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

Marie Fertin,Olivia Beseme,Florence Pinet,Gilles Lemesle,Christophe Bauters,Maggy Chwastyniak,Annie Turkieh,Philippe Amouyel,Kent E Vrana

doi:10.1371/journal.pone.0071280

Abstract

ObjectiveLeft 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.MethodsThis 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.ResultsBaseline 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).ConclusionBaseline serum MMP-8 is a significant predictor of LV remodeling and cardiovascular outcome after MI and may help to improve risk stratification.

Highlights

Left ventricular (LV) remodeling after myocardial infarction (MI) is characterized by progressive LV dilatation [1] and associated with increased risk of heart failure and cardiovascular death [2]
Baseline levels of matrix metalloproteinases (MMPs)-8 and MMP-9 were positively associated with changes in LVEDV (P = 0.01 and 0.02, respectively)
Baseline serum MMP-8 is a significant predictor of LV remodeling and cardiovascular outcome after MI and may help to improve risk stratification

Summary

Introduction

Left ventricular (LV) remodeling after myocardial infarction (MI) is characterized by progressive LV dilatation [1] and associated with increased risk of heart failure and cardiovascular death [2]. Recent studies have shown that LV remodeling remains relatively frequent after MI, despite high acute reperfusion rates and widespread prescription of secondary prevention medications [3,4]. Several variables – such as MI size – have been identified as risk factors [5], LV remodeling remains difficult to predict in clinical practice. In various animal MI models, increased MMP expression occurs during the development of heart failure [8], MMP inhibition attenuates LV remodeling [9], and TIMP deficiency accelerates adverse LV remodeling by promoting ECM degradation [10]

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Results

Conclusion