title: Shortened telomere length is associated with paroxysmal atrial fibrillation among cardiovascular patients enrolled in the Intermountain Heart Collaborative Study.
abstract: BACKGROUND
  Atrial fibrillation (AF) diminishes quality of life and accounts for approximately one-third of all strokes. Studies have associated mitochondrial dysfunction with both AF and telomere length (TL).
  
  
  OBJECTIVE
  The purpose of this study was to test the hypothesis of a relationship between AF and TL.
  
  
  METHODS
  Blood was collected from consenting participants in the Intermountain Heart Collaborative Study (n = 3576) and DNA extracted. TL was determined by multiplex quantitative polymerase chain reaction, normalized to a single copy gene, and reported as telomere/single gene ratio (t/s). Patient information was extracted from Intermountain Healthcare's electronic records database. Prevalent AF was determined by discharge ICD-9 code. AF subtype (paroxysmal [Px], persistent [Ps], long-standing persistent/permanent [Pm]) was determined by chart review.
  
  
  RESULTS
  The t/s decreased with age (P <.00001). Subjects with a history of AF (n = 379 [10.6%] had shorter telomeres (mean t/s ± SD = 0.87 ± 0.29) compared to subjects without AF (mean t/s 0.95 ± 0.32, P <.0001). The association remained after adjustment for age (P = .017) and cardiovascular risk factors (P = .016). AF subtype was determined for 277 subjects; 110 (39.7%) had Px AF, 65 (23.5%) Ps, and 102 (36.8%) Pm AF. Mean t/s did not differ between Ps, Pm, and subjects without AF (0.94 ± 0.40, 0.94 ± 0.27, and 0.95 ± 0.32, respectively). However, the mean t/s for Px (0.81 ± 0.22) was significantly shorter than for Ps (P = .026), Pm (P = .004), or subjects without AF (P <.0001).
  
  
  CONCLUSIONS
  The present study supports an association between Px AF and TL. Short TL may be a previously unrecognized risk factor for AF with potential applications in diagnosis and therapy.
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah; Department of Medicine, Division of Cardiology, University of Utah School of Medicine, Salt Lake City, Utah;. Electronic address: john.carlquist@imail.org.
authors.forename: John F
authors.initials: JF
authors.lastname: Carlquist
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah.
authors.forename: Stacey
authors.initials: S
authors.lastname: Knight
authors.affiliation: Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Cawthon
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah.
authors.forename: Viet T
authors.initials: VT
authors.lastname: Le
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah.
authors.forename: T
authors.initials: T
authors.lastname: Jared Bunch
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Horne
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Rollo
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah.
authors.forename: John A
authors.initials: JA
authors.lastname: Huntinghouse
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah; Department of Medicine, Division of Cardiology, University of Utah School of Medicine, Salt Lake City, Utah;
authors.forename: J
authors.initials: J
authors.lastname: Brent Muhlestein
authors.affiliation: Intermountain Heart Institute, Intermountain Medical Center, Murray, Utah; Department of Medicine, Division of Cardiology, University of Utah School of Medicine, Salt Lake City, Utah;
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Anderson
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics / Q000503:physiopathology; D004249:DNA Damage / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012307:Risk Factors; D013223:Statistics as Topic; D059505:Telomere Homeostasis; D059506:Telomere Shortening
keywords: Cardiovascular; Intermountain Heart Study; Paroxysmal atrial fibrillation; Telomere