DENTAL INFECTIONS AND THE ATHEROSCLEROSIS RISK IN A SUBPOPULATION OF SOUTH ROMANIA

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1 Oral Pathology DENTAL INFECTIONS AND THE ATHEROSCLEROSIS RISK IN A SUBPOPULATION OF SOUTH ROMANIA Alexandru Andrei ILIESCU, Paula PERLEA, Ruxandra Diana SINESCU, Delia VOICULESCU, Laura DÂRŢU, Georgiana ILIESCU, Anca TORCĂTORU 7, Irina GHEORGHIU 8, Bogdan VLĂDILĂ 9, Oana Andreea DIACONU 0, Cristian PETCU, Andrei ILIESCU, Ion Bogdan CODOREAN Senior lecturer, DMD, DDS, PhD, Faculty of Dental Medicine, University of Craiova, Romania Senior lecturer, DMD, PhD, Faculty of Dental Medicine, Carol Davila University of Bucharest, Romania Assoc. Prof., MD, PhD, Elias Emergency Teaching Hospital, Carol Davila University of Bucharest, Romania MD, PhD student, Cardiology Clinic, SCUBA, Bucharest, Romania Senior lecturer, PhD, Faculty of Medical Dentistry, Apollonia University of Iaşi, Romania DMD, PhD student, Faculty of Dental Medicine, Carol Davila University of Bucharest, Romania 7 Univ. Assist., DMD, PhD, Faculty of Dental Medicine, University of Târgu Mureş, Romania 8 Senior lecturer, DMD, PhD, Faculty of Dental Medicine, Carol Davila University of Bucharest, Romania 9 DMD, PhD student, private practice, Bucharest, Romania 0 Senior lecturer, DMD, PhD, Faculty of Dental Medicine, University of Craiova, Romania Univ. Assist., DMD, PhD, Faculty of Dental Medicine, University of Craiova,Romania Profesor, DMD, PhD, Faculty of Medical Dentistry, Apollonia University of Iaşi, Romania Univ.Assist., MD, PhD, Universitary Emergency Military Central Hospital, Carol Davila University of Bucharest, Romania Corresponding author: prof.andrei.iliescu@gmail.com Abstract Periodontal disease and chronic apical periodontitis are considered risk factors for cardiovascular diseases. This cross-sectional study, performed in a subpopulation living in the South area of Romania, investigated the association between the afore-mentioned oral lesions and atherosclerosis. The research was focused on common carotid artery intima-media wall thickness IMT and dislipidemia, in a batch of 0 subjects, age -0. Over 0% of the patients diagnosed with periodontal disease and/or chronic apical periodontitis developed subclinical atherosclerosis. Associated dyslipidemia to an increased IMT over 0.9 mm in subjects affected by periodontal disease or combined lesions with chronic apical periodontitis might be considered a strong predictor of future cardiovascular events. Keywords: periodontal disease, chronic apical periodontitis, atherosclerosis, dislipidemia, IMT. INTRODUCTION The concept linking the oral pathology and systemic diseases is not a new one. Over the past century, the focal infection theory resulted in millions of tooth extractions, claiming that periodontal and apical lesions represent the main risk for systemic inflammatory and infectious complications []. Even if, initially, this undiscriminating therapeutic attitude was not supported by rigorous scientific evidence, current epidemiologic studies relate an increasing relationship between oral diseases and systemic pathology, such as atherosclerosis, cardiovascular diseases, diabetes, adverse pregnancy outcome or lung diseases [,]. Along with age, hypertension, diabetes, smoking, total cholesterol, high triglycerides, CRP (C-reactive protein), to date chronic periodontal and apical inflammations are also considered risk factors for cardiovascular diseases [-]. This issue is of paramount importance, as anaerobic gram-negative bacteria from periodontal deep pockets or infected tooth root canals, such as Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, appeared as involved in multiple pathogenic mechanisms, including the direct invasion of endothelial cells []. Considering the above-mentioned pathogenic hypothesis, the objective of the present crosssectional study was to illustrate the possible association between periodontal disease and chronic apical periodontitis and atherosclerosis, International Journal of Medical Dentistry

2 Alexandru Andrei ILIESCU, Paula PERLEA, Ruxandra Diana SINESCU, Delia VOICULESCU, Laura DÂRŢU, Georgiana ILIESCU, Anca TORCĂTORU, Irina GHEORGHIU, Bogdan VLĂDILĂ, Oana Andreea DIACONU, Cristian PETCU, Andrei ILIESCU, Ion Bogdan CODOREAN in a subpopulation living in the South area of Romania.. MATERIALS AND METHOD 0 consecutive cardiac patients with confirmed hypertension (systolic blood pressure 0 mm Hg or diastolic blood pressure 90 mm Hg), with ages between -0 years and no history of myocardial infarction or stroke, were recruited. A similar (as to age, gender, smoking habits, and residence) number of 0 matched clinically patients were enrolled as controls. Patients with other chronic infections than dental disease were excluded. The same exclusion and inclusion criteria were applied to both groups of subjects who underwent a comprehensive oral examination to diagnose periodontitis, defined by an attachement loss mm, and apical periodontitis. A calibration exercise was previously performed to obtain acceptable intra-examiner reproducibility for probing depth and recession of the gingival margin. Panoramic radiographs of the jaws were taken and, in case of apical radiolucensis, additional isolated periapical radiographs for irrespective tooth. A single specialist performed all radiographic examinations. Blood samples were collected to evaluate serum total cholesterol and triglycerides, and common carotid artery intima-media wall thickness (cimt) was measured in each patient, using a high-resolution B-mode ultrasound carotid scan KI-lM00HDPE (Siemens), at a frequency of 0-0Hz.. RESULTS As general characteristics, women and men were present in equal ratios in both groups, but women were younger (. vs.0) so that, according to age, the distribution is unequal (Fig.). pacients number y y y y y y 7y 8y 9y 0y men women Fig.. Distribution of subjects according to age As expected, average plaque thickness registered higher average values in subjects, comparatively with the group (0.9 mm vs 0.87 mm). However, the average plaque thickness size had close values in both men and women (Fig.), with discretely higher records in men (0.88 mm vs 0.87 mm in, respectively 0.9 vs 0.9 in ones). volume 9 issue April / June 0 pp. -

3 DENTAL INFECTIONS AND THE ATHEROSCLEROSIS RISK IN A SUBPOPULATION OF SOUTH ROMANIA In subjects, out of 0 (.%) had IMT 0.9 mm, as compared to the ones, where 9 out of 0 (.%) recorded similar values. 0,9 0,9 average IMT 0,88 0,87 men women Fig.. Average IMT values in and subjects Combined lesions (periodontitis and chronic apical periodontitis) and periodontitis are prevalent in subjects, comparatively with the ones (Fig.) Periodontitis Chronic apical periodontitis Combined Fig.. Distribution of periodontitis and chronic apical periodontitis International Journal of Medical Dentistry

4 Alexandru Andrei ILIESCU, Paula PERLEA, Ruxandra Diana SINESCU, Delia VOICULESCU, Laura DÂRŢU, Georgiana ILIESCU, Anca TORCĂTORU, Irina GHEORGHIU, Bogdan VLĂDILĂ, Oana Andreea DIACONU, Cristian PETCU, Andrei ILIESCU, Ion Bogdan CODOREAN Dislipidemia was considered when serum total cholesterol increased > 00 mg/dl, serum triglycerides were > 0 mg/dl or both were increased. The occurrence of dislipidemia is illustrated in relation with oral pathology (Fig.) and IMT (Fig.). 7 0 Periodontitis Chronic apical periodontitis Combined No lesion Fig.. Dislipidemia vs dental and periodontal pathology subjects number 0 0 0,7mm 0,8mm 0,9mm mm,mm,mm Fig.. Dislipidemia vs IMT volume 9 issue April / June 0 pp. -

5 DENTAL INFECTIONS AND THE ATHEROSCLEROSIS RISK IN A SUBPOPULATION OF SOUTH ROMANIA. DISCUSSION Atherosclerosis is a multifactorial disease and its conventional risk factors, such as age, sex, smoking, diabetes, obesity, systolic blood pressure, low- and high-density lipoprotein cholesterol, triglycerides, are well understood []. Unfortunately, they can justify only 0-70% of the clinical events [7]. Among other putative factors in the biological background of atherosclerosis, a pivotal pathogenic role is played low-grade chronic inflammation and infection [8,9]. Dental infections, periodontal disease and apical periodontitis are favorable candidates as trigger factors of atherosclerosis and cardiovascular diseases [0-]. It was proved that, in patients with periodontal disease, atherosclerotic complications - such as coronary artery disease, myocardial infarction and stroke - are strongly associated. Moreover, they depend on the severity of gingival inflammation and bone resorption [7,7]. As to the connection between chronic apical periodontitis and the subsequent in time occurring cardiovascular events, current reports are still confusing. Though the pathogenic mechanisms of periodontal disease and chronic apical periodontitis and their link to cardiovascular diseases might be similar, clinical evidence does not support an association between chronic apical inflammatory lesions and cardiovascular diseases [8]. Apparently, the association between chronic apical periodontitis and cardiovascular diseases is more obvious in young people. It is assumed that, in older subjects, some other mechanisms might prevail in developing a cardiovascular disease [,8,]. The purpose of this cross-sectional study was to determine to what extent the periodontal disease and chronic apical periodontitis are associated with carotid artery intima-media wall thickness (IMT), a widely adopted surrogate for predicting rates of cardiovascular events [,8,9]. The control group had no cardiovascular events or current clinical heart disturbances. However, in.% of the subjects, the IMT value was 0.9 mm, which means that they had already developed subclinical atherosclerosis. As expected, the average IMT counts were higher in subjects, compared to the ones. The present study also revealed a higher prevalence of dislipidemia in periodontal disease and combined lesions. In periodontal disease, no differences were observed between and subjects. Surprisingly, in chronic apical periodontitis, the values of dislipidemia were higher in subjects, as compared to ones. Probably, our results converge to the above-mentioned reports on the association of chronic apical periodontitis with heart diseases, as the participants in our group of study were not exactly young (between 0 and 0 years). Moreover, some dislipidemic subjects were not affected by any inflammatory or infective oral disease prone to initiate a cardiovascular disease. It has also to be highlighted that, when IMT exceeds 0.9 mm, which is an overt signal of atherosclerosis, the prevalence of dislipidemia in subjects shows a strong trend to equalize the similar IMT value in ones. While the pathogenic link of gingival inflammation with cardiovascular diseases is already accepted, the role of chronic apical periodontitis is still confusing and controversial. According to our results, it seems that root canal infection might be only a cumulative contributor to developing a cardiovascular disease, associated to a previous or simultaneous periodontal disease. However, it has to be considered that, in patients affected by periodontal disease and/or chronic apical periodontitis, association of dislipidemia with an increased IMT are strong predictors of future cardiovascular events.. CONCLUSIONS. Over 0% of the patients (age 0-0) diagnosed with periodontal disease and/or chronic apical periodontitis developed subclinical atherosclerosis.. Associated dislipidemia to an increased IMT over 0.9 mm in patients affected by periodontal disease or combined lesions with International Journal of Medical Dentistry

6 Alexandru Andrei ILIESCU, Paula PERLEA, Ruxandra Diana SINESCU, Delia VOICULESCU, Laura DÂRŢU, Georgiana ILIESCU, Anca TORCĂTORU, Irina GHEORGHIU, Bogdan VLĂDILĂ, Oana Andreea DIACONU, Cristian PETCU, Andrei ILIESCU, Ion Bogdan CODOREAN chronic apical periodontitis might be considered a strong predictor of future cardiovascular events. References. Lindhe J, Karring T, Lang NP. Clinical periodontology and implant dentistry. th edition. Oxford: Blackwell Munksgaard; 00. Chapter, Williams RC, Paquette D. Periodontitis as a risk for systemic disease; p -8.. Marton, IJ. How does the periapical inflammatory process compromise general health? Endod Topics. 00; 8:-.. Baldassarre D, Veglia F, Hamsten A, Humphries SE, Rauramaa R, de Faire U, Smit AJ, Giral P, Kurl S, Mannarino E, Grossi E, Paoletti R, Tremoli E. Progression of carotid intima-media thickness as predictor of vascular events. Arterioscler Thromb Vasc Biol. 0; : Caplan D. Epidemiologic issues in studies of association between apical periodontitis and systemic healt. Endod Topics. 00; 8:-.. Reyes L, Herrera D, Kozarov E, Roldan S, Progulske- Fox A. Periodontal bacterial invasion and infection: contribution to atherosclerotic pathology. J Clin Periodontol. 0; 0:S0-S0.. Desvarieux M, Demmer RT, Rundek T, Boden- Albala B, Jacobs DR, Papapanou PN, Sacco RL. Relationship between periodontal disease, tooth loss, and carotid artery plaque. The oral infections and vascular disease epidemiology study (INVEST). Stroke. 00; : Haynes WG, Stanford C. Periodontal disease and atherosclerosis. From dental to arterial plaque. Arterioscler Thromb Vasc Biol. 00; : Cotti E, Dessi C, Piras A, Mercuro G. Can chronic dental infection be considered a cause of cardiovascular diseases? A review of the literature. Int J Cardiol. 0; 8: Yu YH, Chasman DI, Buring JE, Rose L, Ridker PM. Cardiovascular risks associated with incident and prevalent periodontal disease. J Clin Periodontol. 0; : Beck JD, Pankow J, Tyroler HA, Offenbacher S. Dental infections and atherosclerosis. Am Heart J. 999; 8:8-.. Deshpande RG, Khan MB, Genco CA. Invasion of aortic and heart endothelial cells by Porphyromonas gingivalis. Infect Immun. 998; :7-.. Haraszthy V, Zambon J, Trevisan M. Identification of periodontal pathogens in atheromatous plaques. J Periodontol. 000; 7:-0.. Abbas M, Bignamini V, Corea F. Effects of chronic microbial infection on atherosclerosis. Atherosclerosis. 00; 87: Joshipura KJ, Pitiphat W, Hung H, Willett WC, Colditz GA, Douglass CW. Pulpal inflammation and incidence of coronary heart disease. J Endod. 00; : Niedzielska I, Janic T, Cierpka S, Swietochowska E. The effect of chronic periodontitis on the development of atherosclerosis: review of the literature. Med Sci Monit. 008; :0-0.. Willershausen B, Kasaj A, Willershausen I, Zahorka D, Briseno B, Blettner M, Genth-Zotz S, Münzel T. Association between chronic dental infection and acute myocardial infarction. J Endod. 009; : Söder PO, Söder B, Nowak J, Jogestrand T. Early carotid atherosclerosis in subjects with periodontal diseases. Stroke. 00; : Engebretson SP, Lamster IB, Elkind MSV, Rundek T, Serman NJ, Demmer RT, Sacco RL, Papapanou PN, Desvarieux M. Radiographic measures of chronic periodontitis and carotid artery plaque. Stroke. 00; :-. 9. Finn AV, Kolodgie FD, Virmani R. Correlation between carotid intimal/medial thickness and atherosclerosis. A point of view from pathology. Arterioscler Thromb Vasc Biol. 00; 0:77-8. volume 9 issue April / June 0 pp. -