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Hypo- and hyperglycemia predict outcome in patients with left ventricular dysfunction after acute myocardial infarction: data from EPHESUS
Authors:Ukena Christian  Dobre Daniela  Mahfoud Felix  Kindermann Ingrid  Lamiral Zohra  Tala Stephane  Rossignol Patrick  Turgonyi Eva  Pitt Bertram  Böhm Michael  Zannad Faiez
Affiliation:1. Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany;2. INSERM, Center of Clinical Investigation 9501, University Hospital Nancy, Lorrain Institute of Heart and Vessels Louis Mathieu, Vandoeuvre-les-Nancy, France;3. European Drug Development Hub, Transplantation Foundation, Nancy, France;4. INSERM U961 and Nancy University, Nancy, France;5. Pfizer, New York, New York;6. Department of Internal Medicine, Division of Cardiology, University of Michigan Medical Center, Ann Arbor, Michigan;7. INSERM U961 and Department of Cardiology, University Hospital Nancy, Nancy University, Nancy, France;1. Department of Cardiology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel;2. Department of Nephrology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel;1. Steadman Philippon Research Institute, Vail, CO, USA;2. The Steadman Clinic, Vail, CO, USA;3. Department of Trauma Surgery and Sports Traumatology, Medical University Innsbruck, Innsbruck, Austria;4. Department of Trauma and Reconstructive Surgery, University of Leipzig, Leipzig, Germany
Abstract:BackgroundHyperglycemia predicts death in cardiovascular disease, but intensive glucose-lowering strategies increase mortality rates in diabetes. The present analysis investigated the prognostic value of postadmission blood glucose (BG) concentration on clinical outcomes in high-risk patients with heart failure after acute myocardial infarction.Methods and ResultsA total of 6,496 patients from the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) were categorized into 4 groups by plasma glucose concentration: ≤4.5 mmol/L (hypoglycemia), 4.5–5.5 mmol/L (normoglycemia), 5.5–8.3 mmol/L (elevated glucose level), and >8.3 mmol/L (severe hyperglycemia). We evaluated the time to all-cause death (primary end point) and time to cardiovascular death or hospitalization (secondary end point). Hypo- and severe hyperglycemia were prevalent in 509 (8%) and 1,588 (24%) patients, respectively. There was a U-shaped relationship between BG level and incidence of all-cause death (11.8% in patients with normoglycemia vs 15.1% and 19.9% in those with hypo- and severe hyperglycemia; P < .001). The incidence of the secondary end point was increased only in hyperglycemic patients (36% vs 23% in normoglycemic patients; P < .001). In multivariate Cox regression analysis, hypoglycemia (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.06–1.81; P = .002) and severe hyperglycemia (HR 1.52, CI 1.27–1.83; P < .0001) proved to be strong predictors of all-cause death. There was no significant interaction between eplerenone treatment and blood glucose levels regarding clinical outcomes.ConclusionsIn heart failure after acute myocardial infarction, both hypo- and hyperglycemia at the postacute phase identify patients with increased risk of death during long-term follow-up.
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