title: Stroke in patients with aortic stenosis: the Simvastatin and Ezetimibe in Aortic Stenosis study.
abstract: OBJECTIVE
  There are limited data on risk stratification of stroke in aortic stenosis. This study examined predictors of stroke in aortic stenosis, the prognostic implications of stroke, and how aortic valve replacement (AVR) with or without concomitant coronary artery bypass grafting influenced the predicted outcomes.
  
  
  METHODS
  Patients with mild-to-moderate aortic stenosis enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Diabetes mellitus, known atherosclerotic disease, and oral anticoagulation were exclusion criteria. Ischemic stroke was the primary end point, and poststroke survival a secondary outcome. Cox models treating AVR as a time-varying covariate were adjusted for atrial fibrillation and congestive heart failure, hypertension, age≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years and female sex (CHA2DS2-VASc) scores.
  
  
  RESULTS
  One thousand five hundred nine patients were followed for 4.3±0.8 years (6529 patient-years). Rates of stroke were 5.6 versus 21.8 per 1000 patient-years pre- and post-AVR; 429 (28%) underwent AVR and 139 (9%) died. Atrial fibrillation (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.1-6.6), CHA2DS2-VASc score (HR 1.4 per unit; 95% CI, 1.1-1.8), diastolic blood pressure (HR, 1.4 per 10 mm Hg; 95% CI, 1.1-1.8), and AVR with concomitant coronary artery bypass grafting (HR, 3.2; 95% CI, 1.4-7.2, all P≤0.026) were independently associated with stroke. Incident stroke predicted death (HR, 8.1; 95% CI, 4.7-14.0; P<0.001).
  
  
  CONCLUSIONS
  In patients with aortic stenosis not prescribed oral anticoagulation, atrial fibrillation, AVR with concomitant coronary artery bypass grafting, and CHA2DS2-VASc score were the major predictors of stroke. Incident stroke was strongly associated with mortality.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00092677.
authors.affiliation: From the Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark (A.M.G., M.D., C.N.B., L.K.); Department of Cardiology, OUH Svendborg Sygehus, Denmark (K.E.); Department of Cardiology, Manchester Academic Health Sciences Center, Manchester, United Kingdom (S.R.); Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden (K.B.); Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway (A.B.R.); Department of Cardiology, Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany (C.G.-B.); Department of Cardiology, Weill Cornell Medical College, New York, NY (R.B.D., K.W.); and Department of Cardiology, Glostrup University Hospital, Copenhagen, Denmark (K.W.). greve_anders@outlook.com.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Greve
authors.affiliation: From the Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark (A.M.G., M.D., C.N.B., L.K.); Department of Cardiology, OUH Svendborg Sygehus, Denmark (K.E.); Department of Cardiology, Manchester Academic Health Sciences Center, Manchester, United Kingdom (S.R.); Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden (K.B.); Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway (A.B.R.); Department of Cardiology, Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany (C.G.-B.); Department of Cardiology, Weill Cornell Medical College, New York, NY (R.B.D., K.W.); and Department of Cardiology, Glostrup University Hospital, Copenhagen, Denmark (K.W.).
authors.forename: Morten
authors.initials: M
authors.lastname: Dalsgaard
authors.affiliation: From the Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark (A.M.G., M.D., C.N.B., L.K.); Department of Cardiology, OUH Svendborg Sygehus, Denmark (K.E.); Department of Cardiology, Manchester Academic Health Sciences Center, Manchester, United Kingdom (S.R.); Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden (K.B.); Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway (A.B.R.); Department of Cardiology, Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany (C.G.-B.); Department of Cardiology, Weill Cornell Medical College, New York, NY (R.B.D., K.W.); and Department of Cardiology, Glostrup University Hospital, Copenhagen, Denmark (K.W.).
authors.forename: Casper N
authors.initials: CN
authors.lastname: Bang
authors.affiliation: From the Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark (A.M.G., M.D., C.N.B., L.K.); Department of Cardiology, OUH Svendborg Sygehus, Denmark (K.E.); Department of Cardiology, Manchester Academic Health Sciences Center, Manchester, United Kingdom (S.R.); Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden (K.B.); Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway (A.B.R.); Department of Cardiology, Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany (C.G.-B.); Department of Cardiology, Weill Cornell Medical College, New York, NY (R.B.D., K.W.); and Department of Cardiology, Glostrup University Hospital, Copenhagen, Denmark (K.W.).
authors.forename: Kenneth
authors.initials: K
authors.lastname: Egstrup
authors.affiliation: From the Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark (A.M.G., M.D., C.N.B., L.K.); Department of Cardiology, OUH Svendborg Sygehus, Denmark (K.E.); Department of Cardiology, Manchester Academic Health Sciences Center, Manchester, United Kingdom (S.R.); Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden (K.B.); Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway (A.B.R.); Department of Cardiology, Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany (C.G.-B.); Department of Cardiology, Weill Cornell Medical College, New York, NY (R.B.D., K.W.); and Department of Cardiology, Glostrup University Hospital, Copenhagen, Denmark (K.W.).
authors.forename: Simon
authors.initials: S
authors.lastname: Ray
authors.affiliation: From the Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark (A.M.G., M.D., C.N.B., L.K.); Department of Cardiology, OUH Svendborg Sygehus, Denmark (K.E.); Department of Cardiology, Manchester Academic Health Sciences Center, Manchester, United Kingdom (S.R.); Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden (K.B.); Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway (A.B.R.); Department of Cardiology, Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany (C.G.-B.); Department of Cardiology, Weill Cornell Medical College, New York, NY (R.B.D., K.W.); and Department of Cardiology, Glostrup University Hospital, Copenhagen, Denmark (K.W.).
authors.forename: Kurt
authors.initials: K
authors.lastname: Boman
authors.affiliation: From the Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark (A.M.G., M.D., C.N.B., L.K.); Department of Cardiology, OUH Svendborg Sygehus, Denmark (K.E.); Department of Cardiology, Manchester Academic Health Sciences Center, Manchester, United Kingdom (S.R.); Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden (K.B.); Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway (A.B.R.); Department of Cardiology, Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany (C.G.-B.); Department of Cardiology, Weill Cornell Medical College, New York, NY (R.B.D., K.W.); and Department of Cardiology, Glostrup University Hospital, Copenhagen, Denmark (K.W.).
authors.forename: Anne B
authors.initials: AB
authors.lastname: Rossebø
authors.affiliation: From the Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark (A.M.G., M.D., C.N.B., L.K.); Department of Cardiology, OUH Svendborg Sygehus, Denmark (K.E.); Department of Cardiology, Manchester Academic Health Sciences Center, Manchester, United Kingdom (S.R.); Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden (K.B.); Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway (A.B.R.); Department of Cardiology, Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany (C.G.-B.); Department of Cardiology, Weill Cornell Medical College, New York, NY (R.B.D., K.W.); and Department of Cardiology, Glostrup University Hospital, Copenhagen, Denmark (K.W.).
authors.forename: Christa
authors.initials: C
authors.lastname: Gohlke-Baerwolf
authors.affiliation: From the Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark (A.M.G., M.D., C.N.B., L.K.); Department of Cardiology, OUH Svendborg Sygehus, Denmark (K.E.); Department of Cardiology, Manchester Academic Health Sciences Center, Manchester, United Kingdom (S.R.); Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden (K.B.); Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway (A.B.R.); Department of Cardiology, Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany (C.G.-B.); Department of Cardiology, Weill Cornell Medical College, New York, NY (R.B.D., K.W.); and Department of Cardiology, Glostrup University Hospital, Copenhagen, Denmark (K.W.).
authors.forename: Richard B
authors.initials: RB
authors.lastname: Devereux
authors.affiliation: From the Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark (A.M.G., M.D., C.N.B., L.K.); Department of Cardiology, OUH Svendborg Sygehus, Denmark (K.E.); Department of Cardiology, Manchester Academic Health Sciences Center, Manchester, United Kingdom (S.R.); Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden (K.B.); Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway (A.B.R.); Department of Cardiology, Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany (C.G.-B.); Department of Cardiology, Weill Cornell Medical College, New York, NY (R.B.D., K.W.); and Department of Cardiology, Glostrup University Hospital, Copenhagen, Denmark (K.W.).
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.affiliation: From the Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark (A.M.G., M.D., C.N.B., L.K.); Department of Cardiology, OUH Svendborg Sygehus, Denmark (K.E.); Department of Cardiology, Manchester Academic Health Sciences Center, Manchester, United Kingdom (S.R.); Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden (K.B.); Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway (A.B.R.); Department of Cardiology, Herz-Zentrum Bad Krozingen, Bad Krozingen, Germany (C.G.-B.); Department of Cardiology, Weill Cornell Medical College, New York, NY (R.B.D., K.W.); and Department of Cardiology, Glostrup University Hospital, Copenhagen, Denmark (K.W.).
authors.forename: Kristian
authors.initials: K
authors.lastname: Wachtell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001024:Aortic Valve Stenosis / Q000188:drug therapy / Q000453:epidemiology* / Q000401:mortality / Q000601:surgery; D001384:Azetidines / Q000627:therapeutic use; D015897:Comorbidity; D001026:Coronary Artery Bypass / Q000401:mortality / Q000706:statistics & numerical data; D000069438:Ezetimibe; D005260:Female; D019918:Heart Valve Prosthesis Implantation / Q000401:mortality / Q000706:statistics & numerical data; D006801:Humans; D002546:Ischemic Attack, Transient / Q000453:epidemiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D017063:Outcome Assessment, Health Care; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D019821:Simvastatin / Q000627:therapeutic use; D020521:Stroke / Q000453:epidemiology* / Q000401:mortality
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D019821:Simvastatin; D000069438:Ezetimibe
keywords: aortic valve stenosis; cardiac surgical procedures; risk factors; stroke