From the Greenberg Division of Cardiology, Weill Cornell Medical College, New York, NY (P.M.O., C.N.B., R.B.D.); the Department of Cardiology, Gentofte Hospital, Copenhagen, Denmark (K.W.); Merck Research Labs, West Point, PA (D.A.H.); University of Oslo, Ullevål Hospital, Oslo, Norway (S.E.K.); University of Michigan Medical Center, Ann Arbor, MI (S.E.K.); Sahlgrenska University Hospital/Östra, Göteborg, Sweden (B.D.).
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Background—Prevalent atrial fibrillation (AF) is associated with a higher sudden cardiac death (SCD) rate in some populations, and incident AF predicts increased mortality risk in the general population and after myocardial infarction. However, the relationship of SCD to new-onset AF is unclear.Methods and Results—The relationship of SCD to new-onset AF was evaluated in 8831 hypertensive patients with electrocardiographic left ventricular hypertrophy with no history of AF, in sinus rhythm on their baseline electrocardiogram, randomly assigned to losartan- or atenolol-based treatment. During 4.7±1.1 years mean follow-up, new-onset AF occurred in 701 patients (7.9%) and SCD in 151 patients (1.7%). In univariate Cox analyses, new-onset AF was associated with a >4-fold higher risk of SCD (hazard ratio, 4.69; 95% CI interval, 2.96–7.45; P<0.001). In multivariate Cox analyses adjusting for age, sex, race, diabetes mellitus, history of heart failure, myocardial infarction, ischemic heart disease, stroke, smoking, serum high-density lipoprotein cholesterol, creatinine, glucose, and urine albumin/creatinine ratio as standard risk factors, and for incident myocardial infarction, in-treatment use of digoxin, systolic and diastolic pressure, heart rate, QRS duration, Cornell voltage-duration product, and Sokolow-Lyon voltage left ventricular hypertrophy treated as time-varying covariates, new-onset AF remained associated with a >3-fold increased risk of SCD (hazard ratio, 3.13; 95% confidence interval, 1.87–5.24; P<0.001).Conclusions—Development of new-onset AF identifies hypertensive patients at increased risk of SCD.Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00338260.