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Relationship of long-term prognosis to MMP and TIMP polymorphisms in patients after ST elevation myocardial
Monika Pavkova Goldbergova1, Jiri Jarkovsky2, Jolana Lipkova1
1Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Insights
Genetic variations in MMP and TIMP genes impact outcomes for ST-elevation myocardial infarction (STEMI) patients. Specific MMP-1 gene polymorphisms improve risk prediction beyond standard scores, aiding in identifying high-risk patients.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
Background:
- Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are crucial in extracellular matrix remodeling.
- Genetic polymorphisms in MMP and TIMP genes may influence susceptibility and clinical course of cardiovascular diseases, including myocardial infarction.
Purpose of the Study:
- To investigate the association between polymorphisms in MMP and TIMP genes and clinical outcomes in ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI).
- To evaluate the potential of these genetic markers for improving long-term risk stratification.
Main Methods:
- Analysis of 19 polymorphisms in MMP and TIMP genes in 550 Caucasian STEMI patients.
- Follow-up median of 32 months.
- Statistical analysis including hazard ratios and reclassification methods (NRI, IDI) compared to the GRACE risk score.
Main Results:
- MMP-1 gene polymorphisms (-519A/G and -422A/T) were significantly associated with combined endpoints after myocardial infarction.
- The AT variant of MMP-1 -422A/T showed a hazard ratio of 1.75 (p<0.001).
- MMP-1 polymorphisms provided additional information for risk stratification compared to the GRACE score.
Conclusions:
- Specific MMP-1 gene polymorphisms are predictive of clinical outcomes in STEMI patients.
- Incorporating MMP-1 genotype information may enhance risk stratification and guide therapeutic strategies for post-myocardial infarction management.
Abstract:
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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