Physician Area


Project Connexus was created to prevent diabetes, cardiovascular diseases and periodontitis, because they are serious diseases that are closely correlated to one another.

We know that amongst non-communicable diseases, ACVDs are the leading cause of death and chronic disability in the whole world. In Europe, ACVDs causes 4 Million deaths (45% of all deaths) every year, in Italy it causes 220000 and in the rest of the world 18 millions deaths. The UN defines ACVDs a major barrier to long-term human development. The problem in Italy and in the rest of the world is the great burden of economic expenses.
In 1989, Svrjänen et al. explore the relationship between oral health and stroke. The results have shown a strong association between ischemic stroke, especially in the male population, and oro-dental infections. This study paved the way to a great deal of reports, and, in the last 20 years, there has been an increasing number of clinical studies, systematic revisions with metanalysis, case-control studies, cohort studies and epidemiological studies that have highlighted the association between chronic oral infections, in particular, Periodontitis (PD), [PD]and Atero-cardio-vascular Diseases (ACVDs). [ACVDs].
In 2003, Harvad University published an outstanding work following a cohort study on more than 40000 patients for 12 years to prove a possible association between PD/a reduced teeth number and an increase in stroke incidence. The study considered common risk factors between ACVDs and PD to avoid any elements of confusion. The results have shown a positive association between PD/reduced teeth number and ischemic stroke.
In a study with more than 7600 subjects, Holmlund et al. have highlighted a higher ACVDs-caused mortality amongst those that had < 10 teeth compared to those who had > 25 teeth.
In terms of a public health perspective, the implications are of utter importance.
WHO and EU have both recommended investments that would promote and put measures in place for the prevention of the most common chronic diseases, amongst which there are Periodontal infections and ACVDs, especially for the probable causal link between the two, which is also supported by scientific publications in the last 5 years.
Evidence shows that the causal association between PD and ACVDs derives from the role that systemic inflammation plays in atherosclerosis pathogenesis and in CVDs-related illnesses in general. DNA in Periodontal pathogens was identified in atero-thrombolic tissues, strongly suggesting that periodontal bacteria and their virulence factor are crucial in ateroclerosis pathophysiology.

Insights Video

The Bacterial Oral Flora is the most complex microbiome in the human body, after the gastro-intestinal one.
PD is a chronic inflammatory disease, primarily caused as a response mechanism to a group of well-known bacteria with Gram-negative anaerobic predominance, like Porphyromonas Gingivalis, Aggregatibacter Actinomyecetemcomitans, Tannerrella forsythia, Treponema Denticola and Spirochetes, which are all present in a sub-gingival biofilm. The qualitative and quantitative alteration in the bacterial composition of this biofilm is responsible for the aberrant host-biofilm interaction, which translates in a destructive immuno-inflammatory response for tooth-supporting tissues (the so-called Periodontal Breakdown).
PD prevalence is estimated to be 50% of the global population (between 2.5 and 3 billion of people are affected by a moderate/severe form). In Italy, 1 out of 2 people is affected by different forms of Parodontitis and 10% is affected by severe forms, with immediate tooth loss risk.
From the symptomatologic point of view, PD has a silent onset and a silent progression, which are typical of non-communicable diseases. There are signs and symptoms that an uninformed patient doesn’t recognize most of the time (find more in the recommendations section). Functional and aesthetic disabilities become visible in the most advanced stages of the disease; they become so evident that they prompt the patient to visit a dentist when it is too late.
It’s important to remember that PD is preventable, easily diagnosable and, above all, treatable!
The inflammatory response in periodontal tissues is characterized by the production of inflammatory mediators and enzymes, like C-Reactive protein (CRP) and Interleukins (IL-6, IL-8, IL-1Beta), TNF-alpha, fibrinogen and metalloproteinases. This increase in inflammatory cytokines seems to be an essential factor for systemic inflammation, which is one of the main protagonists of atherosclerosis pathogenesis.
In the last 20 years, the International scientific literature has revealed a series of evidences that support the role of PD as an independent risk factor for ACVDs.
The association is bidirectional. Moreover, PD and ACVDs share many modifiable and non-modifiable risk factors.

Amongst the non-modifiable risk factors there are:

  • Gender (male)
  • Genetic profile in relation to immune function
  • Age
  • Low socio-cultural-economic profile

Amongst the modifiable risk factors

  • Dyslipidemia (in particular, LDL, VLDL, triglycerides)
  • Glucose (HBA1c) metabolism alteration and Type II diabetes
  • Endothelial dysfunction
  • Weight Gain
  • Arterial Hypertension
  • Smoke
  • Alcohol
  • Sedentary lifestyle
  • Eating habits that are not able to prevent risk factors (hypertension, weight gain, Glucose metabolism, dyslipidemia)

Modifiable Risk factor control is utterly important to avoid late diagnosis (which are very common) and poor prognosis, in terms of poor quality of life along with high social and healthcare costs.

Many studies have unquestionably shown that PD drains bacteria in the circulatory system, causing Bacteremias. It is proven that parodontopathogenic bacteria are present in ateromas. Subjects affected by periodontitis have a high risk of developing ACVDs and, in case an ACVD were already present, they increase by 1.5/2 times the risk of having acute complications (especially myocardial infarction and stroke).
Studies have also shown that after periodontal disease therapy, the typical inflammatory markers and of ACVDs drastically decreased compared to those who didn’t receive the treatment. We need to highlight, however, that the reduction in these markers, although it is certain, has been shown to occur a few months after the treatment for periodontal disease due to post-surgical inflammatory activity.

What is the current state of epidemiological evidence?

There are evidences that show that diseased patients present

  1. Sub-clinical cardio-vascular disease manifestations: endothelial dysfunction, which is measured by flow-mediation dilatation (FMD), arterial walls rigidity and increased carotid intimal thickness with elevated calcification score
  2. Increased coronary risk and, therefore, MI and Cerebrovascular events risks
  3. Risk of frequent bacteremias caused by the entrance of local bacterial oral flora in the circulation
  4. Elevated fibrinogen levels with increased thrombotic risk
  5. Dyslipidemia and, especially, increased LDL, VLDL cholesterol and triglycerides levels
  6. Chronic Hypergylcemia and Diabetes type II development
  7. ACVDs genetic factors

An international consensus report, that was published in 2020, states that, independently from other risk factors, Periodontal disease treatment reduces ACVDs progression.

For General Practitioners and other specialists, Dentists with ACVD or High-risk ACVD patients

  • Patients should be informed that PD can have a negative impact on the ACVD course, and it could increase the risk of developing acute events, like myocardial infarction and stroke.
  • Patients should be informed that Periodontal disease treatment, by reducing chronic systemic inflammatory levels, helps maintaining the health of the cardiovascular system.
  • Patients should be sent (if the procedure is not started yet) to a periodontology expert for PD screening and, consequentially, to seek an appropriate treatment.
  • ACVD patients should be asked if there are any PD signs or symptoms:
    • Spontaneous or Iatrogenic (due to oral hygiene procedures) Gingival
    • bleeding
    • Alitosis
    • Teeth mobility
    • Opening of spaces between teeth
    • Swelling associated with gingival/dental sensitivity
    • Tooth loss or reduced teeth number
  • Patients should know that PD could be totally asymptomatic (most of the times). The absence of symptoms doesn’t mean that PD is not present!

Dentists who treat their patients, especially those who were diagnosed with PD, should know:

  • When PD is present concurrently with ACVD, it is necessary to take the proper route of Periodontal treatment in 4 phases, as it is indicated in the guidelines of the European federation of Periodontology and of the Italian Society of Periodontology.
  • Patients with Periodontal disease without diagnosed ACVD (especially if all shared risk factors are present), should be sent to their General Practitioner for preliminary investigations that could confirm the presence of ACVD.
  • A close collaboration with the patient’s GP or other physicians (cardiologist, internist, etc) is necessary before and after Periodontal disease.

From a multi-disciplinary synergic prospective, all medical categories should inform patients on the opportunity to intervene on modifiable risk factors, which may benefit:

  1. Individual health
  2. Increased efficient communication, awareness and diffusion of the message from patients and from the rest of the population
  3. Public Healthcare and costs

Collaborate with us

Contact us via mail or via telephone to build a joint strategy.


An extreme summary of bibliographical references

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