title: Effect of Metformin Treatment on Lipoprotein Subfractions in Non-Diabetic Patients with Acute Myocardial Infarction: A Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) Trial.
abstract: OBJECTIVE
  Metformin affects low density lipoprotein (LDL) and high density (HDL) subfractions in the context of impaired glucose tolerance, but its effects in the setting of acute myocardial infarction (MI) are unknown. We determined whether metformin administration affects lipoprotein subfractions 4 months after ST-segment elevation MI (STEMI). Second, we assessed associations of lipoprotein subfractions with left ventricular ejection fraction (LVEF) and infarct size 4 months after STEMI.
  
  
  METHODS
  371 participants without known diabetes participating in the GIPS-III trial, a placebo controlled, double-blind randomized trial studying the effect of metformin (500 mg bid) during 4 months after primary percutaneous coronary intervention for STEMI were included of whom 317 completed follow-up (clinicaltrial.gov Identifier: NCT01217307). Lipoprotein subfractions were measured using nuclear magnetic resonance spectroscopy at presentation, 24 hours and 4 months after STEMI. (Apo)lipoprotein measures were obtained during acute STEMI and 4 months post-STEMI. LVEF and infarct size were measured by cardiac magnetic resonance imaging.
  
  
  RESULTS
  Metformin treatment slightly decreased LDL cholesterol levels (adjusted P = 0.01), whereas apoB remained unchanged. Large LDL particles and LDL size were also decreased after metformin treatment (adjusted P<0.001). After adjustment for covariates, increased small HDL particles at 24 hours after STEMI predicted higher LVEF (P = 0.005). In addition, increased medium-sized VLDL particles at the same time point predicted a smaller infarct size (P<0.001).
  
  
  CONCLUSIONS
  LDL cholesterol and large LDL particles were decreased during 4 months treatment with metformin started early after MI. Higher small HDL and medium VLDL particle concentrations are associated with favorable LVEF and infarct size.
authors.affiliation: University of Groningen, University Medical Center Groningen, the Department of Cardiology, Groningen, the Netherlands.
authors.forename: Ruben N
authors.initials: RN
authors.lastname: Eppinga
authors.affiliation: University of Groningen, University Medical Center Groningen, the Department of Cardiology, Groningen, the Netherlands.
authors.forename: Minke H T
authors.initials: MH
authors.lastname: Hartman
authors.affiliation: University of Groningen, University Medical Center Groningen, the Department of Cardiology, Groningen, the Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: University of Groningen, University Medical Center Groningen, the Department of Cardiology, Groningen, the Netherlands.
authors.forename: Chris P H
authors.initials: CP
authors.lastname: Lexis
authors.affiliation: LabCorp, Raleigh, North Carolina, United States of America.
authors.forename: Margery A
authors.initials: MA
authors.lastname: Connelly
authors.affiliation: University of Groningen, University Medical Center Groningen, the Department of Cardiology, Groningen, the Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Lipsic
authors.affiliation: University of Groningen, University Medical Center Groningen, the Department of Critical Care, Groningen, the Netherlands.
authors.forename: Iwan C C
authors.initials: IC
authors.lastname: van der Horst
authors.affiliation: University of Groningen, University Medical Center Groningen, the Department of Cardiology, Groningen, the Netherlands.
authors.forename: Pim
authors.initials: P
authors.lastname: van der Harst
authors.affiliation: University of Groningen, University Medical Center Groningen, the Department of Endocrinology, Groningen, the Netherlands.
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D000368:Aged; D001053:Apolipoproteins / Q000097:blood; D017024:Chemotherapy, Adjuvant; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003131:Combined Modality Therapy; D003289:Convalescence; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery; D019906:Nuclear Magnetic Resonance, Biomolecular; D062645:Percutaneous Coronary Intervention; D013318:Stroke Volume; D014280:Triglycerides / Q000097:blood
chemical_list: D001053:Apolipoproteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D006442:Glycated Hemoglobin; D008074:Lipoproteins; D008687:Metformin; D014280:Triglycerides