title: Risk of Stroke in Chronic Heart Failure Patients Without Atrial Fibrillation: Analysis of the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) Trials.
abstract: BACKGROUND
  Our aim was to describe the incidence and predictors of stroke in patients who have heart failure without atrial fibrillation (AF).
  
  
  RESULTS
  We pooled 2 contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca-Heart Failure trial (GISSI-HF). Of the 9585 total patients, 6054 did not have AF. Stroke occurred in 165 patients (4.7%) with AF and in 206 patients (3.4%) without AF (rates 16.8/1000 patient-years and 11.1/1000 patient-years, respectively). Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74). N-terminal pro B-type natriuretic peptide (available in 2632 patients) was also an independent predictor of stroke (hazard ratio, 1.31; 1.11-1.57 per log unit) when added to this model. With the use of a risk score formulated from these predictors, we found that patients in the upper third of risk had a rate of stroke that approximated the risk in patients with AF.
  
  
  CONCLUSIONS
  A small number of demographic and clinical variables identified a subset of patients who have heart failure without AF at a high risk of stroke.
authors: From Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
authors: Azmil H
authors: AH
authors: Abdul-Rahim
authors: From Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
authors: Ana-Cristina
authors: AC
authors: Perez
authors: From Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
authors: Rachael L
authors: RL
authors: Fulton
authors: From Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
authors: Pardeep S
authors: PS
authors: Jhund
authors: From Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
authors: Roberto
authors: R
authors: Latini
authors: From Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
authors: Gianni
authors: G
authors: Tognoni
authors: From Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
authors: John
authors: J
authors: Wikstrand
authors: From Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
authors: John
authors: J
authors: Kjekshus
authors: From Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
authors: Gregory Y H
authors: GY
authors: Lip
authors: From Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
authors: Aldo P
authors: AP
authors: Maggioni
authors: From Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
authors: Luigi
authors: L
authors: Tavazzi
authors: From Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.).
authors: Kennedy R
authors: KR
authors: Lees
authors: From Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom (A.H.A.-R., A.-C.P., R.L.F., P.S.J., K.R.L., J.J.V.M.); IRCCS-RL: Istituto Mario Negri, Milan, Italy (R.L.); Consorzio Mario Negri Sud, S Maria Imbaro, Italy (G.T.); Sahlgrenska Academy, Gothenburg University, Sweden (J.W.); Rikshospitalet University Hospital, Oslo, Norway (J.K.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.); ANMCO Research Center, Florence, Italy (A.P.M.); and Maria Cecilia Hospital, GVM Care&Research - E.S. Health Science Foundation, Cotignola, Italy (L.T.). john.mcmurray@glasgow.ac.uk.
authors: John J V
authors: JJ
authors: McMurray
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000209:etiology; D001562:Benzimidazoles / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds; D002317:Cardiovascular Agents / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D000068718:Rosuvastatin Calcium; D020521:Stroke / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D013318:Stroke Volume; D013449:Sulfonamides / Q000627:therapeutic use*; D013777:Tetrazoles / Q000627:therapeutic use
chemical_list: D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D002317:Cardiovascular Agents; D015525:Fatty Acids, Omega-3; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010446:Peptide Fragments; D011743:Pyrimidines; D013449:Sulfonamides; D013777:Tetrazoles; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000068718:Rosuvastatin Calcium; C081643:candesartan
keywords: atrial fibrillation; heart failure; risk factors; sinus rhythm; stroke; ventricular ejection fraction