title: Cardiac dysfunction and noncardiac dysfunction as precursors of heart failure with reduced and preserved ejection fraction in the community.
abstract: BACKGROUND
  Heart failure (HF) is a clinical syndrome characterized by signs and symptoms involving multiple organ systems. Longitudinal data demonstrating that asymptomatic cardiac dysfunction precedes overt HF are scarce, and the contribution of noncardiac dysfunction to HF progression is unclear. We hypothesized that subclinical cardiac and noncardiac organ dysfunction would accelerate the manifestation of HF.
  
  
  RESULTS
  We studied 1038 participants of the Framingham Heart Study original cohort (mean age, 76±5 years; 39% men) with routine assessment of left ventricular systolic and diastolic function. Major noncardiac organ systems were assessed with the use of serum creatinine (renal), serum albumin (hepatic), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV(1):FVC ratio; pulmonary), hemoglobin concentration (hematologic/oxygen-carrying capacity), and white blood cell count (systemic inflammation). On follow-up (mean, 11 years), there were 248 incident HF events (146 in women). After adjustment for established HF risk factors, antecedent left ventricular systolic dysfunction (hazard ratio, 2.33; 95% confidence interval, 1.43 to 3.78) and diastolic dysfunction (hazard ratio, 1.32; 95% confidence interval, 1.01 to 1.71) were associated with increased HF risk. After adjustment for cardiac dysfunction, higher serum creatinine, lower FEV1:FVC ratios, and lower hemoglobin concentrations were associated with increased HF risk (all P<0.05); serum albumin and white blood cell count were not. Subclinical dysfunction in each noncardiac organ system was associated with a 30% increased risk of HF (P=0.013).
  
  
  CONCLUSIONS
  Antecedent cardiac dysfunction and noncardiac organ dysfunction are associated with increased incidence of HF, supporting the notion that HF is a progressive syndrome and underscoring the importance of noncardiac factors in its occurrence.
authors.affiliation: National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA 01702-5803, USA.
authors.forename: Carolyn S P
authors.initials: CS
authors.lastname: Lam
authors.forename: Asya
authors.initials: A
authors.lastname: Lyass
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kraigher-Krainer
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Lee
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Ho
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
authors.forename: Burkert M
authors.initials: BM
authors.lastname: Pieske
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003404:Creatinine / Q000097:blood; D003971:Diastole / Q000502:physiology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D015994:Incidence; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D008099:Liver / Q000378:metabolism / Q000503:physiopathology*; D008137:Longitudinal Studies; D008168:Lung / Q000503:physiopathology*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D013318:Stroke Volume / Q000502:physiology*; D013599:Systole / Q000502:physiology; D014797:Vital Capacity / Q000502:physiology
chemical_list: D006454:Hemoglobins; D012709:Serum Albumin; D003404:Creatinine