title: Clinical and Echocardiographic Characteristics and Cardiovascular Outcomes According to Diabetes Status in Patients With Heart Failure and Preserved Ejection Fraction: A Report From the I-Preserve Trial (Irbesartan in Heart Failure With Preserved Ejection Fraction).
abstract: BACKGROUND
  In patients with heart failure and preserved ejection fraction, little is known about the characteristics of, and outcomes in, those with and without diabetes mellitus.
  
  
  METHODS
  We examined clinical and echocardiographic characteristics and outcomes in the I-Preserve trial (Irbesartan in Heart Failure With Preserved Ejection Fraction) according to history of diabetes mellitus. Cox regression models were used to estimate hazard ratios for cardiovascular outcomes adjusted for known predictors, including age, sex, natriuretic peptides, and comorbidity. Echocardiographic data were available in 745 patients and were additionally adjusted for in supplementary analyses.
  
  
  RESULTS
  Overall, 1134 of 4128 patients (27%) had diabetes mellitus. Compared with those without diabetes mellitus, they were more likely to have a history of myocardial infarction (28% versus 22%), higher body mass index (31 versus 29 kg/m2), worse Minnesota Living With Heart Failure score (48 versus 40), higher median N-terminal pro-B-type natriuretic peptide concentration (403 versus 320 pg/mL; allP<0.01), more signs of congestion, but no significant difference in left ventricular ejection fraction. Patients with diabetes mellitus had a greater left ventricular mass and left atrial area than patients without diabetes mellitus. Doppler E-wave velocity (86 versus 76 cm/s;P<0.0001) and the E/e' ratio (11.7 versus 10.4;P=0.010) were higher in patients with diabetes mellitus. Over a median follow-up of 4.1 years, cardiovascular death or heart failure hospitalization occurred in 34% of patients with diabetes mellitus versus 22% of those without diabetes mellitus (adjusted hazard ratio, 1.75; 95% confidence interval, 1.49-2.05), and 28% versus 19% of patients with and without diabetes mellitus died (adjusted hazard ratio, 1.59; confidence interval, 1.33-1.91).
  
  
  CONCLUSIONS
  In heart failure with preserved ejection fraction, patients with diabetes mellitus have more signs of congestion, worse quality of life, higher N-terminal pro-B-type natriuretic peptide levels, and a poorer prognosis. They also display greater structural and functional echocardiographic abnormalities. Further investigation is needed to determine the mediators of the adverse impact of diabetes mellitus on outcomes in heart failure with preserved ejection fraction and whether they are modifiable.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.).
authors.forename: Søren L
authors.initials: SL
authors.lastname: Kristensen
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.).
authors.forename: Ulrik M
authors.initials: UM
authors.lastname: Mogensen
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.).
authors.forename: Pardeep S
authors.initials: PS
authors.lastname: Jhund
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.).
authors.forename: Mark C
authors.initials: MC
authors.lastname: Petrie
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.).
authors.forename: David
authors.initials: D
authors.lastname: Preiss
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.).
authors.forename: Sithu
authors.initials: S
authors.lastname: Win
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.).
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.).
authors.forename: Robert S
authors.initials: RS
authors.lastname: McKelvie
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.).
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zile
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.).
authors.forename: Inder S
authors.initials: IS
authors.lastname: Anand
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.).
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.).
authors.forename: John S
authors.initials: JS
authors.lastname: Gottdiener
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.).
authors.forename: Peter E
authors.initials: PE
authors.lastname: Carson
authors.affiliation: From BHF Cardiovascular Research Centre, University of Glasgow, Scotland, UK (S.L.K., U.M.M., P.S.J., M.C.P., J.J.V.M.); Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark (S.L.K., U.M.M., L.K.); Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, UK (D.P.); Mayo Clinic, Rochester, MN (S.W.); Western University, London, ON, Canada (R.S.M.); Ralph H. Johnsons Veterans Affairs Medical Center and Medical University of South Carolina, Charleston (M.R.Z.); Division of Cardiology, University of Minnesota, Minneapolis (I.S.A.); Université Paris 6 and Hospital Pitié-Salpétrière, Paris, France (M.K.); University of Maryland Medical Center, Baltimore (J.S.G.); and Georgetown University and Washington DC Veterans Affairs Medical Center (P.E.C.). john.mcmurray@glasgow.ac.uk.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
mesh_terms: D000368:Aged; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000175:diagnosis; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D000077405:Irbesartan; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D016016:Proportional Hazards Models; D013318:Stroke Volume / Q000502:physiology*; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001713:Biphenyl Compounds; D010446:Peptide Fragments; D013777:Tetrazoles; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D000077405:Irbesartan
keywords: diabetes mellitus; echocardiography; heart failure