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

Ruben N Eppinga, Minke H T Hartman, Dirk J van Veldhuisen, Chris P H Lexis, Margery A Connelly, Erik Lipsic, Iwan C C van der Horst, Pim van der Harst, Robin P F Dullaart, Ruben N Eppinga, Minke H T Hartman, Dirk J van Veldhuisen, Chris P H Lexis, Margery A Connelly, Erik Lipsic, Iwan C C van der Horst, Pim van der Harst, Robin P F Dullaart

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).

Conclusion: 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.

Conflict of interest statement

Competing Interests: The authors of this manuscript have read the journal's policy and have the following competing interests: MAC, PhD is an employee of LabCorp (Raleigh, North Carolina, USA), however this does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Lipoprotein subfraction concentrations and size…
Fig 1. Lipoprotein subfraction concentrations and size using NMR after 4 months according to treatment group (VLDL-P; LDL-P; HDL-P; Lipoprotein size).
Data are presented as median (interquartile range). P-values from unpaired—tests. P-value ≤ 0.0063 placebo vs. Metformin group.

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