Association of Endodontic Infection With Cardiovascular Disease.
Association of Endodontic Infection With Cardiovascular Disease.
Chronic inflammation plays a crucial role in the genesis of atherosclerosis and at the same
 time promotes acute cardiovascular events. Periodontal and pulpal inflammation are two major
 low grade chronic inflammatory infectious disease of oral cavity. Apical periodontitis is an
 inflammatory process, most often chronic in nature, of endodontic origin usually occurring at
 or near apex of the tooth root. The scientific literature has failed to provide the potential
 connection between endodontic infection and CV risk. Few studies have found the possible
 association, yet few studies does not suggest any link. The association between chronic
 inflammatory lesions and endothelial dysfunction can be detected using inflammatory, invasive
 and non-invasive markers. Inflammatory markers such as hs-CRP and Interleukins are not cost
 efficient and invasive markers- Angiography and Plethysmography are unethical to use on
 asymptomatic subjects. Non-invasive markers such as Flow mediated dilatation (FMD) and
 carotid intima media thickness (c-IMT) are inexpensive, fast and safe. The rationale of our
 study is to check the possible association between endodontic infection and CVD using
 non-invasive markers.
Cardiovascular Disease (CVD) is the primary non-communicable cause of global mortality
 killing more than 7 million people per year. Chronic inflammation plays a crucial role in the
 genesis of atherosclerosis which further leads to cardiovascular disease. Apical
 periodontitis is "an acute or chronic inflammatory lesion around the apex of a tooth caused
 by bacterial infection of the pulp canal system". Histologically, it is represented by a
 periapical inflammatory response that arises after resorption of adjacent supporting bone and
 local infiltration of inflammatory cells. In response to chronic inflammation, endothelium
 dysfunction occurs which leads to switch from a Nitric Oxide environment to a reactive oxygen
 dominated (ROS)-dominated inflammatory environment. The nitric oxide environment of the
 normal functional endothelium helps to maintain an equilibrium in the circulating system by
 inhibiting platelet aggregation, monocyte adhesion and vascular smooth muscle cell
 proliferation. Coronary endothelial dysfunction is considered an early stage of
 atherosclerosis and is associated with an increased risk of ischaemic cardiovascular
 outcomes. Several cross-sectional and longitudinal studies has shown the association of
 Apical periodontitis and Cardiovascular disease. Yet some studies states that there is no
 correlation and some showing the result is inconclusive making this link very controversial.
 All the studies are either hospital record based studies or they used inflammatory biomarkers
 for evaluating the association between endodontic infection and CVD which are very expensive.

 Clinically, vasoregulation has been measured in both the coronary and peripheral circulation,
 using changes in vessel diameter as an index of conduit vessel endothelial function. The
 three most common clinically used techniques are-(a) Angiography, (b) Flow mediated
 dilatation (FMD), (c) and Venous plethysmography. Due to the invasive nature of angiography
 and plethysmography, these methods are unsuitable to be used on asymptomatic patients.

 On the other hand, the non-invasive nature of the FMD allows repeated measurements over time
 to study the effectiveness of various interventions that may affect vascular health. The
 sensitivity and specificity of FMD is 95% and 37% respectively. Impaired
 endothelium-dependent dilatation in the coronary circulation is associated with coronary
 atherosclerosis and coronary risk factors and improves with risk reduction therapies. It has
 been shown FMD was an independent predictor of cardiovascular disease. Thus, brachial artery
 flow-mediated dilation prove useful to assess cardio- vascular risk, guide therapy, and judge
 the potential utility of new interventions for cardiovascular disease. FMD, which is most
 widely used non-invasive ultrasound method to assess endothelial function has been used in
 various interventional and cross-sectional studies depicting the link between periodontitis
 and endothelial dysfunction. But no such studies has been done evaluating the link between
 endodontic infection and endothelial dysfunction using these markers.

 Another commonly used non-invasive marker these days is Carotid Intima-media thickness (IMT).
 c-IMT is increasingly used as a surrogate end point of vascular outcomes in clinical trials
 aimed at determining the success of interventions that lower risk factors for atherosclerosis
 and associated diseases (stroke, myocardial infarction and peripheral artery diseases). This
 observer dependable technique, which serves both as an early detector and a follow up tool,
 provides information about common carotid (CCA), bifurcation, internal (ICA) and external
 carotid arteries. It has been established that abnormal baseline and rapid progressive CIMT
 are correlated to more cardiovascular and stroke events. Every 0.1 mm increase in the CIMT
 was associated with a 10-15% increase in the risk of myocardial infarction, and in the same
 line, a 13-18 % increase in stroke events. Many interventional and cross-sectional studies
 have shown the link between periodontitis and c-IMT.

 No prospective observational trial, to the best of our knowledge, has been done till date
 depicting the link between endodontic infection and cardiovascular disease using FMD and
 c-IMT. The aim of the present study is to depict that endodontic infection is also one of the
 novel risk factor of CVD using a non-invasive techniques i.e. Flow mediated dilatation (FMD)
 and c-IMT.

 AIMS AND OBJECTIVES To depict that Endodontic infection is associated with endothelial
 dysfuction by measuring flow mediated dilatation (FMD) of brachial artery and carotid intima
 media thickness (c-IMT) of common carotid artery.

 MATERIALS AND METHODS

 The present study will be done in the department of Radiology, PGIMS, Rohtak and Department
 of Cardiology, PGIMS, Rohtak.

 Study subjects will be obtained from the pool of OPD patients in the Department of
 Conservative dentistry and Endodontics, PGIDS, Rohtak.

 METHODOLOGY 35 patients who consecutively registered for a dental checkup at the OPD and
 fulfilled the previously mentioned criteria will be enrolled.

 Additional 35 patients who were free from clinical and radiographic evidence of AP and met
 the inclusion and exclusion criteria of the study will be included as contols.

 All individuals aged will underwent a complete CV assessment including medical history,
 physical examination, blood pressure measurement and 12-lead electrocardiogram.

 A complete dental examination will be performed on each patient in both groups.

 DENTAL EXAMINATION A panoramic radiograph will be examined and used as initial screening . It
 will be followed by selected periapical radiographs taken on teeth suspected of presenting AP
 and in all teeth with root canal treatments or presenting extensive restorations (including
 prosthetic restorations) with or without previous endodontic treatment.

 Periapical radiographs were taken with a radiographic unit by using a long cone paralleling
 technique.

 By using both radiographic and intraoral evaluations the following parameters were recorded:

 1. Number of teeth present

 2. Number and location of restored teeth

 3. Number of endodontically treated teeth

 4. Number and location of teeth affected by carious processes

 5. Soft tissue assessment (presence and location of swelling/sinus tracts)

 6. Periodontal probing

 7. Number and location of teeth with AP

 8. State of the upper and lower jaws Brachial Artery Assessment Patient preparation 1) Fast
 at least 8-12 hours before study. 2) Should not exercise, should not ingest substances
 like caffeine, high fat foods, vit C or tobacco at least 4-6 hours before study.

 Clinical Procedure The diameter of the target artery (right brachial artery) was measured
 from two- dimensional ultrasound images, with a 70 MHz linear array transducer and a standard
 128XP/10 system (Acuson, Mountain View, California, USA).

 Patient is placed in supine position with arm comfortably placed. Right brachial artery will
 be imaged above antecubital fossa in longitudinal plane.

 In each study 4 scans will be taken:

 Scan1 (At rest) The subject lay at rest for at least 10 min before a first resting scan will
 be recorded.

 Then diameter of the artery will be measured from anterior to the posterior "m" line (the
 interface between intima media and intima adventitia)

 Arterial flow velocity will be measured, by means of a pulsed doppler signal at a 70deg angle
 to the vessel in the centre of the artery.

 Scan 2 (Endothelium dependent FMD) Increased flow was then induced by inflation of a
 pneumatic tourniquet to a pressure of at least 50 mm Hg above systolic pressure for 4-5 min
 (reactive hyperaemia).

 A second scan was taken for 30 s before and 90 s after cuff deflation, including a repeat
 flow velocity recording for the first 15 s after cuff release.

 Brachial Artery diameter will be taken 45-60 sec after cuff deflation.

 Scan3 (Again at rest) At least 10 min of rest is needed after reactive hyperaemia before
 another image is acquired to reflect the re-established baseline conditions.

 Third scan is taken at this point of time. Scan4 (Endothelium independent FMD) Then 0.4 mg of
 nitroglycerine (GTN) is given sublingually. (GTN will be omitted if the patient refuse or if
 the patient had a history of migraine headaches, systolic blood pressure <100 mm Hg, previous
 adverse reaction to nitrates, or critical carotid artery stenosis) After 4 min fourth and
 final scan will be taken. Carotid intima-media thickness (c-IMT) Common carotid artery (CCA)
 will be used because of its convenience and high reproducibility.

 c-IMT will be assessed by M-mode ultrasonography via a vivid 7 MHz linear array transducer
 and a standard 128XP/10 system (Acuson, Mountain View, California, USA) with participants in
 the supine position.

 CCA will be scanned on longitudinal two-dimensional planes. Images will be obtained at the
 level of distal 1.0 cm of the right CCA. When an optimal image will be obtained, it was
 frozen on the R wave of the electro- cardiogram and stored on videotape.

 For each segment, the c-IMT of the posterior wall will be measured automatically over 200
 pixels with computer-assisted electronic callipers.

 Maximal right CCA thickness will be measured and used for analysis. Primary Outcome variable
 The primary outcome variables observed for the study will be the difference in the FMD and
 c-IMT of the test group and control group.
Inclusion Criteria:

 -  20-40 years of Male.

 -  Presence of apical periodontitis as assessed both clinically and radiographically
 (teeth with apical symptoms but without radiographic appearance of AP were not
 include).

 -  Presence of at least 25 teeth.

 -  Echocardiographic Left Ventricle Ejection Fraction (LVEF) value >55%.

 -  Hepatic and renal function within normal limits (bilirubin<1.5mg/dl;
 creatine<2.0mg/dl).

 Exclusion Criteria:

 -  Presence of localized or diffuse periodontal disease.

 -  Presence of non-endodontic lesion in Maxilla/ mandible.

 -  Presence of cardiovascular risk factors(arterial hypertension, dyslipidemia, DM,
 obesity, smoking)

 -  LV hypertrophy at echocardiography previous or current CVD.

 -  Presence of chronic inflammatory conditions in other regions involving systemic
 health.

 -  For women, use of anticonceptive hormones.

 -  Systemic antibiotic treatment within the previous 3 months or any other regular
 medication.