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

R.A. De Boer, M. Nayor, C.R. Defilippi, D. Enserro, V. Bhambhani, J.R. Kizer, M.J. Blaha, F.P. Brouwers, M. Cushman, J.A.C. Lima, H. Bahrami, P. Van Der Harst, T.J. Wang, R.T. Gansevoort, C.S. Fox, H.K. Gaggin, W.J. Kop, K. Liu, R.S. Vasan, B.M. PsatyD.S. Lee, H.L. Hillege, T.M. Bartz, E.J. Benjamin, C. Chan, M. Allison, J.M. Gardin, J.L. Januzzi, S.J. Shah, D. Levy, D.M. Herrington, M.G. Larson, W.H. Van Gilst, J.S. Gottdiener, A.G. Bertoni, J.E. Ho

Research output: Contribution to journalArticleScientificpeer-review

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
Pages (from-to)215-224
JournalJAMA Cardiology
Volume3
Issue number3
DOIs
Publication statusPublished - 2018

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Natriuretic Peptides
Creatinine
Cystatin C
Brain Natriuretic Peptide
Plasminogen Activator Inhibitor 1
Troponin C
Galectin 3
Troponin T
Troponin I
Aldosterone
Interleukin-6
Kidney

Keywords

  • ATHEROSCLEROSIS
  • COMMUNITY-BASED COHORT
  • DISEASE
  • EPIDEMIOLOGY
  • EVENTS
  • FOLLOW-UP
  • FRAMINGHAM
  • GENERAL-POPULATION
  • MICROALBUMINURIA
  • RISK

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
De Boer, R.A. ; Nayor, M. ; Defilippi, C.R. ; Enserro, D. ; Bhambhani, V. ; Kizer, J.R. ; Blaha, M.J. ; Brouwers, F.P. ; Cushman, M. ; Lima, J.A.C. ; Bahrami, H. ; Van Der Harst, P. ; Wang, T.J. ; Gansevoort, R.T. ; Fox, C.S. ; Gaggin, H.K. ; Kop, W.J. ; Liu, K. ; Vasan, R.S. ; Psaty, B.M. ; Lee, D.S. ; Hillege, H.L. ; Bartz, T.M. ; Benjamin, E.J. ; Chan, C. ; Allison, M. ; Gardin, J.M. ; Januzzi, J.L. ; Shah, S.J. ; Levy, D. ; Herrington, D.M. ; Larson, M.G. ; Van Gilst, W.H. ; Gottdiener, J.S. ; Bertoni, A.G. ; Ho, J.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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title = "Association of cardiovascular biomarkers with incident heart failure with preserved and reduced ejection fraction",
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",
keywords = "ATHEROSCLEROSIS, COMMUNITY-BASED COHORT, DISEASE, EPIDEMIOLOGY, EVENTS, FOLLOW-UP, FRAMINGHAM, GENERAL-POPULATION, MICROALBUMINURIA, RISK",
author = "{De Boer}, R.A. and M. Nayor and C.R. Defilippi and D. Enserro and V. Bhambhani and J.R. Kizer and M.J. Blaha and F.P. Brouwers and M. Cushman and J.A.C. Lima and H. Bahrami and {Van Der Harst}, P. and T.J. Wang and R.T. Gansevoort and C.S. Fox and H.K. Gaggin and W.J. Kop and K. Liu and R.S. Vasan and B.M. Psaty and D.S. Lee and H.L. Hillege and T.M. Bartz and E.J. Benjamin and C. Chan and M. Allison and J.M. Gardin and J.L. Januzzi and S.J. Shah and D. Levy and D.M. Herrington and M.G. Larson and {Van Gilst}, W.H. and J.S. Gottdiener and A.G. Bertoni and J.E. Ho",
year = "2018",
doi = "10.1001/jamacardio.2017.4987",
language = "English",
volume = "3",
pages = "215--224",
journal = "JAMA Cardiology",
issn = "2380-6583",
publisher = "American Medical Association",
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}

De Boer, RA, Nayor, M, Defilippi, CR, Enserro, D, Bhambhani, V, Kizer, JR, Blaha, MJ, Brouwers, FP, Cushman, M, Lima, JAC, 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

Association of cardiovascular biomarkers with incident heart failure with preserved and reduced ejection fraction. / De Boer, R.A.; Nayor, M.; Defilippi, C.R.; Enserro, D.; Bhambhani, V.; Kizer, J.R.; Blaha, M.J.; Brouwers, F.P.; Cushman, M.; Lima, J.A.C.; Bahrami, H.; Van Der Harst, P.; Wang, T.J.; Gansevoort, R.T.; Fox, C.S.; Gaggin, H.K.; Kop, W.J.; Liu, K.; Vasan, R.S.; Psaty, B.M.; Lee, D.S.; Hillege, H.L.; Bartz, T.M.; Benjamin, E.J.; Chan, C.; Allison, M.; Gardin, J.M.; Januzzi, J.L.; Shah, S.J.; Levy, D.; Herrington, D.M.; Larson, M.G.; Van Gilst, W.H.; Gottdiener, J.S.; Bertoni, A.G.; Ho, J.E.

In: JAMA Cardiology, Vol. 3, No. 3, 2018, p. 215-224.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

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

AU - De Boer, R.A.

AU - Nayor, M.

AU - Defilippi, C.R.

AU - Enserro, D.

AU - Bhambhani, V.

AU - Kizer, J.R.

AU - Blaha, M.J.

AU - Brouwers, F.P.

AU - Cushman, M.

AU - Lima, J.A.C.

AU - Bahrami, H.

AU - Van Der Harst, P.

AU - Wang, T.J.

AU - Gansevoort, R.T.

AU - Fox, C.S.

AU - Gaggin, H.K.

AU - Kop, W.J.

AU - Liu, K.

AU - Vasan, R.S.

AU - Psaty, B.M.

AU - Lee, D.S.

AU - Hillege, H.L.

AU - Bartz, T.M.

AU - Benjamin, E.J.

AU - Chan, C.

AU - Allison, M.

AU - Gardin, J.M.

AU - Januzzi, J.L.

AU - Shah, S.J.

AU - Levy, D.

AU - Herrington, D.M.

AU - Larson, M.G.

AU - Van Gilst, W.H.

AU - Gottdiener, J.S.

AU - Bertoni, A.G.

AU - Ho, J.E.

PY - 2018

Y1 - 2018

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

KW - ATHEROSCLEROSIS

KW - COMMUNITY-BASED COHORT

KW - DISEASE

KW - EPIDEMIOLOGY

KW - EVENTS

KW - FOLLOW-UP

KW - FRAMINGHAM

KW - GENERAL-POPULATION

KW - MICROALBUMINURIA

KW - RISK

U2 - 10.1001/jamacardio.2017.4987

DO - 10.1001/jamacardio.2017.4987

M3 - Article

VL - 3

SP - 215

EP - 224

JO - JAMA Cardiology

JF - JAMA Cardiology

SN - 2380-6583

IS - 3

ER -