title: Prolongation of QTc and risk of stroke: The REGARDS (REasons for Geographic and Racial Differences in Stroke) study.
abstract: OBJECTIVE
  The purpose of this study was to examine the association between prolongation of QT interval corrected for heart rate (QTc) with incident stroke.
  
  
  BACKGROUND
  Unlike cardiovascular morbidity and mortality, little is known about the relationship between QTc and risk of stroke.
  
  
  METHODS
  A total of 27,411 participants age 45 years and older without previous stroke from the REGARDS (REasons for Geographic and Racial Differences in Stroke) study were included in this analysis. QTc was calculated using Framingham formula (QTc(Fram)). Stroke cases were identified and adjudicated during up to 8.2 years of follow-up (median, 5.1 years).
  
  
  RESULTS
  The risk of incident stroke in study participants with prolonged QTc(Fram) was almost 3 times the risk in those with normal QTc(Fram) (hazard ratio [HR] [95% confidence interval (CI)]: 2.88 [2.12 to 3.92], p < 0.0001). After adjustment for demographics (age, race, and sex), traditional stroke risk factors (antihypertensive medication use, systolic blood pressure, current smoking, diabetes, left ventricular hypertrophy, atrial fibrillation, and previous cardiovascular disease), warfarin use, aspirin use, QRS duration and use of QTc-prolonging drugs, the risk of stroke remained significantly high (HR [95% CI]: 1.67 [1.16 to 2.41], p = 0.0061) and was consistent across several subgroups of REGARDS study participants. Similar results were obtained when the risk of stroke was estimated per 1-SD increase in QTc(Fram), (HR [95% CI]: 1.12 [1.03 to 1.21], p = 0.0053 in multivariable-adjusted model) and when other QTc correction formulas including those of Hodge, Bazett, and Fridericia were used.
  
  
  CONCLUSIONS
  QTc prolongation is associated with a significantly increased risk of incident stroke independent of traditional stroke risk factors. Examining the risk of stroke associated with QTc-prolonging drugs may be warranted.
authors.affiliation: Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. esoliman@wfubmc.edu
authors.forename: Elsayed Z
authors.initials: EZ
authors.lastname: Soliman
authors.forename: George
authors.initials: G
authors.lastname: Howard
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.forename: Brett
authors.initials: B
authors.lastname: Kissela
authors.forename: Dawn
authors.initials: D
authors.lastname: Kleindorfer
authors.forename: Anh
authors.initials: A
authors.lastname: Le
authors.forename: Suzanne
authors.initials: S
authors.lastname: Judd
authors.forename: Leslie A
authors.initials: LA
authors.lastname: McClure
authors.forename: Virginia J
authors.initials: VJ
authors.lastname: Howard
mesh_terms: D000368:Aged; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate; D006801:Humans; D015994:Incidence; D008133:Long QT Syndrome / Q000150:complications* / Q000453:epidemiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D044469:Racial Groups; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D020521:Stroke / Q000208:ethnology / Q000209:etiology*; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology