Role of Periodontal Health in Cardiovascular Diseases.pptx

Role of Periodontal Health in Cardiovascular Diseases.

1. Role of Periodontal Health in Cardiovascular Diseases Arpit Galohda

2. Historical Timeline 1890 2023

3. W. Miller (1891) proposed that the mouth was a focus of infections that spread to other areas of the body Miller WD. 1891. The human mouth as a focus of infection. Lancet. 138(3546):340–342

4. Thomas J. Horder (1909) recognized that the mouth was a major portal for bacterial entry Horder TJ. Infective endocarditis: with an analysis of 150 cases and with special reference to the chronic form of the disease. Q J Med 1909; os2:289–324

5. Okell and Elliott (1935) reported bacteremia of oral origin in the etiology of infective endocarditis Okell C, Elliott TS. 1935. Bacteriaemia and oral sepsis with special reference to the aetiology of subacute endocarditis. Lancet. 2:869–872

6. Mattila et al. (1989) documented the association between poor dental health and coronary heart disease, independent of age, total cholesterol, high-density lipoprotein (HDL), triglycerides, C-peptide, hypertension, diabetes, and smoking Mattila et al. (1989) documented the association between poor dental health and coronary heart disease, independent of age, total cholesterol, high-density lipoprotein (HDL), triglycerides, C-peptide, hypertension, diabetes, and smoking Mattila KJ, Nieminen MS, Valtonen VV, Rasi VP, Kesäniemi YA, Syrjälä SL, Jungell PS, Isoluoma M, Hietaniemi K, Jokinen MJ. 1989. Association between dental health and acute myocardial infarction. BMJ. 298(6676):779–781

7. DeStefano et al. (1993) found participants with periodontitis had a 25% increased risk of coronary heart disease (CHD) relative to those with minimal periodontal disease DeStefano F, Anda RF, Kahn HS, Williamson DF, Russell CM. 1993. Dental disease and risk of coronary heart disease and mortality. BMJ. 306(6879):688–691

8. Beck et al. (1996) proposed mechanism for the interaction between periodontitis and cardiovascular disease Beck J, Garcia R, Heiss G, Vokonas PS, Offenbacher S. 1996. Periodontal disease and cardiovascular disease. J Periodontol . 67( Suppl 10S):1123–1137

9. Ridker (1998) found that CRP levels were excellent predictors of cardiovascular events in healthy women Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. 1998. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation. 98(8):731–733

10. Russell Ross (1999) introduced the concept of a strong inflammatory component in the pathogenesis of atherosclerosis Ross R. 1999. Atherosclerosis—an inflammatory disease. N Engl J Med. 340(2):115–126

11. Haraszthy et al. (2000) were the first to report the detection of periodontal bacterial genome ( Tannerella forsythia, P. gingivalis , A. actinomycetemcomitans and P. intermedia) in atheromas Haraszthy, V. I., Zambon , J. J., Trevisan , M., Zeid , M. & Genco, R. J. (2000) Identification of periodontal pathogens in atheromatous plaques. Journal of Periodontal Research 71, 1554– 1560 .

12. Beck et al. (2001) provided the first indication that periodontitis may play a role in atheroma formation Beck JD, Elter JR, Heiss G, Couper D, Mauriello SM, Offenbacher S. 2001. Relationship of periodontal disease to carotid artery intima-media wall thickness: the Atherosclerosis Risk in Communities (ARIC) study. Arterioscler Thromb Vasc Biol. 21(11):1816–1822

13. Ide et al. (2004 ) showed that chronic periodontitis patients undergoing an episode of subgingival scaling experienced a significant elevation in circulating tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) Ide M, Jagdev D, Coward PY, Crook M, Barclay GR, Wilson RF. 2004. The short-term effects of treatment of chronic periodontitis on circulating levels of endotoxin, C-reactive protein, tumor necrosis factor–alpha, and interleukin-6. J Periodontol . 75(3):420–428

14. Tonetti et al. (2007) showed that intensive periodontal instrumentation is a short term systemic stressor but also documented a net reduction in systemic inflammation after periodontal treatment in the long term Tonetti MS, D’Aiuto F, Nibali L, Donald A, Storry C, Parkar M, Suvan J, Hingorani AD, Vallance P, Deanfield J. 2007. Treatment of periodontitis and endothelial function. N Engl J Med. 356(9):911–920.

15. Bokhari et al. (2012) showed that nonsurgical periodontal therapy significantly reduced systemic levels of CRP, fibrinogen, and white blood cells, all of which have been associated with increased risk for CHD Bokhari SA, Khan AA, Butt AK, Azhar M, Hanif M, Izhar M, Tatakis DN. 2012. Non-surgical periodontal therapy reduces coronary heart disease risk markers: a randomized controlled trial. J Clin Periodontol . 39(11):1065– 1074

16. Zhou et al. (2017) demonstrated for the first time that intensive periodontal therapy without antihypertensive medication may lower blood pressure in patients with prehypertension and periodontitis Zhou QB, Xia WH, Ren J, Yu BB, Tong XZ, Chen YB, Chen S, Feng L, Dai J, Tao J, et al. 2017. Effect of intensive periodontal therapy on blood pressure and endothelial microparticles in patients with prehypertension and periodontitis: a randomized controlled trial. J Periodontol . 88(8):711–722

17. Mechanisms linking Periodontitis and Cardiovascular disease

18. Febbraio M, Roy CB, Levin L. Is There a Causal Link Between Periodontitis and Cardiovascular Disease? A Concise Review of Recent Findings. Int Dent J. 2022 Feb;72(1):37-51.

19. Febbraio M, Roy CB, Levin L. Is There a Causal Link Between Periodontitis and Cardiovascular Disease? A Concise Review of Recent Findings. Int Dent J. 2022 Feb;72(1):37-51.

20. Periodontal Inflammation Proinflammatory condition (1L-1β, TNF-α ,1L-6) ↑↑↑ Reactive Oxygen Species (ROS) ↑↑↑ Cholesterol synthesis (Liver) Lipid peroxidation Periodontopathic Bacteria Endothelial cell invasion Myeloid cell phagocitosis ↑↑↑ Apoptotic bodies ↑↑↑ Foam cells Bacterial Products (LPS, gingipains) Molecular mimicry ↑↑↑ Oxidized LDL ↓↓↓ HDL anti-atherogenic properties ↑↑↑ Atherogenic Profile

21. Periodontal Health and Cardiovascular Diseases: Consensus ? Sanz M, Marco Del Castillo A, Jepsen S, et al. Periodontitis and cardiovascular diseases: consensus report. J Clin Periodontol 2020;47:268–88

22. Epidemiologic Evidence on the Association Between Periodontitis and CVD Do people with periodontitis have a higher prevalence of subclinical cardiovascular disease? Periodontitis patients exhibit significant endothelial dysfunction , arterial stiffness and a significantly greater thickness of the carotid intima‐media

23.   Do people with periodontitis have a higher prevalence of coronary artery disease and risk of myocardial infarction and other coronary events? Positive association between periodontitis and coronary heart disease

24.   Do people with periodontitis have a higher prevalence of cerebrovascular disease and risk of stroke? Positive association between periodontitis and cerebrovascular disease

25. Do people with periodontitis have a higher prevalence and incidence of Peripheral Artery Disease (PAD)? Limited but consistent evidence that individuals with periodontitis have a higher prevalence and incidence of PAD compared to individuals without periodontitis

26. Do people with periodontitis have a higher risk of other CVDs or conditions like heart failure and atrial fibrillation? Positive associations between periodontitis and heart failure and atrial fibrillation

27. Limited scientific evidence that CVD is a risk factor for the onset or progression of periodontitis Do people with a history of cardiovascular disease have a different incidence or progression of periodontitis?

28. Mechanisms That May Explain The Epidemiological Associations Between Periodontitis And CVD Is there evidence of a higher incidence of bacteremia following oral function/intervention in periodontitis patients compared to periodontally healthy subjects? Bacteremia results from daily life activities and oral interventions

29. Is there evidence for the presence of oral bacteria in atheroma lesions? Periodontal pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans have been identified in atherothrombotic tissues

30. Do we have evidence that periodontal bacteria and/or bacterial products and virulence factors influence the pathophysiology of atherosclerosis? Animal models have demonstrated that periodontal pathogens can promote atheroma formation In vivo and in vitro studies demonstrate the importance of the fimbriae of P. gingivalis to host cell entry and to promote athero ‐ thrombotic lesions in experimental models

31. Do we have evidence that periodontitis patients exhibit increased production/ levels of inflammatory mediators that also associated with the pathophysiology of atherosclerosis? Evidence of significantly higher levels of C‐reactive protein (CRP) and serum interleukin (IL)‐6 Periodontal therapy significantly reduces CRP levels, along with improvements in surrogate measurements of cardiovascular health

32. Do periodontitis patients develop elevations in thrombotic factors that are also associated with the pathophysiology of atherothrombosis? Significantly higher levels of fibrinogen and platelet activation markers Evidence of reduction in their levels with periodontal therapy

33. Do we have evidence that periodontitis patients demonstrate elevated serum antibody levels that cross‐react with antigens in cardiovascular tissues? Heat shock proteins (HSPs) from periodontal pathogens generate antibodies that can cross‐react with human HSPs

34. Do we have evidence that periodontitis patients exhibit dyslipidaemia ? Serum total cholesterol levels, LDL, TG, VLDL, oxidized LDL and phospholipase A2 are elevated in periodontitis HDL levels are reduced

35. Do we have evidence for peripheral blood neutrophil hyper‐responsiveness in reactive oxygen species and protease production in periodontitis patients? Peripheral blood neutrophils (PBNs) from periodontitis patients produce higher levels of total and extracellular reactive oxygen species (ROS) than healthy controls Antioxidant levels in serum and gingival crevicular fluid (GCF) are reduced in periodontitis patients, reflecting increased ROS activity

36. Are there common genetic risk factors between periodontitis and CVDs? Evidence of pleiotropy between periodontitis and cardiovascular diseases Evidence for plasminogen (PLG) as a shared genetic risk factor for coronary artery disease and periodontitis

37. Effects Of Periodontal Treatment On Cardiovascular Diseases Primary Prevention Oral health interventions including self‐performed oral hygiene habits (toothbrushing) and periodontal treatment produced a reduction in the incidence of ACVD events including acute myocardial infarction and ischaemic stroke

38. No statistically significant difference in the rate of CVD events between patients who underwent treatment of periodontitis versus community care Secondary Prevention Beck JD, Couper DJ, Falkner KL, Graham SP, Grossi SG, Gunsolley JC, Madden T, Maupome G, Offenbacher S, Stewart DD, Trevisan M, Van Dyke TE, Genco RJ. The Periodontitis and Vascular Events (PAVE) pilot study: adverse events. J Periodontol . 2008 Jan;79(1):90-6. 

39. What is the effect of the treatment of periodontitis in improving surrogate parameters of CVD? O rlandi M, Graziani F, D'Aiuto F. Periodontal therapy and cardiovascular risk. Periodontol 2000. 2020 Jun;83(1):107-124.

40. Periodontal Treatment Inflammation (CRP, IL-6) FMD Blood Pressure Carotid Thickness LDL CVDs CVDs CVDs CVDs CVDs

41. Cardiovascular Risks and Complications of Periodontal Therapeutic Interventions No evidence for specific effects of periodontal treatment procedures on increasing ischaemic cardiovascular risk or adverse cardiovascular events in case of established CVD Delivering periodontal treatment is safe with regard to cardiovascular risk Sanz M, Marco Del Castillo A, Jepsen S, et al. Periodontitis and cardiovascular diseases: consensus report. J Clin Periodontol 2020;47:268–88

42. Rationale For a Causal Link Between Periodontitis and Cardiovascular Diseases Periodontitis has not yet been established as an independent casual factor in the onset and progression of atherosclerosis or CVD Periodontitis and cardiovascular diseases are positively associated Bradford-Hill criteria have been adopted to define causation in disease models not responding to a single causal factor O rlandi M, Graziani F, D'Aiuto F. Periodontal therapy and cardiovascular risk. Periodontol 2000. 2020 Jun;83(1):107-124.

43. Bradford-Hill criteria Statistical strength of association Consistency Specificity Temporal relationship Biologic gradient Biologic plausibility Coherence Experimental reversibility Analogy Weak to moderate Association is consistent but consistency of findings is not absolute Positive association. I schemic stroke but not hemorrhagic stroke is related to periodontitis Periodontitis preceded cardiovascular disease after adjustment for traditional cardiovascular risk factors Increasing severity of periodontitis resulted in higher cumulative incidence of cardiovascular disease after adjusting for potential confounders Experimental evidence proves the biological plausibility of a causal association between periodontitis and cardiovascular disease The association does not conflict with currently established theory and scientific knowledge In vitro and in vivo evidence support a causal role for periodontitis in the development of cardiovascular disease Diabetes can induce cardiovascular disease in humans. Periodontitis can induce cardiovascular disease in animal models

44. Conclusion Causality remains unproven but association is evident Improvement in cardiovascular surrogate markers following periodontal treatment Patients with periodontitis and a diagnosis of CVD should be informed that they should regularly adhere to the recommended dental therapeutic, maintenance and preventive regimes Oral health education and a tailored oral hygiene regime should be provided to all patients