title: Prevalence, Neurohormonal Correlates, and Prognosis of Heart Failure Stages in the Community.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Framingham Heart Study, Framingham, Massachusetts; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts; Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, Massachusetts. Electronic address: vanessax@bu.edu.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Xanthakis
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Enserro
authors.affiliation: Framingham Heart Study, Framingham, Massachusetts; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts; Department of Mathematics and Statistics, Boston University, Boston, Massachusetts.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.affiliation: Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
authors.affiliation: Framingham Heart Study, Framingham, Massachusetts.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.affiliation: Veterans Administration Hospital, West Roxbury, Massachusetts.
authors.forename: Jayashri
authors.initials: J
authors.lastname: Aragam
authors.affiliation: Framingham Heart Study, Framingham, Massachusetts; Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Cardiology Division, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.affiliation: Cardiovascular Engineering, Inc., Norwood, Massachusetts.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Mitchell
authors.affiliation: Framingham Heart Study, Framingham, Massachusetts; Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, Massachusetts; Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
mesh_terms: D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D003324:Coronary Artery Disease / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000453:epidemiology; D005260:Female; D006333:Heart Failure / Q000145:classification / Q000453:epidemiology* / Q000378:metabolism / Q000401:mortality; D006349:Heart Valve Diseases / Q000453:epidemiology*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D017379:Hypertrophy, Left Ventricular / Q000453:epidemiology*; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D009765:Obesity / Q000453:epidemiology; D016017:Odds Ratio; D015995:Prevalence; D011379:Prognosis; D012083:Renin / Q000378:metabolism; D012307:Risk Factors; D012720:Severity of Illness Index; D019210:Troponin I / Q000378:metabolism; D014481:United States / Q000453:epidemiology; D018487:Ventricular Dysfunction, Left / Q000453:epidemiology*
chemical_list: C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D019210:Troponin I; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D002097:C-Reactive Protein; D012083:Renin
keywords: biomarkers; echocardiography; epidemiology; heart failure stages