to large absolute differences in death and HF among patients with abnormal hscTnT and NTproBNP levels. These findings demonstrate that risk associated with elevation of these biomarkers is modifiable with intensive BP control. A prospective, randomized clinical trial is needed to evaluate whether these biomarkers may help guide selection of patients for intensive SBP lowering.

Trial Registration  ClinicalTrials.gov Identifier: NCT01206062

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