13
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Association of Cardiovascular Biomarkers With Incident Heart Failure With Preserved and Reduced Ejection Fraction

      research-article
      , MD, PhD 1 , , MD, MPH 2 , , MD 3 , , PhD 4 , , MS, MPH 2 , 5 , , MD, MSc 6 , 7 , , MD, MPH 8 , , MD, PhD 1 , , MD 9 , , MD 10 , 11 , , MD, PhD, MPH 12 , , MD, PhD 1 , , MD 13 , , MD, PhD 14 , , MD, MPH 15 , , MD, MPH 2 , , PhD 16 , , PhD 17 , , MD 18 , 19 , 20 , 21 , , MD, PhD 22 , 23 , , MD, PhD 24 , , MD, PhD 1 , , MS 25 , , MD, ScM 18 , 19 , 20 , , MS 17 , , MD, MPH 26 , , MD, MBA 27 , , MD 2 , , MD 28 , , MD 15 , 18 , , MD 29 , , ScD 4 , , PhD 1 , , MD 3 , , MD, MPH 30 , , MD 2 , 5 ,
      JAMA Cardiology
      American Medical Association

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Abstract

          This longitudinal multicohort study evaluates the associations of 12 cardiovascular biomarkers with the development of heart failure with preserved ejection fraction vs heart failure with reduced ejection fraction.

          Key Points

          Question

          What cardiovascular biomarkers are associated with the development of heart failure with preserved vs reduced ejection fraction?

          Findings

          Among 22 756 participants enrolled in 4 longitudinal community-based cohorts, several biomarkers of renal dysfunction, endothelial dysfunction, and inflammation, in addition to natriuretic peptides and high-sensitivity troponin, were associated with incident heart failure with reduced ejection fraction. By contrast, only natriuretic peptides and urinary albumin to creatinine ratio were associated with heart failure with preserved ejection fraction.

          Meaning

          These findings highlight the need for future studies focused on identifying novel biomarkers of heart failure with preserved ejection fraction.

          Related collections

          Author and article information

          Journal
          JAMA Cardiol
          JAMA Cardiol
          JAMA Cardiol
          JAMA Cardiology
          American Medical Association
          2380-6583
          2380-6591
          10 January 2018
          March 2018
          10 January 2019
          : 3
          : 3
          : 215-224
          Affiliations
          [1 ]Department of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
          [2 ]Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston
          [3 ]Inova Heart and Vascular Institute, Falls Church, Virginia
          [4 ]Department of Preventive Medicine, Boston University School of Medicine, Boston, Massachusetts
          [5 ]Cardiovascular Research Center, Massachusetts General Hospital, Boston
          [6 ]Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
          [7 ]Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
          [8 ]Ciccarone Center for the Prevention of Heart Disease, The Johns Hopkins University, Baltimore, Maryland
          [9 ]Division of Hematology/Oncology, Department of Medicine, University of Vermont Larner College of Medicine, Burlington
          [10 ]Department of Medicine, Johns Hopkins Medical Institutions, The Johns Hopkins University, Baltimore, Maryland
          [11 ]Department of Cardiology, Heart and Vascular Institute, Johns Hopkins Medical Institutions, The Johns Hopkins University, Baltimore, Maryland
          [12 ]Division of Cardiovascular Medicine, Keck School of Medicine of University of Southern California, Los Angeles
          [13 ]Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
          [14 ]Department of Internal Medicine, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
          [15 ]Center for Population Studies, National Heart, Lung, and Blood Institute, Bethesda, Maryland
          [16 ]Center of Research on Psychology in Somatic Diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands
          [17 ]Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
          [18 ]Framingham Heart Study, Framingham, Massachusetts
          [19 ]Cardiovascular Medicine Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
          [20 ]Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts
          [21 ]Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts
          [22 ]Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle
          [23 ]Kaiser Permanente Washington Health Research Institute, Seattle
          [24 ]Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
          [25 ]Department of Biostatistics, University of Washington, Seattle
          [26 ]Department of Family Medicine and Public Health, University of California, San Diego, La Jolla
          [27 ]Division of Cardiology, Department of Medicine, Rutgers New Jersey Medical School, Newark
          [28 ]Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
          [29 ]Section on Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
          [30 ]Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina
          Author notes
          Article Information
          Accepted for Publication: November 15, 2017.
          Corresponding Author: Jennifer E. Ho, MD, Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, 185 Cambridge St, Simches Research Bldg 3192, Boston, MA 02114 ( jho1@ 123456mgh.harvard.edu ).
          Published Online: January 10, 2018. doi:10.1001/jamacardio.2017.4987
          Author Contributions: Drs de Boer, Nayor, deFilippi, Enserro, van Gilst, Gottdiener, Bertoni, and Ho contributed equally to this work. Dr Ho had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
          Study concept and design: de Boer, Nayor, Enserro, Blaha, Brouwers, Lima, Bahrami, Psaty, Januzzi, Shah, Levy, Larson, van Gilst, Ho.
          Acquisition, analysis, or interpretation of data: de Boer, Nayor, deFilippi, Enserro, Bhambhani, Kizer, Brouwers, Cushman, Lima, Bahrami, van der Harst, Wang, Gansevoort, Gaggin, Kop, Liu, Vasan, Lee, Hillege, Bartz, Benjamin, Chan, Allison, Gardin, Shah, Levy, Herrington, van Gilst, Bertoni, Ho.
          Drafting of the manuscript: de Boer, Nayor, Enserro, Januzzi, Ho.
          Critical revision of the manuscript for important intellectual content: Nayor, deFilippi, Enserro, Bhambhani, Kizer, Blaha, Brouwers, Cushman, Lima, Bahrami, van der Harst, Wang, Gansevoort, Fox, Gaggin, Kop, Liu, Vasan, Psaty, Lee, Hillege, Bartz, Benjamin, Chan, Allison, Gardin, Januzzi, Shah, Levy, Herrington, Larson, van Gilst, Bertoni, Ho.
          Statistical analysis: de Boer, Nayor, Enserro, Bhambhani, Bahrami, Ho.
          Obtained funding: de Boer, van der Harst, Gansevoort, Psaty, Levy, van Gilst, Ho.
          Administrative, technical, or material support: Brouwers, Cushman, Lima, van der Harst, Gansevoort, Lee, Hillege, Bartz, Chan, Ho.
          Study supervision: de Boer, Blaha, Brouwers, Cushman, van der Harst, Benjamin, Allison, Januzzi, Shah, Larson, van Gilst, Ho.
          Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr de Boer reported receiving grants from AstraZeneca, Bristol-Meyers Squibb, and Trevena; serving as a consultant for and receiving research and/or personal honoraria from Roche; and serving as a consultant for and receiving research and/or personal honoraria from Novartis. Dr DeFilippi reported receiving research support from Roche Diagnostics; receiving consulting fees from Roche, Siemens Healthcare Diagnostics, Alere, Metanomics, and Ortho Diagnostics; serving on the end-point committee for Radiometer and Quintiles; and receiving royalties from UpToDate. Dr Kizer reported owning stock in Pfizer, Gilead Sciences, and Amgen. Dr Blaha reported receiving grants and personal fees from Amgen and the US Food and Drug Administration, grants from Aetna, the American Heart Association, the National Institutes of Health; and personal fees from Sanofi, Regeneron, Novartis, and MedImmune. Dr Gaggin reported receiving grants from Roche and Portola and personal fees from Roche Diagnostics, Amgen, Ortho Clinical, EchoSense, and Radiometer. Dr Psaty reported serving on a data and safety monitoring board for a clinical trial funded by the manufacturer (Zoll LifeCor) and serving on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. Ms. Bartz reported receiving grants from the National Institutes of Health. Dr Benjamin reported receiving grants from the National Institutes of Health and from the American Heart Association/National Institutes of Health. Dr Januzzi reported receiving grants and personal fees from Roche, Abbott, Singulex, and Novartis and personal fees from Critical Diagnostics, Janssen, Boehringer-Ingelheim, Abbvie, Pfizer, GE, and Bayer. Dr Herrington reported receiving grants from the National Institutes of Health. Dr Bertoni reported receiving grants from the National Institutes of Health/National Heart, Lung, and Blood Institute. Dr Ho reported receiving grants from the National Institutes of Health and Massachusetts General Hospital. No other disclosures were reported.
          Funding/Support: This work was partially supported by the National Heart, Lung, and Blood Institute (Framingham Heart Study, contract N01-HC25195 and HHSN268201500001I; Cardiovascular Health Study, contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and U01HL130114 and grant U01HL080295). The Multi-Ethnic Study of Atherosclerosis and the Multi-Ethnic Study of Atherosclerosis National Institutes of Health SNP Health Association Resource project are conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with the Multi-Ethnic Study of Atherosclerosis investigators. Support for the Multi-Ethnic Study of Atherosclerosis is provided by contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. Funding support for the Multi-Ethnic Study of Atherosclerosis Renal Function data set was provided by grant DK083538-01. The Cardiovascular Health Study received additional contributions from the National Institute of Neurological Disorders and Stroke and grant R01AG023629 from the National Institute on Aging. A full list of principal Cardiovascular Health Study investigators and institutions can be found at https://chs-nhlbi.org/. A full list of participating Multi-Ethnic Study of Atherosclerosis Renal Function investigators and institutions can be found at https://www.mesa-nhlbi.org. The Prevention of Renal and Vascular End-Stage Disease study has been made possible by grants from the Dutch Kidney Foundation. Dr de Boer is supported by the Netherlands Heart Foundation (CVON-DOSIS, grant 2014-40) and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research (NWO VIDI, grant 917.13.350). Dr Nayor received support from the Clinical Skills Development Core Training grant U10HL110337 from the National Heart, Lung, and Blood Institute and by grant K23-HL138260. Dr Ho is supported by grants K23-HL116780 and R01 HL134893 and a Hassenfeld Research Scholar Award (Massachusetts General Hospital, Boston). Dr Lee is supported by a clinician-scientist award from the Canadian Institutes of Health Research. In Framingham Heart Study samples, measurement of soluble suppressor of tumorigenicity was performed by Critical Diagnostics, Inc, and measurement of high-sensitivity troponin I was performed by Singulex, Inc.
          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.
          Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
          Additional Contributions: Dr Shah is an Associate Editor of JAMA Cardiology but did not participate in any discussions or decisions regarding publication of this manuscript.
          Article
          PMC5862778 PMC5862778 5862778 hoi170074
          10.1001/jamacardio.2017.4987
          5862778
          29322198
          7fc6e884-0baa-467c-838a-1a6ffbcb6415
          Copyright 2018 American Medical Association. All Rights Reserved.
          History
          : 31 August 2017
          : 12 November 2017
          : 15 November 2017
          Categories
          Research
          Research
          Original Investigation
          Featured
          Online First

          Comments

          Comment on this article