title: QT interval and long-term mortality risk in the Framingham Heart Study.
abstract: BACKGROUND
  The association between QT interval and mortality has been demonstrated in large, prospective population-based studies, but the strength of the association varies considerably based on the method of heart rate correction. We examined the QT-mortality relationship in the Framingham Heart Study (FHS).
  
  
  METHODS
  Participants in the first (original cohort, n = 2,365) and second generation (offspring cohort, n = 4,530) cohorts were included in this study with a mean follow up of 27.5 years. QT interval measurements were obtained manually using a reproducible digital caliper technique.
  
  
  RESULTS
  Using Cox proportional hazards regression adjusting for age and sex, a 20 millisecond increase in QTc (using Bazett's correction; QT/RR(1/2) interval) was associated with a modest increase in risk of all-cause mortality (HR 1.14, 95% CI 1.10-1.18, P < 0.0001), coronary heart disease (CHD) mortality (HR 1.15, 95% CI 1.05-1.26, P = 0.003), and sudden cardiac death (SCD, HR 1.19, 95% CI 1.03-1.37, P = 0.02). However, adjustment for heart rate using RR interval in linear regression attenuated this association. The association of QT interval with all-cause mortality persisted after adjustment for cardiovascular risk factors, but associations with CHD mortality and SCD were no longer significant.
  
  
  CONCLUSIONS
  In FHS, there is evidence of a graded relation between QTc and all-cause mortality, CHD death, and SCD; however, this association is attenuated by adjustment for RR interval. These data confirm that using Bazett's heart rate correction, QTc, overestimates the association with mortality. An association with all-cause mortality persists despite a more complete adjustment for heart rate and known cardiovascular risk factors.
authors.affiliation: Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Noseworthy
authors.forename: Gina M
authors.initials: GM
authors.lastname: Peloso
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D004562:Electrocardiography / Q000379:methods / Q000706:statistics & numerical data*; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk; D012307:Risk Factors; D014481:United States / Q000453:epidemiology