Effect of Intensive Blood Pressure Control on Troponin and Natriuretic Peptide Levels: Findings From SPRINT

Jarett D. Berry; Haiying Chen; Vijay Nambi; Walter T. Ambrosius; Simon B. Ascher; Michael G. Shlipak; Joachim H. Ix; Rajesh Gupta; Anthony Killeen; Robert D. Toto; Dalane W. Kitzman; Christie M. Ballantyne; James A. De Lemos

doi:10.1161/CIRCULATIONAHA.122.059960

Effect of Intensive Blood Pressure Control on Troponin and Natriuretic Peptide Levels: Findings From SPRINT

Jarett D. Berry, Haiying Chen, Vijay Nambi, Walter T. Ambrosius, Simon B. Ascher, Michael G. Shlipak, Joachim H. Ix, Rajesh Gupta, Anthony Killeen, Robert D. Toto, Dalane W. Kitzman, Christie M. Ballantyne, James A. De Lemos

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Background: Given the important role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure and strong associations observed between hypertension and its sequelae on hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, we hypothesized that intensive systolic blood pressure (SBP) lowering would decrease levels of hs-cTnT and NT-proBNP. Methods: hs-cTnT and NT-proBNP were measured at baseline and 1 year from stored specimens in SPRINT (Systolic Blood Pressure Intervention Trial). Changes in biomarkers were evaluated continuously on the log scale and according to categories (≥50% increase, ≥50% decrease, or <50% change). The effect of intensive SBP lowering on continuous and categorical changes in biomarker levels were assessed using linear and multinomial logistic regression models, respectively. The association between changes in biomarkers on heart failure and death was assessed using multivariable-adjusted Cox proportional hazards models. Results: Randomization to intensive SBP lowering (versus standard SBP management) resulted in a 3% increase in hs-cTnT levels over 1-year follow-up (geometric mean ratio, 1.03 [95% CI, 1.01-1.04]) and a higher proportion of participants with ≥50% increase (odds ratio, 1.47 [95% CI, 1.13, 1.90]). In contrast, randomization to intensive SBP lowering led to a 10% decrease in NT-proBNP (geometric mean ratio, 0.90 [95% CI, 0.87-0.93]) and a lower probability of ≥50% increase in NT-proBNP (odds ratio, 0.57 [95% CI, 0.46-0.72]). The association of randomized treatment assignment on change in hs-cTnT was completely attenuated after accounting for changes in estimated glomerular filtration rate over follow-up, whereas the association of treatment with NT-proBNP was completely attenuated after adjusting for change in SBP. Increases in hs-cTnT and NT-proBNP from baseline to 1 year were associated with higher risk for heart failure and death, with no significant interactions by treatment assignment. Conclusions: Intensive SBP lowering increased hs-cTnT, mediated by the effect of SBP lowering on reduced kidney filtration. In contrast, intensive SBP lowering decreased NT-proBNP, a finding that was explained by the decrease in SBP. These findings highlight the importance of noncardiac factors influencing variation in cardiac biomarkers and raise questions about the potential role of hs-cTnT as a surrogate marker for heart failure or death in SBP-lowering studies.

Original language	English (US)
Pages (from-to)	310-323
Number of pages	14
Journal	Circulation
Volume	147
Issue number	4
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.122.059960
State	Published - Jan 24 2023

Bibliographical note

Funding Information:
The authors thank the participants and staff members of SPRINT (Systolic Blood Pressure Intervention Trial), which was sponsored by the National Institutes of Health, including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke, under contract numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and Inter-Agency Agreement Number A-HL-13–002-001. SPRINT was also supported in part by resources and use of facilities through the Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. All components of the SPRINT study protocol were designed and implemented by the investigators. The investigative team collected, analyzed, and interpreted the data. All aspects of article writing and revision were carried out by the coauthors. A full list of contributors to SPRINT is available in the supplementary acknowledgment list at https://www.sprinttrial.org/public/dspScience.cfm . Support was also provided by the following Clinical and Translational Science Awards funded by the National Center for Advancing Translational Sciences: Case Western Reserve University: UL1TR000439; Ohio State University: UL1RR025755; University of Pennsylvania: UL1RR024134 and UL1TR000003; Boston University: UL1RR025771; Stanford University: UL1TR000093; Tufts University: UL1RR025752, UL1TR000073, and UL1TR001064; University of Illinois: UL1TR000050; University of Pittsburgh: UL1TR000005; UT Southwestern: 9U54TR000017-06; University of Utah: UL1TR000105-05; Vanderbilt University: UL1TR000445; George Washington University: UL1TR000075; University of California, Davis: UL1TR000002; University of Florida: UL1TR000064; University of Michigan: UL1TR000433; Tulane University: P30GM103337 Centers of Biomedical Research Excellence Award, National Institute of General Medical Sciences; Wake Forest University: UL1TR001420.

Funding Information:
This ancillary study was supported by the National Heart, Lung, and Blood Institute (grant 1R01HL144112-01 to Dr Berry), the National Institute of Diabetes and Digestive and Kidney Diseases (grant R01DK098234 to Drs Shlipak and Ix and grant K24DK110427 to Dr Ix), and the American Heart Association (grant 14EIA18560026 to Dr Ix). Analytical reagents for hs-cTnT (high-sensitivity cardiac troponin T) and NT-pro-BNP (N-terminal pro-B-type natriuretic peptide) measurements were donated by Roche (Indianapolis, IN).

Funding Information:
Acknowledgments The authors thank the participants and staff members of SPRINT (Systolic Blood Pressure Intervention Trial), which was sponsored by the National Institutes of Health, including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke, under contract numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and Inter-Agency Agreement Number A-HL- 13-002-001. SPRINT was also supported in part by resources and use of facilities through the Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. All components of the SPRINT study protocol were designed and implemented by the investigators. The investigative team collected, analyzed, and interpreted the data. All aspects of article writing and revision were carried out by the coauthors. A full list of contributors to SPRINT is available in the supplementary acknowledgment list at https:// www.sprinttrial.org/public/dspScience.cfm. Support was also provided by the following Clinical and Translational Science Awards funded by the National Center for Advancing Translational Sciences: Case Western Reserve University: UL1TR000439; Ohio State University: UL1RR025755; University of Pennsylvania: UL1RR024134 and UL1TR000003; Boston University: UL1RR025771; Stanford University: UL1TR000093; Tufts University: UL1RR025752, UL1TR000073, and UL1TR001064; University of Illinois: UL1TR000050; University of Pittsburgh: UL1TR000005; UT Southwestern: 9U54TR000017-06; University of Utah: UL1TR000105-05; Vanderbilt University: UL1TR000445; George Washington University: UL1TR000075; University of California, Davis: UL1TR000002; University of Florida: UL- 1TR000064; University of Michigan: UL1TR000433; Tulane University: P30GM103337 Centers of Biomedical Research Excellence Award, National Institute of General Medical Sciences; Wake Forest University: UL- 1TR001420. Sources of Funding This ancillary study was supported by the National Heart, Lung, and Blood Institute (grant 1R01HL144112-01 to Dr Berry), the National Institute of Diabetes and Digestive and Kidney Diseases (grant R01DK098234 to Drs Shlipak and Ix and grant K24DK110427 to Dr Ix), and the American Heart Association (grant 14EIA18560026 to Dr Ix). Analytical reagents for hs-cTnT (high-sensitivity cardiac troponin T) and NT-pro-BNP (N-terminal pro-B-type natriuretic peptide) measurements were donated by Roche (Indianapolis, IN).

Publisher Copyright:
© 2022 American Heart Association, Inc.

Keywords

biomarkers
blood pressure
heart failure

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10.1161/CIRCULATIONAHA.122.059960

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Berry, J. D., Chen, H., Nambi, V., Ambrosius, W. T., Ascher, S. B., Shlipak, M. G., Ix, J. H., Gupta, R., Killeen, A., Toto, R. D., Kitzman, D. W., Ballantyne, C. M., & De Lemos, J. A. (2023). Effect of Intensive Blood Pressure Control on Troponin and Natriuretic Peptide Levels: Findings From SPRINT. Circulation, 147(4), 310-323. https://doi.org/10.1161/CIRCULATIONAHA.122.059960

@article{9bc88deca0a54c58a7fac9c9deb15aa2,

title = "Effect of Intensive Blood Pressure Control on Troponin and Natriuretic Peptide Levels: Findings From SPRINT",

abstract = "Background: Given the important role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure and strong associations observed between hypertension and its sequelae on hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, we hypothesized that intensive systolic blood pressure (SBP) lowering would decrease levels of hs-cTnT and NT-proBNP. Methods: hs-cTnT and NT-proBNP were measured at baseline and 1 year from stored specimens in SPRINT (Systolic Blood Pressure Intervention Trial). Changes in biomarkers were evaluated continuously on the log scale and according to categories (≥50% increase, ≥50% decrease, or <50% change). The effect of intensive SBP lowering on continuous and categorical changes in biomarker levels were assessed using linear and multinomial logistic regression models, respectively. The association between changes in biomarkers on heart failure and death was assessed using multivariable-adjusted Cox proportional hazards models. Results: Randomization to intensive SBP lowering (versus standard SBP management) resulted in a 3% increase in hs-cTnT levels over 1-year follow-up (geometric mean ratio, 1.03 [95% CI, 1.01-1.04]) and a higher proportion of participants with ≥50% increase (odds ratio, 1.47 [95% CI, 1.13, 1.90]). In contrast, randomization to intensive SBP lowering led to a 10% decrease in NT-proBNP (geometric mean ratio, 0.90 [95% CI, 0.87-0.93]) and a lower probability of ≥50% increase in NT-proBNP (odds ratio, 0.57 [95% CI, 0.46-0.72]). The association of randomized treatment assignment on change in hs-cTnT was completely attenuated after accounting for changes in estimated glomerular filtration rate over follow-up, whereas the association of treatment with NT-proBNP was completely attenuated after adjusting for change in SBP. Increases in hs-cTnT and NT-proBNP from baseline to 1 year were associated with higher risk for heart failure and death, with no significant interactions by treatment assignment. Conclusions: Intensive SBP lowering increased hs-cTnT, mediated by the effect of SBP lowering on reduced kidney filtration. In contrast, intensive SBP lowering decreased NT-proBNP, a finding that was explained by the decrease in SBP. These findings highlight the importance of noncardiac factors influencing variation in cardiac biomarkers and raise questions about the potential role of hs-cTnT as a surrogate marker for heart failure or death in SBP-lowering studies.",

keywords = "biomarkers, blood pressure, heart failure",

author = "Berry, {Jarett D.} and Haiying Chen and Vijay Nambi and Ambrosius, {Walter T.} and Ascher, {Simon B.} and Shlipak, {Michael G.} and Ix, {Joachim H.} and Rajesh Gupta and Anthony Killeen and Toto, {Robert D.} and Kitzman, {Dalane W.} and Ballantyne, {Christie M.} and {De Lemos}, {James A.}",

note = "Funding Information: The authors thank the participants and staff members of SPRINT (Systolic Blood Pressure Intervention Trial), which was sponsored by the National Institutes of Health, including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke, under contract numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and Inter-Agency Agreement Number A-HL-13–002-001. SPRINT was also supported in part by resources and use of facilities through the Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. All components of the SPRINT study protocol were designed and implemented by the investigators. The investigative team collected, analyzed, and interpreted the data. All aspects of article writing and revision were carried out by the coauthors. A full list of contributors to SPRINT is available in the supplementary acknowledgment list at https://www.sprinttrial.org/public/dspScience.cfm . Support was also provided by the following Clinical and Translational Science Awards funded by the National Center for Advancing Translational Sciences: Case Western Reserve University: UL1TR000439; Ohio State University: UL1RR025755; University of Pennsylvania: UL1RR024134 and UL1TR000003; Boston University: UL1RR025771; Stanford University: UL1TR000093; Tufts University: UL1RR025752, UL1TR000073, and UL1TR001064; University of Illinois: UL1TR000050; University of Pittsburgh: UL1TR000005; UT Southwestern: 9U54TR000017-06; University of Utah: UL1TR000105-05; Vanderbilt University: UL1TR000445; George Washington University: UL1TR000075; University of California, Davis: UL1TR000002; University of Florida: UL1TR000064; University of Michigan: UL1TR000433; Tulane University: P30GM103337 Centers of Biomedical Research Excellence Award, National Institute of General Medical Sciences; Wake Forest University: UL1TR001420. Funding Information: This ancillary study was supported by the National Heart, Lung, and Blood Institute (grant 1R01HL144112-01 to Dr Berry), the National Institute of Diabetes and Digestive and Kidney Diseases (grant R01DK098234 to Drs Shlipak and Ix and grant K24DK110427 to Dr Ix), and the American Heart Association (grant 14EIA18560026 to Dr Ix). Analytical reagents for hs-cTnT (high-sensitivity cardiac troponin T) and NT-pro-BNP (N-terminal pro-B-type natriuretic peptide) measurements were donated by Roche (Indianapolis, IN). Funding Information: Acknowledgments The authors thank the participants and staff members of SPRINT (Systolic Blood Pressure Intervention Trial), which was sponsored by the National Institutes of Health, including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke, under contract numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and Inter-Agency Agreement Number A-HL- 13-002-001. SPRINT was also supported in part by resources and use of facilities through the Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. All components of the SPRINT study protocol were designed and implemented by the investigators. The investigative team collected, analyzed, and interpreted the data. All aspects of article writing and revision were carried out by the coauthors. A full list of contributors to SPRINT is available in the supplementary acknowledgment list at https:// www.sprinttrial.org/public/dspScience.cfm. Support was also provided by the following Clinical and Translational Science Awards funded by the National Center for Advancing Translational Sciences: Case Western Reserve University: UL1TR000439; Ohio State University: UL1RR025755; University of Pennsylvania: UL1RR024134 and UL1TR000003; Boston University: UL1RR025771; Stanford University: UL1TR000093; Tufts University: UL1RR025752, UL1TR000073, and UL1TR001064; University of Illinois: UL1TR000050; University of Pittsburgh: UL1TR000005; UT Southwestern: 9U54TR000017-06; University of Utah: UL1TR000105-05; Vanderbilt University: UL1TR000445; George Washington University: UL1TR000075; University of California, Davis: UL1TR000002; University of Florida: UL- 1TR000064; University of Michigan: UL1TR000433; Tulane University: P30GM103337 Centers of Biomedical Research Excellence Award, National Institute of General Medical Sciences; Wake Forest University: UL- 1TR001420. Sources of Funding This ancillary study was supported by the National Heart, Lung, and Blood Institute (grant 1R01HL144112-01 to Dr Berry), the National Institute of Diabetes and Digestive and Kidney Diseases (grant R01DK098234 to Drs Shlipak and Ix and grant K24DK110427 to Dr Ix), and the American Heart Association (grant 14EIA18560026 to Dr Ix). Analytical reagents for hs-cTnT (high-sensitivity cardiac troponin T) and NT-pro-BNP (N-terminal pro-B-type natriuretic peptide) measurements were donated by Roche (Indianapolis, IN). Publisher Copyright: {\textcopyright} 2022 American Heart Association, Inc.",

year = "2023",

month = jan,

day = "24",

doi = "10.1161/CIRCULATIONAHA.122.059960",

language = "English (US)",

volume = "147",

pages = "310--323",

journal = "Circulation",

issn = "0009-7322",

publisher = "Lippincott Williams and Wilkins",

number = "4",

}

TY - JOUR

T1 - Effect of Intensive Blood Pressure Control on Troponin and Natriuretic Peptide Levels

T2 - Findings From SPRINT

AU - Berry, Jarett D.

AU - Chen, Haiying

AU - Nambi, Vijay

AU - Ambrosius, Walter T.

AU - Ascher, Simon B.

AU - Shlipak, Michael G.

AU - Ix, Joachim H.

AU - Gupta, Rajesh

AU - Killeen, Anthony

AU - Toto, Robert D.

AU - Kitzman, Dalane W.

AU - Ballantyne, Christie M.

AU - De Lemos, James A.

N1 - Funding Information: The authors thank the participants and staff members of SPRINT (Systolic Blood Pressure Intervention Trial), which was sponsored by the National Institutes of Health, including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke, under contract numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and Inter-Agency Agreement Number A-HL-13–002-001. SPRINT was also supported in part by resources and use of facilities through the Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. All components of the SPRINT study protocol were designed and implemented by the investigators. The investigative team collected, analyzed, and interpreted the data. All aspects of article writing and revision were carried out by the coauthors. A full list of contributors to SPRINT is available in the supplementary acknowledgment list at https://www.sprinttrial.org/public/dspScience.cfm . Support was also provided by the following Clinical and Translational Science Awards funded by the National Center for Advancing Translational Sciences: Case Western Reserve University: UL1TR000439; Ohio State University: UL1RR025755; University of Pennsylvania: UL1RR024134 and UL1TR000003; Boston University: UL1RR025771; Stanford University: UL1TR000093; Tufts University: UL1RR025752, UL1TR000073, and UL1TR001064; University of Illinois: UL1TR000050; University of Pittsburgh: UL1TR000005; UT Southwestern: 9U54TR000017-06; University of Utah: UL1TR000105-05; Vanderbilt University: UL1TR000445; George Washington University: UL1TR000075; University of California, Davis: UL1TR000002; University of Florida: UL1TR000064; University of Michigan: UL1TR000433; Tulane University: P30GM103337 Centers of Biomedical Research Excellence Award, National Institute of General Medical Sciences; Wake Forest University: UL1TR001420. Funding Information: This ancillary study was supported by the National Heart, Lung, and Blood Institute (grant 1R01HL144112-01 to Dr Berry), the National Institute of Diabetes and Digestive and Kidney Diseases (grant R01DK098234 to Drs Shlipak and Ix and grant K24DK110427 to Dr Ix), and the American Heart Association (grant 14EIA18560026 to Dr Ix). Analytical reagents for hs-cTnT (high-sensitivity cardiac troponin T) and NT-pro-BNP (N-terminal pro-B-type natriuretic peptide) measurements were donated by Roche (Indianapolis, IN). Funding Information: Acknowledgments The authors thank the participants and staff members of SPRINT (Systolic Blood Pressure Intervention Trial), which was sponsored by the National Institutes of Health, including the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke, under contract numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, and HHSN268200900049C and Inter-Agency Agreement Number A-HL- 13-002-001. SPRINT was also supported in part by resources and use of facilities through the Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. All components of the SPRINT study protocol were designed and implemented by the investigators. The investigative team collected, analyzed, and interpreted the data. All aspects of article writing and revision were carried out by the coauthors. A full list of contributors to SPRINT is available in the supplementary acknowledgment list at https:// www.sprinttrial.org/public/dspScience.cfm. Support was also provided by the following Clinical and Translational Science Awards funded by the National Center for Advancing Translational Sciences: Case Western Reserve University: UL1TR000439; Ohio State University: UL1RR025755; University of Pennsylvania: UL1RR024134 and UL1TR000003; Boston University: UL1RR025771; Stanford University: UL1TR000093; Tufts University: UL1RR025752, UL1TR000073, and UL1TR001064; University of Illinois: UL1TR000050; University of Pittsburgh: UL1TR000005; UT Southwestern: 9U54TR000017-06; University of Utah: UL1TR000105-05; Vanderbilt University: UL1TR000445; George Washington University: UL1TR000075; University of California, Davis: UL1TR000002; University of Florida: UL- 1TR000064; University of Michigan: UL1TR000433; Tulane University: P30GM103337 Centers of Biomedical Research Excellence Award, National Institute of General Medical Sciences; Wake Forest University: UL- 1TR001420. Sources of Funding This ancillary study was supported by the National Heart, Lung, and Blood Institute (grant 1R01HL144112-01 to Dr Berry), the National Institute of Diabetes and Digestive and Kidney Diseases (grant R01DK098234 to Drs Shlipak and Ix and grant K24DK110427 to Dr Ix), and the American Heart Association (grant 14EIA18560026 to Dr Ix). Analytical reagents for hs-cTnT (high-sensitivity cardiac troponin T) and NT-pro-BNP (N-terminal pro-B-type natriuretic peptide) measurements were donated by Roche (Indianapolis, IN). Publisher Copyright: © 2022 American Heart Association, Inc.

PY - 2023/1/24

Y1 - 2023/1/24

N2 - Background: Given the important role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure and strong associations observed between hypertension and its sequelae on hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, we hypothesized that intensive systolic blood pressure (SBP) lowering would decrease levels of hs-cTnT and NT-proBNP. Methods: hs-cTnT and NT-proBNP were measured at baseline and 1 year from stored specimens in SPRINT (Systolic Blood Pressure Intervention Trial). Changes in biomarkers were evaluated continuously on the log scale and according to categories (≥50% increase, ≥50% decrease, or <50% change). The effect of intensive SBP lowering on continuous and categorical changes in biomarker levels were assessed using linear and multinomial logistic regression models, respectively. The association between changes in biomarkers on heart failure and death was assessed using multivariable-adjusted Cox proportional hazards models. Results: Randomization to intensive SBP lowering (versus standard SBP management) resulted in a 3% increase in hs-cTnT levels over 1-year follow-up (geometric mean ratio, 1.03 [95% CI, 1.01-1.04]) and a higher proportion of participants with ≥50% increase (odds ratio, 1.47 [95% CI, 1.13, 1.90]). In contrast, randomization to intensive SBP lowering led to a 10% decrease in NT-proBNP (geometric mean ratio, 0.90 [95% CI, 0.87-0.93]) and a lower probability of ≥50% increase in NT-proBNP (odds ratio, 0.57 [95% CI, 0.46-0.72]). The association of randomized treatment assignment on change in hs-cTnT was completely attenuated after accounting for changes in estimated glomerular filtration rate over follow-up, whereas the association of treatment with NT-proBNP was completely attenuated after adjusting for change in SBP. Increases in hs-cTnT and NT-proBNP from baseline to 1 year were associated with higher risk for heart failure and death, with no significant interactions by treatment assignment. Conclusions: Intensive SBP lowering increased hs-cTnT, mediated by the effect of SBP lowering on reduced kidney filtration. In contrast, intensive SBP lowering decreased NT-proBNP, a finding that was explained by the decrease in SBP. These findings highlight the importance of noncardiac factors influencing variation in cardiac biomarkers and raise questions about the potential role of hs-cTnT as a surrogate marker for heart failure or death in SBP-lowering studies.

AB - Background: Given the important role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure and strong associations observed between hypertension and its sequelae on hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, we hypothesized that intensive systolic blood pressure (SBP) lowering would decrease levels of hs-cTnT and NT-proBNP. Methods: hs-cTnT and NT-proBNP were measured at baseline and 1 year from stored specimens in SPRINT (Systolic Blood Pressure Intervention Trial). Changes in biomarkers were evaluated continuously on the log scale and according to categories (≥50% increase, ≥50% decrease, or <50% change). The effect of intensive SBP lowering on continuous and categorical changes in biomarker levels were assessed using linear and multinomial logistic regression models, respectively. The association between changes in biomarkers on heart failure and death was assessed using multivariable-adjusted Cox proportional hazards models. Results: Randomization to intensive SBP lowering (versus standard SBP management) resulted in a 3% increase in hs-cTnT levels over 1-year follow-up (geometric mean ratio, 1.03 [95% CI, 1.01-1.04]) and a higher proportion of participants with ≥50% increase (odds ratio, 1.47 [95% CI, 1.13, 1.90]). In contrast, randomization to intensive SBP lowering led to a 10% decrease in NT-proBNP (geometric mean ratio, 0.90 [95% CI, 0.87-0.93]) and a lower probability of ≥50% increase in NT-proBNP (odds ratio, 0.57 [95% CI, 0.46-0.72]). The association of randomized treatment assignment on change in hs-cTnT was completely attenuated after accounting for changes in estimated glomerular filtration rate over follow-up, whereas the association of treatment with NT-proBNP was completely attenuated after adjusting for change in SBP. Increases in hs-cTnT and NT-proBNP from baseline to 1 year were associated with higher risk for heart failure and death, with no significant interactions by treatment assignment. Conclusions: Intensive SBP lowering increased hs-cTnT, mediated by the effect of SBP lowering on reduced kidney filtration. In contrast, intensive SBP lowering decreased NT-proBNP, a finding that was explained by the decrease in SBP. These findings highlight the importance of noncardiac factors influencing variation in cardiac biomarkers and raise questions about the potential role of hs-cTnT as a surrogate marker for heart failure or death in SBP-lowering studies.

KW - biomarkers

KW - blood pressure

KW - heart failure

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UR - http://www.scopus.com/inward/citedby.url?scp=85147047652&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.122.059960

DO - 10.1161/CIRCULATIONAHA.122.059960

M3 - Article

C2 - 36533535

AN - SCOPUS:85147047652

SN - 0009-7322

VL - 147

SP - 310

EP - 323

JO - Circulation

JF - Circulation

IS - 4

ER -

Effect of Intensive Blood Pressure Control on Troponin and Natriuretic Peptide Levels: Findings From SPRINT

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