European Journal of Cardiovascular Medicine

The notion of focal infection, which gained traction in the late 19th and early 20th centuries, postulated that sepsis "foci" were to blame for the start and development of numerous inflammatory illnesses, including appendicitis, peptic ulcers, and arthritis.1. Because of the widespread acceptance of the focused infection theory, therapeutic edentulation was frequently used in the oral cavity. The notion was criticised and largely ignored for many years because numerous teeth were taken despite any indication of getting sick, which resulted in little symptom improvement. A more accurate evaluation of the significance of oral focal infection has been possible due to recent improvements in the classification and identification of oral bacteria as well as the discovery that some microbes are typically exclusive to the oral cavity. It is becoming more and more obvious that the oral cavity can serve as the source from which pathogenic organisms spread to other parts of the body, particularly in immunocompromised hosts like those with rheumatoid arthritis, diabetes, cancer, or who are receiving corticosteroid or other immunosuppressive treatments. Oral infection, particularly marginal and apical periodontitis, has been implicated in multiple epidemiological investigations as a possible susceptibility indicator for systemic disorders.

The human teeth are the sole non-shedding surfaces, and each milligramme of dental plaque can harbour up to 1011 germs. Human endodontitis and periodontitis are linked to intricate microfloras, wherein about 200 species have been identified in apical periodontitis (as described in reference 2) and over 500 species in marginal periodontitis (as described in reference 3). The majority of these infections are anaerobic, and the most frequent isolates are gram-negative rods. These microfloras' anatomic proximity to the bloodstream may contribute to bacteremia and the systemic dissemination of bacterial elements, products, and immunocomplexes. The frequency and severity of odontogenic infections in patients visiting hospital emergency departments (EDs) appear to be rising, according to data from advanced countries.4, 5, 6

Several of them have late-stage, spreading infections that may necessitate admission to the intensive care unit (ICU) and surgical therapy. Others have early infections, but due to complicated barriers to dental treatment, they seek urgent medical treatment rather than outpatient dental care.8 Deep neck infections are frequently the result of orthodontia infections that extend outside of the jawbone, posing a major risk to the airway.7. There have been reports of severe side effects, including as necrotizing faciitis, toxic shock syndrome, descending mediastinitis, and an abscess in the brain. Foetal distress requiring urgent delivery^8,9 and the development of methicillin-resistant Staphylococcus aureus (MRSA) while in the ICU.2 These adverse outcomes could have been avoided if the patient had sought early dental treatment at the onset of the symptoms.

The investigation involved the enrollment of 326 healthy controls, patients with CHD, and patients with periodontitis at the Research Centre Bhopal, MP and the Department of Oral and Maxillofacial Surgery, Peoples College of Dental Sciences. To provide a comparable distribution of age groups, the patients were selected within the age range of 40-65, guaranteeing that a minimum of 50% of them were male. Groups 1, healthy controls; 2, periodontitis; 3, patients with CHD; and 4, patients with periodontitis + CHD comprised the recruited patients. According to the recently established classification of periodontal diseases1, patients with periodontitis met the following inclusion requirements: 1) at least 15 teeth; 2) at least 40% of sites with a clinical attachment level (CAL) of at least 2 mm and a probing depth (PD) of at least 4 mm; 3) at least 40% of sites with bleeding on probing (BOP); 4) at least two sites with radiographically validated alveolar bone loss (ABL) of at least 2 mm on periapical Rinn X-rays.

The CHD group's patients met the following requirements for inclusion: When at least one coronary artery has ≥50% stenosis, a coronary angiography or percutaneous coronary intervention is used to diagnose CHD. Clinical history, prior medical records, and the pharmacological treatment for congestive heart failure were documented in CHD patients during the initial visit. Additionally, an ECG was performed on the patents to check for the existence of additional pathological diseases, such as atrial fibrillation. The same calibrated operator thoroughly examined the information in the medical and diagnostic records before making the diagnosis of CHD in each patient in the CHD group. Individual eligibility requirements for both the periodontitis and CHD groups were met by patients in the combination periodontitis + CHD cohort. Patients in good health showed no signs of systemic disorders and did not use any medications. On periapical Rinn X-rays, no areas with PD or CAL ≥4 mm or evidence of ABL of ≥2 mm were seen in either the CHD patients or the healthy controls.

The following exclusion criteria applied to all enrolled patients: (1) use of contraceptive medication within six months of the investigation's start; (2) use of antibiotics, immune-suppress anti-inflammatory medications, or medications that could diagnose gingival hyperplasia within six months of the research's start; (3) pregnancy or lactation; (4) history of heavy drinking; (5) allergy or intolerance to medications; (6) diabetes; and (7) periodontal treatment within the six months prior to the study. As a result, following this initial screening round, 204 people were eliminated from the study because they did not meet the inclusion criteria (n= 138), refused participation in the study (n= 39) or were absent at the first visit (n= 27) (Fig. 1). Following the elimination of patients, the final enrollment comprised of 33 healthy controls, 31 patients with 

age, education level, body mass index (BMI), and the existence of any comorbidities or medications were noted during the initial appointment. Additionally, each patient's socioeconomic status, including their overall work experience, economic standing, and social standing, was noted and categorised into three categories (high, middle, and low)31. The patient's weight was divided by the square of his height to determine his BMI, which was then stated in kg/m2. Based on the patient's medical records or the existence of fasting blood glucose levels ≥125 mg/dl, the diagnosis of diabetes was determined. All enrolled patients were classified based on their smoking history as normal smokers, ex-smokers (at least ≥5 years), and non-smokers.

Periodontal status was recorded in all patients and included assessment of probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), plaque score (PI)28 and ABL. The CAL was recorded using the cementoenamel junction as a reference by adding the PD to the gingival recession. ABL was measured on the mesial and distal root surfaces of each tooth, using intraoral periapical radiographs. In all patients, the registration of the periodontal indexes was carried out, on six sites per tooth, on all the present teeth by means of a periodontal probe‡ by two independent calibrated examiners (a principal examiner, G.I. and a control examiner, A.P.), not involved in the subsequent phases of the study.

Figure 1: Median values (25%; 75% percentiles) of suPAR levels in plasma and saliva. 2A, serum suPAR analysis; 2B, salivary suPAR analysis. Differences among four groups were calculated by using Kruskall Wallis test (p<0.001). *p<0.001, significant differences vs healthy controls (derived by Dunn’s test). † p<0.001, significant differences vs CHD patients (derived by Dunn’s test). P-trend <0.001 (obtained by Jonckheere- Terpstra test).

Figure 3: Correlation analysis of plasma and salivary suPAR levels with hs-CRP

Table 1. Demographic characteristics of patients. Data are represented as median (25th; 75th percentiles) or number with percentage. CHD, coronary heart disease.

Table 2. Periodontal characteristics of the sample. Data are represented as median (25th; 75th percentile). CAL, clinical attachment level; PD, probing pocket depth; BOP, bleeding on probing; ABL, alveolar bone loss; PI, Plaque index; CHD, coronary heart disease

Regular dental treatment, whether at home or in a dental clinic, is essential to preventing the worsening of periodontitis since people who ignore maintenance frequently get periodontal abscesses. A growing periodontal abscess is regarded as a dental emergency because it might spread gram-negative anaerobic bacteria throughout the body. It is essential to treat periodontitis properly to stop it from becoming an alveolar abscess that requires emergency medical intervention. While there are many infection-related issues that affect the elderly, Martín et al.10 highlighted three that are particularly important: 1) Immunological functioning losses associated with ageing, 2) concomitant malnourishment, and 3) a high mortality risk from infections. Considering our patient's age of 78 years, the aforementioned things may applicable to her. There are some reports wherein oral infections have developed to septicemia or DIC.¹¹

  The following are the recurrent themes in these papers: 1) an aged patient; 2) an infection of the oral cavity; 3) malnourishment related to the condition; and 4) issues related to diabetes or malignant neoplasms. In one of these instances, the patient had an alveolar abscess that inadvertently got worse because of septicemia, leading to DIC and, eventually, death.¹² Because of this, even in patients with a straightforward alveolar abscess, it's important to take into account the possibility that the patient is elderly and needs cautious medication because there may be other complicating variables present. Another account states that a senior citizen who had root canal therapy for dental pain died from septic shock. Inflammation from the operation soon spread to the cheek and neck regions.¹³ Thus, in the event that the patient is elderly and undergoing standard endodontic treatment or has an alveolar abscess, meticulous treatment planning and consideration of the patient's overall state are necessary.

According to Carter and Lowis¹⁴, a patient's impaired immune function as a result of chronic lymphocytic leukaemia may have contributed to their mortality following a dental infection that quickly became septicemia. Thus, in older patients with typically compromised immune systems and undernourished states, medical professionals must remember that infection progresses dramatically if the patient also has a malignant tumour. The family of our patient refused to undergo an autopsy, thus a clear diagnosis was not possible; nonetheless, pleural effusion, pulmonary infiltration, and pulmonary shadow were seen on diagnostic imaging of the chest. Hence, the potential exists that the sharp increase in septicemia's development was caused by a malignant tumour. In one case of diabetes-related post-extraction infection, early, rigorous therapy prevented consequences from septicemia and deep vein thrombosis.¹⁵

Usually, there is little hope of preserving a patient's life if DIC exacerbates septicemia. However, the aforementioned research recommends that physicians and dentists collaborate in order to appropriately evaluate the general health of a patient; in the event that symptoms do not improve, a diagnosis should be made promptly, and treatment should get vigorous. According to our findings, older patients presenting with oral infection symptoms—such as pus discharge or an abscess—should start taking antibacterial treatment right soon in real-world medical environments. Sterilisation should be done consistently and daily while keeping a careful eye on the patient's progress. Additionally, it's critical to confirm that the patient is receiving an adequate amount of food and drink.

When treating patients who are not improving or who are not eating enough, medical practitioners should work in conjunction with a general hospital that offers critical care. This is due to the possibility of septicemia, which can swiftly aggravate the situation. Additionally, these findings demonstrated a strong positive association between soluble urokinase-type plasminogen activator receptor (suPAR), Aggregatibacter actinomycetemcomitans (AA), and asymmetric dimethylarginine (ADMA) and systemic disorders such as cardiovascular disease and periodontal disease.^{16, 17} Apart from standard infection signs such as WBC and CRP, high-risk people should be thoroughly assessed with appropriate testing to identify ADMA, suPAR, and AA. Furthermore, some studies have demonstrated that infection significantly reduces the prognosis for HIV-positive people. Following dental implant placement, patients should schedule follow-up sessions because oral infections in this patient population often worsen. Complete biomaterial covering of the wound surface has been demonstrated to be beneficial in individuals whose mouth infection is likely to worsen following invasive procedures. It has also been suggested that using appropriate implant insertion methods could reduce the risk of diseases.

Many methods have been developed over the past few decades to find biomarkers that can be used for CVD and periodontitis early diagnosis and detection. The results of the research show that, in comparison to CHD patients and healthy controls, patients with periodontitis and those with periodontitis + CHD had greater plasma and salivary levels of suPAR. Furthermore, the findings demonstrated that high levels of salivary suPAR and plasma were negatively correlated with periodontitis and high hs-CRP, correspondingly. Accordingly, the research's findings imply that periodontitis, with its concentration of periodontal bacteria, may raise the levels of suPAR and hs-CRP in saliva and plasma. SuPAR has shown to be a useful predictive biomarker of CHD and periodontitis in the current investigation.

1. Scannapieco F A. Position paper: periodontal disease as a potential risk factor for systemic diseases. J Periodontol. 1998;69:841–850
2. Tronstad L. Recent development in endodontic research. Scan J Dent Res. 1992;100:52–59. 
3. Moore W E C, Moore L V H. The bacteria of periodontal disease. Periodontol 2000. 1994;5:66–77.
4. Uluibau IC, Jaunay T, Goss AN. Severe odontogenic infections. Aust Dent J 2005;50:S74–81.
5. Sundararajan K, GopaldasJA, Somehsa H, et al. Morbidity and mortality in patients admitted with submandibular space infections to the intensive care unit. Anaesth Intensive Care 2015;43:420
6. Seppänen L, Lauhio A, Lindqvist C, et al. Analysis of systemic and local odontogenic infection complicationsrequiring hospital care. J Infect 2008;57:116–22.
7. Thomas SJ, Atkinson C, Hughes C, et al. Is there an epidemic of admissions for surgical treatment of dental abscesses in the UK? BMJ 2008;336:1219–20.
8. Salomon D, Heidel RE, Kolokythas A, et al. Does restriction of public health care dental benefits affect the volume, severity, or cost of dentalrelated hospital visits? J Oral Maxillofac Surg 2017;75:467–74.
9. Burnham R,BhandariR,BridleC.Changesin admission ratesforspreading odontogenic infection resulting from changes in government policy about the dental schedule and remunerations. Br J Oral Maxillofac Surg 2011;49:26–8.

Martín S, Pérez A, Aldecoa C. Sepsis and immunosenescence in the elderly patient: a review. Front Med. 2017;4:20.