Association of Endodontic Infection With Cardiovascular Disease Via Non-invasive Assessment of Endothelial Function

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.