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 J.
AU - Brouwers, Frank P.
AU - Cushman, Mary
AU - Lima, Joao A.C.
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.
N1 - Funding Information:
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.
Funding Information:
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 AtherosclerosisNationalInstitutesofHealthSNPHealth 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 InstituteonAging.AfulllistofprincipalCardiovascular HealthStudyinvestigatorsandinstitutionscanbefound 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 possiblebygrantsfromtheDutchKidneyFoundation. 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.
Funding Information:
Dr Ho reported receiving grants from the National Institutes of Health and Massachusetts General Hospital. No other disclosures were reported.
PY - 2018/3
Y1 - 2018/3
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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U2 - 10.1001/jamacardio.2017.4987
DO - 10.1001/jamacardio.2017.4987
M3 - Article
C2 - 29322198
AN - SCOPUS:85045905051
VL - 3
SP - 215
EP - 224
JO - JAMA Cardiology
JF - JAMA Cardiology
SN - 2380-6583
IS - 3
ER -