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Atherosclerotic diseases such as coronary artery disease (CAD) and peripheral arterial disease (PAD) are the leading cause of morbidity and mortality in the industrialized world.
An interaction between the development of atherosclerotic diseases and the oral and enteral microbiome composition has already been demonstrated in the past. The microbiome is a double-edged sword which can convey protective and detrimental cardiovascular effects. While it can promote the development of atherosclerosis through the production of atherogenic metabolites such as trimethylamine N-oxide (TMAO) it can also generate a protective effect through the production of metabolites such as short chain fatty acids (SCFA). Preliminary data suggest that atherosclerotic disease itself can induce a dysbiosis of the microbiome.
Aim of this study is to determine the differences in coronary artery disease and peripheral arterial disease on the oral-enteral microbiome axis and downstream microbiome-dependent metabolites.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acute Coronary Syndrome (ACS) | Patients presenting to the clinic with acute coronary syndrome. This includes: ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UAP) with confirmed diagnosis of coronary artery disease. |
| |
| Chronic Coronary Syndrome (CCS) | Patients presenting to the clinic with chronic coronary syndrome and confirmed diagnosis of coronary artery disease. |
| |
| Critical limb ischemia (CLI) | Patients presenting to the clinic with critical limb ischemia. This includes: Resting limb pain (Fontaine III), ulcerations (Fontaine IV) and Ankle brachial index (ABI) < 0,6 and confirmed diagnosis of peripheral artery disease. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standard of care treatment | Other | Standard of care treatment including percutaneous interventions was performed in all participants. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change of enteral microbiome composition after presentation with ACS/CCS/CLI | Stool samples are collected at the below mentioned time points. DNA isolation will be performed with consecutive 16S-RNA analysis and cluster analysis. | Sampling will be performed within 24 hours of presentation to the clinic, at day 3, day 7, day 14 and at day 28 (+/- 2 days) after initial presentation. |
| Change of oral microbiome composition after presentation with ACS/CCS/CLI | Oral samples are collected at the below mentioned time points. DNA isolation will be performed with consecutive 16S-RNA analysis and cluster analysis. | Sampling will be performed within 24 hours of presentation to the clinic, at day 3, day 7, day 14 and at day 28 (+/- 2 days) after initial presentation. |
| Measure | Description | Time Frame |
|---|---|---|
| Change of TMAO serum levels after presentation with ACS/CCS/CLI | Blood samples are collected at the below mentioned time points. TMAO serum levels will be measured by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). | Sampling will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation. |
| Measure | Description | Time Frame |
|---|---|---|
| Change of left ventricular global longitudinal strain (GLS) after presentation with ACS/CCS/CLI | Echocardiographical strain analysis will be performed at the below mentioned time points. | Echocardiography will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation. |
Inclusion Criteria:
Exclusion Criteria:
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Patients older than 18 years presenting to the clinic with acute coronary syndrome (ACS), chronic coronary syndrome (CCS) or critical limb threatening ischemia (CLI) who can be included into the study within a 24 hours time frame after presentation.
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| Name | Affiliation | Role |
|---|---|---|
| Christos Rammos, Prof. Dr. | University Clinic Essen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Essen, Clinic of Cardiology and Angiology | Essen | North Rhine-Westphalia | 45147 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40804540 | Derived | Messiha D, Lange E, Tratnik A, M Westendorf A, Rinke M, Lenz S, Hendgen-Cotta UB, Buer J, Rassaf T, Rammos C. The influence of acute and chronic coronary syndrome on the gut microbiome and downstream microbiome-derived metabolites-Microbiome in acute myocardial infarction-MIAMI-Trial. Basic Res Cardiol. 2025 Oct;120(5):913-924. doi: 10.1007/s00395-025-01134-9. Epub 2025 Aug 13. |
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| ID | Term |
|---|---|
| D003141 | Communicable Diseases |
| D003324 | Coronary Artery Disease |
| D009203 | Myocardial Infarction |
| D054058 | Acute Coronary Syndrome |
| D058729 | Peripheral Arterial Disease |
| D000089802 | Chronic Limb-Threatening Ischemia |
| ID | Term |
|---|---|
| D007239 | Infections |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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stool and blood samples
| Change of SCFA serum levels after presentation with ACS/CCS/CLI | Blood samples are collected at the below mentioned time points. SCFA serum levels will be measured by high-performance liquid chromatography (HPLC). | Sampling will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation. |
| Change of inflammatory profile (CRP, PCT, Interleukin panel) after presentation with ACS/CCS/CLI |
Blood samples are collected at the below mentioned time points. |
| Sampling will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation. |
| Change of blood pressure after presentation with ACS/CCS/CLI | Blood pressure will be measured at the below mentioned time points. | Blood pressure measurements will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation. |
| Change of pulse wave velocity (PWV) after presentation with ACS/CCS/CLI | PWV will be measured at the below mentioned time points. | PWV measurements will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation. |
| Change in nitrite metabolism after presentation of ACS/CCS/CLI | Nitrite metabolism will be assed by chemiluminescence detection (CLD). | Nitrite metabolism will be performed within 24 hours of presentation to the clinic and at day 28 (+/- 2 days) after initial presentation. |
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D007238 | Infarction |
| D007511 | Ischemia |
| D009336 | Necrosis |
| D050197 | Atherosclerosis |
| D016491 | Peripheral Vascular Diseases |
| D002908 | Chronic Disease |