Comparative Analysis of The Relationship between Periodontitis and Cardiovascular Diseases: A Review

International Journal of Dental Science and Innovative Research (IJDSIR) IJDSIR : Dental Publication Service Available Online at:www.ijdsir.com Volume – 8, Issue – 5, October – 2025, Page No. : 60 - 68 Corresponding Author: Dr Shreya Manohar Hiwalkar, ijdsir, Volume – 8 Issue - 5, Page No. : 60 - 68 Page60 ISSN: 2581-5989 PubMed - National Library of Medicine - ID: 101738774 Comparative Analysis of The Relationship between Periodontitis and Cardiovascular Diseases: A Review 1Dr Shreya Manohar Hiwalkar, BDS, MBS, University of Alabama at Birmingham, Alabama, USA. 2Dr Renuka Adbol, BDS, Postgraduate Student, Department of Periodontology, G D Pol foundation, YMT Dental College and Hospital, India. Corresponding Author: Dr Shreya Manohar Hiwalkar, BDS, MBS, University of Alabama at Birmingham, Alabama, USA. Citation of this Article: Dr Shreya Manohar Hiwalkar, Dr Renuka Adbol, “Comparative Analysis of The Relationship between Periodontitis and Cardiovascular Diseases: A Review”, IJDSIROctober – 2025, Volume – 8, Issue – 5, P. No. 60 – 68. Copyright: © 2025, Dr Shreya Manohar Hiwalkar, et al. This is an open access journal and article distributed under the terms of the creative common’s attribution non-commercial License. Which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given, and the new creations are licensed under the identical terms. Type of Publication: Review Article Conflicts of Interest: Nil Abstract Periodontitis and cardiovascular diseases are prevalent conditions in today's society. The review underscores both the similarities and disparities in prevalence rates, risk factors, and underlying mechanisms, offering insight into the intricate interplay between these two conditions. This study also aims to investigate the possible associations between periodontitis and cardiovascular diseases. Research has demonstrated that, even in the absence of known cardiovascular risk factors, periodontal disease is linked to CRP. In response to inflammatory cytokines, the liver is the primary site of production for 1214 CRP, an acute-phase reactant. Cross-sectional evidence from over a dozen prospective epidemiologic studies showed that CRP was predictive of subsequent vascular events, such as stroke, myocardial infarction, peripheral artery disease, and sudden cardiac death. The relationship between periodontal disease and levels of CRP and IL-6 in racial/ethnic minority groups— especially in the different population—has not received much attention in the literature, despite the abundance of research on the relationship between periodontal disease status and CVD biomarkers." It may be possible to assess periodontal tissue degeneration and forecast the risk of cardiovascular disease in these patients by using several clinical indicators such as CRP level and IL-6. Keywords: Periodontitis, Cardiovascular Diseases, Inflammation, Dietary Pattern, Infection, C-Reactive Protein (CRP). Introduction An overview of (CVDs) and Periodontitis: Cardiovascular diseases (CVDs) are a major global cause of death, accounting for 17.9 million deaths annually (or 31% of all deaths 1,2. Cardiovascular diseases are leading cause of death in India and United states of America. Based on an analysis of data from the National Health Dr Shreya Manohar Hiwalkar, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page61 Page61 Page61 Page61 Page61 Page61 Page61 Page61 Page61 Page61 Page61 Page61 Page61 Page61 Page61 Page61 Page61 Page61 Page61 and Nutrition Examination Survey (NHANES) spanning from 2009 to 2014, it's estimated that approximately 42% of dentate adults aged 30 years or older in the United States exhibit some degree of periodontitis (mild, moderate, or severe). Similarly, a multicentric oral health survey conducted under the Government of India and the World Health Organization collaborative program in 2004 aimed to establish baseline data, revealing that around 51% of individuals have some form of periodontitis.3,4 Exploring the potential link between periodontitis and cardiovascular disease (CVD) is crucial, considering their shared inflammatory pathways and risk factors. Numerous investigations have documented a favorable correlation between periodontitis and cardiovascular disease (CVD) in populations of Indian and American descent. According to an Indian study, people with severe periodontitis were more likely than people without or with mild periodontitis to develop coronary artery disease (CAD). In a similar vein, research conducted in the United States has discovered that periodontitis significantly predicts cardiovascular disease (CVD), which includes peripheral artery disease, heart attack, and stroke.5–7 Methodology Objective of the Review The primary objective of this review is to analyze and summarize existing research on the association between periodontitis and cardiovascular diseases, focusing on potential mechanisms, common inflammatory pathways, and biomarkers like C-reactive protein (CRP). The review aims to compare findings from diverse populations (e.g., Indian, American, European), providing a global perspective on the correlation. Search Strategy  Databases: The literature search will include multiple databases such as:  PubMed  MEDLINE  Scopus  Cochrane Library  Google Scholar  Boolean Operators: Boolean operators (AND, OR) will be used to refine the search strategy. Example: ("Periodontitis" AND "Cardiovascular diseases") OR ("Inflammation" AND "CRP" AND "Atherosclerosis").  Time Frame: The search will be restricted to articles published between 2000 and the present to capture the most recent data on the subject. However, older seminal works may be included if they are foundational to understanding the link between periodontitis and CVD. Data Extraction A standardized data extraction form will be used to gather information from the selected studies. Data to be extracted include:  Study details: Author, year, country, study design, sample size.  Population characteristics: Age, gender, health status, and geographic location.  Periodontitis-related variables: Severity of periodontitis, diagnostic criteria, periodontal pathogens.  CVD-related variables: Types of cardiovascular diseases (e.g., coronary artery disease, stroke), diagnostic criteria, clinical outcomes.  Biomarkers: CRP levels, IL-6, and other relevant inflammatory markers.  Key findings: Association between periodontitis and CVD, statistical significance, and reported mechanisms. Dr Shreya Manohar Hiwalkar, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page62 Page62 Page62 Page62 Page62 Page62 Page62 Page62 Page62 Page62 Page62 Page62 Page62 Page62 Page62 Page62 Page62 Page62 Page62 Data Synthesis  Qualitative Analysis: The extracted data will be synthesized qualitatively, focusing on recurring themes and patterns across studies. Special attention will be given to the inflammatory mechanisms linking periodontitis and CVD, the role of CRP as a biomarker, and variations across populations.  Comparative Analysis: The review will compare studies from different regions (India, U.S., Europe) to highlight geographical differences in the prevalence and severity of periodontitis and CVD, as well as how these affect the correlation.  Mechanistic Discussion: The review will analyze biological pathways, focusing on inflammation, endothelial dysfunction, and bacterial translocation as mediators of the relationship between periodontitis and CVD. Risk of Bias Assessment Although this is a narrative review, the quality of the included studies will be assessed. The Newcastle-Ottawa Scale (NOS) will be used to evaluate the quality of observational studies, and the Cochrane Risk of Bias tool will be employed for RCTs. Studies with a high risk of bias will be included in the review but flagged and considered in the interpretation of the results. Result This review's findings demonstrates the strong correlation between periodontitis and cardiovascular diseases (CVD), with inflammation serving as a key mediator between the two illnesses. The severity of periodontitis and the elevated risk of cardiovascular events, such as coronary artery disease, stroke, and atherosclerosis, are consistently correlated with elevated levels of inflammatory biomarkers, such as C-reactive protein (CRP) and interleukin-6 (IL-6). Smoking, poor dental hygiene, and systemic inflammation are examples of shared risk factors that highlight the relationship even more. Studies across various populations reveal that patients with advanced periodontitis often exhibit higher CRP levels, even after controlling for traditional CVD risk factors such as smoking, hypertension, and diabetes. Clinical trials have also shown improvements in endothelial function and reductions in CRP following periodontal therapy, further supporting the causal link. Moreover, the review highlights how bacterial translocation, systemic inflammation, and immune dysregulation contribute to the pathophysiology of cardiovascular diseases in individuals with chronic periodontitis. The variability in findings between different ethnic groups and regions suggests that genetic, environmental, and lifestyle factors also play a role, underscoring the importance of population-specific studies and interventions. Discussion Periodontitis and CVD ADA defines Periodontitis as “Periodontal disease is a chronic infection that can result in the destruction of tooth-supporting structures (i.e., the gingiva, periodontal ligament, and/or alveolar bone) and eventual tooth loss. It is a multifactorial infectious disease influenced by several risk factors such as genetics, environment and the host immune system.8 Although microorganisms are implicated as the etiologic agent responsible for the inflammatory lesion, the products of inflammation play an important role in the loss of connective tissue as well as in the loss of supportive alveolar bone. CVDs definition & characteristics The American Heart Association defines cardiovascular diseases (CVD) as a group of conditions that affect the heart and blood vessels, including coronary artery disease, heart failure, stroke, and high blood pressure. Dr Shreya Manohar Hiwalkar, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page63 Page63 Page63 Page63 Page63 Page63 Page63 Page63 Page63 Page63 Page63 Page63 Page63 Page63 Page63 Page63 Page63 Page63 Page63 These conditions can lead to serious complications and have a significant impact on overall health and quality of life. Preventive measures such as adopting a healthy lifestyle, managing risk factors like high cholesterol and hypertension, and seeking prompt medical attention are crucial in reducing the burden of cardiovascular diseases.9 The liver produces C-reactive protein (CRP), an acutephase protein, in reaction to inflammation. It has a complex and important association to cardiovascular disease (CVD): **Marker of Inflammation**: An important mechanism in the initiation and advancement of atherosclerosis, the main cause of CVD, is inflammation, which is indicated by elevated CRP levels. Plaque accumulation in the arteries due to persistent inflammation raises the risk of heart attacks and strokes.10 **Predictive Value**: Even in those who don't exhibit any outward signs of cardiovascular disease, elevated CRP levels are linked to a higher chance of subsequent cardiovascular events. Lower levels of the protein can be found via high-sensitivity CRP (hs-CRP) testing, which improves the risk assessment for CVD.11 **Therapeutic Target**: Although CRP is mainly a marker, there is evidence that it is directly involved in the pathophysiology of cardiovascular disease. Further research is required to establish the potential reduction of cardiovascular risk by anti-inflammatory medications that lower CRP levels.12 Overall, CRP is a significant biomarker for cardiovascular health that helps with the diagnosis, treatment, and prognosis of cardiovascular illness. Mechanism and association between CVDs and Periodontitis The following could be potential mechanisms: endothelial dysfunction, bacterial translocation, and inflammation as they relate to periodontitis and CVD. One of the risk factors for CVD is atherosclerosis, which can arise as a result of periodontitis-induced inflammation. Improved blood flow can raise the risk of cardiovascular disease (CVD) due to endothelial dysfunction brought on by periodontitis. The spread of bacterial toxins into the circulation as a consequence of periodontitis-induced bacterial translocation might induce systemic inflammation and raise the risk of cardiovascular disease (CVD). Chronic gum inflammation, or periodontitis, has been connected in a number of ways to cardiovascular disease (CVD), including through its association with C-reactive protein (CRP). 1,7This is how they are related to one other: Systemic Inflammation: Inflammatory indicators such as CRP are raised as a result of the systemic inflammatory response that is sparked by periodontitis. One wellestablished risk factor for the onset and advancement of atherosclerosis—the accumulation of plaque in the arteries that causes CVD—is chronic inflammation. Increased CRP Levels: As a reaction to inflammation, periodontitis can raise CRP levels. Elevations in CRP are linked to a higher chance of cardiovascular disease (CVD), which makes CRP a valuable biomarker for determining cardiovascular risk in those with periodontal disease.13,14 Atherosclerosis and Plaque Formation: Atherosclerosis can be initiated and progressed in part by the inflammation brought on by periodontitis. One of the main mechanisms in CVD is the promotion of inflammation and plaque formation in the arteries by bacteria from periodontal diseases that can reach the bloodstream. Endothelial Dysfunction: Endothelial dysfunction is a disorder in which the inner lining of blood vessels Dr Shreya Manohar Hiwalkar, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page64 Page64 Page64 Page64 Page64 Page64 Page64 Page64 Page64 Page64 Page64 Page64 Page64 Page64 Page64 Page64 Page64 Page64 Page64 malfunctions. It is often brought on by chronic inflammation from periodontitis. Atherosclerosis and other cardiovascular diseases start with this dysfunction. Several studies have demonstrated that people with periodontitis have elevated CRP levels and are more vulnerable to cardiovascular events including strokes and heart attacks. Reductions in CRP levels and enhancements in endothelial function have been linked to periodontitis treatment, indicating a possible benefit for cardiovascular health.6 The comparative study of the populations around the world is especially significant because of the variations in the incidence and severity of CVDs and periodontitis in these two groups. Numerous studies have explored the link between periodontal disease and cardiovascular disease, consistently finding positive associations even after adjusting for multiple risk factors. Understanding this connection across diverse demographics can significantly improve intervention and treatment strategies.5 Table 1: Author, Year of study country Study design Age of experimental group Population Biomarkers assessed Conclusion A Sharma, M Astekar, 2014 sharma(15) India RCT 25-60 Indian CRP significantly higher levels of CRP .CRP levels among periodontitis patients Nicole Delange1 Suzanne Lindsay, 2017(16) USA Crosssectional 21-43 American Indian/ Alaskian CRP, IL-6 This study shows that in this relatively young adult AI/AN population, increasing levels of IL-6 are linked to moderate periodontal disease. But could not provide a significant relationship between CRP and periodontitis A. Pejcic, L. J. Kesic & J. Milasin, 2011 (17) Serbia RCT 23-58 Serbian CRP This study was able to indicate that elevated CRP levels tended to be more closely related to gingival bleeding, poor oral hygiene and the presence of periodontal microorganisms (P. gingivalis and A. actinomycetemcomitans) D’Aiuto F, UK Cross-sectional 37-55 UK CRP,IL-6 This study indicated Serum Dr Shreya Manohar Hiwalkar, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page65 Page65 Page65 Page65 Page65 Page65 Page65 Page65 Page65 Page65 Page65 Page65 Page65 Page65 Page65 Page65 Page65 Page65 Page65 Ready D, Tonetti MS,2004(18) concentrations of the tested inflammatory markers, IL-6 and CRP, were significantly correlated with the extent and severity of periodontitis Salde, Elissa .M Ghezzi,2003(19) USA Crosssectional 52-75 USA CRP The results of this study demonstrated elevated concentration of serum CRP in individuals with extended periodontitis Further Mechanistic Insights and Emerging Evidence: Recent studies continue to strengthen the understanding of biological mechanisms connecting periodontitis and cardiovascular diseases (CVDs). Beyond CRP and IL-6, other biomarkers such as tumor necrosis factor-alpha (TNF-α), matrix metalloproteinases (MMPs), and fibrinogen have been identified as key players in systemic inflammation initiated by periodontitis. These molecules can significantly influence vascular integrity and accelerate the atherosclerotic process.20,21 Immune Dysregulation and Vascular Impact: Periodontitis triggers a dysregulated immune response, characterized by excessive neutrophil activity and upregulated pro-inflammatory cytokines. These immune responses contribute to vascular endothelial activation and damage. When the endothelial lining becomes dysfunctional, it fails to regulate vascular tone and permeability effectively, thereby facilitating lipid infiltration and plaque formation within arterial walls. Bacteremia and Direct Pathogen Involvement: Transient bacteremia, commonly observed during activities like tooth brushing or dental procedures in patients with periodontitis, allows periodontal pathogens like Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans to enter systemic circulation. These microorganisms can localize within atherosclerotic plaques, as demonstrated by PCR and immunohistochemical studies, suggesting a direct microbial contribution to plaque development and instability.22 Molecular Mimicry and Autoimmunity: Emerging research highlights the role of molecular mimicry in the development of autoimmune responses in CVD. Antigens from periodontal bacteria may resemble host antigens, leading to the production of autoantibodies that damage vascular tissues. This autoimmune mechanism may partly explain the persistent inflammation and progression of atherosclerosis in patients with periodontal disease.23 Public Health Significance and Socioeconomic Considerations Periodontitis and CVDs share not only biological mechanisms but also social determinants of health, including socioeconomic status, education, access to healthcare, and lifestyle behaviors. This intersection significantly affects global disease burden, especially in lowand middle-income countries. Health Inequities: Populations in rural and underserved areas often face barriers to both dental and cardiovascular care, resulting in delayed diagnosis and management. These disparities compound the risk of developing chronic conditions and experiencing adverse outcomes. Dr Shreya Manohar Hiwalkar, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page66 Page66 Page66 Page66 Page66 Page66 Page66 Page66 Page66 Page66 Page66 Page66 Page66 Page66 Page66 Page66 Page66 Page66 Page66 Economic Burden: The co-occurrence of periodontitis and CVD leads to increased healthcare utilization and expenditure. Managing advanced stages of both conditions requires costly interventions, including cardiac surgeries and periodontal surgeries, underscoring the importance of early preventive care and integrated management.24 Educational Campaigns: Public awareness initiatives promoting oral hygiene and heart health can play a vital role in primary prevention. Programs aimed at educating patients about the systemic implications of oral health, particularly in high-risk communities, may help reduce the incidence of both conditions. Clinical Implications and Multidisciplinary Management The bidirectional relationship between oral and cardiovascular health necessitates a collaborative approach between medical and dental professionals. Early screening, shared electronic health records, and coordinated care models are essential in addressing this interconnection. Role of Dental Professionals: Dentists and periodontists should consider systemic risk assessment as part of periodontal evaluation. Incorporating CRP or other inflammatory marker testing in dental clinics could provide valuable insights into a patient’s cardiovascular risk profile. Role of Cardiologists and Primary Care Providers: Cardiologists and primary care physicians should be aware of periodontal health as a potential modifiable risk factor for CVD. Referrals to dental professionals for patients with uncontrolled cardiovascular risk factors could form part of routine care. Evidence from Interventional Studies: A number of clinical trials suggest that periodontal treatment, including scaling and root planing (SRP), significantly reduces systemic inflammation. For instance, Tonetti et al. (2007) demonstrated a reduction in CRP and improved endothelial function following intensive periodontal therapy in otherwise healthy patients.18 Future Research Directions: Despite strong associative evidence, questions regarding causality and intervention efficacy remain. Longitudinal, multi-center, randomized controlled trials with robust methodology are needed to explore: Long-Term Impact of Periodontal Therapy: Future studies should assess whether sustained periodontal health translates into a decreased incidence of major adverse cardiovascular events (MACE) such as myocardial infarction and stroke.25 Personalized Risk Profiling: Research should explore genetic, microbiomic, and immunologic factors that may predispose certain individuals to both periodontitis and CVD. Understanding these individualized risk profiles could guide personalized prevention strategies.26 Novel Biomarkers and Diagnostic Tools: Advancements in salivary diagnostics and point-of-care testing offer non-invasive tools for early detection of systemic inflammation. Salivary CRP and IL-6 measurement could become part of routine screening for at-risk populations.27 Digital Health and AI Integration: The integration of artificial intelligence in analyzing large datasets from electronic health records can aid in identifying patterns and predictive factors linking oral and cardiovascular health. AI models could stratify patients based on periodontal and cardiovascular risk for proactive interventions.28 Conclusion Treating periodontitis has the potential not solely to improve oral wellness but also to reduce systemic Dr Shreya Manohar Hiwalkar, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page67 Page67 Page67 Page67 Page67 Page67 Page67 Page67 Page67 Page67 Page67 Page67 Page67 Page67 Page67 Page67 Page67 Page67 Page67 inflammation and perhaps minimize the risk of cardiovascular challenges. In order to further understand the link between cause and effect and investigate the efficacy of anti-inflammatory treatments that target CRP and other indicators in lowering the risk of CVD in patients with periodontitis, future research should concentrate on longitudinal studies. Adopting action to address this relationship may have substantial effects on public health, particularly for populations where both illnesses are highly prevalent. Given the shared pathophysiological pathways and modifiable nature of periodontitis, a multidisciplinary approach integrating dental and cardiovascular care is warranted. Dental professionals should be involved in chronic disease prevention strategies, while cardiologists should be aware of oral health as a contributing factor in systemic inflammation and vascular dysfunction. Future research should concentrate on well-designed longitudinal studies. Additionally, public health initiatives promoting oral-systemic health education could have substantial impacts, especially in regions where both diseases are highly prevalent. References 1. Beck J, Garcia R, Heiss G, Vokonas PS, Offenbacher S. Periodontal disease and cardiovascular disease. J Periodontol. 1996;67(10 Suppl):1123–37. 2. Beck JD, Offenbacher S. The association between periodontitis and cardiovascular disease: epidemiology and biological mechanisms. Curr Opin Periodontol. 1998;5:3–12. 3. Genco R, Offenbacher S, Beck J. Periodontal disease and cardiovascular disease: epidemiology and possible mechanisms. Ann Periodontol. 2002;8 (1): 12–20. 4. Slade GD, Ghezzi EM, Heiss G, Beck JD, Riche E, Offenbacher S. Relationship between periodontal disease and C-reactive protein among adults in the Atherosclerosis Risk in Communities study. Arch Intern Med. 2003;163(10):1172–9. 5. Joshipura KJ, Wand HC, Merchant AT, Rimm EB. Periodontal disease and biomarkers related to cardiovascular disease. J Dent Res.2004;83(2):151– 5. 6. D’Aiuto F, Ready D, Tonetti MS. Periodontal disease and C-reactive protein–associated cardiovascular risk. J Dent Res. 2004;83(2):156–60. 7. Beck JD, Offenbacher S. Systemic effects of periodontitis: epidemiology of periodontal disease and cardiovascular disease. J Periodontol. 2005;76 (11 Suppl):2089–100. 8. Demmer RT, Desvarieux M. Periodontal infections and cardiovascular disease: the heart of the matter. Am J Epidemiol. 2006;163(1):12–9. 9. Behle JH, Papapanou PN. Periodontal infections and atherosclerotic vascular disease: an update. Int Dent J. 2006;56(3 Suppl 1):256–62. 10. Sanz M, D’Aiuto F, Deanfield J, Fernandez-Avilés F. European workshop in periodontal health and cardiovascular disease—scientific evidence on the association between periodontal and cardiovascular diseases: a review of the literature. Eur Heart J Suppl. 2010;12(Suppl B):B3–12. 11. Demmer RT, Desvarieux M. Periodontal infections and cardiovascular disease: the heart of the matter. Am J Prev Med. 2010;38(4 Suppl):S502–6. 12. Oh J, Teoh H, Leiter LA. Should C-reactive protein be a target of therapy? Diabetes Care. 2011;34(Suppl 2):S155–60. 13. Pejcic A, Kesic LJ, Milasin J. C-reactive protein as a systemic marker of inflammation in periodontitis. J Oral Sci. 2011;53(4):475–82. Dr Shreya Manohar Hiwalkar, et al. International Journal of Dental Science and Innovative Research (IJDSIR) ©2025 IJDSIR, All Rights Reserved Page68 Page68 Page68 Page68 Page68 Page68 Page68 Page68 Page68 Page68 Page68 Page68 Page68 Page68 Page68 Page68 Page68 Page68 Page68 14. Sharma A, Astekar M, Metgud R, Soni A, Verma M, Patel S. A study of C-reactive protein, lipid metabolism and peripheral blood to identify a link between periodontitis and cardiovascular disease. Biotech Histochem. 2014;89(8):577–82. 15. Vijay Kumar PK, Gottlieb RA, Lindsay S, Delange N, Penn TE, Calac D, et al. Metagenomic analysis uncovers strong relationship between periodontal pathogens and vascular dysfunction in American Indian population. bioRxiv. 2018;250324. 16. Amezcua-Castillo E, González-Pacheco H, Martín ASS, Méndez-Ocampo P, Gutierrez-Moctezuma I, Massó F, et al. C-Reactive Protein: The Quintessential Marker of Systemic Inflammation in Coronary Artery Disease—Advancing toward Precision Medicine. IntJMol Sci.2023;24(15): 11865. 17. Rizo-Téllez SA, Sekheri M, Filep JG. C-reactive protein: a target for therapy to reduce inflammation. Front Immunol. 2023;14:1237729. 18. Huang X, Xie M, Lu X, Mei F, Song W, Liu Y, et al. The Roles of Periodontal Bacteria in Atherosclerosis. Int J Mol Sci. 2023;24(16):12861. 19. American Dental Association. Periodontitis. 2024. 20. American Heart Association. What Is Cardiovascular Disease? 2024. 21. Varma S, Thomas B, Subrahmanyam K, Duarte K, Alsaegh MA, Gopinath D, et al. Salivary levels of inflammatory and anti-inflammatory biomarkers in periodontitis patients with and without acute myocardial infarction: implications for cardiovascular risk assessment. Front Oral Health. 2024;5:1332980. 22. Meng R, Xu J, Fan C, Liao H, Wu Z, Zeng Q. Effect of non-surgical periodontal therapy on risk markers of cardiovascular disease: a systematic review and meta-analysis. BMC Oral Health. 2024;24(1):692. 23. Arbildo-Vega HI, Cruzado-Oliva FH, CoronelZubiate FT, Meza-Málaga JM, Luján-Valencia SA, Luján-Urviola E, et al. Periodontal disease and cardiovascular disease: umbrella review. BMC Oral Health. 2024;24:1308. 24. Schulze-Späte U, Wurschi L, van der Vorst EPC, Hölzle F, Craveiro RB, Wolf M, et al. Crosstalk between periodontitis and cardiovascular risk. Front Immunol. 2024;15:1468013. 25. Angjelova A, Jovanova E, Polizzi A, Laganà L, Santonocito S, Ragusa R, et al. Impact of periodontitis on endothelial risk dysfunction and oxidative stress improvement in patients with cardiovascular disease. J Clin Med. 2024;13 (13): 3781. 26. Foroughi M, Torabinejad M, Angelov N, Ojcius DM, Parang K, Ravnan M, et al. Bridging oral and systemic health: exploring pathogenesis, biomarkers, and diagnostic innovations in periodontal disease. Infection. 2025;53(1):e02568. 27. Attia AM. Troponins as a major cardiac biomarkers and periodontitis: systematic review. J Periodontal Res. 2025;60(2):e14210. 28. Schulze-Späte U, Wurschi L, van der Vorst EPC, Hölzle F, Craveiro RB, Wolf M, et al. Crosstalk between periodontitis and cardiovascular risk. Front Immunol. 2024;15:146801. 29. Attia AM. Troponins as a major cardiac biomarkers and periodontitis: systematic review. J Periodontal Res. 2025;60(2):e14210. 30. Foroughi M, Torabinejad M, Angelov N, Ojcius DM, Parang K, Ravnan M, et al. Bridging oral and systemic health: exploring pathogenesis, biomarkers, and diagnostic innovations in periodontal disease. Infection. 2025;53(1):e02568.