Periodontal Disease And Systemic Disease- Is There A Link?

Question 1

Periodontal disease as a risk factor for systemic diseases:

Answer 1

●Coronary heart disease/Stroke
●Diabetes
●Adverse pregnancy outcome
●Chronic obstructive airways disease
●Rheumatoid arthritis, cognitive impairment, chronic renal disease, metabolic syndrome, cancer………

Question 2

Oral sepsis causes diseases such as

Answer 2

tonsillitis, middle ear infections, endocarditis, empyema, meningitis and osteomyelitis”

Question 3

Theory behind the link relates to…

Answer 3

The mouth as a portal of entry for bacteria into the systemic circulation

Question 4

Example of a systemic condition with acting as a portal of entry for bacteria into the systemic circulation? And a condition that is similar to a periodontal pocket?

Answer 4

Diabetic foot ulcer. It is a chronic wound, large ulceration, lots of bacteria present esp staphylococcus. The area will bleed and if the blood vessels are damaged then bacteria can get into the systemic circulation. It will be cleaned with iodine and other sterilising agents like to how a periodontal pocket would be cleaned (but with different means).

Question 5

Periodontitis is a

Answer 5

Infected chronic wound in the mouth. Chronic because there is chronic inflammation of the tissues. Infected because of the biofilm on the surface of the roots. Pocket wall is ulcerated and very inflammed. Hence similar to a diabetic foot ulcer.

Question 6

More on how the mouth is a portal of entry for bacteria for the systemic circulation…

Answer 6

We are treating individual pockets for a patients, taking all the pockets together as a cumulative wound and you measure the size of the wound then a patient who has generalised advanced perio disease affecting all the dentition and you add it up= approx. The size of a wound approx of the palm of the hand. On the root surface is a biofilm full of bacteria.
Therefore a patient with periodontitis has in their mouth a portal of entry of bacteria into the systemic circulation.

Question 7

Periodontal disease and an increased risk of cardiovascular disease… (flossing is good for your heart)

Answer 7

Lots of longstanding evidence about the mouth and oral sepsis as a potential risk factor for systemic disease.
Matilla 1995 was a case sontrol study of a group of patients who died from a heart attack compared to patients who had no cardiac history. Studied their perio health and general health, total dental index which looked at health of the mouth including things like number of missing teeth number of fillings, and also periodontal condition. And there was evidence that there might be a link between oral health and cardiac disease.
First well designed study focused solely on periodontal disease and its link to CHD reported was Beck 1996- cohort study, following a number of patients over several years, looked at outcomes such as coronary heart disease, death due to CHD and stroke. Then they linked that back to the level of periodontal disease through alveolar bone loss. This showed a significantly increased risk of having periodontal disease leading to these outcomes. Particularly strong for stroke- if you had periodontal disease then you were almost three times as likely to have a stroke over the period of a subsequent number of years.

Question 8

Other studies?

Answer 8

Case control study looking at patients who were confirmed as having CHD and comparing them with patients who had no history of cardiac disease.
Relatively small case control study- results include angiogram showing narrowing of the coronary artery vessels. 92 cases with this.
79 controls.
All the patients also had a full periodontal assessment with indices and radiographs taken. Much greater, statistically significant increase in perio disease with those who had CHD than with those without it.
The data was reviewed and other confounding variables were taken into account (smoking, academic achievement, alcohol consumption etc.). The adjusted odds ratio was still over 3 and the confidence interval was greater than 1 so statistically significant.

Question 9

More studies…(international)

Answer 9

Meta-analysis of cohort studies from US and Finland, those with periodontal disease had a 24 percent increased risk for CHD.
Particularly strong for middle aged male patients.

Question 10

Epidemiological studies from around the world were showing that there was a link between periodontitis and CHD. And for patients who had periodontitis there seemed to be an increased risk of CHD.
Why might that be?

Answer 10

Potential for shared risk factors.

For perio…
oral hygiene
●smoking
●diabetes
●genetic
●stress
●low socio-economic status

For CHD
●elevated LDL cholesterol
●hypertension
●family history
●smoking
●severe obesity
●diabetes
●stress
●low socio-economic status

Question 11

Describe the correlation between periodontal disease and systemic conditions

Answer 11

●100 million bacteria in one pocket related to one surface of one tooth
●Frequent transient bacteraemias occur in patients with periodontal disease
● increase in intensity of bacteraemias correlates with the extent and severity of periodontitis

Question 12

Potential biological mechanism linking perio disease with CHD?

Answer 12

Either by shared risk factors or by bacteriaemia and the translocation of cytokines…
At the site of a periodontal pocket (ulcerated and inflammed gums cause a systemic inflammatory response…) there is a significant increase in cytokine release. Things like ILs, prostaglandins, chemokines. These can translocate into the systemic circulation. We know that those cytokines can also get into the vasculature. There is the potential for translocation of bacteria and inflammatory cytokines around the body to different organs and different sites. For example if they (LPS from a bacterial pathogen) go into the liver, this will stimulate the release of systemic inflammation by liver cells. So things like C-reactive protein, IL-6 and Fibrinogen. These will all increase in response to pathogens reaching the liver. These three markers CRP IL6 and Fibrinogen are all markers for increased risk of CHD.
Similarly, increased pathogens, cytokines, LPS translocating directly to the coronary artery epithelium can all increase the stickiness through increased adhesion molecules thereby increasing the risk of atheroma formation- atherosclerosis is now considered to be an inflammatory condition.
Anything that will increase inflammation in coronary artery walls, in the endothelial cells will then cause an increase risk of atheroma formation.
We know that pathogens like P gingivalis can increase platelet aggregation and platelet aggregation can lead to thrombus formation and atheroma formation, hence CHD.
So there are also mechanisms now linking this translocation of cytokines, cytokines, pathogens in the periodontal pocket to the liver or to the coronary artery endothelial cells and therefore increasing risk of CHD.

Question 13

We can test this potential biological mechanism with intervention studies.

Answer 13

By treating the periodontal disease and looking at the systemic effects of that treatment. It can take a long time for these studies to be completed if the outcome measure is a heart attack/ coronary artery problem, so instead can measure markers of risk such as CRP (C-reactive protein).
Several studies have looked at periodontal disease and CRP levels in the blood. What most studies have found is that by treating the patients and therefore reducing the level of inflammation and the amount of pocketing present in the oral cavity, this will lead to reduced levels of CRP in the circulation. This by definition leads to reduced risk,. This is because we know that high levels of CRP in the blood is a known risk factor of CHD. A mechanism to reduce levels of CRP would reduce risk of cardiac disease.

Question 14

Role of periodontal pathogens

Answer 14

. P gingivalis expresses platelet aggregation activity (and therefore increased risk of thrombus formation)
●P gingivalis and A actinomycetemcomitans isolated from human atheroma
●2 studies reported a correlation between periodontal status and the presence of pathogens in the atheroma

Question 15

Studies on the association between periodontal disease and CHD – negative findings ie not supporting the link?

Answer 15

Prospective Cohort Study….

Almost 2000 of the patients had periodontal disease, 2400 with gingivitis and then almost 4000 controls with a healthy periodontium. They were followed over a 10 year period and during this time there were over 12 hundred cardiac events.
When researchers compared the three groups of patients, so the controls, the gingivitis patients and the periodontitis patients they did not find that having gingivitis or periodontitis increased the likelihood of having cardiac events.
They put the perceived link between these conditions primarily down to smoking as a shared risk factor.

So this lead to, in 2013 the EFP and AAP considered all the published evidence regarding supposed link between periodontitis and systemic disease tried to come up with a consensus report…..summary of findings was….

Question 16

Summary of findings of the consensus report from Joint EFP/ AAP Workshop on Periodontitis and Systemic Diseases

Epidemiology?
Plausibility
Intervention

Answer 16

●There is strong and consistent epidemiologic evidence that periodontitis imparts increased risk for future cardiovascular disease; *****particularly in males and in younger individuals.

Risk for stroke is greater than for CVD.

No increased risk in over 65s.

Question 17

Plausibility?

Answer 17

Periodontitis leads to bacteraemia, activating the host inflammatory response which favours atheroma formation.

Question 18

Intervention?

Answer 18

Moderate evidence that periodontal treatment reduces serum CRP levels and improves markers of endothelial function;

limited evidence for improvement in coagulation;

no effect on lipid profiles

Question 19

Gum disease and CAD evidence?

Answer 19

American Association for Periodontology

●Researchers have found that people with gum disease are almost twice as likely to suffer from coronary artery disease.

Question 20

Impact on clinical care- gingivitis and CAD risk

Answer 20

At present:

●insufficient data to impact on treatment planning
●good motivational tool

Question 21

Periodontal disease and the risk of adverse pregnancy outcomes?

Answer 21

Preterm, low birthweight babies
●less than 2.5 kgs birthweight
●less than 36 weeks gestation
●1 in 10 deliveries in US

●significant cause of perinatal mortality & morbidity
●60% infant mortality linked to low birthweight

Question 22

Periodontitis and Low birthweight (LBW)- evidence base/ studies?

Answer 22

Case control study
Cases were the mothers of low birth weight babies and the control mothers of normal birth weight babies.
Small study comparing the two groups’ periodontal status using logistic regression analysis.
Results- multivariate log regression analysis showed almost 8 fold increase in odds ratio for periodontitis and Low birth weight babies. Significantly higher than the other risk factors considered such as treated GU infection and age.
Based on this evidence more studies were carried out- above North Carolina group published a further study- case control- comparing mothers with mild perio disease with those with significant perio disease and measured pregnancy outcome , significant difference seen.

But davenport studies in London found no significantly increased risk of preterminal birth weight outcomes if the mother had periodontal disease, ie no link between low birthweight and perio disease.

Therefore some difference in findings.

Question 23

Periodontal disease and low birth weight- shared risk factors-

Answer 23

Perio disease risk factors…

. oral hygiene
●smoking*
●diabetes*
●genetic
●stress
●low socio-enomic status***

Low birth weight risk factors…

. maternal age <17 or>34
●low socio-economic status
●inadequate pre-natal care
●smoking
●alcohol abuse
●genito-urinary tract infections
●diabetes
●multiple pregnancies

Question 24

Biological mechanism underlying perioontal disease and low birth weight?

Answer 24

Periodontal pocket has Ulcerated epithelium… increased Bacteria + LPS….

Bacateraemia travel to
Fetal-placental unit…

Inflammatory response occurs…

This Induces expression of PGE2, TNFa

This causes
Premature uterine contraction Cervical dilation

Question 25

How were animal models used to prove this?

Answer 25

Pregnant hamster
Subcutaneous implantation of bacteria (Pg)
Measure birth-weight

Question 26

What did these animal studies show??

Answer 26

15-18% decrease in birth weight in animals receiving P gingivalis

Question 27

What other animal studies were performed?

Answer 27

Experimental periodontal disease
Mate animals
Measure their litter weights

Question 28

What did this show?

Answer 28

Decrease in litter weights in periodontitis group
•Increased levels of PGE2 and TNF-α in amniotic fluid

Question 29

Intervention studies measuring this association?? Describe

Answer 29

Initial studies indicated a reduced incidence of PLBW in treated group

•Successful treatment was associated with a 6-fold greater chance of full-term birth compared with those who were refractory to treatment

Question 30

Example of study measuring treatment of perio disease and effect on birthweight?

Answer 30

Intra pregnancy non surgical periodontal treatment and pregnancy outcome: an RCT

Question 31

Outcome of this?

Answer 31

Intra-pregnancy non-surgical periodontal treatment, completed at 20-24 weeks, did not reduce the risk of preterm, low-birthweight delivery in this population

Question 32

So basically evidence there is supported by animal studies but conflicted by the previous study and this one- New England Journal of Medicine…

Answer 32

Tx of perio disease in pregnant women improves perio disease and is safe but does not reduce the rates of preterm birth or low birthweight

Question 33

Periodontal disease and diabetes….

Answer 33

Poor diabetic control is a risk factor for periodontal disease.
But the question being asked now is, is periodontal disease a risk factor for diabetic control?

Question 34

Potential biological mechanism linking the two has been posed…

Answer 34

Linking the translocation of cytokines and bacteria from the oral cavity ie the site of periodontitis resulting in increased levels of systemic cytokines. That is known to increase insulin resistance and therefore increase the risk of type II diabetes.
There is a potential link between having periodontal disease and increasing insulin resistance and therefore increasing the risk of developing or progressing type II diabetes.

Question 35

What is the epidemiological evidence?

Answer 35

●Emerging evidence indicates an increased risk of developing diabetes in patients with severe periodontitis;

●Moderate/severe periodontitis is associated with an increased risk of end-stage renal disease, cardio-renal mortality and calcification of atherosclerotic plaques;

●Severe periodontitis adversely affects HbA1c levels

Question 36

Studies?

Answer 36

Numerous studies were carried out in late 90s early 2000. Some showed no impact of periodontal treatment in the mean HbA1c levels but some did, the latter including systemic antimicrobial therapy. The ones that did show impact showed reduced glycated haemoglobin levels and that equates to an improvement of diabetic status.

Question 37

Systematic reviews and meta-analyses
Treatment of periodontal disease for glycaemic control in people with diabetes?….

Answer 37

A reduction in HbA1c of approximately 0.4% following non-surgical periodontal therapy

Question 38

Effect of NSPT on glycaemic control…

Answer 38

●Mean reduction in HbA1c of 0.4% following NSPT
●Normal range 4-6%
●Target for diabetics <6.5%

Every 1% reduction in HbA1c is associated with significantly reduced risk of diabetes-related complications

Question 39

Periodontal disease and respiratory disease?…

Answer 39

•aspiration of oropharyngeal secretions
•‘aspiration pneumonia from anaerobic organisms usually occurs in patients with periodontal disease’.

Question 40

Periodontal disease and respiratory disease… evidence base/studies have shown?…

Answer 40

●patients with poor oral hygiene levels had an increased risk of developing COPD
●patients with COPD had more periodontal attachment loss than healthy controls
●improving oral hygiene significantly reduced the occurrence of respiratory disease
●studies provide evidence of an association between oral health and both pneumonia and COPD, with the evidence for the link to pneumonia being stronger

Question 41

Periodontal disease and respiratory disease conclusion from studies?….

Answer 41

●Improve oral hygiene of older patients, especially bedridden, debilitated patients who cannot adequately perform routine toothbrushing

Question 42

Periodontitis and systemic conditions: where are we now?

Answer 42

●Good evidence that periodontal disease is an independent risk factor for systemic conditions

●Plausible biological mechanisms exist

●Clinical intervention studies have not provided definitive outcomes

Question 43

Conclusions
This multicenter randomized clinical trial of nonsurgical periodontal
treatment for participants with type 2 diabetes and chronic periodontitis did not demonstrate a benefit for measures of glycemic control. Although periodontal treatment improved clinical measures of chronic periodontitis in patients with diabetes, the findings do not support the use of nonsurgical periodontal treatment for the purpose of lowering levels of HbA1c.

Question 44

Evidence is conflicting though again because ….
Conclusions…

Answer 44

JAMA 2013 effect of NSPT on glycated Hb levels in persons with type 2 diabetes and chronic periodontitis RCT

did not demonstrate a benefit for measures of glycemic control. Although periodontal treatment improved clinical measures of chronic periodontitis in patients with diabetes, the findings do not support the use of nonsurgical periodontal treatment for the purpose of lowering levels of HbA1c.