Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels with Outcomes after Intensive Blood Pressure Lowering: Findings from the SPRINT Randomized Clinical Trial

Jarett D. Berry, Vijay Nambi, Walter T. Ambrosius, Haiying Chen, Anthony A. Killeen, Addison Taylor, Robert D. Toto, Elsayed Z. Soliman, John W. McEvoy, Ambarish Pandey, Parag H. Joshi, Stefan Blankenberg, Dalane W. Kitzman, Christie M. Ballantyne, James A. De Lemos

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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: Identifier: NCT01206062.

Original languageEnglish (US)
Pages (from-to)1397-1405
Number of pages9
JournalJAMA cardiology
Issue number12
Early online dateSep 1 2021
StatePublished - Dec 2021

Bibliographical note

Funding Information:
AstraZeneca, and Sanofi. Dr Kitzman reported receiving honoraria outside the present study as a consultant for AbbVie, Bayer, Merck, Medtronic, Relypsa, Corvia Medical, Boehringer Ingelheim, Novo Nordisk, AstraZeneca, and Novartis; grant funding outside the present study from Novartis, Bayer, and AstraZeneca; and stock ownership in Gilead Sciences. Dr Ballantyne reported receiving grant/research support from Abbott Diagnostic, Akcea, Amgen, Esperion, Novartis, Regeneron, Roche Diagnostics, the NIH, the AHA, and American Diabetes Association; and receiving consulting fees from Abbott Diagnostics, Akcea, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Corvidia, Denka Seiken, Esperion, Gilead, Janssen, Matinas BioPharma Inc, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostics, and Sanofi-Synthelabo. Dr de Lemos reported receiving grant support from Roche Diagnostics and Abbott Diagnostics; consulting fees from Roche Diagnostics, Abbott Diagnostics, Ortho Clinical Diagnostics, Quidel Cardiovascular Inc, and Siemen’s Health Care Diagnostics; and being named a co-owner on a patent awarded to the University of Maryland (US patent application 15,309,754) entitled: “Methods for Assessing Differential Risk for Developing Heart Failure.” No other disclosures were reported. Funding/Support: The conduct of the study was supported by grants R01HL144112 and R01HL107257 from the NIH. Roche provided in-kind support of materials for biomarker assays. Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Funding Information:
receiving grant support from the National Institutes of Health (NIH), Roche Diagnostics, and Abbott Diagnostics; and consulting fees from Roche Diagnostics, AstraZeneca, and the Cooper Institute. Dr Nambi reported receiving grant support via VA MERIT grant 1I01CX001112-01; being named on provisional patent 61,721,475 “Biomarkers to Improve Prediction of Heart Failure Risk” filed by Baylor College of Medicine and Roche; and being the site principal investigator for a study sponsored by Amgen. Dr Toto reported receiving grant support from NIH; being a consultant to and receiving honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Otsuka, Reata, and Relypsa; and receiving support from the Houston J. and Florence A. Dosswell and Mary M. Conroy Endowments. Dr McEvoy reported receiving grant funding from the Irish Health Research Board. Dr Joshi reported receiving grant support from Novo Nordisk, the American Heart Association (AHA), and NASA; consulting fees from Bayer and Regeneron; equity in G3 Therapeutics; and serving as a site investigator with all funding to the institution for Novartis, GlaxoSmithKline,

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© 2021 American Medical Association. All rights reserved.


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