title: Histamine H2 Receptor Antagonists, Left Ventricular Morphology, and Heart Failure Risk: The MESA Study.
abstract: BACKGROUND
  Myocardial H2 receptor activation may promote cardiac fibrosis and apoptosis in pre-clinical models and histamine H2 receptor antagonist (H2RA) use may improve symptoms in participants with heart failure (HF); however, relationships between H2RA use, incident HF, and longitudinal change in left ventricular (LV) morphology are not known.
  
  
  OBJECTIVE
  This study sought to determine whether H2RA use is associated with incident HF and change in LV morphology over time.
  
  
  METHODS
  We included 6,378 men and women from MESA (Multi-Ethnic Study of Atherosclerosis), a multicenter prospective observational cohort of participants without cardiovascular disease at baseline. Cox proportional hazards were used to estimate the association between H2RA use and incident HF in adjusted models. In participants with cardiac magnetic resonance imaging, associations between H2RA use, baseline LV morphology (n = 4,691), and longitudinal change in the LV (n = 2,806) were estimated using linear regression.
  
  
  RESULTS
  H2RAs were used by 313 participants but not by the other 6,065 individuals. During a median follow-up of 11.2 years, 236 participants developed HF. In adjusted models, baseline H2RA use relative to nonuse was associated with 62% lower risk for incident HF (p = 0.02). H2RA use was associated with preserved stroke volume, LV end-diastolic volume, and mass/volume ratio as measured by cardiac magnetic resonance imaging over approximately 10 years (all p < 0.05). There were no associations between H2RA use and LV mass or ejection fraction.
  
  
  CONCLUSIONS
  H2RA use was associated with reduced risk for incident HF. Left heart morphology over time suggests less age-related change in H2RA users. These associations suggest histamine signaling may be important in the pathogenesis of HF. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington. Electronic address: learyp@uw.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Leary
authors.affiliation: Department of Medicine, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Tedford
authors.affiliation: National Institutes of Health Clinical Center, Radiology and Imaging Sciences, Bethesda, Maryland.
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.affiliation: Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bristow
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, Washington.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.affiliation: Departments of Medicine and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kawut
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Eric V
authors.initials: EV
authors.lastname: Krieger
authors.affiliation: Department of Medicine, Johns Hopkins Hospital, Baltimore, Maryland; Department of Radiology, Johns Hopkins Hospital, Baltimore, Maryland.
authors.forename: Joao A
authors.initials: JA
authors.lastname: Lima
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Carolina S
authors.initials: CS
authors.lastname: Masri
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: David D
authors.initials: DD
authors.lastname: Ralph
authors.affiliation: Departments of Medicine and Epidemiology, Columbia University, New York City, New York.
authors.forename: Steven
authors.initials: S
authors.lastname: Shea
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, Washington.
authors.forename: Noel S
authors.initials: NS
authors.lastname: Weiss
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kronmal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000453:epidemiology*; D006352:Heart Ventricles / Q000000981:diagnostic imaging*; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D013318:Stroke Volume; D014481:United States / Q000453:epidemiology
chemical_list: D006635:Histamine H2 Antagonists
keywords: cardiac magnetic resonance imaging; heart failure; prevention