Tk NEW ENGLAND JOURNAL MEDICINE ORIGINAL ARTICLE Obstructive Sleep Apnea as a Risk Factor for Stroke and Death H.Klar Yaggi,M.D.,M.P.H..John Concato,M.D..M.P.H Walter N.Kemnan,M.D..Judith H.Lichtman,Ph.D.M.P.H Lawrence M.Brass,M.D.,and Vahid Mohsenin,M.D. ABSTRACT c hne spome sted that the obstr ay be ar ETHODS Y the ahsobentioalothotottanetientcteienmeatDegogoe2p papnea syndrome was basedon ea index of5 or higher Haven.Conn.Addre oportional-haz rds susedtodeterminf come ofstroke or death from any cause RESULTS s.697(68p t)had theab s网a号am drome.At baseline.the nean apnea-hyr 1120t nce o s mellitus,hype 5percentconfidenceinterval,1..01).Inatrend analysis,increased sever ciated with an increased risk of the developmen CONCLUSIONS hypertension. 2034 N ENGLJ MED 353:19 WWW.NEJM.ORG NOVEMBER 10,200 Downloaded from www.nejm.org on January 23,2010.Copyright05 Massachusetts Medical Society.All rights reserved.original article The new england journal of medicine 2034 n engl j med 353;19 www.nejm.org november 10, 2005 Obstructive Sleep Apnea as a Risk Factor for Stroke and Death H. Klar Yaggi, M.D., M.P.H., John Concato, M.D., M.P.H., Walter N. Kernan, M.D., Judith H. Lichtman, Ph.D., M.P.H., Lawrence M. Brass, M.D., and Vahid Mohsenin, M.D. From the Section of Pulmonary and Criti￾cal Care Medicine, Yale Center for Sleep Medicine (H.K.Y., V.M.), the Section of General Medicine (J.C., W.N.K.), and the Departments of Epidemiology and Public Health (J.H.L., L.M.B.) and Neurology (L.M.B.), Yale University School of Medi￾cine, New Haven, Conn.; and the Section of Pulmonary and Critical Care Medicine (H.K.Y.), the Clinical Epidemiology Re￾search Center (H.K.Y., J.C.), and the Sec￾tion of Neurology (L.M.B.), Veterans Af￾fairs Connecticut Healthcare System, West Haven, Conn. Address reprint requests to Dr. Mohsenin at the Yale Center for Sleep Medicine, 300 Cedar St., TAC 441, P.O. Box 208057, New Haven, CT 06520. N Engl J Med 2005;353:2034-41. Copyright © 2005 Massachusetts Medical Society. background Previous studies have suggested that the obstructive sleep apnea syndrome may be an important risk factor for stroke. It has not been determined, however, whether the syn￾drome is independently related to the risk of stroke or death from any cause after adjust￾ment for other risk factors, including hypertension. methods In this observational cohort study, consecutive patients underwent polysomnography, and subsequent events (strokes and deaths) were verified. The diagnosis of the ob￾structive sleep apnea syndrome was based on an apnea–hypopnea index of 5 or higher (five or more events per hour); patients with an apnea–hypopnea index of less than 5 served as the comparison group. Proportional-hazards analysis was used to determine the independent effect of the obstructive sleep apnea syndrome on the composite out￾come of stroke or death from any cause. results Among 1022 enrolled patients, 697 (68 percent) had the obstructive sleep apnea syn￾drome. At baseline, the mean apnea–hypopnea index in the patients with the syndrome was 35, as compared with a mean apnea–hypopnea index of 2 in the comparison group. In an unadjusted analysis, the obstructive sleep apnea syndrome was associated with stroke or death from any cause (hazard ratio, 2.24; 95 percent confidence interval, 1.30 to 3.86; P=0.004). After adjustment for age, sex, race, smoking status, alcohol-consump￾tion status, body-mass index, and the presence or absence of diabetes mellitus, hyper￾lipidemia, atrial fibrillation, and hypertension, the obstructive sleep apnea syndrome retained a statistically significant association with stroke or death (hazard ratio, 1.97; 95 percent confidence interval, 1.12 to 3.48; P=0.01). In a trend analysis, increased sever￾ity of sleep apnea at baseline was associated with an increased risk of the development of the composite end point (P=0.005). conclusions The obstructive sleep apnea syndrome significantly increases the risk of stroke or death from any cause, and the increase is independent of other risk factors, including hypertension. abstract Downloaded from www.nejm.org on January 23, 2010 . Copyright © 2005 Massachusetts Medical Society. All rights reserved