Serum MMP-8: a novel indicator of left ventricular remodeling and cardiac outcome in patients after acute myocardial infarction

PLoS One. 2013 Aug 14;8(8):e71280. doi: 10.1371/journal.pone.0071280. eCollection 2013.

Abstract

Objective: Left ventricular (LV) remodeling following myocardial infarction (MI) is characterized by progressive alterations of structure and function, named LV remodeling. Although several risk factors such as infarct size have been identified, LV remodeling remains difficult to predict in clinical practice. Changes within the extracellular matrix, involving matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), are an integral part of left ventricular (LV) remodeling after myocardial infarction (MI). We investigated the temporal profile of circulating MMPs and TIMPs and their relations with LV remodeling at 1 year and clinical outcome at 3 years in post-MI patients.

Methods: This prospective multicentre study included 246 patients with a first anterior MI. Serial echocardiographic studies were performed at hospital discharge, 3 months, and 1 year after MI, and analysed at a core laboratory. LV remodeling was defined as the percent change in LV end-diastolic volume (EDV) from baseline to 1 year. Serum samples were obtained at hospital discharge, 1, 3, and 12 months. Multiplex technology was used for analysis of MMP-1, -2, -3, -8, -9, -13, and TIMP-1, -2, -3, -4 serum levels.

Results: Baseline levels of MMP-8 and MMP-9 were positively associated with changes in LVEDV (P = 0.01 and 0.02, respectively). When adjusted for major baseline characteristics, MMP-8 levels remained an independent predictor LV remodeling (P = 0.025). By univariate analysis, there were positive relations between cardiovascular death or hospitalization for heart failure during the 3-year follow-up and the baseline levels of MMP-2 (P = 0.03), MMP-8 (P = 0.002), and MMP-9 (P = 0.03). By multivariate analysis, MMP-8 was the only MMP remaining significantly associated with clinical outcome (P = 0.02).

Conclusion: Baseline serum MMP-8 is a significant predictor of LV remodeling and cardiovascular outcome after MI and may help to improve risk stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Biomarkers / blood
  • Electrocardiography
  • Endpoint Determination
  • Female
  • Heart / physiopathology*
  • Humans
  • Male
  • Matrix Metalloproteinase 8 / blood*
  • Middle Aged
  • Myocardial Infarction / blood*
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / physiopathology*
  • Prognosis
  • Tissue Inhibitor of Metalloproteinases / blood
  • Ventricular Remodeling*

Substances

  • Biomarkers
  • Tissue Inhibitor of Metalloproteinases
  • Matrix Metalloproteinase 8

Grant support

Marie Fertin was a recipient of “Federation Francaise de Cardiologie/Société Francaise de Cardiologie” fellowship. This work was supported by a grant from ANR (ANR-11-EMMA-029-01), from Inserm-Transfert and from E.U. FP7 (HOMAGE project 305507). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.