Plasma matrix metalloproteinasis as predictors of prognosis and left ventricular remodelling after acute myocardial infarction

The basis of this thesis was to investigate the role of MMP's and their natural inhibitors' tissue inhibitors of metalloproteinases (TIMP's) in the process of left ventricular remodelling, clinical heart failure and adverse prognosis post acute myocardial infarction (AMI). Methods: We recruited patients post AMI. Stage 1 aimed to examine the temporal profile of several MMP's and their relationship with markers of LV function, volumes and remodelling in a limited population size (n=91). Stage 2 investigated a more extensive population (n=404), concentrating on a limited number of MMP's/TIMP's and included clinical follow up to identify subjects with adverse prognosis. All patients were recruited from the CUU units of the University Hospitals of Leicester. All donated venous blood samples at 0-12hurs, 12-24hrs and at 24hr intervals post symptoms until discharge for measurement of MMP/TIMP's and underwent echocardiographic studies during their index admission and at follow up. During stage 2 all subjects were additionally followed for the clinical endpoints of death or heart failure. Results: We present convincing data to implicate the MMP system in both LV remodelling and adverse prognosis post AMI. Stage I demonstrates individual temporal profiles of MMP's and presents data on determinants of MMP expression. We show an association between MMP-9 and LV dysfunction, volumes and remodelling post AMI. Stage 2 confirms both this data and observes similar results for TIMP-1. In addition we demonstrate the association between both MMP-9 and TIMP-1 with adverse prognosis and compare with N terminal pro BNP as a prognostic marker. A retrospective audit of the effects of diabetes and stress hyperglycaemic is a hypothesis generating chapter which presents association between post MI hyperglycaemia, elevated MMP's and adverse LV function. Summary: Altered MMP/TIMP expression occurs post AMI and is associated with LV dysfunction and remodelling, and with adverse prognosis. The MMP system may represent a potential therapeutic target post AMI.