Plasma TIMP-4 predicts left ventricular remodeling after acute myocardial infarction

J Card Fail. 2011 Jun;17(6):465-71. doi: 10.1016/j.cardfail.2011.02.002. Epub 2011 Mar 25.

Abstract

Background: Alterations in the balance between matrix metalloproteinases and their endogenous tissue inhibitors (TIMPs) are associated with left ventricular (LV) remodeling after acute myocardial infarction (AMI). No relationships have been identified between TIMPs and serial postinfarction change in LV function.

Methods and results: Plasma concentrations of TIMP-1, -2, -4 were measured at baseline (mean 46 h) and at 24 weeks in 100 patients (age 58.9 ± 12 years, 77% male) admitted with AMI and LV dysfunction, with cardiac magnetic resonance imaging at each time point. TIMP-1 concentration was reduced, whereas TIMP-2 and -4 concentrations were elevated at baseline compared with a reference control population. TIMP-1 decreased and TIMP-2 increased significantly over time; there was an incremental trend in TIMP-4 concentration. Baseline TIMP-4 correlated with change in LV end-systolic volume index (∆LVESVI; r = 0.24; P = .023) and change in LV end-diastolic volume index (∆LVEDVI; r = 0.25; P = .015). ∆TIMP-4 also correlated with ∆LVESVI and with ∆LVEDVI, as did ∆TIMP-2. On multivariable analysis, baseline TIMP-4 concentration was an independent predictor of ∆LVESVI.

Conclusions: Plasma TIMP-4 concentration, measured early after AMI, may assist in the prediction of LV remodeling and therefore in the assessment of prognosis. Further study of the role of the TIMPs in the pathophysiology of postinfarction remodeling is warranted.

Trial registration: ClinicalTrials.gov NCT00132093.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood*
  • Myocardial Infarction / physiopathology*
  • Predictive Value of Tests
  • Systole
  • Tissue Inhibitor of Metalloproteinase-1 / blood
  • Tissue Inhibitor of Metalloproteinase-2 / blood
  • Tissue Inhibitor of Metalloproteinase-4
  • Tissue Inhibitor of Metalloproteinases / blood*
  • Ventricular Dysfunction, Left / blood
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Remodeling*

Substances

  • TIMP1 protein, human
  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinases
  • Tissue Inhibitor of Metalloproteinase-2

Associated data

  • ClinicalTrials.gov/NCT00132093