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JAMA Cardiol. 2018 Mar 1;3(3):215-224. doi: 10.1001/jamacardio.2017.4987.

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

Author information

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.

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.

PMID:
29322198
PMCID:
PMC5862778
DOI:
10.1001/jamacardio.2017.4987
[Indexed for MEDLINE]
Free PMC Article

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