Association of cardiovascular biomarkers with incident heart failure with preserved and reduced ejection fraction

Rudolf A. De Boer, Matthew Nayor, Christopher R. DeFilippi, Danielle Enserro, Vijeta Bhambhani, Jorge R. Kizer, Michael Blaha, Frank P. Brouwers, Mary Cushman, Joao Lima, Hossein Bahrami, Pim Van Der Harst, Thomas J. Wang, Ron T. Gansevoort, Caroline S. Fox, Hanna K. Gaggin, Willem J. Kop, Kiang Liu, Ramachandran S. Vasan, Bruce M. Psaty & 16 others Douglas S. Lee, Hans L. Hillege, Traci M. Bartz, Emelia J. Benjamin, Cheeling Chan, Matthew Allison, Julius M. Gardin, James L. Januzzi, Sanjiv J. Shah, Daniel Levy, David M. Herrington, Martin G. Larson, Wiek H. Van Gilst, John S. Gottdiener, Alain G. Bertoni, Jennifer E. Ho

Research output: Contribution to journalArticle

Abstract

IMPORTANCE Nearly half of all patients with heart failure have preserved ejection fraction (HFpEF) as opposed to reduced ejection fraction (HFrEF), yet associations of biomarkers with future heart failure subtype are incompletely understood. OBJECTIVE To evaluate the associations of 12 cardiovascular biomarkers with incident HFpEF vs HFrEF among adults from the general population. DESIGN, SETTING, AND PARTICIPANTS This study included 4 longitudinal community-based cohorts: The Cardiovascular Health Study (1989-1990; 1992-1993 for supplemental African-American cohort), the Framingham Heart Study (1995-1998), the Multi-Ethnic Study of Atherosclerosis (2000-2002), and the Prevention of Renal and Vascular End-stage Disease study (1997-1998). Each cohort had prospective ascertainment of incident HFpEF and HFrEF. Data analysis was performed from June 25, 2015, to November 9, 2017. EXPOSURES The following biomarkers were examined: N-terminal pro B-type natriuretic peptide or brain natriuretic peptide, high-sensitivity troponin T or I, C-reactive protein (CRP), urinary albumin to creatinine ratio (UACR), renin to aldosterone ratio, D-dimer, fibrinogen, soluble suppressor of tumorigenicity, galectin-3, cystatin C, plasminogen activator inhibitor 1, and interleukin 6. MAIN OUTCOMES AND MEASURES Development of incident HFpEF and incident HFrEF. RESULTS Among the 22 756 participants in these 4 cohorts (12 087 women and 10 669 men; mean [SD] age, 60 [13] years) in the study, during a median follow-up of 12 years, 633 participants developed incident HFpEF, and 841 developed HFrEF. In models adjusted for clinical risk factors of heart failure, 2 biomarkers were significantly associated with incident HFpEF: UACR (hazard ratio [HR], 1.33; 95%CI, 1.20-1.48; P < .001) and natriuretic peptides (HR, 1.27; 95%CI, 1.16-1.40; P < .001), with suggestive associations for high-sensitivity troponin (HR, 1.11; 95%CI, 1.03-1.19; P = .008), plasminogen activator inhibitor 1 (HR, 1.22; 95%CI, 1.03-1.45; P = .02), and fibrinogen (HR, 1.12; 95%CI, 1.03-1.22; P = .01). By contrast, 6 biomarkers were associated with incident HFrEF: natriuretic peptides (HR, 1.54; 95%CI, 1.41-1.68; P < .001), UACR (HR, 1.21; 95%CI, 1.11-1.32; P < .001), high-sensitivity troponin (HR, 1.37; 95%CI, 1.29-1.46; P < .001), cystatin C (HR, 1.19; 95%CI, 1.11-1.27; P < .001), D-dimer (HR, 1.22; 95%CI, 1.11-1.35; P < .001), and CRP (HR, 1.19; 95%CI, 1.11-1.28; P < .001). When directly compared, natriuretic peptides, high-sensitivity troponin, and CRP were more strongly associated with HFrEF compared with HFpEF. CONCLUSIONS AND RELEVANCE Biomarkers of renal dysfunction, endothelial dysfunction, and inflammation were associated with incident HFrEF. By contrast, only natriuretic peptides and UACR were associated with HFpEF. These findings highlight the need for future studies focused on identifying novel biomarkers of the risk of HFpEF.

Original languageEnglish (US)
Pages (from-to)215-224
Number of pages10
JournalJAMA Cardiology
Volume3
Issue number3
DOIs
StatePublished - Mar 1 2018

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Heart Failure
Biomarkers
Natriuretic Peptides
Albumins
Creatinine
C-Reactive Protein
Cystatin C
Troponin
Brain Natriuretic Peptide
Plasminogen Activator Inhibitor 1
Fibrinogen
Troponin C
Galectin 3
Troponin T
Troponin I
Aldosterone
Renin
African Americans
Chronic Kidney Failure
Blood Vessels

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

De Boer, R. A., Nayor, M., DeFilippi, C. R., Enserro, D., Bhambhani, V., Kizer, J. R., ... Ho, J. E. (2018). Association of cardiovascular biomarkers with incident heart failure with preserved and reduced ejection fraction. JAMA Cardiology, 3(3), 215-224. https://doi.org/10.1001/jamacardio.2017.4987

Association of cardiovascular biomarkers with incident heart failure with preserved and reduced ejection fraction. / De Boer, Rudolf A.; Nayor, Matthew; DeFilippi, Christopher R.; Enserro, Danielle; Bhambhani, Vijeta; Kizer, Jorge R.; Blaha, Michael; Brouwers, Frank P.; Cushman, Mary; Lima, Joao; Bahrami, Hossein; Van Der Harst, Pim; Wang, Thomas J.; Gansevoort, Ron T.; Fox, Caroline S.; Gaggin, Hanna K.; Kop, Willem J.; Liu, Kiang; Vasan, Ramachandran S.; Psaty, Bruce M.; Lee, Douglas S.; Hillege, Hans L.; Bartz, Traci M.; Benjamin, Emelia J.; Chan, Cheeling; Allison, Matthew; Gardin, Julius M.; Januzzi, James L.; Shah, Sanjiv J.; Levy, Daniel; Herrington, David M.; Larson, Martin G.; Van Gilst, Wiek H.; Gottdiener, John S.; Bertoni, Alain G.; Ho, Jennifer E.

In: JAMA Cardiology, Vol. 3, No. 3, 01.03.2018, p. 215-224.

Research output: Contribution to journalArticle

De Boer, RA, Nayor, M, DeFilippi, CR, Enserro, D, Bhambhani, V, Kizer, JR, Blaha, M, Brouwers, FP, Cushman, M, Lima, J, Bahrami, H, Van Der Harst, P, Wang, TJ, Gansevoort, RT, Fox, CS, Gaggin, HK, Kop, WJ, Liu, K, Vasan, RS, Psaty, BM, Lee, DS, Hillege, HL, Bartz, TM, Benjamin, EJ, Chan, C, Allison, M, Gardin, JM, Januzzi, JL, Shah, SJ, Levy, D, Herrington, DM, Larson, MG, Van Gilst, WH, Gottdiener, JS, Bertoni, AG & Ho, JE 2018, 'Association of cardiovascular biomarkers with incident heart failure with preserved and reduced ejection fraction', JAMA Cardiology, vol. 3, no. 3, pp. 215-224. https://doi.org/10.1001/jamacardio.2017.4987
De Boer, Rudolf A. ; Nayor, Matthew ; DeFilippi, Christopher R. ; Enserro, Danielle ; Bhambhani, Vijeta ; Kizer, Jorge R. ; Blaha, Michael ; Brouwers, Frank P. ; Cushman, Mary ; Lima, Joao ; Bahrami, Hossein ; Van Der Harst, Pim ; Wang, Thomas J. ; Gansevoort, Ron T. ; Fox, Caroline S. ; Gaggin, Hanna K. ; Kop, Willem J. ; Liu, Kiang ; Vasan, Ramachandran S. ; Psaty, Bruce M. ; Lee, Douglas S. ; Hillege, Hans L. ; Bartz, Traci M. ; Benjamin, Emelia J. ; Chan, Cheeling ; Allison, Matthew ; Gardin, Julius M. ; Januzzi, James L. ; Shah, Sanjiv J. ; Levy, Daniel ; Herrington, David M. ; Larson, Martin G. ; Van Gilst, Wiek H. ; Gottdiener, John S. ; Bertoni, Alain G. ; Ho, Jennifer E. / Association of cardiovascular biomarkers with incident heart failure with preserved and reduced ejection fraction. In: JAMA Cardiology. 2018 ; Vol. 3, No. 3. pp. 215-224.
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abstract = "IMPORTANCE Nearly half of all patients with heart failure have preserved ejection fraction (HFpEF) as opposed to reduced ejection fraction (HFrEF), yet associations of biomarkers with future heart failure subtype are incompletely understood. OBJECTIVE To evaluate the associations of 12 cardiovascular biomarkers with incident HFpEF vs HFrEF among adults from the general population. DESIGN, SETTING, AND PARTICIPANTS This study included 4 longitudinal community-based cohorts: The Cardiovascular Health Study (1989-1990; 1992-1993 for supplemental African-American cohort), the Framingham Heart Study (1995-1998), the Multi-Ethnic Study of Atherosclerosis (2000-2002), and the Prevention of Renal and Vascular End-stage Disease study (1997-1998). Each cohort had prospective ascertainment of incident HFpEF and HFrEF. Data analysis was performed from June 25, 2015, to November 9, 2017. EXPOSURES The following biomarkers were examined: N-terminal pro B-type natriuretic peptide or brain natriuretic peptide, high-sensitivity troponin T or I, C-reactive protein (CRP), urinary albumin to creatinine ratio (UACR), renin to aldosterone ratio, D-dimer, fibrinogen, soluble suppressor of tumorigenicity, galectin-3, cystatin C, plasminogen activator inhibitor 1, and interleukin 6. MAIN OUTCOMES AND MEASURES Development of incident HFpEF and incident HFrEF. RESULTS Among the 22 756 participants in these 4 cohorts (12 087 women and 10 669 men; mean [SD] age, 60 [13] years) in the study, during a median follow-up of 12 years, 633 participants developed incident HFpEF, and 841 developed HFrEF. In models adjusted for clinical risk factors of heart failure, 2 biomarkers were significantly associated with incident HFpEF: UACR (hazard ratio [HR], 1.33; 95{\%}CI, 1.20-1.48; P < .001) and natriuretic peptides (HR, 1.27; 95{\%}CI, 1.16-1.40; P < .001), with suggestive associations for high-sensitivity troponin (HR, 1.11; 95{\%}CI, 1.03-1.19; P = .008), plasminogen activator inhibitor 1 (HR, 1.22; 95{\%}CI, 1.03-1.45; P = .02), and fibrinogen (HR, 1.12; 95{\%}CI, 1.03-1.22; P = .01). By contrast, 6 biomarkers were associated with incident HFrEF: natriuretic peptides (HR, 1.54; 95{\%}CI, 1.41-1.68; P < .001), UACR (HR, 1.21; 95{\%}CI, 1.11-1.32; P < .001), high-sensitivity troponin (HR, 1.37; 95{\%}CI, 1.29-1.46; P < .001), cystatin C (HR, 1.19; 95{\%}CI, 1.11-1.27; P < .001), D-dimer (HR, 1.22; 95{\%}CI, 1.11-1.35; P < .001), and CRP (HR, 1.19; 95{\%}CI, 1.11-1.28; P < .001). When directly compared, natriuretic peptides, high-sensitivity troponin, and CRP were more strongly associated with HFrEF compared with HFpEF. CONCLUSIONS AND RELEVANCE Biomarkers of renal dysfunction, endothelial dysfunction, and inflammation were associated with incident HFrEF. By contrast, only natriuretic peptides and UACR were associated with HFpEF. These findings highlight the need for future studies focused on identifying novel biomarkers of the risk of HFpEF.",
author = "{De Boer}, {Rudolf A.} and Matthew Nayor and DeFilippi, {Christopher R.} and Danielle Enserro and Vijeta Bhambhani and Kizer, {Jorge R.} and Michael Blaha and Brouwers, {Frank P.} and Mary Cushman and Joao Lima and Hossein Bahrami and {Van Der Harst}, Pim and Wang, {Thomas J.} and Gansevoort, {Ron T.} and Fox, {Caroline S.} and Gaggin, {Hanna K.} and Kop, {Willem J.} and Kiang Liu and Vasan, {Ramachandran S.} and Psaty, {Bruce M.} and Lee, {Douglas S.} and Hillege, {Hans L.} and Bartz, {Traci M.} and Benjamin, {Emelia J.} and Cheeling Chan and Matthew Allison and Gardin, {Julius M.} and Januzzi, {James L.} and Shah, {Sanjiv J.} and Daniel Levy and Herrington, {David M.} and Larson, {Martin G.} and {Van Gilst}, {Wiek H.} and Gottdiener, {John S.} and Bertoni, {Alain G.} and Ho, {Jennifer E.}",
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TY - JOUR

T1 - Association of cardiovascular biomarkers with incident heart failure with preserved and reduced ejection fraction

AU - De Boer, Rudolf A.

AU - Nayor, Matthew

AU - DeFilippi, Christopher R.

AU - Enserro, Danielle

AU - Bhambhani, Vijeta

AU - Kizer, Jorge R.

AU - Blaha, Michael

AU - Brouwers, Frank P.

AU - Cushman, Mary

AU - Lima, Joao

AU - Bahrami, Hossein

AU - Van Der Harst, Pim

AU - Wang, Thomas J.

AU - Gansevoort, Ron T.

AU - Fox, Caroline S.

AU - Gaggin, Hanna K.

AU - Kop, Willem J.

AU - Liu, Kiang

AU - Vasan, Ramachandran S.

AU - Psaty, Bruce M.

AU - Lee, Douglas S.

AU - Hillege, Hans L.

AU - Bartz, Traci M.

AU - Benjamin, Emelia J.

AU - Chan, Cheeling

AU - Allison, Matthew

AU - Gardin, Julius M.

AU - Januzzi, James L.

AU - Shah, Sanjiv J.

AU - Levy, Daniel

AU - Herrington, David M.

AU - Larson, Martin G.

AU - Van Gilst, Wiek H.

AU - Gottdiener, John S.

AU - Bertoni, Alain G.

AU - Ho, Jennifer E.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - IMPORTANCE Nearly half of all patients with heart failure have preserved ejection fraction (HFpEF) as opposed to reduced ejection fraction (HFrEF), yet associations of biomarkers with future heart failure subtype are incompletely understood. OBJECTIVE To evaluate the associations of 12 cardiovascular biomarkers with incident HFpEF vs HFrEF among adults from the general population. DESIGN, SETTING, AND PARTICIPANTS This study included 4 longitudinal community-based cohorts: The Cardiovascular Health Study (1989-1990; 1992-1993 for supplemental African-American cohort), the Framingham Heart Study (1995-1998), the Multi-Ethnic Study of Atherosclerosis (2000-2002), and the Prevention of Renal and Vascular End-stage Disease study (1997-1998). Each cohort had prospective ascertainment of incident HFpEF and HFrEF. Data analysis was performed from June 25, 2015, to November 9, 2017. EXPOSURES The following biomarkers were examined: N-terminal pro B-type natriuretic peptide or brain natriuretic peptide, high-sensitivity troponin T or I, C-reactive protein (CRP), urinary albumin to creatinine ratio (UACR), renin to aldosterone ratio, D-dimer, fibrinogen, soluble suppressor of tumorigenicity, galectin-3, cystatin C, plasminogen activator inhibitor 1, and interleukin 6. MAIN OUTCOMES AND MEASURES Development of incident HFpEF and incident HFrEF. RESULTS Among the 22 756 participants in these 4 cohorts (12 087 women and 10 669 men; mean [SD] age, 60 [13] years) in the study, during a median follow-up of 12 years, 633 participants developed incident HFpEF, and 841 developed HFrEF. In models adjusted for clinical risk factors of heart failure, 2 biomarkers were significantly associated with incident HFpEF: UACR (hazard ratio [HR], 1.33; 95%CI, 1.20-1.48; P < .001) and natriuretic peptides (HR, 1.27; 95%CI, 1.16-1.40; P < .001), with suggestive associations for high-sensitivity troponin (HR, 1.11; 95%CI, 1.03-1.19; P = .008), plasminogen activator inhibitor 1 (HR, 1.22; 95%CI, 1.03-1.45; P = .02), and fibrinogen (HR, 1.12; 95%CI, 1.03-1.22; P = .01). By contrast, 6 biomarkers were associated with incident HFrEF: natriuretic peptides (HR, 1.54; 95%CI, 1.41-1.68; P < .001), UACR (HR, 1.21; 95%CI, 1.11-1.32; P < .001), high-sensitivity troponin (HR, 1.37; 95%CI, 1.29-1.46; P < .001), cystatin C (HR, 1.19; 95%CI, 1.11-1.27; P < .001), D-dimer (HR, 1.22; 95%CI, 1.11-1.35; P < .001), and CRP (HR, 1.19; 95%CI, 1.11-1.28; P < .001). When directly compared, natriuretic peptides, high-sensitivity troponin, and CRP were more strongly associated with HFrEF compared with HFpEF. CONCLUSIONS AND RELEVANCE Biomarkers of renal dysfunction, endothelial dysfunction, and inflammation were associated with incident HFrEF. By contrast, only natriuretic peptides and UACR were associated with HFpEF. These findings highlight the need for future studies focused on identifying novel biomarkers of the risk of HFpEF.

AB - IMPORTANCE Nearly half of all patients with heart failure have preserved ejection fraction (HFpEF) as opposed to reduced ejection fraction (HFrEF), yet associations of biomarkers with future heart failure subtype are incompletely understood. OBJECTIVE To evaluate the associations of 12 cardiovascular biomarkers with incident HFpEF vs HFrEF among adults from the general population. DESIGN, SETTING, AND PARTICIPANTS This study included 4 longitudinal community-based cohorts: The Cardiovascular Health Study (1989-1990; 1992-1993 for supplemental African-American cohort), the Framingham Heart Study (1995-1998), the Multi-Ethnic Study of Atherosclerosis (2000-2002), and the Prevention of Renal and Vascular End-stage Disease study (1997-1998). Each cohort had prospective ascertainment of incident HFpEF and HFrEF. Data analysis was performed from June 25, 2015, to November 9, 2017. EXPOSURES The following biomarkers were examined: N-terminal pro B-type natriuretic peptide or brain natriuretic peptide, high-sensitivity troponin T or I, C-reactive protein (CRP), urinary albumin to creatinine ratio (UACR), renin to aldosterone ratio, D-dimer, fibrinogen, soluble suppressor of tumorigenicity, galectin-3, cystatin C, plasminogen activator inhibitor 1, and interleukin 6. MAIN OUTCOMES AND MEASURES Development of incident HFpEF and incident HFrEF. RESULTS Among the 22 756 participants in these 4 cohorts (12 087 women and 10 669 men; mean [SD] age, 60 [13] years) in the study, during a median follow-up of 12 years, 633 participants developed incident HFpEF, and 841 developed HFrEF. In models adjusted for clinical risk factors of heart failure, 2 biomarkers were significantly associated with incident HFpEF: UACR (hazard ratio [HR], 1.33; 95%CI, 1.20-1.48; P < .001) and natriuretic peptides (HR, 1.27; 95%CI, 1.16-1.40; P < .001), with suggestive associations for high-sensitivity troponin (HR, 1.11; 95%CI, 1.03-1.19; P = .008), plasminogen activator inhibitor 1 (HR, 1.22; 95%CI, 1.03-1.45; P = .02), and fibrinogen (HR, 1.12; 95%CI, 1.03-1.22; P = .01). By contrast, 6 biomarkers were associated with incident HFrEF: natriuretic peptides (HR, 1.54; 95%CI, 1.41-1.68; P < .001), UACR (HR, 1.21; 95%CI, 1.11-1.32; P < .001), high-sensitivity troponin (HR, 1.37; 95%CI, 1.29-1.46; P < .001), cystatin C (HR, 1.19; 95%CI, 1.11-1.27; P < .001), D-dimer (HR, 1.22; 95%CI, 1.11-1.35; P < .001), and CRP (HR, 1.19; 95%CI, 1.11-1.28; P < .001). When directly compared, natriuretic peptides, high-sensitivity troponin, and CRP were more strongly associated with HFrEF compared with HFpEF. CONCLUSIONS AND RELEVANCE Biomarkers of renal dysfunction, endothelial dysfunction, and inflammation were associated with incident HFrEF. By contrast, only natriuretic peptides and UACR were associated with HFpEF. These findings highlight the need for future studies focused on identifying novel biomarkers of the risk of HFpEF.

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