Periodontal Disease, Inflammation and Acute Coronary Syndromes

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:

• to study the correlation between PD and coronary plaque vulnerability
• to assess the correlation between PD and severity of coronary atherosclerosis
• 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:

• recording of demographic and clinical data (age, gender, personal history)
• determination of serum lipids, blood counts, glycemia, urea, creatinine, liver enzymes
• determination of the biomarkers expressing the severity of the acute coronary syndrome and heart damage (hs-Troponin, NT-proBNP)
• determination of serum levels inflammatory biomarkers and adhesion molecules at the moment of the index event (hs-CRP, matrix metalloprotease, interleukin-6, VCAM, ICAM)
• determination of specific micro-RNAs related to plaque vulnerability
• echocardiography (+ speckle tracking) for assessment of left ventricular function and size
• full characterization of PD (dental plaque/tartar, gingival retraction, gingival bleeding, etc.)
• microbiological determination of oral bacteria from the periodontal pockets
• 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
• 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.
• 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.

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.