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J Am Coll Cardiol, 2006; 47:362-367, doi:10.1016/j.jacc.2005.08.067 (Published online 22 December 2005).
© 2006 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: CARDIAC RHYTHM DISORDER

Prolonged QTc Interval and Risk of Sudden Cardiac Death in a Population of Older Adults

Sabine M.J.M. Straus, MD, PhD*,{dagger},{ddagger}, Jan A. Kors, PhD{dagger}, Marie L. De Bruin, PhD§, Cornelis S. van der Hooft, MD{dagger},||, Albert Hofman, MD, PhD*, Jan Heeringa, MD*, Jaap W. Deckers, MD, PhD*, J. Herre Kingma, MD, PhD||, Miriam C.J.M. Sturkenboom, PhD*,{dagger}, Bruno H. Ch. Stricker, PhD*,||,* and Jacqueline C.M. Witteman, PhD*

* Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, the Netherlands
{dagger} Department of Medical Informatics, Erasmus Medical Center, Rotterdam, the Netherlands
{ddagger} Medicines Evaluation Board, the Hague, the Netherlands
§ Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht, the Netherlands
|| Inspectorate for Healthcare, the Hague, the Netherlands
Department of Clinical Pharmacology, University of Groningen, Groningen, the Netherlands.

Manuscript received May 22, 2005; revised manuscript received July 11, 2005, accepted August 1, 2005.

* Reprint requests and correspondence: Dr. Bruno H. Ch. Stricker, Department of Epidemiology and Biostatistics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, the Netherlands. (Email: b.stricker{at}erasmusmc.nl).

OBJECTIVES: This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the general population.

BACKGROUND: In developed countries, sudden cardiac death is a major cause of cardiovascular mortality. Prolongation of the QTc interval has been associated with ventricular arrhythmias, but in most population-based studies no consistent association was found between QTc prolongation and total or cardiovascular mortality. Only very few of these studies specifically addressed sudden cardiac death.

METHODS: This study was conducted as part of the Rotterdam Study, a prospective population-based cohort study that comprises 3,105 men and 4,878 women aged 55 years and older. The QTc interval on the electrocardiogram was determined during the baseline visit (1990 to 1993) and the first follow-up examination (1993 to 1995). The association between a prolonged QTc interval and sudden cardiac death was estimated using Cox proportional hazards analysis.

RESULTS: During an average follow-up period of 6.7 years (standard deviation, 2.3 years) 125 patients died of sudden cardiac death. An abnormally prolonged QTc interval (>450 ms in men, >470 ms in women) was associated with a three-fold increased risk of sudden cardiac death (hazard ratio, 2.5; 95% confidence interval, 1.3 to 4.7), after adjustment for age, gender, body mass index, hypertension, cholesterol/high-density lipoprotein ratio, diabetes mellitus, myocardial infarction, heart failure, and heart rate. In patients with an age below the median of 68 years, the corresponding relative risk was 8.0 (95% confidence interval 2.1 to 31.3).

CONCLUSIONS: Abnormal QTc prolongation on the electrocardiogram should be viewed as an independent risk factor for sudden cardiac death.

Abbreviations and Acronyms
  AAI = ankle-arm index
  CI = confidence interval
  HR = hazard ratio
  LBBB = left bundle branch block
  SD = standard deviation
  QTc interval = heart rate-corrected QT interval




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