title: Thyroid-stimulating hormone and clinical outcomes: the CORONA trial (controlled rosuvastatin multinational study in heart failure).
abstract: OBJECTIVE
  This study sought to examine the association between thyroid status and clinical outcomes in patients in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study.
  
  
  BACKGROUND
  Hypo- and hyperthyroidism were associated with worse clinical outcomes in the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial).
  
  
  METHODS
  In CORONA, 4,987 patients underwent baseline thyroid-stimulating hormone (TSH) measurement, 237 of which (4.8%) were receiving thyroid replacement therapy (TRT). Patients were classified as euthyroid (TSH: 0.3 to 5.0 μU/ml, and no TRT), hyperthyroid (<0.3 μU/ml and no TRT), or hypothyroid (>5.0 μU/ml and no TRT). The outcome composites of cardiovascular (CV) death or hospitalization for heart failure (HF), the components of this composite, and all-cause death were compared among hyperthyroid, hypothyroid, and euthyroid states, using multivariable models adjusting for previously reported prognostic variables.
  
  
  RESULTS
  A total of 91.3% of patients were euthyroid, 5.0% were hypothyroid, and 3.7% were hyperthyroid. Compared with euthyroid patients, hypothyroid patients were more likely to have a history of stroke, had worse renal function and higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, were more likely to be treated with an antiarrhythmic drug (or have an implantable cardioverter defibrillator), and were less likely to smoke or be treated with a beta-blocker or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. In univariate analyses, hypothyroidism was associated with an increased risk of the composite outcome of CV death or HF hospitalization (hazard ratio: 1.29; 95% confidence interval: 1.07 to 1.57; p = 0.008), as well as all-cause death (HR: 1.36; 95% confidence interval: 1.03 to 1.76; p = 0.004). However, after adjustment for other known predictors of outcome, the associations were weakened, and when NT-proBNP was added to the models, the association between hypothyroidism and all outcomes was eliminated.
  
  
  CONCLUSIONS
  Thyroid status is not an independent predictor of outcome in heart failure with reduced ejection fraction. (Controlled Rosuvastatin Multinational Study in Heart Failure [CORONA]; NCT00206310).
authors.affiliation: BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Perez
authors.affiliation: BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland.
authors.forename: Pardeep S
authors.initials: PS
authors.lastname: Jhund
authors.affiliation: Department of Academic Geriatric Medicine, Walton Building, Glasgow Royal Infirmary, Glasgow, Scotland.
authors.forename: David J
authors.initials: DJ
authors.lastname: Stott
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, and K. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.affiliation: Hull York Medical School, Kingston-Upon-Hull, United Kingdom.
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.affiliation: University Medical Centre, Groningen, the Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
authors.forename: John
authors.initials: J
authors.lastname: Wikstrand
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, and K. G. Jebsen Cardiac Research Centre and Centre for Heart Failure Research, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: John
authors.initials: J
authors.lastname: Kjekshus
authors.affiliation: BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland. Electronic address: john.mcmurray@glasgow.ac.uk.
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage*; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D045265:Natriuretic Peptides / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage*; D000068718:Rosuvastatin Calcium; D013318:Stroke Volume / Q000502:physiology; D013449:Sulfonamides / Q000008:administration & dosage*; D013959:Thyroid Diseases / Q000150:complications* / Q000401:mortality; D013972:Thyrotropin / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D045265:Natriuretic Peptides; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D013972:Thyrotropin
keywords: clinical outcome; hyperthyroidism; hypothyroidism