Aims: Tissue inhibitors of metalloproteinase (TIMPs) bind to active matrix metalloproteinase (MMPs), and thereby inhibit their proteolytic activity. We investigated the role of polymorphisms in the gene for TIMP-1 and serum levels of TIMP-1 in association with postmyocardial infarction (MI), left ventricular (LV) dysfunction, and symptoms of acute heart failure (AHF) in patients treated with primary percutaneous coronary intervention. Methods: In total, 556 patients with STEMI were evaluated. Levels of TIMP-1 were measured at admission and 24 h after MI onset. The TIMP-1 exon 5 SNP rs4898 (F124F with T > C) located at X chromosome was assayed. Results: TIMP-1 levels were higher for men with AHF as well as for men with LV dysfunction (ejection fraction [EF] < 40%). According to multivariate analysis, the TIMP-1 level was a factor with an independent negative relationship to EF and AHF in men. An independent relationship between exon 5 TIMP-1 gene polymorphism and EF, AHF or TIMP-1 level was not documented. Conclusion: These results provide evidence that a higher level of circulating TIMP-1 is independently associated with worse EF and AHF.

The influence of polymorphisms in the large group of MMP and TIMP genes on clinical outcomes in patients after ST elevation myocardial infarction (STEMI) treated with primary PCI was analysed. In total, 550 consecutive Caucasian patients with STEMI were included in the present study, with a median of 32 months. We analysed 19 polymorphisms in the genes coding MMP and TIMP genes. The MMP-1 -519A/G and -422A/T polymorphisms are associated with combined endpoint after myocardial infarction. The hazard ratio for AT variant of MMP-1 -422A/T was 1.75 (p < 0.001); the variants with at least one A allele of MMP-1 -519A/G have less risk of combined endpoint. The TT variants of -1562C/T MMP-9 and at least one T allele of +92C/T MMP-13 were considered in a trend to affect disease progression and long-term survival after myocardial infarction. According to reclassification analysis NRI and IDI, long-term risk stratification using MMP-1 -422A/T and -519A/G polymorphisms gives additional information to the commonly used GRACE risk score. Patient stratification after myocardial infraction (MI) according to risk genotypes of MMP-1 polymorphisms could have important clinical implications for identification of patients at risk and therapeutic strategies.

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