Heart and blood vessel diseases (CVDs) kill and hurt more people than any other noncommunicable disease, making them a big global health issue [1]. Over the past few decades, the number of people under 55 who have CVDs has gone up greatly, especially those who have had a myocardial attack or a stroke [2]. A lot of data supports this trend, showing that being exposed to cardiovascular risk factors early in life is a key part of getting the disease [3].
Being overweight or obese can make a lot of health problems worse, like heart disease, diabetes, some cancers, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis [4,5]. You can connect adipose tissue and CVDs in two ways: directly, and tangentially, through other health issues that are linked to fat. Because of this, being overweight or fat can make you more likely to get diabetes, bad cholesterol, and high blood pressure [6]. Obstructive sleep apnea caused by obesity can also raise the chance of CVD through low oxygen levels, irregular heartbeats, insulin resistance, and high blood pressure [7].
New data points to a connection between the microbiota in the mouth, obesity, and metabolic disorders, both in terms of the types of microbes involved and how the diseases start [8,9]. Oral microbiome dysbiosis—a change from harmless to possibly harmful species—is caused by a lot of different things working together [10,11]. Periodontal diseases (PDs), caused by opportunistic anaerobic bacteria, are chronic inflammatory and immune-mediated conditions that damage the gingiva, periodontal ligaments, and alveolar bone [12]. Numerous periodontopathogenic species have been identified, and research continues to explore their characteristics and pathogenic potential [13,14].
One idea is that CVDs and PDs are linked in more than one way. Some of these are systemic inflammation, the harmful effects of bacteria and their products in the bloodstream, and changes in the gut microbiome caused by germs from the mouth going there [15]. A lot of people believe that systemic inflammation is a main reason why gum disease and heart disease are connected [16,17]. Having high amounts of inflammation markers like erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6) has been linked to more heart disease and death [18]. There is some evidence that inflammation caused by gingivitis may play a role in arterial failure [19].
The hematogenous route makes it easier for mouth bacteria to spread to faraway places through bacteremia. These bacteria come from sore epithelium in periodontal pockets [20]. Bacteria like P. gingivalis, P. intermedia, A. actinomycetemcomitans, T. forsythensis, and T. denticola have been found in 20–70% of artery atheromas, according to new study [21]. Cross-sectional studies have shown over and over that people with gum disease are more likely to have atherosclerotic problems. For instance, the NHANES III group showed that people with serious periodontal disease were almost four times more likely to have a myocardial attack than people who did not have periodontitis [22]. Similarly, a study of 52,677 people with high blood pressure found a link between bad mouth health and a higher chance of CVD [23].
The oral cavity is now recognized as the second-largest microbial ecosystem in the human body, hosting over 500 identified bacterial species. These microbes play essential roles in maintaining systemic health and preventing disease onset [24]. Oral dysbiosis is linked to gum disease and is also becoming more and more linked to metabolic diseases like CVDs [25]. Deaths and illnesses caused by CVD are still major public health problems around the world [26]. Ischemic heart disease, stroke, and heart failure caused by high blood pressure are the main reasons people die from CVD [27].
Oral microbiota may serve as emerging indicators for both halitosis and systemic metabolic diseases. Working together with people from different fields could help find and treat mouth and systemic diseases, like CVDs, earlier. The study's goal is to find out how common it is for people of different ages and weights to have certain gum bacteria. These pathogens are P. gingivalis, A. actinomycetemcomitans, and T. forsythia. The study also wants to find out how periodontal disease and cardiovascular disease are related. It will do this by looking at risk factors like high blood pressure, lipid profiles, cholesterol levels, IL-6, TNF-α, and CRP, as well as cardiovascular risk assessments such as the Finnish Diabetes Risk Index (FINDRISC), Systematic Coronary Risk Evaluation (SCORE), and relative risk (RR).
The cross-sectional observational study took place from January 1, 2024, to June 30, 2024. Its goal was to find out how common Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Tannerella forsythia were in people of different ages and body masses, as well as how they might be linked to cardiovascular disease (CVD) risk factors. Subgingival samples and gingival crevicular fluid were collected from patients diagnosed with periodontitis using sterile swabs, and preserved in appropriate transport media such as VMGA III or PBS to ensure the viability of the microorganisms. For microbial identification, samples were cultured on selective media: P. gingivalis was grown on blood agar or Brucella blood agar enriched with vitamin K and hemin, and incubated anaerobically at 37°C for 7–10 days; A. actinomycetemcomitans was cultured on tryptic soy agar (TSA) with blood under 5–10% CO₂ at 37°C for 48–72 hours; T. forsythia was isolated using fastidious anaerobe agar (FAA) with blood and N-acetyl muramic acid (NAM), incubated anaerobically at 37°C for 5–7 days. Gram staining was used for microscopic examination, revealing Gram-negative rods for P. gingivalis and T. forsythia, and Gram-negative coccobacilli for A. actinomycetemcomitans. Further identification was performed using biochemical assays: P. gingivalis was tested for protease activity via collagenase and BAPNA tests; A. actinomycetemcomitans was examined for leukotoxin (ltxA) production; and T. forsythia was evaluated using the gelatin hydrolysis and N-acetyl-β-glucosaminidase tests. In addition, systemic biomarkers were assessed to explore cardiovascular risk. Blood samples were collected to measure inflammatory markers CRP, IL-6, and TNF-α—using the sandwich ELISA technique. Lipid profile parameters, including total cholesterol, HDL, LDL, and triglycerides (mg/dL), were analyzed using a spectrophotometer. Cardiovascular risk was also assessed using standardized tools such as the Finnish Diabetes Risk Score (FINDRISC), Systematic Coronary Risk Evaluation (SCORE), and Relative Risk (RR).
SPSS version 26 was used to look at the quantitative data. Rates and frequencies are used to show the outcomes. For factors that were spread out normally, two-tailed independent and dependent t-tests were used. It was possible to use the Mann-Whitney U test, the Wilcoxon test, and the Chi-square test on factors that were not spread out regularly. People used to think that a p-value less than 0.05 was statistically important.
It was okay with the human ethics committee at Al-Habbobi Teaching Hospital to do the study. People who took part in the study were told about it and asked to sign a form saying they agreed to take part. Also, the person was told that no one else would see his information.
Comparison of Sociodemographic Characteristics of Study Participants (Age, Gender, BMI, Hypertension, and Diabetes) Between Patients and Healthy Controls with Statistical Significance.
In Table 1, you can see how the 150 cases and 50 healthy controls are different. Their BMI was higher (29.4 vs. 24.1, P<0.001), their blood pressure was higher (55% vs. 10%, P<0.001), and their diabetes was higher (45% vs. 7%, P<0.001). But neither the age nor the gender changed in a big way. That means there is a link between the illness and having diabetes, a higher BMI, or high blood pressure.
| Variable | Patients Group (n=150) | Control Group (n=50) | p-value |
|---|---|---|---|
| Age (years) | 58.7 ± 12.5 | 56.2 ± 11.3 | 0.321 |
| Gender (M/F) | 85 / 65 | 26 / 24 | 0.722 |
| BMI (kg/m²) | 29.4 ± 5.1 | 24.1 ± 3.7 | < 0.001 |
| Hypertension (%) | 55% | 10% | < 0.001 |
| Diabetes (%) | 45% | 7% | < 0.001 |
Prevalence of Periodontal Pathogens (P. gingivalis, A. actinomycetemcomitans, T. forsythia). Between Patients and Healthy Controls with Statistical Significance.
In Table 2, patients had much higher rates of P. gingivalis (74% vs. 28%, P<0.001), A. actinomycetemcomitans (56% vs. 20%, P<0.001), and T. forsythia (62% vs. 22%, P<0.001) than healthy controls. This shows that there is a strong link between these pathogens and the disease.
| Pathogen | Patients (n = 150) | Healthy Controls (n = 50) | P-value |
|---|---|---|---|
| P. gingivalis (%) | 74% | 28% | < 0.001 |
| A. actinomycetemcomitans (%) | 56% | 20% | < 0.001 |
| T. forsythia (%) | 62% | 22% | < 0.001 |
Inflammatory Markers (CRP, IL-6, TNF-α) CRP، IL-6، TNF-α). Between Patients and Healthy Controls with Statistical Significance.
There was a strong link between the disease and high levels of these inflammatory markers, as shown in Table 3. Patients had much higher levels of CRP (14.5±6.2 mg/L vs. 3.2±1.1 mg/L, P<0.001), IL-6 (88.7±17.4 pg/mL vs. 26.4±6.5 pg/mL, P<0.001), and TNF-α (85.4±18.3 vs. 31.5±9.2 pg/mL, P<0.001).
| Biomarker | Patients (n = 150) | Healthy Controls (n = 50) | P-value |
|---|---|---|---|
| CRP (mg/L) | 14.5 ± 6.2 | 3.2 ± 1.1 | < 0.001 |
| IL-6 (pg/mL) | 88.7 ± 17.4 | 26.4 ± 6.5 | < 0.001 |
| TNF-α (pg/mL) | 85.4 ± 18.3 | 31.5 ± 9.2 | < 0.001 |
Cardiovascular Risk Factors (Cholesterol, HDL, LDL, Triglycerides) Between Patients and Healthy Controls with Statistical Significance.
Total Cholesterol, HDL, LDL, and Triglycerides are cardiovascular risk factors that are compared between patients and healthy groups in the table. Total Cholesterol, LDL, and Triglyceride levels are much higher in patients than in controls (P-value < 0.001). HDL values are lower in patients. These results show that patients have a higher chance of heart disease as shown in table 4.
| Risk Factor | Patients (n = 150) | Healthy Controls (n = 50) | P-value |
|---|---|---|---|
| Total Cholesterol (mg/dL) | 210.6 ± 43.5 | 180.2 ± 29.3 | < 0.001 |
| HDL (mg/dL) | 42.5 ± 9.2 | 54.8 ± 11.3 | < 0.001 |
| LDL (mg/dL) | 133.4 ± 35.7 | 103.2 ± 24.1 | < 0.001 |
| Triglycerides (mg/dL) | 174.2 ± 56.1 | 120.8 ± 40.2 | < 0.001 |
Association of Periodontal Pathogens with Cardiovascular Disease Between Severity, (Mild CVD, Moderate CVD, Severe CVD),with Statistical Significance.
The table 5, shows a significant association between oral microorganisms and cardiovascular disease severity. P. gingivalis increases from 52% in mild to 84% in severe CVD (P < 0.001). A. actinomycetemcomitans and T. forsythia also show increased percentages with disease severity, with T. forsythia reaching 78% in severe CVD (P < 0.001). These results highlight the strong correlation between oral bacteria and CVD severity.
| Periodontal Pathogen | Mild CVD (n = 50) | Moderate CVD (n = 50) | Severe CVD (n = 50) | P-value |
|---|---|---|---|---|
| P. gingivalis (%) | 52% | 71% | 84% | < 0.001 |
| A. actinomycetemcomitans (%) | 45% | 55% | 63% | 0.038 |
| T. forsythia (%) | 49% | 66% | 78% | < 0.001 |
Heart disease and stroke have been the world's top causes of death for decades, affecting people of all races and cultures [28]. If you have the right tools, the World Health Organization (WHO) says that you can avoid or treat more than 75% of cardiovascular illnesses (CVDs) [29]. There wasn't a big difference in age between the groups in this study (58.7 ± 12.5 vs. 56.2 ± 11.3 years, P = 0.321). Gender distribution was similar (P = 0.722). However, patients had a significantly higher BMI (29.4 ± 5.1 vs. 24.1 ± 3.7 kg/m², P < 0.001) and a greater prevalence of hypertension (55% vs. 10%, P < 0.001) and diabetes (45% vs. 7%, P < 0.001) compared to healthy controls. The amount of T. denticola found depended on the person's body mass index (BMI). People of all ages did this. The only thing that was different between men and women was that men had more T. denticola than women did. The study found that P. gingivalis and P. intermedia was found about as often as each other. People who don't have type 2 diabetes are much less likely to have A. actinomycetemcomitans, F. nucleatum, and T. forsythia. According to another study [30], P. gingivalis was found more often in overweight people with type 2 diabetes? The study looks at how many types of germs are in the mouths of healthy people and people who have periodontal illnesses. It was found that only 28% of healthy controls have P. gingivalis, while 74% of cases do (P > 0.001). Only 20% of healthy people and 56% of people with the disease have A. actinomycetemcomitans (P < 0.001). This is because only 22% of healthy controls have T. forsythia, while 62% of cases do (P < 0.001). It is clear from this that there is a strong and statistically significant link between the disease and having germs in your mouth. Another study found that T. forsythia was more common in adults younger than 35 and A. actinomycetemcomitans was more common in adults older than 35. Males were more likely than females to have T. denticola, which was one of the different types of bacteria [31]. A study in people in the Middle East and North Africa who did not have advanced periodontitis found that P. gingivalis and P. intermedia were more common than A. actinomycetemcomitans. Statistics showed that there was a strong link between P. gingivalis and A. actinomycetemcomitans. There wasn't a strong link between A. actinomycetemcomitans and P. intermedia [32]. People with the disease had much higher amounts of CRP (14.5±6.2 mg/L vs. 3.2±1.1 mg/L, P<0.001), IL-6 (88.7±17.4 pg/mL vs. 26.4±6.5 pg/mL, P<0.001), and TNF-α (85.4±18.3 pg/mL vs. 31.5±9.2 pg/mL, P<0.001) compared to healthy controls. Lots of these inflammation factors in the blood are linked to the disease in a strong way. In a different study, people who took atorvastatin or simvastatin had lower amounts of periodontal indices and inflammation markers (IL-6, CRP, and TNF-α) in their blood [33,34]. IL-6, IL-8, MMPs, and prostaglandin E2 (PGE2) are some other chemicals that make the inflammation response stronger at the cellular level. Two important cytokines that do this are IL-1 and TNF-α. Chemokines in Parkinson's disease hurt cells and make them swell up. Experiments on animals have shown that cytokines like IL-1 and TNF-α are bad for you. They make the damage to periodontal tissues worse and are a main reason why the disease gets worse [34]. The pathogen causes oxidative stress and then an inflammatory reaction in the blood vessels. Interferon-γ (IFN-γ), IL-1β, IL-6, and TNFα all grow in the EC. These are all pro-inflammatory factors. The monocytes can move and stick together better because of this, which helps AS form [35]. The study looked at blood pressure, cholesterol, HDL, LDL, and triglycerides levels in both sick and healthy people to see how they compared. These three types of cholesterol are much higher in patients than in controls (P-value < 0.001). HDL values are lower in patients. These results show that patients have a higher chance of heart disease. A review of 29 studies showed that there is a link between gingivitis and dyslipidaemia. Specifically, people with periodontitis had much higher amounts of TC, LDL, and TG, while their HDL values were lower[36]. Several pieces of data showed that people with dyslipidaemia had higher levels of TNF-α in their blood. This level was significantly linked to VLDL, triglycerides, and cholesterol, and it was negatively related to HDL cholesterol [37,38]. This study showed a significant association between oral microorganisms and cardiovascular disease severity. P. gingivalis increases from 52% in mild to 84% in severe CVD (P < 0.001). A. actinomycetemcomitans and T. forsythia also show increased percentages with disease severity, with T. forsythia reaching 78% in severe CVD (P < 0.001). These results highlight the strong correlation between oral bacteria and CVD severity. Also, T. forsythia and BspA raise blood levels of CRP and LDL while lowering HDL, which helps atherosclerosis grow even more [39]. This is becoming more and more clear that T. forsythia, the third and most well-known important part of the red complex bacteria that is linked to gum disease, is also linked to heart disease. A strong link has been found between T. forsythia and atherosclerosis in more than one study. At the time of the study, T. forsythia was found in 43.7% of arterial plaques in coronary vessels [40].
The findings show a strong link between gum infections and cardiovascular diseases (CVD). It was much more common for patients to have P. gingivalis, A. actinomycetemcomitans, and T. forsythia than for healthy controls, and it got worse as the CVD got worse. Periodontal infections were also linked to elevated systemic inflammatory markers (CRP, IL-6, TNF-α) and higher cardiovascular risk factors, including increased cholesterol and triglyceride levels. These findings support the hypothesis that periodontal infections contribute to the progression of CVD, highlighting the importance of oral health care as part of preventive and therapeutic strategies for cardiovascular diseases.
Med., vol. 2022, p. 8678967, 2022.