Biomarkers and SNP-polymorphisms in Post-infarction Cardiac Remodeling

Study Overview
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Brief Summary
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The purpose of this study is to explore the serum levels of pro- and anti-inflammatory biomarkers and angiogenic growth factors and SNP polymorphisms of the promoter regions of their genes as well as to determine their role in the development of adverse cardiac remodeling in patients with acute ST-segment elevation myocardial infarction.

Detailed Description
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The widespread introduction of modern methods of treatments of myocardial infarction in routine clinical practice has lead not only to a decrease in mortality, but also to an increase in the number of patients with chronic heart failure. It is known that inflammation develops in myocardial infarction in response to cell damage, which is accompanied by activation of the cells of the immune system and eventually with scarring. Chronic aseptic inflammation is not only a universal biological reaction in response to necrosis of cardiomyocytes, but the cellular molecular basis of post-infarction cardiac remodeling. At the same time, the imbalance of pro- and anti-inflammatory mediators can have some negative effects on the healing processes of the damaged myocardium and subsequent remodeling of the heart. In adverse heart remodeling, elevated levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α, etc.) and reduced secretion of anti-inflammatory cytokines (IL-4, IL-10, etc.) persist for a long time. Recently, the endotoxin hypothesis of cytokine production has been of great interest among scientists. Endotoxin is a molecule of the lipopolysaccharide (LPS) of the outer cell wall of gram-negative bacteria. LPS is a powerful inducer of cytokine release, and chronic endotoxin load is at least one of the reasons for the activation of the innate immune system. One of the most important and unresolved problems in pathophysiology is the study of the nature of the inflammatory response, or rather the cytokine response cascade, reparation and neoangiogenesis developing in the myocardium in response to ischemic damage, as well as genetically determined regulation of these processes. Factors determining the dual role of cytokines in the development of adverse cardiac remodeling can be polymorphisms of their genes, in particular, single nucleotide polymorphism of genes - SNP (single nucleotide polymorphism) with replacement of one nucleotide by another. SNP in promoter regions regulate the intensity of gene expression, different levels of secretion and function of interleukins, growth factors, and, accordingly, their biological effects. Uncovering the mechanisms that regulate the secretion of angiogenic growths factors, pro- and anti-inflammatory cytokines in patients with AMI could potentially become the basis for developing new treatment tactics based on modulating the immune response and neoangiogenesis in AMI by introducing into ischemic tissues of cytokines or angiogenic growth factors in the form recombinant proteins or as a part of genetic constructs to stimulate regeneration. A total of 200 patients with acute primary myocardial infarction with ST segment elevation will be recruited. Upon admission, all patients receive standard therapy, as recommended for the treatment of myocardial infarction. Within 24 hours of admission, coronary angiography and revascularization of the infarct-related artery are performed. On the days 1 and 7 of hospitalization and on the day of discharge, blood will be taken to determine the dynamics of serum concentrations of pro- and anti-inflammatory biomarkers, markers of myocardial necrosis; gene polymorphisms will be studied; echocardiography will be performed to assess the structural and functional characteristics of the heart after AMI. After 3 and 12 months, patients undergo studies to dynamically assess the structural and functional state of the heart.

Official Title
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Angiogenic Growth Factors, Pro- and Anti-inflammatory Biomarkers, and Genetic Polymorphisms of Their Promoter Regions in Patients With Post-infarction Cardiac Remodeling

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Genetic: SNP polymorphisms of the promoter regions pro - and anti-inflammatory cytokines and angiogenic growth factor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years at time of randomization Patients with acute coronary syndrome with ST segment elevation Signed informed consent to participate in the study Admission to the intensive care unit within 24 hours from the onset of the disease Coronary angiography within 24 hours of the onset of the disease Exclusion Criteria: Long persistent form of atrial fibrillation Valvular heart disease Shock of different genesis Multiple organ failure Chronic heart failure with a severe decrease in the left ventricular ejection fraction Sepsis Severe concomitant pathology

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: SNP polymorphisms of the promoter regions pro - and anti-inflammatory cytokines and angiogenic growth factor|blood sampling|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the left ventricular end-diastolic volume index (percent) | Change in the left ventricular end-diastolic volume index (percent) is assessed in patients with myocardial infarction at 1-year follow-up with intermediate assessments at day 7 and month 3 after onset. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of mortality (percent) | Incidence rate of mortality (percent) is measured 1 year after myocardial infarction onset. | 1 year | 
| Incidence of stroke (percent) | Incidence rate of stroke (percent) is measured 1 year after myocardial infarction onset. | 1 year | 
| Incidence of unstable angina (percent) | Incidence rate of unstable angina (percent) is measured 1 year after myocardial infarction onset. | 1 year | 
| Incidence of chronic heart failure > II NYHA (percent) | Incidence rate of chronic heart failure (percent) is measured 1 year after myocardial infarction onset. | 1 year | 
| Incidence of recurrent myocardial infarction (percent) | Incidence rate of recurrent myocardial infarction (percent) is measured 1 year after myocardial infarction onset. | 1 year | 
| Change in pro-inflammatory cytokine (pg/mL) | Changes in the serum levels of pro-inflammatory cytokines (pg/mL) in patients with myocardial infarction is assessed at 1-year follow-up with intermediate assessments at days 1, 7 and 14 and month 3 after onset. | 1 year | 
| Change in anti-inflammatory cytokine (pg/mL) | Changes in the serum levels of anti-inflammatory cytokines (pg/mL) in patients with myocardial infarction is assessed at 1-year follow-up with intermediate assessments at days 1, 7 and 14 and month 3 after onset. | 1 year | 
| Change in angiogenic growth factor (pg/mL) | Changes in the serum levels of angiogenic growth factors (pg/mL) in patients with myocardial infarction at 1-year follow-up with intermediate assessments at days 1, 7 and 14 and month 3 after onset. | 1 year | 
| Change in endotoxin (ng/mL) | Changes in the serum levels of endotoxin (ng/mL) in patients with myocardial infarction at 1-year follow-up with intermediate assessments at days 1, 7 and 14 and month 3 after onset. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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remodeling, inflammation, polymorphism, endotoxin, heart failure