Introduction Periodontitis is a multifactorial oral disease causing destruction of the periodontium. Systemic diseases can exacerbate periodontal inflammation through immune dysregulation. N-terminal-probrain natriuretic peptide (NT-proBNP) a prohormone, released by myocardial cells is a known biomarker for cardiovascular disease (CVD). Existing literature discloses a bidirectional relationship between periodontitis and CVD. NT-proBNP release can be regulated by mediators of the systemic inflammation. Cardiocyte NT-proBNP release might get stimulated through proinflammatory cytokines. NT-proBNP levels can also be influenced by systemic inflammation in the absence of cardiac dysfunction. Accordingly, we postulated that the inflammation of periodontium could aid in increased levels of NT-proBNP in serum and saliva in participants without cardiovascular disorders. Saliva is said to be the mirror of the body. Assessing NT-pro BNP in saliva allows for a non-invasive method. The present research evaluated the salivary and serum concentrations of NT-proBNP in a healthy group, patients suffering from periodontal disease and periodontal disease along with myocardial infarction (MI). Material and method A total of 90 patients, 30 in each group i.e., healthy group, periodontitis patients and patients suffering from periodontitis with myocardial infarction, were enrolled. The periodontitis patients were selected according to the Classification of Periodontal and Peri-implant Diseases and Conditions 2017. Patients clinically diagnosed with MI by the physician were selected following World Health Organization criteria for detection of MI. Case history was recorded and periodontal parameter analysis like plaque index (PI), gingival index (GI), probing pocket depth (PPD) and clinical attachment loss (CAL) were measured. Salivary and serum samples were collected from the participants after obtaining informed consent. The samples were subjected to human NT-proBNP sandwich type enzyme-linked immunosorbent assay (ELISA) for quantitative evaluation. The obtained data was analysed and compared using ANOVA, Tukey's post hoc test and Pearson's correlation. The p-value<0.05 was considered statistically significant. Result PI and GI were highest in subjects with periodontitis only (p<0.05). Patients suffering from periodontitis with MI exhibited significantly higher PPD and CAL values (p<0.05). Salivary and serum concentrations of NT-proBNP were significantly higher with p-value=0.000 in subjects suffering from periodontitis with MI. The salivary NT-proBNP levels were significantly higher than serum NT-proBNP levels in periodontitis and periodontitis with MI patients. The levels of NT-proBNP in periodontitis along with MI patients were 1.570 pg/mL in serum and 1.694 pg/mL in saliva. Conclusion Salivary NT-proBNP levels were highest in subjects affected from periodontitis along with MI. Elevated salivary NT-proBNP levels can be due to systemic inflammation and cardiovascular stress linking periodontitis to MI. The positive correlation between periodontal parameters and NT-proBNP levels validates the biomarker's role in reflecting the extent of periodontal destruction and its association with cardiovascular stress. Salivary NT-proBNP can be used as a non-invasive diagnostic marker for diagnosing periodontitis and MI. Future research could explore targeted therapies for the shared inflammatory pathways between periodontitis and MI., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Krishna Vishwa Vidyapeeth (Deemed to be University) issued approval 014/2022-2023. This cross-sectional study was conducted at the Department of Periodontology, School of Dental Sciences, Karad, following approval from the Ethical Committee of Krishna Vishwa Vidyapeeth (Deemed to be University), Karad (Protocol number: 014/2022-2023, dated: 09/08/2022). Informed consent was obtained from all the subjects before commencing the study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mohite et al.)