Periodontal Disease, Inflammation and Acute Coronary Syndromes

NCT ID: NCT03395041

Last Updated: 2022-08-02

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 149 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-05-15
• Study Completion Date: 2021-06-01

Brief Summary

Recent studies have shown that the systemic inflammation caused by periodontal disease (PD) can determine important changes in the coronary arteries, favoring atherosclerosis progression and development of acute coronary syndromes (ACS). The aim of ATHERODENT study is to assess the interrelation between PD, inflammation and progression of coronary atherosclerosis in patients with ACS. Material and methods: This case-control observational study will enroll 100 patients (group 1 - ACS and associated PD, and group 2 -ACS and no PD), in whom the following data will be collected: (1) demographic and clinical data, (2) cardiovascular risk factors, (3) full characterization of PD markers, (4) systemic inflammatory biomarkers, (5) imaging biomarkers derived from transthoracic echocardiography, computed tomography, coronary angiography, optical coherence tomography and intravascular ultrasound, and (6) assessment of the presence of specific oral bacteria in samples of coronary plaques collected by coronary atherectomy, which will be performed during percutaneous revascularization interventions, when indicated in selected cases, in the atherectomy sub-study. The follow-up will be performed at 1, 3, 6, 12, 15, 18 and 24 months. The primary endpoint of the study will be represented by the rate of major adverse cardiovascular events (MACE rates) in PD vs non-PD patients and in correlation with: (1) the level of systemic inflammation triggered by PD and/or by ACS at baseline; (2) the vulnerability degree of atheromatous plaques in the coronary tree (culprit and non-culprit lesions); and (3) the presence and burden of oral bacteria in atheromatous plaques. Secondary endpoints will be represented by: (1) the rate of progression of vulnerability degree of non-culprit coronary plaques; (2) the rate of progression of atheromatous burden and calcium scoring of the coronary tree; and (3) the rate of occurrence of left ventricular remodeling and postinfarction heart failure.

Detailed Description

ATHERODENT is a case-controlled observational clinical study, conducted in two clinical sites: University of Medicine and Pharmacy Tirgu Mures, Romania, and Cardio Med Medical Center - Laboratory of Advanced Research in Multimodality Imaging.

The primary objective of ATHERODENT is to assess the interrelation between PD, inflammation and atherosclerosis progression in patients who suffered an ACS and have concomitant PD vs those with ACS and no PD, using (1) invasive and non-invasive imaging techniques for characterization of vulnerable coronary plaques; (2) full characterization of PD; and (3) complex assessment of systemic vulnerability based on systemic inflammation-related biomarkers.

The secondary objectives of ATHERODENT are:

1. to study the correlation between PD and coronary plaque vulnerability

2. to assess the correlation between PD and severity of coronary atherosclerosis

3. to assess the presence and burden of oral bacteria in coronary atheromatous plaques collected during atherectomy and their relation with plaque vulnerability and evolution following an ACS (in the atherectomy sub-study).

Baseline will be considered as the moment of the index event and related hospitalization. The index event will be considered the ACS and patients will be randomized in the study at maximum 7 days post ACS. The follow-up visits will be performed at 1, 3, 6, 12, 15, 18 and 24 months after randomization.

The following procedures will be performed at baseline:

1. recording of demographic and clinical data (age, gender, personal history)

2. determination of serum lipids, blood counts, glycemia, urea, creatinine, liver enzymes

3. determination of the biomarkers expressing the severity of the acute coronary syndrome and heart damage (hs-Troponin, NT-proBNP)

4. determination of serum levels inflammatory biomarkers and adhesion molecules at the moment of the index event (hs-CRP, matrix metalloprotease, interleukin-6, VCAM, ICAM)

5. determination of specific micro-RNAs related to plaque vulnerability

6. echocardiography (+ speckle tracking) for assessment of left ventricular function and size

7. full characterization of PD (dental plaque/tartar, gingival retraction, gingival bleeding, etc.)

8. microbiological determination of oral bacteria from the periodontal pockets

9. non-invasive imaging by coronary angioCT for all the coronary tree and characterization of vulnerability markers and atherosclerosis severity, using surrogate imaging biomarkers such as calcium score, necrotic core, plaque burden, low density atheroma, positive remodeling, epicardial fat volume

10. invasive imaging performed during invasive revascularization procedures, using intracoronary imaging techniques (OCT, IVUS) and quantification of invasive imaging biomarkers in culprit and non-culprit lesions, such as macrophage content, thickness of fibrous cap and necrotic core.

11. atherectomy of coronary culprit atheromatous plaques (in the atherectomy sub-study), performed during the revascularization procedure when indicated, in selected cases, followed by histological examination of the samples collected in order to identify specific antigens related to oral microbiota in the atheromatous tissue of coronary vulnerable plaques.

Follow-up will be performed at 1, 3, 6, 12, 15, 18 and 24 months after randomization, including assessment of clinical data, echocardiography and registration of MACE and adverse events.

In addition, complex imaging assessment using Angio CT will be performed at 2 years to assess atherosclerosis progression.

Conditions

Coronary Stenosis; Periodontal Diseases; Acute Coronary Syndrome; Non-ST Elevation Myocardial Infarction; Unstable Angina; Acute Myocardial Infarction; Atherosclerosis; Atheromatous Plaques

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

ATD - SG 01

Patients with acute coronary syndrome in whom dental examination performed in the first 7 days after the index event revealed the presence of periodontal disease.

They will undergo complex cardiac imaging tests to assess plaque vulnerability and severity of coronary artery disease.

cardiac imaging tests

Intervention Type: DIAGNOSTIC_TEST

cardiac computed tomography, echocardiography, intravascular ultrasound, optical coherence tomography

ATD - SG 02

Patients with acute coronary syndrome in whom dental examination performed in the first 7 days after the index event did not reveal the presence of periodontal disease.

They will undergo complex cardiac imaging tests to assess plaque vulnerability and severity of coronary artery disease.

cardiac imaging tests

Intervention Type: DIAGNOSTIC_TEST

cardiac computed tomography, echocardiography, intravascular ultrasound, optical coherence tomography

Interventions

cardiac imaging tests

cardiac computed tomography, echocardiography, intravascular ultrasound, optical coherence tomography

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Patients aged at least 18 years;
• Patients who have signed the written informed consent;
• Patients with ACS (unstable angina or non-ST segment elevation myocardial infarction) occurring with maximum 7 days prior to enrollment

Exclusion Criteria

• Patient's refusal to participate in the study;
• Sensitivity to the contrast substance;
• Women of reproductive age who do not use contraceptive methods;
• Pregnant women;
• Any malignancy within the last 5 years;
• Any disease or comorbidity that can reduce life expectancy to less than 2 years;
• Acute or chronic renal failure;
• Non-compliant patients who, in the opinion of the investigators, will not present to follow-up.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Targu Mures, Romania

OTHER

Sponsor Role: collaborator

University Hospital of Targu Mures, Romania

OTHER

Sponsor Role: collaborator

Cardio Med Medical Center

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Theodora Benedek, Prof

Role: PRINCIPAL_INVESTIGATOR

University of Medicine and Pharmacy Tirgu Mures, CardioMed Medical Center

Locations

Cardio Med

Târgu Mureş, Mureș County, Romania

Countries

Romania

Other Identifiers

CM0117-ATD

Identifier Type: -

Identifier Source: org_study_id