• Rudolf A de Boer, Matthew Nayor, Christopher R deFilippi, Danielle Enserro, Vijeta Bhambhani, Jorge R Kizer, Michael J Blaha, Frank P Brouwers, Mary Cushman, LimaJoao A CJACDepartment of Medicine, Johns Hopkins Medical Institutions, The Johns Hopkins University, Baltimore, Maryland.Department of Cardiology, Heart and Vascular Institute, Johns Hopkins Medical Institutions, The Johns Hopkins University, Baltimor, 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, 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, and Jennifer E Ho.
• Department of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
• JAMA Cardiol. 2018 Mar 1; 3 (3): 215-224.

ImportanceNearly 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.ObjectiveTo evaluate the associations of 12 cardiovascular biomarkers with incident HFpEF vs HFrEF among adults from the general population.Design, Setting, And ParticipantsThis 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.ExposuresThe 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 MeasuresDevelopment of incident HFpEF and incident HFrEF.ResultsAmong 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 RelevanceBiomarkers 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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