LPS and Platelet Activation in Myocardial Infarction

NCT03675789 | Completed DMC

• 1 other identifier: EMI-Sapienza
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Platelets play a key role in the athero-thrombotic process. However, the in vivo mechanism accounting for thrombus growth at site of coronary atherosclerotic lesion has not been fully elucidated. While platelet adhesion and aggregation on the thrombogenic core of atherosclerotic plaque is an established mechanism for thrombus growth, the role of systemic factors, which may contribute to thrombus via amplification and propagation of platelet aggregation, is still to be clarified. There is a growing body of evidence that lipopolysaccharides (LPS), are implicated in athero-thrombosis. Circulating levels of endotoxins have been associated with human atherosclerosis progression, particularly in smokers or in patients with infections. Furthermore, endotoxins seem to be implicated in the thrombotic process through several mechanisms including up-regulation of macrophage tissue factor expression and amplification of platelet response upon interaction with Toll-like receptor 4. The relationship between endotoxins and platelets may be relevant in the context of acute coronary syndromes as endotoxins could locally amplify platelet-derived thrombus growth but this issue is still unexplored. Previous studies demonstrated that low-grade endotoxemia is detectable in human circulation, likely as consequence of enhanced gut permeability, and may be responsible for leucocyte-platelet aggregate and eventually thrombosis. The investigators hypothesize that low-grade endotoxemia may be observed in patients with coronary heart disease and may favor, at site of coronary unstable plaque, thrombus growth. To explore this issue, Escherichia Coli (EC)-LPS concentration and biomarkers of platelet activation will be measured in coronary thrombus and intra-coronary blood of patients with STEMI and stable angina (SA), respectively, and in peripheral circulation of both patients and controls. EC DNA will be searched in serum of all patients by polymerase chain reaction (PCR). Furthermore, to substantiate that LPS could be biologically active, immune-histochemical analysis of thrombi and in vitro studies will be performed to assess the interplay between LPS and platelet activation.

Conditions

Myocardial Infarction; Acute Coronary Syndrome

Keywords

Thrombi; LPS; Platelet Thrombus

Outcome Measures

Primary Outcomes (1)

• LPS in blood of STEMI, SA patients and controls.

  LPS will be measured in serum and expressed as concentration (pg/ml)

  1 year

Secondary Outcomes (9)

• LPS in thrombus and intra-coronary blood of STEMI and SA patients.

  1 year

• sP-selectin in thrombus and intra-coronary blood of STEMI and SA patients.

  1 year

• sCD40L in thrombus and intra-coronary blood of STEMI and SA patients.

  1 year

• Escherichia coli-DNA

  1 year

• Histologic and immunohistochemical analyses of thrombus fragments aspirated from a subset of STEMI patients.

  1 year

Study Arms (3)

STEMI

50 STEMI patients treated with standard therapy undergoing to primary percutaneous coronary internention (PPCI). Thromboaspiration will be performed whenever possible (when the anatomy of the coronary artery - curve and size- allowed it) in all patients with a TIMI Flow 0 and in all patients with a visible thrombus if TIMI Flow was 1 or more.

Stable angina

50 stable angina (SA) patients on standard therapy, undergoing to intracoronary blood aspiration during elective diagnostic and/or interventional coronary procedure, matched for age, sex and comorbidities with the 50 STEMI patients.

Controls

50 outpatients without coronary heart disease, matched for age gender and comorbidities like diabetes and hypertension with the 50 STEMI patients. Peripheral blood samples will be collected during routine patient monitoring.

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

1. STEMI patients referred to the catheterization laboratory for PPCI, who will undergo to manual coronary thrombo-aspiration, that fulfilled the inclusion/exclusion criteria, with a sufficient thrombotic material (≥1 mm3). 2. patients with chronic stable angina (SA) undergoing elective diagnostic and/or interventional coronary procedure, undergoing to intracoronary blood aspiration 3. outpatients without coronary heart disease matched for age, gender and comorbidities like diabetes and hypertension

You may qualify if:

• For STEMI patients:
• diagnosis of STEMI based on the current European Guidelines
• For SA patients:
• diagnosis of SA defined according to the European Guidelines as lack of episodes of coronary instability for at least 6 months prior to admission
• For control subjects:
• outpatients without diagnosis of coronary heart disease

You may not qualify if:

• estimated glomerular filtration rate less than 30 ml/min/m2
• acute or recent systemic infections (3 weeks)
• treatment with systemic corticosteroids
• treatment with oral anticoagulants
• malignancy
• lack of consent to participate

Sponsors & Collaborators

• University of Roma La Sapienza: lead
• Neuromed IRCCS: collaborator

Study Sites (1)

Internal and Medical Specialities Department - Policlinico Umberto I

Rome, 00162, Italy

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Peripheral blood, aspirated intra-coronary blood, aspirated coronary thrombi, aspirated plaque fragments from coronary culprit lesions.

MeSH Terms

Conditions

Myocardial Infarction; Acute Coronary Syndrome; Thrombosis

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Embolism and Thrombosis

Study Officials

• Francesco Violi, MD

  University of Roma La Sapienza

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Head of Internal Medicine, Clinical Professor

Study Record Dates

• First Submitted: September 15, 2018
• First Posted: September 18, 2018
• Study Start: January 2, 2013
• Primary Completion: July 6, 2018
• Study Completion: November 5, 2018
• Last Updated: November 21, 2018

Record last verified: 2018-11

Locations

IT (1)