Author + information
- Received June 25, 2020
- Revision received July 17, 2020
- Accepted July 20, 2020
- Published online September 14, 2020.
- Navin Suthahar, MD, MSca,∗,
- Emily S. Lau, MDb,∗,
- Michael J. Blaha, MD, MPHc,
- Samantha M. Paniagua, MPHb,
- Martin G. Larson, ScDd,e,
- Bruce M. Psaty, MD, PhDf,
- Emelia J. Benjamin, MD, ScMe,
- Matthew A. Allison, MD, MPHg,
- Traci M. Bartz, MSh,
- James L. Januzzi Jr., MDb,
- Daniel Levy, MDe,i,
- Laura M.G. Meems, MD, PhDa,
- Stephan J.L. Bakker, MD, PhDj,
- Joao A.C. Lima, MDk,
- Mary Cushman, MD, MScl,
- Douglas S. Lee, MD, PhDl,m,n,
- Thomas J. Wang, MDo,
- Christopher R. deFilippi, MDp,
- David M. Herrington, MDq,
- Matthew Nayor, MD, MPHb,
- Ramachandran S. Vasan, MDe,
- Julius M. Gardin, MD, MBAr,
- Jorge R. Kizer, MD, MScs,
- Alain G. Bertoni, MD, MPHt,
- Norrina B. Allen, PhDu,
- Ron T. Gansevoort, MD, PhDj,
- Sanjiv J. Shah, MDv,
- John S. Gottdiener, MDp,
- Jennifer E. Ho, MDb,†∗∗ (, )@JenHoCardiology and
- Rudolf A. de Boer, MD, PhDa,†∗ (, )@rudolf_deboer
- aDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- bCardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- cCiccarone Center for the Prevention of Heart Disease, The Johns Hopkins University, Baltimore, Maryland
- dDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
- eBoston University School of Medicine and School of Public Health, and NHLBI and Boston University’s Framingham Heart Study, Framingham, Massachusetts
- fDepartments of Medicine, Epidemiology and Health Services, University of Washington, and Kaiser Permanente Washington Health Research Institute, Seattle, Washington
- gDepartment of Family Medicine and Public Health, University of California, San Diego, La Jolla, California
- hDepartment of Biostatistics, University of Washington, Seattle, Washington
- iCenter for Population Studies, National Heart, Lung, and Blood Institute, Bethesda, Maryland
- jDepartment of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- kDepartment of Medicine, Johns Hopkins Medical Institutions, and Department of Cardiology, Heart and Vascular Institute, The Johns Hopkins University, Baltimore, Maryland
- lDepartment of Medicine and Pathology & Laboratory Medicine, University of Vermont Larner College of Medicine, Burlington, Vermont
- mInstitute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
- nUniversity of Toronto, Toronto, Ontario, Canada
- oDepartment of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas
- pInova Heart and Vascular Institute, Falls Church, Virginia
- qSection on Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
- rDivision of Cardiology, Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey
- sDepartments of Medicine, Epidemiology and Biostatistics, San Francisco Veterans Affairs Health Care System and University of California-San Francisco, San Francisco, California
- tDivision of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina
- uDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- vDivision of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- ↵∗Address for correspondence:
Dr. Rudolf A. de Boer, Department of Cardiology, University Medical Centre Groningen, P.O. Box 30.001, 9700 RB, Groningen, the Netherlands.
- ↵∗∗Dr. Jennifer E. Ho, Cardiovascular Research Center and Cardiology Division, Department of Medicine, Massachusetts General Hospital, 185 Cambridge Street, CPZN #3192, Boston, Massachusetts 02114.
Background Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear.
Objectives The purpose of this study was to evaluate sex-specific associations of CV risk factors and biomarkers with incident HF.
Methods The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio.
Results Among 22,756 participants (mean age 60 ± 13 years, 53% women), HF occurred in 2,095 participants (47% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p < 0.001), and the combined clinical model had good discrimination in men (C-statistic = 0.80) and in women (C-statistic = 0.83). The majority of biomarkers were strongly and similarly associated with HF in both sexes. The clinical model improved modestly after adding natriuretic peptides in men (ΔC-statistic = 0.006; likelihood ratio chi-square = 146; p < 0.001), and after adding cardiac troponins in women (ΔC-statistic = 0.003; likelihood ratio chi-square = 73; p < 0.001).
Conclusions CV risk factors are strongly and similarly associated with incident HF in both sexes, highlighting the similar importance of risk factor control in reducing HF risk in the community. There are subtle sex-related differences in the predictive value of individual biomarkers, but the overall improvement in HF risk estimation when included in a clinical HF risk prediction model is limited in both sexes.
↵∗ Drs. Suthahar and Lau contributed equally to this work and are joint first authors.
↵† Drs. Ho and de Boer contributed equally to this work and are joint senior authors.
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, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086, and grants U01HL080295 and U01HL130114). 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 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). Dr. Shah has been supported by grants from the National Institutes of Health (R01 HL107577, R01 HL127028, R01 HL140731, and R01 HL149423) and the American Heart Association (#16SFRN28780016). The Cardiovascular Health Study has received additional contributions from the National Institute of Neurological Disorders and Stroke and grant R01AG023629 from the National Institute on Aging. The Framingham Heart Study was supported by HHSN268201500001I; N01-HC 25195. Dr. Benjamin has been supported by grants from the National Institutes of Health R01 HL128914 and 2R01 HL092577, and grant 18SFRN34110082 from the American Heart Association. Dr. Nayor has been supported by grant K23-HL138260. Dr. Ho has been supported by grants R01 HL134893 and R01 HL140224. In Framingham Heart Study samples, measurement of sST2 was performed by Critical Diagnostics, Inc.; and measurement of high-sensitivity troponin I was performed by Singulex, Inc. The Prevention of Renal and Vascular End-Stage Disease study has been made possible by grants, including grant E.013 from the Dutch Kidney Foundation. Drs. de Boer and Suthahar are supported by the Netherlands Heart Foundation (CVON SHE-PREDICTS-HF, grant 2017-21). Dr. de Boer has been further supported by the Netherlands Heart Foundation (CVON-DOSIS, grant 2014-040; CVON RED-CVD, grant 2017-11; and CVON PREDICT2, grant 2018-30), and the European Research Council (ERC CoG 818715, SECRETE-HF). 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. The views expressed in this paper are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. The UMCG, which employs Drs. Suthahar, Meems, Bakker, Gansevoort, and de Boer, has received research grants and/or fees from AstraZeneca, Abbott, Bristol-Myers Squibb, Novartis, Novo Nordisk, and Roche. Dr. Blaha has received grants and personal fees from Amgen and the U.S. Food and Drug Administration; has received grants from Aetna, the American Heart Association, and the National Institutes of Health; and has received personal fees from Sanofi, Regeneron, Novartis, and MedImmune. Dr. Psaty has served on a data and safety monitoring board for a clinical trial funded by the manufacturer (ZollLifeCor); and has served on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. Dr. Benjamin has received grants from the National Institutes of Health and the American Heart Association/National Institutes of Health. Dr. Januzzi has received grants and personal fees from Roche, Abbott, Singulex, and Novartis; and has received personal fees from Critical Diagnostics, Janssen, Boehringer Ingelheim, Abbvie, Pfizer, General Electric, and Bayer. Dr. Cushman has received research funding in the form of assay costs from Sphingotec. Dr. Lee is supported by a Ted Rogers Chair in Heart Function Outcomes. Dr. DeFilippi has received research support from Roche Diagnostics; has received consulting fees from Roche, Siemens Healthcare Diagnostics, Alere, Metanomics, and Ortho Diagnostics; has served on the endpoint committee for Radiometer and Quintiles; and has received royalties from UpToDate. Dr. Herrington has received grants from the National Institutes of Health. Dr. Kizer has owned stock in Bristol-Myers Squibb, Johnson and Johnson, Medtronic, Merck, and Pfizer. Dr. Bertoni has received grants from the National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Shah has received research grants from Actelion, AstraZeneca, Corvia, Novartis, and Pfizer; and has received consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Axon Therapeutics, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardiora, CVRx, Cytokinetics, Eisai, GlaxoSmithKline, Ionis, Ironwood, Merck, MyoKardia, Novartis, Pfizer, Sanofi, Shifamed, Tenax, and United Therapeutics. Dr. Ho has received grants from the National Institutes of Health and Gilead Sciences; and has received research support from Bayer and EcoNugenics. Dr. de Boer has received speaker fees from Abbott, AstraZeneca, Novartis, and Roche. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Javed Butler, MD, MPH, MBA, served as Guest Associate Editor for this paper. P.K. Shah, MD, served as Guest Editor-in-Chief for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received June 25, 2020.
- Revision received July 17, 2020.
- Accepted July 20, 2020.
- 2020 The Authors