Gut Microbiota in Patients With Peripheral Arterial Disease and Chronic Limb-threatening Ischemia

Study Overview
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Brief Summary
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Microbiota has been associated with risk factors for cardiovascular diseases (hypertension, obesity, dyslipidemia, diabetes mellitus, heart failure). In animal models, the gut microbiota produces pro-inflammatory proteoglycans that increase the extent of myocardial infarction, reduced by treatment with probiotics (Lactobacillus). TMAO, a blood metabolite directly dependent on the gut microbiota is related to atherosclerotic plaque instability and major adverse cardiovascular events (MACE) in humans. Recent data demonstrate that blood levels of TMAO directly correlate with the risk of major MACE and mortality in patients with peripheral arterial disease (PAD). The goal of this observational study is to evaluate the association between gut microbiota and TMAO serum levels and MACE and major adverse limb events (MALE) in patients with PAD and chronic limb threatening ischemia (CLTI) requiring a procedure of endovascular revascularization. The main questions it aims to answer are: association between gut microbiota and TMAO serum levels and MALE after lower extremity revascularization. association between gut microbiota and TMAO serum levels and MACE after lower extremity revascularization. Patients with CLTI requiring lower extremity endovascular revascularization will undergo stool sampling for determination of gut microbiota and blood sampling for the dosage of circulating TMAO before the endovascular procedure. Incidence of MALE and MACE will be collected in a 24-months follow-up and will be associated with gut microbiota and TMAO serum levels.

Official Title
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Gut Microbiota and Failure of Endovascular Revascularization in Diabetic Patients With Peripheral Arterial Disease and Chronic Limb-threatening Ischemia

Conditions
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Peripheral Arterial Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age of at least 18 years Ankle/Brachial Index (ABI) of less than 80 at least one lower limb stenosis greater than 50% documented by Ultrasound Color Doppler (US) stage 4 or 5 PAD diagnosis according to the Rutherford classification presence of chronic limb-threatening ischemia indication for LER of the target arterial stenosis Exclusion Criteria: acute infections at present or in the previous month antibiotic treatment in the previous month primary hyperparathyroidism revascularization of the lower limb in the previous 3 months diabetic foot ulcers with signs of active infection or osteomyelitis organ transplantation active cancer liver disease at functional status B or C according to Child-Pugh absolute contraindication to antiplatelet therapy thrombophilia contraindication to endovascular revascularization

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between incidence of MALE and gut microbiota and TMAO serum levels | To evaluate the association between gut microbiota and TMAO serum levels before endovascular revascularization and incidence of MALE during the follow-up period. | 24-months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between incidence of myocardial infarction and gut microbiota and TMAO serum levels | To evaluate the association between gut microbiota and TMAO serum levels before endovascular revascularization and incidence of myocardial infarction during the follow-up period. | 24-months follow-up | 
| Association between incidence of stroke and gut microbiota and TMAO serum levels | To evaluate the association between gut microbiota and TMAO serum levels before endovascular revascularization and incidence of stroke during the follow-up period. | 24-months follow-up | 
| Association between incidence of cardiovascular death and gut microbiota and TMAO serum levels | To evaluate the association between gut microbiota and TMAO serum levels before endovascular revascularization and incidence of cardiovascular death during the follow-up period. | 24-months follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiota, gut microbiota, TMAO, MACE, MALE