Author + information
- Received December 7, 2015
- Revision received March 22, 2016
- Accepted May 2, 2016
- Published online October 1, 2016.
- Vanessa Xanthakis, PhDa,b,c,∗ (, )
- Danielle M. Enserro, MAb,
- Martin G. Larson, ScDa,b,d,
- Kai C. Wollert, MDe,
- James L. Januzzi, MDf,
- Daniel Levy, MDa,
- Jayashri Aragam, MDg,
- Emelia J. Benjamin, MDa,c,
- Susan Cheng, MDh,
- Thomas J. Wang, MDi,
- Gary F. Mitchell, MDj and
- Ramachandran S. Vasan, MDa,c,k
- aFramingham Heart Study, Framingham, Massachusetts
- bDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachusetts
- cSection of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, Massachusetts
- dDepartment of Mathematics and Statistics, Boston University, Boston, Massachusetts
- eDivision of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany
- fCardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- gVeterans Administration Hospital, West Roxbury, Massachusetts
- hDivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- iCardiology Division, Vanderbilt University Medical Center, Nashville, Tennessee
- jCardiovascular Engineering, Inc., Norwood, Massachusetts
- kDepartment of Epidemiology, Boston University School of Public Health, Boston, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. Vanessa Xanthakis, Department of Medicine, Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, 801 Massachusetts Avenue, Suite 470, Boston, Massachusetts 02118.
Objectives The purpose of this study was to describe the prevalence and prognosis of HF stages in the community; to evaluate if preclinical HF stages are characterized by elevation of pro-inflammatory (C-reactive protein), neurohormonal activation (B-type natriuretic peptide, renin and aldosterone), and cardiac stress biomarkers (high-sensitivity troponin I, ST-2, and growth differentiation factor-15).
Background The American Heart Association/American College of Cardiology heart failure (HF) classification has 3 stages. Knowledge regarding the community burden of HF stages is limited, and data on the biomarker profile associated with HF stages are scarce, although higher concentrations of certain biomarkers are associated with preclinical HF.
Methods We evaluated 6,770 participants (mean age 51 years; 54% women) from the Framingham Study, defining 4 stages: 1) healthy: no risk factors; 2) stage A: presence of HF risk factors (hypertension, diabetes, obesity, coronary artery disease), no cardiac structural/functional abnormality; 3) stage B: presence of prior myocardial infarction, valvular disease, left ventricular (LV) systolic dysfunction, LV hypertrophy, regional wall motion abnormality, or LV enlargement; 4) stage C/D: prevalent HF.
Results The prevalence of HF stages A and B were 36.5% and 24.2%, respectively, rising with age (odds ratio: 1.70 [95% confidence interval: 1.64 to 1.77] per decade increment). In age- and sex-adjusted models, we observed a gradient of increasing biomarker levels across HF stages (p < 0.05; n = 3,416). Adjusting for age and sex, mortality rose across HF stages (232 deaths, mean follow-up 7 years), with 2- and 8-fold mortality risks for stages B and C/D, respectively, compared with healthy.
Conclusions Approximately 60% of our sample has preclinical HF, and those in stage B had higher concentrations of HF biomarkers and experienced a substantial mortality risk.
This work was supported by American Heart Association Clinical Research Program 13CRP14090010 (Dr. Xanthakis), by N01-HC-25915 (National Heart, Lung, and Blood Institute, by R00-HL-107642) and from Ellison Foundation (Dr. Cheng). Dr. Januzzi is supported by DeSanctis Clinical Scholar Endowment. Dr. Wollert is supported by the German Ministry of Education and Research. Dr. Januzzi is supported by the Roman W. DeSanctis Clinical Scholar Endowment. Assays for biomarkers were provided by Critical Diagnostics, Singulex, Inc., and Roche Diagnostics, Inc., but these companies did not have access to study data or analysis and interpretation. Dr. Wollert is named as co-inventor on a patent for the use of GDF-15 for cardiovascular applications and has a contract with Roche Diagnostics for the development of a GDF-15 assay. Dr. Januzzi has reported significant grant funding from Roche Diagnostics, Siemens, Thermo-Fisher, and Singulex; and significant consulting income from Roche Diagnostics, Critical Diagnostics, Sphingotec, Amgen, and Novartis.
John R. Teerlink, MD, served as Guest Editor for this paper.
- Received December 7, 2015.
- Revision received March 22, 2016.
- Accepted May 2, 2016.
- 2016 American College of Cardiology Foundation