Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation

Abhinav Sharma, Ziad Hijazi, Ulrika Andersson, Sana M. Al-Khatib, Renato D. Lopes, John H. Alexander, Claes Held, Elaine M. Hylek, Sergio Leonardi, Michael Hanna, Justin A. Ezekowitz, Agneta Siegbahn, Christopher B. Granger, Lars Wallentin

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

BACKGROUND: Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 levels are predictive of cardiovascular events and total cardiovascular death in anticoagulated patients with atrial fibrillation. The prognostic utility of these biomarkers for cause-specific death is unknown.

METHODS: The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients (1.9 years median follow-up). Cox models were used to identify clinical variables and biomarkers independently associated with each specific cause of death.

RESULTS: In total, 1272 patients died: 652 (51%) cardiovascular, 32 (3%) bleeding, and 588 (46%) noncardiovascular/nonbleeding deaths. Among cardiovascular deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure deaths, and 106 (16%) stroke/systemic embolism deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; P<0.001), NT-proBNP with heart failure death (HR, 1.62; P<0.001), and growth differentiation factor-15 with bleeding death (HR, 1.72; P=0.028). Prior stroke/systemic embolism (HR, 2.58; P>0.001) followed by troponin T (HR, 1.45; P<0.0029) were the most predictive for stroke/ systemic embolism death. Adding all biomarkers to clinical variables improved discrimination for each cause-specific death.

CONCLUSIONS: Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients' risks for different causes of death. These data suggest a potential role of biomarkers for the identification of patients at risk for different causes of death in patients anticoagulated for atrial fibrillation.

CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.

Original languageEnglish
Pages (from-to)1666-1676
Number of pages11
JournalCirculation
Volume138
Issue number16
DOIs
Publication statusPublished - Oct 16 2018

Fingerprint

Atrial Fibrillation
Cause of Death
Biomarkers
Troponin T
Stroke
Embolism
Growth Differentiation Factor 15
Brain Natriuretic Peptide
Sudden Cardiac Death
Warfarin
Random Allocation
Sudden Death
Proportional Hazards Models
Interleukin-6
Heart Failure
Clinical Trials
Hemorrhage

Keywords

  • atrial fibrillation
  • biomarkers
  • cause of death
  • prediction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Sharma, A., Hijazi, Z., Andersson, U., Al-Khatib, S. M., Lopes, R. D., Alexander, J. H., ... Wallentin, L. (2018). Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation. Circulation, 138(16), 1666-1676. https://doi.org/10.1161/CIRCULATIONAHA.118.034125

Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation. / Sharma, Abhinav; Hijazi, Ziad; Andersson, Ulrika; Al-Khatib, Sana M.; Lopes, Renato D.; Alexander, John H.; Held, Claes; Hylek, Elaine M.; Leonardi, Sergio; Hanna, Michael; Ezekowitz, Justin A.; Siegbahn, Agneta; Granger, Christopher B.; Wallentin, Lars.

In: Circulation, Vol. 138, No. 16, 16.10.2018, p. 1666-1676.

Research output: Contribution to journalArticle

Sharma, A, Hijazi, Z, Andersson, U, Al-Khatib, SM, Lopes, RD, Alexander, JH, Held, C, Hylek, EM, Leonardi, S, Hanna, M, Ezekowitz, JA, Siegbahn, A, Granger, CB & Wallentin, L 2018, 'Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation', Circulation, vol. 138, no. 16, pp. 1666-1676. https://doi.org/10.1161/CIRCULATIONAHA.118.034125
Sharma A, Hijazi Z, Andersson U, Al-Khatib SM, Lopes RD, Alexander JH et al. Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation. Circulation. 2018 Oct 16;138(16):1666-1676. https://doi.org/10.1161/CIRCULATIONAHA.118.034125
Sharma, Abhinav ; Hijazi, Ziad ; Andersson, Ulrika ; Al-Khatib, Sana M. ; Lopes, Renato D. ; Alexander, John H. ; Held, Claes ; Hylek, Elaine M. ; Leonardi, Sergio ; Hanna, Michael ; Ezekowitz, Justin A. ; Siegbahn, Agneta ; Granger, Christopher B. ; Wallentin, Lars. / Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation. In: Circulation. 2018 ; Vol. 138, No. 16. pp. 1666-1676.
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AU - Sharma, Abhinav

AU - Hijazi, Ziad

AU - Andersson, Ulrika

AU - Al-Khatib, Sana M.

AU - Lopes, Renato D.

AU - Alexander, John H.

AU - Held, Claes

AU - Hylek, Elaine M.

AU - Leonardi, Sergio

AU - Hanna, Michael

AU - Ezekowitz, Justin A.

AU - Siegbahn, Agneta

AU - Granger, Christopher B.

AU - Wallentin, Lars

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N2 - BACKGROUND: Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 levels are predictive of cardiovascular events and total cardiovascular death in anticoagulated patients with atrial fibrillation. The prognostic utility of these biomarkers for cause-specific death is unknown.METHODS: The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients (1.9 years median follow-up). Cox models were used to identify clinical variables and biomarkers independently associated with each specific cause of death.RESULTS: In total, 1272 patients died: 652 (51%) cardiovascular, 32 (3%) bleeding, and 588 (46%) noncardiovascular/nonbleeding deaths. Among cardiovascular deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure deaths, and 106 (16%) stroke/systemic embolism deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; P<0.001), NT-proBNP with heart failure death (HR, 1.62; P<0.001), and growth differentiation factor-15 with bleeding death (HR, 1.72; P=0.028). Prior stroke/systemic embolism (HR, 2.58; P>0.001) followed by troponin T (HR, 1.45; P<0.0029) were the most predictive for stroke/ systemic embolism death. Adding all biomarkers to clinical variables improved discrimination for each cause-specific death.CONCLUSIONS: Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients' risks for different causes of death. These data suggest a potential role of biomarkers for the identification of patients at risk for different causes of death in patients anticoagulated for atrial fibrillation.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.

AB - BACKGROUND: Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 levels are predictive of cardiovascular events and total cardiovascular death in anticoagulated patients with atrial fibrillation. The prognostic utility of these biomarkers for cause-specific death is unknown.METHODS: The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients (1.9 years median follow-up). Cox models were used to identify clinical variables and biomarkers independently associated with each specific cause of death.RESULTS: In total, 1272 patients died: 652 (51%) cardiovascular, 32 (3%) bleeding, and 588 (46%) noncardiovascular/nonbleeding deaths. Among cardiovascular deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure deaths, and 106 (16%) stroke/systemic embolism deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; P<0.001), NT-proBNP with heart failure death (HR, 1.62; P<0.001), and growth differentiation factor-15 with bleeding death (HR, 1.72; P=0.028). Prior stroke/systemic embolism (HR, 2.58; P>0.001) followed by troponin T (HR, 1.45; P<0.0029) were the most predictive for stroke/ systemic embolism death. Adding all biomarkers to clinical variables improved discrimination for each cause-specific death.CONCLUSIONS: Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients' risks for different causes of death. These data suggest a potential role of biomarkers for the identification of patients at risk for different causes of death in patients anticoagulated for atrial fibrillation.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.

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KW - cause of death

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