Perio Final

"Perio - systemic relationships" To be honest with you, this is very extremely unbelievable, ununderstandable, uncontrollable, unexpectable, unexplainable, the hardest, the most difficult, the most complicated, antimemorising, antifinishing lecture so, if you want to skip lectures then this is the lecture of choice to skip, but if you are intransigent (‫ )معند‬then prepare yourself to the war against this evil lecture. And as usual I copied what is in the slides and not mentioned by doctor in small font (they are many, and most of them not well understood so you can skip them if you like), now let's fight…

This is the good news: doctor said you don’t need to know all the studies, but you should know the end conclusion (for example the end conclusion of perio with PT/LBW positive or negative, the end conclusion with cardiovascular, with intervention studies…) and doctor will not ask us about numbers (as 18% become 10% after treatment), but she want us to understand. (this information mentioned in the end of the lecture)

You will see in this lecture how much we affect medicine, and you will see that by this small pocket and inflammation we destroy them, so you have to see yourself as a strong people. You studied previously how systemic disease could affect the periodontium and could aggravate the periodontal disease like diabetes, syndromes….etc, and how they can affect the situation by hormones and other things, now we are going to study the other side of the story.

The mouth is the mirror of the health of the body: a lot of diseases you can pick them very easily when you look inside the patient mouth like immune diseases, anemia, leukemia and a lot of other diseases. Because the periodontal disease as we all agreed on is infection associated with bacteria (bad bacteria) which secretes toxins and lipopolysaccharides, so this bacteria and its products is going to affect the mouth and can seed to the body, either it (bacteria) can go to the arteries, to the veins through the lymphatics or its products can go. What will happen when we have bacteria in our body? There will be immune reactions which will form mediators, then these mediators will cause destruction to the tissues which they are in (this is as local effect), also it can go through the lymphatics and blood to any part so it can damage your liver, heart, brain….etc. So this is basically is our lecture and this is the end of the lecture, you can go (this is jock from doctor don’t believe yourself).

Perio-systemic relationship-a two way street: Perio-systemic disease relationship is a two way street, when you are in a two way street you can go and come which means the systemic diseases aggravate perio and perio "cause" and aggravate the systemic diseases, but regarding perio that it "causes" perio it has question mark because we can't guarantee 100% that it causes disease (heart disease for example).

If we want to know that perio causes disease we should have: Cohort study: to bring someone who don’t have any systemic diseases then infect him with perio disease then follow him in the following years to see if there is any changes (for example heart changes…etc). Or another study which is randomize controlled trial (intervention study): you bring someone by random who has perio disease and you treat him, and you bring another one who also has perio disease but you don`t treat him, and the one you treat for example: his cardiac marker become better and the one you don`t treat developed heart attacks….etc. And these are the strongest studies that gives you causality (cohort and randomize), but randomize is easier than cohort because the condition here is established so it`s very easy, but the cohort study needs long breath (‫ )نفس طويل‬especially if we are searching on heart diseases to happen, so it takes a long time maybe 20 years will pass and patient lost all his teeth without developing any heart problems so it`s not easy, the cohort study should be fast thing like herpes virus in which after two days you see changes this is something easy, otherwise it takes long time and maybe the patient will die without knowing about him because it takes time

Now systemic risk factor associated with periodontal disease: The strongest thing is the smoking and it’s the most common in the studies, diabetes also is very strong and it has odd ratio about 24 (odd ratio will be discussed later), also smoking has the same odd ratio as doctor said. •

•

Hereditary: familial history and host for the patient.

Association of periodontitis with systemic disease: The most common in the literature are: preterm low birth weight: to have a new born with low birth weight and size (low birth weight), or for less than 37 weeks

intrauterine*(preterm), the child will be premature even if he is healthy and continued his life, but if it`s more than 37 weeks then this is normal child Cardiovascular disease: including heart attacks, ischemias, cerebrovascular accidents….etc, all these things associated with the heart. Pulmonary disease, Diabetic control *remember the baby should stay 40 weeks and if stayed for less than 37 weeks he will need incubator ( ‫)خداج‬

Nowadays there are a lot of investigations on diseases even on things like stomach ulcer, rheumatoid arthritis …. Everything in the body you can think about periodontal disease as risk factor or prognostic factor for that disease.

Periodontal disease: Periodontal disease is common, in general in the studies in USA 50% or more have gingivitis. Periodontitis if we are talking about moderate periodontitis it reaches 30-50%, and if we are talking about severe or advance it reaches 10% (that’s what doctor said but in the slides it`s as below):

•

Periodontitis-35% of adults>=30year

•

22%mild, and 13% moderate or severe

If we are talking in general, these numbers means that periodontitis is fairly common disease, for example when we are talking about 10% with severe periodontitis it’s a good number because almost the end result of it is loss of teeth with a lot of problems. When you have a patient like this (pic slide 5 page 1): you are going to find inflammation, attachment loss, bone loss, probing depths, mobility…… and all signs of periodontal disease.

For this patient once you see the picture like this then for sure the inflammation is not just gonna be local in this area, it's like ulcer for example when someone injured his hand the doctor ask him to take systemic antibiotics because this ulcer sometimes may cause bacteremia with increase body temperature and other systemic complications, and the mouth is the same because it's very easy to leak to the body and cause infection and cause infection inside it.

what happens in the periodontal disease: is that there will be elevation in the: •

Inflammatory mediators (interleukins 1B, prostaglandins tumor necrosis factor-a). 



E2,

C-reactive protein (CRP): here the doctor forgot about the lecture and she (

‫ )بلشت‬of C-reactive protein which is in the end of the slides

C-reactive protein is an enzyme or protein secreted from liver with inflammation, it’s a risk factor for atheroma formation, vessels constriction, platelet or clot formation, so this CRP has become a dependable marker for future heart attack. For example: a patient came to you with previous heart attack, you measure the level of CRP*, in addition to the other things like blood pressure, triglycerides, cholesterol…….etc, to expect if there will not be another heart attack, so it become *as you know a patient with previous heart attack is subjected to another attack or ischemia at anytime.

A dependable marker because they noticed that the patients whose CRP increases has more chances to develop heart attacks. When you go to the laboratory to measure CRP, if you are not very sick they give you the result as positive or negative, have high value or not. C-reactive is very sensitive like ESR and it increases in any inflammation in the body but it's more accurate than ESR regarding its relation with cardiovascular diseases. Why we are focusing on cardiovascular diseases? Because in general all over the world the most common cause of death is cardiovascular diseases, that’s why any one came to us with an idea to decrease it is very welcomed. So they made on this C-reactive protein (‫)سمعة كبيرة‬, so every patient did CRP and they consider it something very important (‫ )اشي كبير‬as if you are examining for positive or negative hepatitis, and if you have high Creactive then you will have cardiac problems or second attack or anything. But the significance for it is debatable because as you know any test done is sometimes for trade purposes means companies advertise to it, for

example when the doctor was in USA they were saying that jewish people are the most common supporting it, of course it may be partly correct and evidence based, but not that accuracy that it’s a must that if

CRP increased then the next day you should have heart attack. You will notice that whenever you develop in medicine you will always hear about CRP and as we said previously that sometimes you get results in positive or negative but sometimes you may get numbers, for example: if you get result 2 its normal and if you get 2.7 its high, So if you asked the laboratory about numbers (the exact titer of antibodies), they will give you the amount of titer of CRP.

The doctor is making study with one of her Ms students, they treat perio disease and they measure the change in CRP before and after treatment on 3 and 6 months, so if they prove that with treatment of perio disease CRP changes that will be great. The old studies said that it (CRP) changes slightly but this change was momentarily _ means immediately after treatment only or with the next week_ but after period it quickly returned to its previous values. Remember that when making a study on CRP you have to take into consideration that the patient should not take antibiotics or subjected to infections, because if the patient for example gets influenza or something like that the CRP values will change, so in the study the patient should be healthy and has perio disease only.

The C-reactive protein subject is very big and if you searched on the net about it you will see big results, the doctor will show us Meta analysis (daily) that tries to answer the question: is it really effective that perio treatment affect CRP level? Because if we proved that with perio treatment we change or modify it then our clinics will be full of people who come to treat perio only to lower their CRP level, so getting rid of being in danger of heart attacks. For example if you tell anyone even your father that if you clean his teeth (treat perio) he will not have heart problems in the future he will agree with you to be away from heart problems even if they did not happen.  Bacterial antigens and lipopolysaccharides. •

Potential effect on vascular integrity

 Activation of endothelial cells, monocytes and platelets.

They use the perio-systemic relationship in USA as a device of advertisement to attract patients, for example: in the waiting area they put videos about arteries, gum, bacteria, and how bacteria enter through the arteries and block them and make problems...etc, so the patient will think that he should treat perio immediately or he will get pulmonary or heart disease….etc. We will see in one of the slides (floss or die), yes it happen because it’s a matter of bringing vision (not sure)because as we said perio disease is a silent disease and needs to lose your teeth according to previous studies 10 years so it takes time to lose a tooth, and if we waited to lose a tooth the patient will never come to our clinic to do perio, but if we told him that if the inflammation continues (perio inflammation) you will have systemic effects he will come right away because his health is more important to him than losing a tooth (he will say to lose all my teeth is better than MI then die). Strength of the association research, who knows maybe it's correct, biologically it make sense because there is inflammatory mediators, infection, bacteria…etc. But how strong is this association, so the problem of joining between periodontal diseases and systemic diseases arose from that both of them are chronic conditions and multifactorial, for example no one get MI without anything, but there should be many reasons like smoking, stress, family history, triglycerides….etc, all these things together and also it takes time, and the same thing is the perio disease its chronic and multifactorial, and the factors that affect perio is the same factors that affect heart disease as for example smoking, so there is a shared factors between them. So when we do study we should make adjustment for all these factors, for example we shouldn’t test one who is non smoker and other one who is smoker, and then say that there is periodontal disease affect with heart disease, no there is should be adjustment for all these factors together. After they did adjustment for all these factors they found that there is a significant association and that there is increase risk of these diseases. The chart in page 2 slide 1 explain what happens that bacteria secrete enzymes, toxins, byproducts, fatty acids, LPS, PGE2, IL- 1,6,8, TNF-a, MMP`s and

other cytokines, antibodies from the pocket in to the body and cause problems. The next slide (possible by which gingival inflammation may modulate systemic disease) this chart shows you the pathway and how things develop and reach the heart, the brain, so it's all from the inflammation that is taking place, and it can target any part of your body, the previous is what doctor said but I (mun) think it's good to study the whole chart because it explains the whole idea.

Diabetes: You know many things about this disease, but we will concentrate on only one thing which is to measure the control of your diabetic patient, and the best test is HbA1c (glycocelated hemoglobin level that connect on RBC), and it’s the best because it gives you the reading for a long period 120 days which is the age of RBCs (in the slides 2-3 months) as a range, but if you used fasting then it will be only for that day. Previously they depended on fasting, random glucose tolerance test….etc, and they found that many diabetic people develop complications (like blindness, died…) without knowing (because these results were normal), so nowadays we depend on HbA1c because as we said it give us reading for a long time and it give us general reading about the patient, not because he is fasting or has any other variables. Previously 8 value of HbA1c was acceptable (normal non-diabetic people has value between 4 and 5), but they found later that people with 8 value also develop complications.

The problem of diabetes is that it’s a silent disease and has a lot of complications, a lot of people died just because they are diabetic because they end up with neuropathy, nephropathy, kidney failure…etc, and all

these things happen because the blood sugar is not well controlled, if it was controlled the situation of patients will be better. So to keep good control you have to keep HbA1c about 6.5 and below to be in the safe side, so the 8 value is not acceptable because it reflects as you see in the (3rd slide page2) 205mg/dl mean plasma glucose _remember normal glucose level is between 80 and 120_, and this is too high so to make sure that our diabetic patient is well controlled we should have HbA1c reading and this reading should be 6.5 or below (always come in exams). (%)A1c

6

7

8

9

10

11

12

Mean plasma glucose

135mg/ dl

170mg/ dl

205mg/ dl

240mg/ dl

275mg/ dl

310mg/ dl

345mg/ dl

Patients can expect 25-30% reductions in microvascular complications for every 1% reduction in A1c!!!!!!.

Now what is the difference between controlled and uncontrolled? The uncontrolled patient has many problems and his perio will be also affected (‫ _ )ملخبطة‬remember perio don’t like uncontrolled diabetes_ but with controlled diabetes perio can remain (‫)بتقول البريو بقدر اعيش‬.

Studies which talk about diabetes and perio:  It

demonstrates that individuals with diabetes tend to have a higher prevalence and more severe periodontitis than nondiabetics, and you have to remember that diabetes does not begin perio but it propagate it (the severity increase with it), and we will see later that diabetes don’t have effect on the extent of perio disease.  Patients

with poor control of diabetes experience more periodontitis than well controlled diabetics, so there will be more tendency to have periodontitis with them.  Severe periodontitis was associated with poor glycemic control and exacerbated diabetes-induced hyperglycaemia  Previous studies involving periodontal treatment alone reported improvement in periodontal status only  Few studies including systemic antibiotics accompanying mechanical therapy reported an improvement in both periodontal status and glycaemic control

 Moreover , it has been reported that non-surgical therapy including oral hygiene instruction and scaling root planning in type 2 diabetics resulted in better metabolic control of the diabetes

What can you do for diabetic patient if you treat periodontal disease? You can bring his blood sugar more under control because you are removing infection from his body (remember that what elevates blood sugar mainly is infection)*1. How infection increase blood sugar, is by all the cytokines that are secreted….etc, also the body become in need to blood sugar, and decrease in storage of it, so all these things will increase the level of sugar. So if you removed the infection you will control the blood sugar and that what happened in the studies, but also it was debatable, someone said you made the study on small number of patients, others said that not scaling or root planning who decrease the infection and glucose but the antibiotics which you used when you treated perio (remember many periodontists use antibiotics with scaling and root planning) and the infection may not be only in perio but maybe in your arm or leg and it's not the treatment of perio who decrease infection and blood sugar. Do we really can treat periodontal disease? You will see in the fifth year that you will treat patients with 5 or 6 mm pocket depth and on reevaluation you will see bleeding, pocket still present…etc, so it's not like caries where you remove all caries and you restore the tooth and you can be 100% sure (‫ )بتبصم‬that the tooth is caries free, in periodontal disease especially periodontitis not gingivitis whatever you are (even the most professional periodontist) you can`t be 100%sure that you removed periodontal disease completely. The only way to be sure 100% is by surgery and opening a flap and do complete pocket reduction and change the Position of gingiva, ending up with long teeth and furcation exposure which is not acceptable nowadays, so we can`t treat periodontal disease*2. To get rid of all the previous debates what should be the best design of our study? The doctor designed a study with one of her Ms students and its under progress right now, they extract the teeth of some of their diabetic patients, and they do not extract to the others, and they follow the level of HbA1c, so the base level of HbA1c should change*3 on 3,6 months and 1 year, because

if it only changed on 3 months then this maybe momentarily changes of the body because of extraction, but if it continued improving to 6 months this will be perfect.(remember the patient during this time should not take antibiotics or going through any major infection in his body or anything that might cause problem for him_ I(mun) think doctor meant anything that change HbA1c_ ). *1stress also elevates blood sugar but it`s not the main one (doctor said that we always put stress in everything) *2 she said here we can`t treat perio but I (mun) think that she meant we can`t be sure 100% of treating it *3 the doctor kept saying the word change but as you understood from the context she meant decrease)

The doctor said if this study completed (‫ )على خير‬it will be perfect, because that’s it (you took the tooth out, HbA1c is changing _ I(mun) think she meant decrease_), but of course remember that it's not the solution to extract the teeth, but we prove with this study that perio disease has systemic effect on the body. Spanish group showed that perio treatment lower HbA1c at 3 and 6 months. 

Periodontal status of diabetics compared with non diabetics: a Meta analysis  This meta-analysis was based on 18 comparative cross-sectional studies, three prospective cohort studies and baseline data of two clinical trials that compared oral hygiene, gingival and periodontal status between diabetics and non diabetics  RESULTS demonstrated that diabetes had significantly worse oral hygiene as measured by the average of plaque index (p1I), higher severity of gingival index (GI) and higher severity of periodontal disease as measured by the average of probing pocket depth (PPD) and clinical attachment loss (CAL).

However when they made meta analysis (doctor yousef khader alqaood did it)*, it showed that diabetics had similar extent of oral hygiene, gingival and periodontal disease as measured by percentages of surfaces or sites with specific scores of plaque index, gingival index, BOP,PPD and CAL. 

So the conclusion is that: diabetics had a significantly higher severity but the same extent of periodontal disease than non diabetics. What is the difference between extent and severity: extent is the percentage of affected sites (like in chronic periodontitis more than 30% is generalized and less than that is localized), but the severity measures the changes (like for example CAL and anything that measure changes)

Now what does meta analysis mean: it`s bringing all the studies that has been published on any topic and do analysis for them, and remember that there should be homogeneity between them ( not to have for example one study on animal with another one on human), also the definition of periodontal disease, changes, improvement and compounds should be the same. So you collect all these data and take the sum up, for example: if a study said that there is change 60% and other said 40% then you take the average. Meta analysis is stronger than only one study because it`s more than one study and it gives you sum up and summary of all what is going on. * Here doctor discovered that we didn’t take biostatistics and we don’t know anything about studies that’s why she was in valley and we are in another one.

The difference between meta analysis and systematic review is that in systematic review there isn`t always analysis (‫)مش شرط‬, for example it (systematic) tells you that on certain subject there is 10 cohort studies and 5 case control studies and those 10 studies showed that the disease increase with increase something but it don’t have figures (numbers or odd ratios) unlike meta analysis which has numbers (odd ratio). Odd ratio: is the percentage of risk of something to happen in people with risk factor in relation to people without that risk factor, for example two groups smokers and non smokers, the smokers for example the smokers has two times chance to develop perio disease then the odd ratio will be two times (when you divide the percentage of periodontitis in smokers_ example 70%_ on the percentage in non smokers _example 30%_). Whenever the odd ratio is more than 2 then this is a strong association, and whenever it`s 3 or 4 this is very strong association, and when it`s 2 it`s moderate association, and below two is weak association, and when the odd ratio equal 1 then there is no association (means for example: if you are smoker or not it’s the same and if you divide the percentage of them on each other the result will be one because you divide number on number equal to it). Premature birth Low birth weight and periodontitis:

It's an issue that all care about because it's common every where it's about 10% (imagine every 100 there is 10 Childs with low weight or premature birth). As we said previously it's when the child born in less than 37 weeks, or if the child born with low birth weight (less than 2.5 kg or less than 5.5 pounds) so your child in the future should be more than 2.5kg. The problem with those Childs is that they need incubators (‫)خداج‬ which is so expensive ($5 billion annual costs) and it`s not present in all hospitals, and if we did not put them in the incubators they will end up with death or congenital abnormalities (preterm birth is the second leading cause of infant mortality).

So because of this (it`s costly and common) people search on the reasons that cause it, nowadays there is no definite cause but it`s multifactorial like maybe the mother is so young or very thin or alcoholic or smoker or has systemic infection or previous history of PT/LBW or drug abuse or low socioeconomic status or parity or the race (black>whites), so there is no definite cause to say for example if the mother is alcoholic then the child should be premature or with low birth weight.

Mun: If you thought that you are about to finish this lecture look to the thickness of it and you will discover the disastrous unpleasant catastrophic truth

Association of infection with preterm (PT) birth: 

Microbiologic evidence. Positive membrane cultures (30-60%)



Bacterial urinary tract infections

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Bacterial vaginosis



Periodontal disease?

The periodontists said why we don’t come on the line (‫( )نيجي عالخط‬for Malaysian it means participate).

In 1996 in North Carolina where there is a lot of black people and very low socioeconomic status and periodontal diseases, a scientist called Offonbachor noticed that women with perio problems had low birth weight Childs, so to prove this he made a study (case control study). He took women who had low birth weight (LBW)or premature Childs (PM) and women who had normal Childs, and he compared the perio

condition of both and he found that the first group has periodontal disease more than the other with very high odd ratio (about 7), so he was so happy and he said "that’s it we have to look for perio of mothers and by that we decrease LBW/PM Childs and we spare a lot of money instead of spending it on incubators", and these results made a revolution (‫ )حرب‬in 1996 and ADA put a recommendation that any pregnant woman should not only visit prenatal care but also the dentist and it was really a big big thing. After this study Offonbachor and Jeffcoat in Philadelphia University continued making studies on other things like prostaglandins_ remember that prostaglandin level increase in perio disease because it's like cytokines and others, and prostaglandin is bad to pregnancy because it cause premature contraction to the uterus and cause labor also from slides it cause cervical softening _ so if they prove that prostaglandin increases in periodontitis (pockets and gingival crevicular fluid …) this means 100% that perio can cause these previous things. And they did the study and they found that the prostaglandin level was very high in the amniotic fluid, and not only that but they found bacteria seeding in the uterus and a lot of other things, so they persuaded all people of their results. That’s what doctor said and this is the exact slide to have the complete information: •

PT/LBW mothers had significantly elevated 

Gingival fluid PgE2 levels



amniotic fluid pge2 and IL-6



Periodontal pathogens elevated in pockets.

PTB/LBW association with periodontitis- a Meta analysis: After the previous studies, the doctors ( Khader and ta`ani) did meta analysis on many studies that done on the same subject like (Offonbachor, Dasanayake, Jeffcoat, lopez) and they found a high odd ratio (about 5.4_in slides its 5.28_), in addition to that almost all the studies that was done in USA proved that there is association except one study done by Dasanayake in UK, so you sometimes find negative studies but in general all the results supported more and more that there is association.

This is what is written in the slides about that Meta analysis (1996-2002, 2 case control studies, 3prospective cohorts, 80-1,313 women, adjusted for risk factors). And this is the next slide (slide 5 page 5) (what level of increased risk is clinically significant?) it`s about odd ratio and it was explained •

Relative risk of 1: no increased risk.

•

relative risk of 3 or more: Likely to be clinically significant, 23% of PT/LBW-no known risk factor, periodontal infection –a possibility? 

Limitations: not read also: Studies were graded as poor to fair quality, limited number of studies, generalizability of findings?

Bottom line: not read also • data support a moderate positive association between periodontal disease and adverse pregnancy outcomes in certain populations 

Causality unclear

Also they decided to do intervention study (means treating pregnant women and see if there is reduction in the percentage of PM/LBW Childs, for example if the attributable risk of pregnant women is with periodontal disease is 18% and after treatment it decreased to 7or 6% then this will be perfect), then they did this study and they found the results as in this table. Reference

Treatment

Control

Mitchell-Lewis

13.5%

18.9%

Lopez

1.84%

10.11%

So these results also supported that there is association and that if you treat perio you will reduce PM/LBW. -Remember when you do study on the pregnant women you don’t deprive them completely from treatment, but you give them OHI, and basically they will not lose their teeth because it`s short period (9 months).

Things continued supporting that there is association until a scientist called Michalowicz did multicenter study (which means to do the study in many places and not only in a specific place or range or race), and he made sure of treating perio disease very well, but when the study completed he destroyed everything (‫)خرب الدنيا‬, he didn’t find any association*, and his results were published in New England Journal of

Medicine (NEJM) which is one of top journals and when you publish in it this means that your search is evidence based , very strong and has very very high impact factor (I (mun) don’t know about this impact factor) and there is no debate on it, the number was as in the slides (12% in the treatment group and 12.8% in the control group, p=0.7) so there is no association. After these results the group of Offonbachor, Jeffcoat… tried to disprove (‫ )دحض‬the study and to prove that the problem is in the study not in the results, because these results will make major change either there is association or not!!!!!!. The last study by Michalowicz proved that there is no association and that perio association is empty talk (‫ )حكي فاضي‬but up to date we can`t say that it`s empty talk, because biologically there is increase in prostaglandins, cytokines….etc, so the recommendation is to have further studies to confirm the association.

Bottom line: currently limited evidence to recommend that patients undergo periodontal treatment to reduce the risk of adverse pregnancy outcomes.

Further research needs: •

Additional epidemiologic or case control studies:



High risk populations, different geographic areas.

•

Additional intervention studies

Recommendations: The recommendations nowadays by American academy of periodontology: Recommends any pregnant woman to have a periodontal evaluation and appropriate follow up. 

Women who are already pregnant when periodontal disease detected you should do (in the slides are ideally treated) scaling and root planning in the second trimester and you give her OHI, at least you should inform her that there is risk but we might improve things for you. 

Doctor said that the pregnant woman can sew a case on you if you knew that she had a perio disease and you didn’t treat her and later on she delivered a LBW or PM Child. 

*Doctor said: even the opposite, people who were treated their Childs were not as they wanted.

Nowadays almost all prenatal care (in developed countries) involves folic acid, iron... and also at the same time to see if there is periodontal disease. 

Periodontitis-cardiovascular disease:  Involve: coronary heart disease, cerebrovascular disease, peripheral vascular disease, cardiac failure. 

Affects majority of USA adult >60 years.



Leading cause of death in the USA (50% of death American heart association).



Major contributing factor is atherosclerosis.

We talked about most of the information, and we said that cardiovascular diseases (CVD) and periodontitis share many factors*, and they are both chronic inflammatory response to a given stimulus, and again because they share the same factors it`s not a rule that perio is the one who make the condition of CVD worse.

Role of inflammation in atherosclerosis: Everybody knows how atheroma forms, once we have inflammation there will be inflammatory mediators and there will be atheroma and narrowing to the blood vessels and plaque formation so it`s easy to form heart attack. That`s what doctor said and here what is in the diagram (slide2 page 8): Lipid imbalance, hemodynamic stress, immune reaction arterial inflammation macrophage/foam cells release: IL`s, TNF, inflammatory substances, adhesion factors, growth factors end result: proliferation of smooth muscle, leukocyte proliferation, plaque rupture.

Bacteria in atherosclerotic plaques: Previously they thought that the most common bacteria that isolated from formed atheroma is the bacteria that come from the bronchus and other parts of the respiratory system (RS) like clamedia pneumonia, and they were well persuaded by this, because it makes sense since the respiratory system is near the cardiovascular system (CVS), so if there is infection in the RS it`s easy to infect CVS. But in 2000 they tested atheroma and they found about 26% P.gingivalis and that’s a lot even greater than the percentage of C.pneumonia, and it appeared as we challenged medicine people that our bacteria is stronger than their bacteria in causing heart problems. •

C.pneumoniae long associated with atherosclerosis.

•

Periodontal pathogens (DNA) in carotid atheromas

 T.forsythensis-30%, P.gingivalis-26%, actinomycetemcomitans-18%, P.intermedia-14%, C.pneumoniae-18%. *age, male, smoking, diabetes, socioeconomic status, stress, genetics, 50% of coronary artery disease explained by conventional risk factors.

But someone might say that maybe C.pneumonia invaded the artery and destroyed it first then P.gingivalis came on the destroyed artery, but nobody can prove that unless we follow the situation from the start and take biopsy from atheroma in its beginning stages to see if there is P.gingivalis, but just only its presence in the atheroma in that big percentage make you believe more that we can cause cardiovascular disease*. Epidemiologic evidence:

explained previously and here what is in the slide:



What is the relationship between periodontitis and cardiovascular disease?



Commonality or causality?????

Meta analysis-CHD, CVD and periodontal disease: There are two studies mentioned in the (slide 5 page 8) but doctor talked only about the second study (Khader study).

In the next study the doctor didn’t talk about the details of the Meta analysis study but I copied them: •

11 studies (1990s-2002) met inclusion criteria  7 Prospective, 4 crosses sectional and retrospective, 1, 147 to 44,199 participants, 25-84 years.

•

Variables controlled: 

Age, diabetes, hypertension, smoking, body mass index, abnormal lipids.

In the slides there are two separate meta analysis studies one between perio and coronary heart disease, and the other between perio and cerebrovascular disease, but the doctor talked

was about 1.15 odd ratio which means almost there is no association. in general about the result which

Here are the details of the results from the slides: Periodontitis and Coronary heart disease- 8 studies: •

8 studies: 6 prospective and 2 cross sectional

• Subjects with periodontitis had a higher risk (1.15, p=0.0001) of CHD compared to healthy subjects after adjusting for confounders. Periodontitis and cerebrovascular disease- 6 studies:

•

6 studies: 4 prospective and 2 other.

• Subjects with periodontitis had an overall adjusted relative risk of CVD of 1.13 compared to healthy people.

Note that studying the relation of perio with cardiovascular system is harder than studying the relation between perio and PT/LBW, because the cardiovascular disease has much more factors and also it needs more time (for example some studies continue until there is change in Creactive, other until heart stroke happen and others even until death), but in PT/LBW it`s just only 9 months until delivery. *we should be happy at one point that we will have many patients in our clinics but we should be sad that it’s a big thing that just a tooth problem may end your life.

Yes the association was very weak in the meta analysis, but at least all the studies that done agreed together that there is association (no one found negative association*or no association), so remember it’s a weak association but don’t tell your patient about that (doctor said).

Cardiovascular disease and periodontal disease:

discussed previously but I

copied the slide for you

• Periodontal disease maybe modestly associated with atherosclerosis, MI and CVD. • Presently, insufficient evidence is available to justify intervention to prevent onset or progression of atherosclerosis.

Limitations: (things make doing your study hard) •

periodontal assessment

periodontal screening indices itself, Self reported in some studies it self 

•

difficulty addressing confounding variables many shared risk factors

 

Smoking, Hyper-inflammatory profile?

Because as we said both diseases are multifactorial, and whatever you made adjustment in the analysis it`s hard to collect all factors (for example you might forget stress which maybe a major factor more than perio itself). •

Studies to date focus on:

 Clinical measures and events. •

Have not studied potential mechanisms  Microflora  Inflammatory marker.

Subclinical mechanisms: •

Association between periodontal microflora and atherosclerosis development?

•

Effect of periodontal treatment on biologic risk markers of CVD, i.e. CRP?

C-reactive protein: we talked about it previously and here what is in the slides •

Marker of inflammation:

Hepatic protein stimulated by inflammation, IL-6 stimulates CRP *Negative association (odd ratio less than one) means that if you have perio disease your heart become better

•

Possible effect in atherosclerosis

Induces: adhesion molecule expression, IL-6, monocyte chemoattractant protein-1 endothelial cells, activates complement, recruitment of monocytes and lymphocytes, LDL uptake by macrophage. Also the next two slides (4 and 5 page 10) skipped also but I also copied them here: Systemic inflammatory markers are elevated in atherosclerosis: •

Serum C-reactive protein (CRP):

Reflects chronic low-grade inflammation, 2 fold higher in men with CHD, 4 folds higher in men with MI. •

As predictive as low density lipoproteins in healthy persons.

• Extensive periodontal disease (>30% of site with PD>4mm) and BMI are associated with increased CRP levels.

This is the good news: doctor said you don’t need to know all the studies, but you should know the end conclusion (for example the end conclusion of perio with PT/LBW positive or negative, the end conclusion with cardiovascular, with intervention studies…) and doctor will not ask us about numbers (as 18% become 10% after treatment), but she want us to understand, so that when we talk to people we talk more with science _ not only to say (‫ )و الله‬perio disease is a very bad disease_.

Effect of periodontal treatment on C-reactive protein (CRP): Periodontal treatment (nonsurgical) reduces serum levels of CRP and IL-6. •

• Two contemporary meta-analysis performed evaluating outcomes of periodontal treatment on serum (CRP) level (Ioannidou ET a1. 2006, paraskevas et. 2008) both reported the same opinion concerning the elevation of this marker in periodontitis patients comparing with the periodontal healthy individuals... means at least the studies

proved that if you have periodontitis this CRP will be higher than if you don’t have, but the debate is on can we lower it by treatment or not, but at least your perio disease will increase the risk of elevating CRP. • Ioannidou et a.,(2006)mentioned the importance of expanding researches to sustain the intervention periodontal therapy task in dropping(CRP) levels in the general population. • in addition, paraskevas et a1.,(2008)meta-analysis opened the door to whether periodontal treatment will have the impact in reducing(CVD)risk, while there is scare modest evidence of intervention periodontal treatment effect in reducing(CRP)levels.

When the doctor was in England in huddle (‫ )مؤتمر‬for periodontists, the periodontists said "until what we should still depend on bleeding on probing, pocket depth….etc", which we all know that it`s an empty talk(not useful),because for example bleeding on probing doesn’t mean that the patient will lose his tooth, many many times a patient came to you with bleeding on probing and he keeps his teeth more than other one who don’t have that much inflammation, so they think of more important thing other than these local things, and they direct their thoughts to systemic things something like blood marker( something like ESR in Rheumatoid arthritis in which they measure it and determine if there will be complications), and to measure it and determine if there will be complications this is their dream. As doctor Khansa told us they tried to measure meatalloprotieneases MMPA29 in the gingival crevicular fluid or any marker of inflammation, but also it`s not enough, we want something big that we can depend on and to say for example because it`s elevated you will have aggressive periodontitis.

Floss or die: we talked about it We want to finish with "you should floss or die" so it`s very important to take care of your teeth. Healthy gums, healthy heart? •

Both are inflammatory diseases

• Unclear if periodontal disease contributes to atherosclerosis by exacerbating systemic inflammatory state • Pilot studies suggest that periodontal therapy may reduce levels of surrogate serum markers of CVD, such as CRP.

Future studies:

We want more future studies about all markers, and controlled more, confounders more, and hopefully in the future we will have strong evidence that perio treatment will help the society by reducing the risk of systemic diseases. That was what doctor said about the slide and here is the slide: •

Longitudinal, controlled studies.

•

Large scale intervention studies to evaluate effect of periodontal treatment on:

Biologic markers, atheroma initiation, incidence of CVD events, diabetic control, reduction of LBW incidence.

You should by now be proud because you are dentist or periodontist (doctor said), but I (mun) say: you should go to sleep right now if you reached to this point peacefully.

The war is over Done by: muntaser ghassan toffaha.