Clinical trial NCT03395041: Periodontal Disease, Inflammation and Acute Coronary Syndromes
Official title: Periodontal Disease, Inflammation and Atherosclerosis Progression in Patients With Acute Coronary Syndromes - the ATHERODENT Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Stenosis
Periodontal Diseases
Acute Coronary Syndrome
Non-ST Elevation Myocardial Infarction
Unstable Angina
Acute Myocardial Infarction
Atherosclerosis
Atheromatous Plaques
Keywords: vulnerable plaque, CT imaging, oral bacteria, inflammation
Lead sponsor: Cardio Med Medical Center
Sponsor class: INDUSTRY
Collaborators: name: University of Targu Mures, Romania
name: University Hospital of Targu Mures, Romania
First posted: 2018-01-10
Enrollment: 149
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with acute coronary syndromes (unstable angina or NSTEMI), who undergo invasive coronary angiography +/- revascularization (according to local protocols).

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.

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.

Primary outcomes:
measure: The rate of major adverse cardiovascular events (MACE rates).
timeFrame: 24 months
Secondary outcomes:
measure: The rate of progression of vulnerability degree of non-culprit coronary plaques
timeFrame: 24 months
measure: The rate of progression of atheromatous burden and calcium scoring
timeFrame: 24 months
measure: The occurrence of left ventricular remodeling and post-infarction heart failure
timeFrame: 24 months
Other outcomes:
Locations:
city: Târgu-Mureş
country: Romania
facility: Cardio Med
state: Mures
Study officials:
affiliation: University of Medicine and Pharmacy Tirgu Mures, CardioMed Medical Center
name: Theodora Benedek, Prof
role: PRINCIPAL_INVESTIGATOR
References: