Association Between Apical Periodontitis and Atherosclerotic Cardiovascular Diseases

Study Overview
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Brief Summary
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The aim of the study is to evaluate the association between apical periodontitis (AP) and atherosclerotic cardiovascular disease (ASCVD) by assessing the multiplicative effect of AP on secondary outcomes of ASCVD. Sixty-two subjects will be enrolled from the Unit of Endodontics and Restorative dentistry and allocated into 2 distinct groups depending on the presence or absence of periapical lesions. Group 1 will be composed of 31 patients with radiographic signs of AP. On the contrary, another 31 healthy individual (free from clinical and radiographic evidence of AP) meeting the inclusion and exclusion criteria were included as controls (group 2) A complete dental examination will performed on each patient in both groups. All the patients will be subjected to a cardiovascular examination to assess carotid intima-media thickness (cIMT), presence of abdominal aortic aneurysm, presence of peripheral pulses through echo-color-doppler.

Detailed Description
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The aim of the present case-control study is to evaluate the multiplicative effect of AP on secondary outcomes of ASCVD. Sixty-two subjects will be enrolled from the Unit of Endodontics and Restorative dentistry of the university of Siena. The inclusion criteria of the study are healthy patients older than 40 years old, the presence of at least 24 teeth and the ability and willingness to give informed consent.Participants affected by any systemic disease or being administered either antibiotics in the last 6 months or antiaggregant, antiplatelet and antihypertensive medications will be excluded from this study. The atherosclerosis risk factors excluded in our study are prior or existing signs of CVD, smoking habits, diabetes, obesity, arterial hypertension, dyslipidemia, and echocardiographically detectable left ventricular hypertrophy. Patients with periodontal disease and lesions other than endodontic etiology in maxilla/mandible are also excluded from this study. Participants that were pregnant or lactating females, non-Italian, or only English-speaking are also excluded from the study, as well as those who were unable or unwilling to give informed consent. Sixty-two subjects fulfilling the previously described criteria will be enrolled from the outpatient department and allocated into two distinct groups depending on the presence or absence of periapical lesions. Group 1 will be composed of 31 patients with radiographic signs of AP. On the contrary, another 31 healthy individuals (free from clinical and radiographic evidence of AP) meeting the inclusion and exclusion criteria will be included as controls (group 2) and matched on age, BMI, sex, and physical characteristics. AP cases will be designated those patients with at least one tooth exhibiting radiographic evidence of apical radiolucency exceedingly twice the width of the periodontal ligament space. A complete dental examination will be performed on each patient in both groups. To perform the initial screening, patients will undergo panoramic radiography and clinical examination followed by periapical radiographs of the teeth suspected of AP using the long cone paralleling technique with a film holder. The following parameters will be recorded: The number of decayed, missing, and filled teeth (DMFT index) The number of teeth with AP Periapical Index Score All measurements will be recorded by one endodontist (GM). All individuals will undergo cardiovascular examination in the Unit of Vascular Surgery, University of Siena (Siena, Italy). The cardiovascular assessment included physical examination, blood pressure measurement, past medical history, and echo-color-doppler where carotid intima-media thickness (cIMT), presence of abdominal aortic aneurysm, presence of peripheral pulses through echo-color-doppler will b assessed. The results expected from this study are: a significant increase in ASCVD secondary parameters (outcomes) in patients with PA (exposure factor), compared with subjects without PA; significant association between BP and the presence of peripheral pulses and abdominal aortic aneurysm, respectively.

Official Title
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Association Between Apical Periodontitis and Atherosclerotic Cardiovascular Diseases: a Case-control Study

Conditions
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Apical Periodontitis, Atherosclerotic Cardiovascular Disease

Intervention / Treatment
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* Diagnostic Test: Echo-color-doppler


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients older than 40 years old the presence of at least 24 teeth the ability and willingness to give informed consent Exclusion Criteria: any systemic diseases antibiotic administration in the last 6 months antiaggregant, antiplatelet and antihypertensive medications existing signs of CVD smoking habits, diabetes obesity arterial hypertension dyslipidemia periodontal disease lesions other than endodontic etiology in maxilla/mandible were also excluded from this study pregnant or lactating females non-Italian or only English speaking inability or unwillingness to give informed consent.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Apical Periodontitis<br>Patients with radiographic signs of Apical Periodontitis. The inclusion criteria of the study are healthy patients older than 40 years old, the presence of at least 24 teeth and the ability and willingness to give informed consent. Participants affected by any systemic disease or being administered either antibiotics in the last 6 months or antiaggregant, antiplatelet and antihypertensive medications are excluded from this study. The atherosclerosis risk factors excluded in our study are signs of CVD, smoking habits, diabetes , obesity, arterial hypertension, dyslipidemia. Patients with periodontal disease and lesions other than endodontic etiology in maxilla/mandible will be also excluded from this study ). Participants that were pregnant or lactating females, non-Italian or only English speaking will also also excluded from the study, as well as those who were unable or unwilling to give informed consent. | Diagnostic Test: Echo-color-doppler<br>* To perform the initial screening patients will undergo panoramic radiography and clinical examination followed by periapical radiographs of the teeth suspected of AP using the long cone paralleling technique with a film holder. The following parameters will be recorded: The number of decayed, missing and filled teeth (DMFT index) The number of teeth with AP Periapical Index Score All individuals will undergo a cardiovascular examination in the Unit of Vascular Surgery, University of Siena (Siena, Italy). The cardiovascular assessment included physical examination, blood pressure measurement, past medical history and echo-color-doppler for the assessment of carotid intima-media thickness (cIMT), presence of abdominal aortic aneurysm and presence of peripheral pulses.<br>* Other names: Cardiovascular Examination;|
| Control<br>healthy individual free from clinical and radiographic evidence of AP. The inclusion criteria of the study are healthy patients older than 40 years old, the presence of at least 24 teeth and the ability and willingness to give informed consent. Participants affected by any systemic disease or being administered either antibiotics in the last 6 months or antiaggregant, antiplatelet and antihypertensive medications are excluded from this study. The atherosclerosis risk factors excluded in our study are signs of CVD, smoking habits, diabetes , obesity, arterial hypertension, dyslipidemia. Patients with periodontal disease and lesions other than endodontic etiology in maxilla/mandible will be also excluded from this study ). Participants that were pregnant or lactating females, non-Italian or only English speaking will also also excluded from the study, as well as those who were unable or unwilling to give informed consent. | Diagnostic Test: Echo-color-doppler<br>* To perform the initial screening patients will undergo panoramic radiography and clinical examination followed by periapical radiographs of the teeth suspected of AP using the long cone paralleling technique with a film holder. The following parameters will be recorded: The number of decayed, missing and filled teeth (DMFT index) The number of teeth with AP Periapical Index Score All individuals will undergo a cardiovascular examination in the Unit of Vascular Surgery, University of Siena (Siena, Italy). The cardiovascular assessment included physical examination, blood pressure measurement, past medical history and echo-color-doppler for the assessment of carotid intima-media thickness (cIMT), presence of abdominal aortic aneurysm and presence of peripheral pulses.<br>* Other names: Cardiovascular Examination;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Carotid Intima medial Thickness (c-IMT) | C-IMT measurements are done in mm, and they are taken from the right and left common carotid artery (CCA) and they are used as surrogate endpoints to diagnose early signs of carotid atherosclerotic cardiovascular diseases. | The time frame for this observational study is defined by the initial assessment conducted at baseline. No follow-up measurements are scheduled, and the study aims to explore associations and characteristics at a single time point | 
| Presence of Carotid Plaque | the presence of atherosclerotic plaques is considered as a surrogate endpoint point variable to diagnose early alterations of carotid atherosclerotic cardiovascular disease. Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. | The time frame for this observational study is defined by the initial assessment conducted at baseline. No follow-up measurements are scheduled, and the study aims to explore associations and characteristics at a single time point | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| North American Symptomatic Carotid Endarterectomy Trial (NASCET) | The NASCET method is used to calculate the percentage of stenosis in carotid arteries. The NASCET percentage is the ratio between the residual diameter at the stenosis and the surface of the distal normal lumen where there is no stenosis subtracted by the residual diameter at the stenosis. | The time frame for this observational study is defined by the initial assessment conducted at baseline. No follow-up measurements are scheduled, and the study aims to explore associations and characteristics at a single time point | 
| Ankle Brachial Index (ABI) | The ankle-brachial index (ABI) is a non-invasive tool for the assessment of vascular status. It consists of the ratio between the systolic blood pressure of the lower extremity (i.e., the ankle) and the upper extremity. | The time frame for this observational study is defined by the initial assessment conducted at baseline. No follow-up measurements are scheduled, and the study aims to explore associations and characteristics at a single time point | 
| Right and Left Common Iliac Arteries (CIA) diameter | Measuring the diameter of the CIAs (mm) can be done to assess for potential conditions such as peripheral artery disease (PAD) or an abdominal aortic aneurysm (AAA | The time frame for this observational study is defined by the initial assessment conducted at baseline. No follow-up measurements are scheduled, and the study aims to explore associations and characteristics at a single time point | 
| Abdominal aorta maximum diameter | Measuring the diameter of the abdominal aorta (mm) can be done to assess for potential abdominal aortic aneurism. | The time frame for this observational study is defined by the initial assessment conducted at baseline. No follow-up measurements are scheduled, and the study aims to explore associations and characteristics at a single time point |