Coronary Artery Disease

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TARRSON FAMILY ENDOWED CHAIR IN PERIODONTICS
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UCLA School of Dentistry
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Presents
Dr. E. Barrie KenneyProfessor ChairmanSection
of Periodontics
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Periodontal Disease as a Predictor of
Atherosclerosis
E. Barrie Kenney B.D.Sc., D.D.S., M.S.,
F.R.A.C.D.S. Tarrson Family Endowed Chair in
Periodontics. Professor and Chairman Division of
Associated Clinical Specialties UCLA School of
Dentistry
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CoronaryArtery Disease
6
Epidemiological connection between coronary
artery disease and periodontal disease
7
6.9 Million people have coronary heart disease in
USA
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Atherosclerosis Leading Cause of Death in USA
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Coronary Artery Disease (C.A.D) kills 500,000
people a year. One of every 4.6 deaths due to
C.A.D
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Periodontal Disease in the United States

• 54 of U.S. population 13 years and older has
  gingival bleeding on probing
• In adults an average 19.6 of teeth have
  periodontal attachment loss of 3mm or more
• Based on data from NHANES III survey 1988-19994

11
Association between dental health and acute
myocardial infarction

• Matilla KJ et al
• Brit. Med. J. 1989 298 774

12

• Used index based on caries, periodontal disease,
  periapical lesions, pericoronitis.
• Patients admitted for acute myocardial infarction
  had higher scores than matched controls.

13
Patients above the upper quartile had twice the
risk of acute myocardialinfarction than did
thosewith a score of zero.
14
This was comparable to risk of cigarette smoking,
hypercholesterolemia and hypertension.
15
Dental Disease and Risk of Coronary Heart Disease
and Mortality

• De Stefano F et al
• Brit. Med. J. 1993, 306 688

16

• Analyzed data from National Health and Nutrition
  examination study I. 1971 1974.
• 20,249 subjects aged 25 to 74 followed up in 1982
  1985 (only 55 years and older at entry) and
  1986 1987.

17
Excluded subjects with history of heart disease
stroke or cancer.Not all subjects were
evaluated for smoking so had a subset with known
history of smoking (1163 subjects)
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Admitted for Coronary Artery Disease or died of
Coronary Artery Disease as indicators of disease
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Dental evaluation at baseline

• Number of carious teeth
• Periodontal status healthy, gingivitis
  periodontitis no teethoral hygiene index 6
  teeth 0-3 for debris0-3 for calculus combined to
  give OHI.Also periodontal index 0 to 8 for each
  tooth and average for each patient.

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Percentage of subjects
No No Disease Gingivitis Periodontitis Tooth

• death from CHD 2.6 4.1 8.4 11.9
• admission for CHD 6.5 7.4 14.4 19.2

De stefano
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ODDS Ratios

• Risk Women Men
• Factors 25-49 Mortality 25-49
• No disease 1.00 1.00 1.00 1.00
• Gingivitis 1.05 0.98 1.23 1.42
• Periodontitis 1.25 1.72 1.46 2.12
• No teeth 1.23 1.71 1.46 2.60
• Periodontal index 1.04 1.09 1.09 1.11
• Oral hygiene index 1.12 1.11 1.15 1.23

adjusted for age, sex education, poverty level,
marital status, blood pressure, cholesterol,
diabetes, weight, physical activity, alcohol,
smoking
De Stefano
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Analysis of these with data on smoking showed
the same pattern.
23
No association between active caries and CHD
24
Periodontal Disease and Coronary Heart Disease
Risk

• Hujoel P.P., et al
• J.A.M.A. 2000, 2841406

25
Used NHANES population 8032 dentate adults aged
25 to 74 years with no history of cardiovascular
disease. 1859 had periodontitis, 2421 had
gingivitis, 3752 healthy. Russel index used.
Subjects with prior history of cardiovascular
disease eliminated.
26
At follow up 1265 subjects had at least 1
coronary heart disease event, either death,
hospitalization or coronary revascularization
therapy.
27
Periodontal Disease and Myocardial Disease have
common risk factors, age, smoking, stress, social
economics status, body fat, and so potential for
confounding is substantial.
28
Periodontitis Gingivitis Healthy
Diabetes 5.2 2.7 2.0 Alcohol glass per
day 0.81 0.73 0.55 Pack years smoking 15.9 10.4 8.
8 Total cholesterol 222.1 215.4 212.74 Age 52.4 43
.0 42.0 Male 50.4 38.4 30.5 White 70.2 77.5 8
8.7 African American 28.0 21.1 10.4 Education
years 9.6 11.1 12.4
Hujoel et al.
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Hazard RatiosCompared to Healthy

• Unadjusted Adjusted for Confounders
• periodontitis 2.66 1.14
• gingivitis 1.20 1.05

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While this study did provide convincing evidence
regarding the absence of a moderate to large
association between periodontitis and CHD, a
small causal association could not be ruled out.
31
Oral Health and Systemic Disease Periodontitis
and Cardiovascular Disease

• Beck J.D. Offenbacher S.
• J. Dent. Edu. 1998, 62859

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Odds ratio with more or less sites p.d gt 3mm

• CHD Fatal Stroke CHD
• 31 28 19

1147 Male Veterans from Boston
Beck
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Number of sites with 20or more bone loss

• ODDS Ratio for CHD
• 1-2 0.8
• 3-5 1.4
• 6-10 1.9
• 11-20 2.1

Beck et al
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Periodontal Disease and prevalent Coronary Heart
Disease in the ARIC study

• Beck J.D et al
• J. Dent. Res. 2000. 79. abst. 2269

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ODDS Ratio for C.H.D.

• per cent sites with attachment loss 3mm or
  more Males Females
• 0 6.4 1.0 1.0
• 6.5 15.1 1.7 0.7
• 15.2 31.0 1.5 0.8
• 31.1 100 1.7 0.9

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Atherosclerosis Risk in Communities study 13.6
of males 5.5 of females had coronary heart
disease
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Investigation of the Association Between
Angiographically Defined Coronary Artery Disease
and Periodontal Disease

• Matthaner, S. S. et al.
• J. Periodontol 731169 2002

38
100 patients 53 with coronary artery disease (50
stenosis of at least one vessel) 47 no coronary
artery disease (less than 50 stenosis in all
arteries

• 53 CAD ve 83 male average 65.3 years
• 47 CAD -ve 40.4 male average 60.8 years
• All non diabetics, non smokers for at least 5
  years
• CAD ve 66 former smokers 15.8 pack years
• CAD -ve 24.4 former smokers 4.5 pack years

Matthaner,
39

• CAD ve CAD -ve Sites with CALgt6mm 6.85 3.32
• Radiographic bone loss 3.60mm 3.18mm
• Mean probing depth 2.67mm 2.59mm
• Tooth loss 8.9 9.1
• When corrected for age previous smoking history
• Odds ratio 1.06 Mean CAL
• Odds ratio 1.03 CALgt6mm
• Odds ratio 1.31 Radiographic bone loss
• Odds ratio 2.54 Mean probing depth
• These patients had minimal periodontal disease so
  CAL may be recession or pocket related

Matthaner,
40
Ratio of Cigarette Smoking in the Association
Between Periodontal Disease and Coronary Heart
Disease

• Hyman, J. J. et al.
• J. Periodontol 73988 2002

41
5285 Subjects from NHANES 1988-94,40 years or
older

• Loss of Attachment Odds ratio for heart attack
  history
• 2.00 - 2.99mm 2.64
• 3.00-3.99mm 3.84
• 4mm or more 5.87

Hyman,
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Oral Health and Peripheral Arterial Disease

• Hung, H.C. et al
• Circulation 20031071152
• 45,136 male health workers free of cardiovascular
  disease followed for 12 years.
• 342 cases of peripheral arterial disease.
• Patient repords and diagnosis or treatment of
  claudication of leg arteries.
• Self report of periodontal disease

43
Odds RatioPeripheral Cardiovascular DiseaseAnd

• Periodontal Disease 1.41
• Tooth Loss 1.39
• Periodontal Disease Tooth Loss 1.88
• No Periodontal Disease and Tooth
  Loss 0.92Controlled for traditional risk
  factors for cardiovascular disease.

Hung, H.C. et al
44
Severity of Periodontal Disease and number of
remaining teeth are related to the prevalence of
Infarction and Myocardial Hypertension in a study
based on 4254 subjects.

• Holmlund. A. et al J. Periodontol 2006 77 1173

45
Odds Ratio Periodontal bone lossAnd Myocardial
Infarction

• Periodontal Disease 2.69
• Smoking 0.69
• Gender
  0.62
• Age
  1.09 Controlled for
  traditional risk factors for cardiovascular
  disease.Aged 40 to 60 years old.

46
TREATMENT OF PERIODONTITIS AND ENDOTHELIAL
FUNCTION. TONETTI M S et al NEJMED.356911,
2007
59 PATIENTS SEVERE PERIODONTITIS GOT PROPHY TYPE
CARE
61 GOT ROOT PLANING ARESTIN AND EXTRACTION
HOPELESS TEETH
MEASURED BRACHIAL ARTERY FLOW BEFORE AT 1,
7, 30, 60, 180 DAYS AFTER
AT 1 DAY INTENSIVE GROUP LOWER VESSEL DILATION
THAN PROPHY GROUP
AT 60 , 180 DAYS INTENSIVE GREATER DILATION THAN
PROPHY
ENDOTHELIAL FUNCTION IMPROVEMENTS CORRELATED
WITH PERIODONTAL TREATMENT SUCCESS
47
CORRELATIONS BETWEEN CLINICAL MEASUREMENTS OF
PERIODONTAL DISEASE AND PRESENCE OF BACTERIAL
ANTIGENS IN HUMAN ATHEROSCLEROSIS. PUCAR A
KENNEY EB etal 2007
36 patients got vascular surgery for atheroma
10 ext carotid 3 aorta 5 femoral or iliac
18 coronary
P.C. R on vessels and dental plaque
forP.gingivalis P,intermedia, Aa
.T.forsythensis,C. pneumoniae. C.M.V
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10 ARTERIES --VE, 14 VE FOR 1 PERIO BACTERIA.
10 VE FOR 2, 2VE FOR 3 20 HAD C.M.V 10 HAD
CHLAMYDIA
POSITIVE CORRELATION BETWEEN POCKETS 6MM. OR
GREATER AND PRESENCE OF P. gingivalis AND
P.intermedia. C.M.V AND CHLAMYDIA NEGATIVE
CORRELATION WITH PERIODONTAL INDEX
49
Coronary Artery DiseaseIn Women
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Lipid managementand control of othercoronary
risk factors inpost menopausal women

• J. Womens Health and Gender related Med.
  9235,2000

51
Stroke and myocardial infarctionNumber one
killer of women with 500,000 deaths per year
52
African American and Hispanic women at greater
risk than Caucasian women
53
This is more than the next 16 causes of death
combined
54
Risk of Myocardial infarction lower in women than
men
55
First myocardial infarction in women is more
severe and more lethal than they are in men
56
Womens mortality rate at 6 months post
myocardial infarction double that of men
57
Analysis of 350,000 patients after fibrinolytic
therapy for infarction. Mortality for women
9.3, men 4.5
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Without fibrinolytic therapy

• 16 mortality for women
• 10.9 for men

59
Coronary artery bypass surgery operative
mortality 4.5 women, 2.6 men
60
Menopause often causes increase in total
cholesterol and LDL
61
Estrogen increase HDL levels
62
Post menopausal hormonal therapy gave 53
reduction in death from CHD instudy using
121,700 registered nurses
63
Framingham Study. Risk of coronary artery
disease doubles with onset of menopause
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Cardiovascular Disease During 6.9 Years of
Hormone Therapy

• 20 centers with 2,763 post menopausal with C.H.D.
  average age 67 years.
• Hormone group got 0.6625mg conjugated estrogen,
  2.5mg medroxyprogesterone acetate daily.
• Hormones gave no significant decrease in C.H.D.
  events - infarct or death hospitalization angina
  revascularization, congestive heart failure,
  stroke, ischemia or ventricular arrhythmia
• Another study on same population showed hormone
  group had increased rated of venous
  thrombo-embolism and biliary tract surgery.
• 261 deaths compared to 239 in controls

Grady, D. et al JAMA 2002, 28849
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ESTROGEN THERAPY AND CORONARY ARTERY
CALCIFICATION. MANSON, J. E. et al NEJM. 2007
356 2591
1064 WOMEN 50 TO 59 YEARS OLD AFTER HYSTERECTOMY
RANDOMLY GOT 0.625 ESTROGEN PER DAY OR
PLACEBO EVALUATED CORONARY ARTERY CALCIFICATION
ESTROGEN GROUP SCORE 83.1 CONTROL GROUP
SCORE 123.1
66
Periodontal flap surgery to treat periodontitis.
Note loss of crestal bone.
67
Periodontitis.Histopathologyof intrabony defect
showing bone resorption (yellow), inflammation
(green) and epithelial proliferation (white).
68
Pathogenesis of Atheroma

• 1. Fatty streak development
• 2. Atheromatous plaque development
• 3. Thrombus development

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Fatty streak development
70
Dr. Enos and Holmes reported on autopsis of 2000
dead soldiers in Korean War average age 22.

• 35 had fatty streaks in coronary arteries
• 42 had had established atheroma

71
Average adult Aorta, mild fatty streaks, early
atheroma.
72
Aorta. Arrow at prominent fatty streak
73
Initiation of atheroma by damage to endothelium
which becomes more porous to lipids and monocytes
74
Monocytes from blood stream pass through
endothelium into blood vessel wall
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Healthy Coronary Artery cross section
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Bacteria
Hypertension
Homocysteine
Smoking
Diabetes
Initiators of Endothelial Dysfunction
79
Oxidized LDL
Coronary Artery Disease
Cytokines
Glycolatedend products
Initiation of Monocyte attachment with activation
of endothelial transcription nuclear factor Kb
(TNF-Kb) by oxidized low density lipids,
cytokines, and glycolated end products seen in
diabetes.
80
Vascular cell wall adhesion molecule (VCAM-1) is
induced by TNF-Kb
81
VACM-1
VACM-1
Vascular cell wall adhesion molecule (VCAM-1) is
induced by TNF-Kb
82
VACM-1
MCP1
VACM-1
VCAM-1 and chemokine monocytic chemotactic
protein I localizes monocytes in vessel wall.
83
Low Density Lipids (LDL) pass through damaged
endothelium into blood vessel wall
84
LDL
O
LDLO
LDLO
LDLO
LDLO
Coronary Artery Disease
LDL
O
LDLO
LDLO
LDLO
LDLO
LDL
O
LDLO
LDLO
LDLO
LDLO
Low density lipids (LDL) oxidized in vessel wall
85
LDLs are oxidized and then induce production of
bio active molecules such as Interleukin 1,
Interleukin 6, matrix metalloproteases,
Prostaglandins. Platelet Derived Growth Factor,
Tumor Necrosis Factor Alpha.
86
LDLO
MMP
Cytokines
LDLO
Cytokines
LDLO
MMP
87
Monocytes transform to macrophages and take up
LDL to form foam cells
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Monocytes trigger chronic inflammatory reaction
with lymphocytes andthis results in tissue
necrosis and fibrosis
90
LDLO
MMP
Cytokines
LDLO
Cytokines
LDLO
MMP
91
LDLO
MMP
Cytokines
LDLO
Cytokines
LDLO
MMP
Circulating bacteria and cytokines add to
inflammation. This leads to Atheromatous plaque
formation
92
High Density Lipids (HDL) inhibit oxidation of
LDL
93
High Density Lipids (HDL)

• HDL are a heterogeneous lipoproteins produced in
  the liver and small intestine. HDL contains 70
  phospholipid and protein, 25 cholesterol, 5
  triglycerides.
• HDL has 2 antioxidant enzymes
• Paraoxonase
• Platelet activating factor acetyl
  hydrolaseApolipoprotein A-1 stabilizes
  paraoxonase

94
Enzymes associated with HDL apolipoproptein
(apoAL) and para-oxenase (PON) protect by
destroying the oxidized pro-inflammatory lipids
from LDL
95
PON also inhibitsLDL induced Monocyte
Migration.Periodontitis may cause reduction in
Apo AI and PON and so increasethe level of
oxidized lipidsand monocytes in blood vessels
walls.
96
HDL
O
LDL
HDL
O
LDL
HDL
O
LDL
97
O
HDL
LDL
HDL
LDL
HDL
O
LDL
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ATHEROMATOUS PLAQUE DEVELOPMENT
99
Blood vessel wall becomes distended and continues
to accumulate cholesterol, some areas become
calcified
100
Coronary artery with atheromatous plaques
(arrows)
101
THROMBUS DEVELOPMENT
102
Coronary Artery with stable atheroma. Inflamation
and necrosis have replaced the smooth muscle but
there is a dense layer of collagen next to lumen
(arrows)
103
MMP
MMP
MMP
MMP s from macrophages and proteases from
circulating bacteria can destroy collagen to
form an unstable atheromatous plaque
104
Blood vessel wall can rupture and then get
thrombus formed at region of ulceration
105
Endothelium is destroyed with exposure of
collagen and plaque to arterial blood.
106
Coronary Artery Disease
Platelets aggregate on exposedcollagen to form a
thrombus.
107
Thrombus formation
108
Oral Bacteria
Circulating oral bacteria have peptides that
cause platelet aggregation
109
Increase thrombosis can lead to suddenocclusion
of vessel
110
Coronary Artery occluded by thrombosis
111
Thrombus formation on atheromataous plaque.
Slits of cholesterol crystals seen in vessel
wall.
112
Narrowed Lumen
Coronary artery with narrowed lumen and
thrombosis (arrows)
113
Oral Bacteria
114
Thrombosis can give occlusion of vessel.This is
responsible for 50 of cases of myocardial
infarction
115
lumen
Calcification (blue area) and distended vessel
wall with narrowed lumen of Coronary Artery.
116
Ultrafast CAT Scanof Thorax ShowingCross-Section
of Heart.Calcified Tissues Stained Pink.Note
Calcified Atheromatous Plaques in Coronary
Arteries
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BACTERIA
124
Bacteria

• A number of bacteria and bacterial products have
  been associated with coronary artery disease.
  These include Chlamydia pneumoniae, Heliobacter
  pylori and gram negative bacteria found in dental
  plaque.

125
Gram negative bacteria or LPS given systemically
can give following changes in major blood vessels

• inflammatory cell infiltrate
• smooth muscle proliferation
• fatty degeneration
• intravascular coagulation

126
Gram Negative Bacterial Infections

• Chlamydia pneumonie CHD risk factor
  2.3Heliobactor pylori MI risk factor
  1.3Chlamydia also seen in fatty streaks and
  atheroma plaques at autopsy

127
CORRELATION BETWEEN ATHEROSCLEROSIS AND
PERIODONTAL PUTATIVE PATHOGENIC BACTERIA IN
CORONARY AND INTRENAL MAMMARY ARTERIES

• PUCAR A M ILASIN J LEKOVIC V KENNEY E B ET
  AL . IN PRESS J. PERIODONTOL.

128
15 PATIENTS AT SURGERY TOOK CORONARY AND
INTERNAL MAMMARY ARTERY SECTIONS

• 9 OF 15 CORONARY VE FOR PERIODONTAL BACTERIA
  DNA. ALL OF INTERNAL MAMMARIES NEGATIVE.BUT 6
  HAD CMV, 7 HAD CHLAMYDIA C/F 10 AND 5 FOR
  CORONARY

129
Identificationof Pathogens in Atheromatous
Plaques

• Haraszthy V.I et al
• J. Dent. Res. 1998 71. 666.

130
Looked at bacterial DNA in 27 Atheromatous
Coronary Vessels obtained during
endarterectomy19 were positive.

• A. actinomycetemcomitans 6 cases
• P. Gingivalis 6 cases
• P. Intermedia 7 cases

131
Frequency and Distribution of Periodontal
Pathogensin the Atheromas of Coronary Arteries.

• Meyers G.S.
• Balint Orban Competition
• AAP Annual Meeting September 2000

132
Used PCR to detect bacterial D.N.A in
atheromatous coronary vessels from 42 post
mortems. 95 of atheromas had bacterial D.N.A
from periodontal pathogens.
133
Frequency

• A. actinomycetemcomitans 29
• B. Forsythus 24
• P. Gingivalis 0
• P. Intermedia 2
• F. Nucleatum 29

134
CAROTID ARTERY.POSITIVE FOR P. GINGIVALIS
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ELECTRO N MICROGRAPH OF MACROPHAGE
137
GRAM NEGATIVE BACTERIA IN MACROPHAGE
138
Other periodontalbacteria such as, Porphyromonas
gingivalis have also been shown to infect
endothelial cells.

• Progulske-Fox, A. et.al.J. Dent. Res. 1999,
  34393

139
Electron Micrograph of endothelial cells in
culture with Fusobacterium nucleatum bacteria
seen on surface and in cytoplasm of epithelial
cells. This shows the ability of periodontaal
bacteria to infect endothelium, (Haake, S. et.al.)
140
Bacterial Involvementin Atheroma

• Periodontal bacteria, Chlamydia pneumoniae and
  virus all seen in high frequency in atheromatous
  plaques. Gram negative periodontal bacteria have
  the ability to adhere to endothelial cells.
• Dorn, B.R. et.al. Infect. Immun. 1999 675792
• Eikenella corrodens Porphyromas gingivalis and
  Prevotella intermedia invaded human coronary
  artery endothelial and smooth muscle cells in
  culture.
• Lee J.K. et.al. Invasion of human endothelial
  cells by Fuscobacterium nucleatum J. Dent. Res.
  81-A114 2002

141
CORRELATION BETWEEN ATHEROSCLEROSIS AND
PERIODONTAL PUTATIVE PATHOGENIC BACTERIAL
INFECTIONS IN CORONARY AND INTRNAL MAMMARY
ARTERIES . PUCAR A , KENNEY EB et al J.
PERIODONT. 2007 78677
CORONARY GRAFT SURGERY IN 15 PATIENTS WITH INT.
MAMMARY REPLACEMENT
P.C.R. TEST OF BLOOD VESSELS FOR
P.gingivalis, H actinomycetemcomitans P.
intermedia T forsythensis AND C.pneumoniae Human
cyto megalic virus.
142
CORONARY ARTERIES
P. g IN 8 H.a IN 4 P.i IN 5 T.f IN 2 C, p
IN 5 CMV IN 10
INTERNAL MAMMARY ARTERIES
0 PERIODONTAL BACTERIA C.p IN 6 CMV IN 7
143
Establishmentof a mouse model of infective
induced atheroma formation

• Chung H.J. et al
• J. Dent. Res. 2000 79 1356

144
Used atheroslerosis susceptible mouse with
subcutaneous chamber in which was placed live P.
Gingivalis and measured atheroma in aorta. Mice
had been primed with previous infection of P.
Gingivalis
145
Mean area ofatheroma after 3 weeks

• P. Gingivalis 162.1Mm2
• Control broth 88.6Mm2

Chung et al
146
TNF and PGE levels in chamber were correlated
with area of atheroma TNF associated with serum
cholesterol. Cholesterol associated with area of
atheroma.
147
Bacterial induced periodontal disease increases
circulating cytokines which can accentuate
inflammation in atheromatous vessels.
148
Early gingivitis with margin of gingiva showing
edema, redness and bleeding on probing.
149

Cytokines in Periodontal Inflammation

• IL1ß Recruits inflammatory cells. Stimulates PMNS
  increased synthesis of prostaglandin and metallo
  proteinases (MMP). Inhibits collagen synthesis.
  Activates B and T lymphocytes
• TNF alpha Stimulates apoptosis, bone resorption,
  MMP and IL-6 production.
• IL-6 Stimulate osteoclasts and T cell
  differentiation.

150
Circukating and local Interleukin 1-b levels
(Lemus, C., Haake, S.)

• Periodontitis Group Health Group
• Serum IL-1b 2,55pg/ml 0.76 pg/ml
• Gingival fluid 5.96 pg/ml 0.42 pg/ml

151
Chronic bacterial infections including
periodontal disease also increase circulating C
Reactive Substance
152

• C Reactive substance is a marker for inflammation
  and is predictive of future myocardial infarction
  and stroke.
• Periodontitis patients have increased levels of
  C Reactive Substance.

153
543 Healthy men who developed MI or stroke
compared to controlsC Reactive proteinMI or
stroke 1.51 mg/lControls 1.13 mg/lHigh versus
lowest quartile of C-Reactive protein had risk
factor for MI 2.9
154
Bacteria from the oral cavity and dental plaque
can stimulate platelet aggregation.
155
Streptococcus sanguis expresses a cell wall bound
protein (PAAP) that induces activation and
aggregation of platelets.PAAP contains a
collagen-like platelet interactive domain in a 23
kDa protein fragment.This explains similar
platelet effects of collagen and PAAP as well as
their immunologic cross reactivity.Erickson,
P.R. et. Al. J. Biol. Chem 1993 2681646
156
Strep Sanguis isolated from infective
endocarditis has an adhesin identified by
monoconal antibody, which binds to platelets and
hydroxy apatite. This adhesin is common in a
variety of Viridans group of streptococci,
similar findings with P. Gingivalis reported at
American Society for Microbiology 1994

• Song K.E., Ouyang T., Herzberg M.C.
• Infect. Immun. 1998, 66 5388

157
Effects oforal flora on plateletsPossible
consequences incardiovascular disease

• Herzberg, M. Mayer, M. W.
• J. Periodont. 1996 671138

158
In rabbits S. Sanguis caused platelet
aggregation. Hearts had ischemic areas.
Infusion of S. Sanguis caused changes in
electrocardiogram, blood pressure, heart rate and
cardiac contractility all dose dependant and all
related to early signs of myocardial infarction.
159
Hyperlipedemia caused increased cardiac effects
ofS. Sanguis. Also have seen similar effects in
platelets with P. Gingivalis.
160
Inoculation of Strep Sanguis Strain 133-79 caused
cardiac contractility to fall 60Strep Sanguis
Strain L47 does not affect platelets gave no
cardiac changes when inoculated into rabbits
161
Rabbits on high fat diet with hypercholesterolemia
In vitro platelet aggregation response to strain
133-79 accelerated over that seen on normal diet
162
Bacteria
Hypertension
Homocysteine
Smoking
Diabetes
Initiators of Endothelial Dysfunction
163
HYPERTENSION
164
Hypertensionincrease chance of endothelial injury
165
Bacteria
Hypertension
Homocysteine
Smoking
Diabetes
Initiators of Endothelial Dysfunction
166
HOMOCYSTEINE
167
High levels of the Amino acid homocysteine
increase risk of coronary artery disease by being
toxic to endothelium.
168
Folic acid vitamin B6, B12 reduce levels of
homocysteine
169
Hyperhomocysteinema odds ratio CHD 1.7In 28,263
post menopausal women 3 year follow up those with
top quartile homocysteine twice the risk of
Myocardial infarction or stroke.Suggested
supplement intake of 0.4mg folic acid, 2mg vit B6
vit B12
170
Bacteria
Hypertension
Homocysteine
Smoking
Diabetes
Initiators of Endothelial Dysfunction
171
SMOKING
172
Toxic factors in cigarette smoke increase risk
endothelial injury
173
Smokers 2.5 times more likely to have heart attack
174
Bacteria
Hypertension
Homocysteine
Smoking
Diabetes
Initiators of Endothelial Dysfunction
175
DIABETES
176
Hyperglycemiacauses endothelial dysfunction by a
number of mechanisms including inhibition of
endothelial derived nitric oxide which reduces
the ability of vessel to respond with vasodilation

• Consentino, F. et. al. Cardiovasc. Pharmacol.
  1998 32 suppl 3s54.

177
Diabetes increase risk of atheroma because of
hyperlipemia
178
Diabetes has high triglycerides And low HDL
179
Low density lipidscan initiate endothelial
dysfunction and monocyte attachment. LDLs also
interact with periodontal inflammation.
180
Antioxidants increase resistance of LDL to
oxidation. Vitamin E reduces risks of atheroma
production
181
Risk of CVD and MI reduced 77 with 800 IU
tocopherol400 IU gave a 47 reduction
182
Vitamin E has little or no effect on established
atheroma
183
Association between Periodontitis and
Hyperlipidemia Cause or Effect?

• Cutler C.W et al
• Periodontol 1999 121429

184
51 subjects, 26 with chronic adult
periodontitis,25 healthy controls looked at
triglycerides, cholesterol, antibodies againstP.
Gingivalis and L.P.S.and periodontal status.
185
Relationship with Periodontal Disease and other
variables

• odds ratio
• Age gt 50 years 3.5
• Serum triglyceride gt 100mg/dl 8.6
• Serum cholesterol gt 200mg/dl 7.0
• LPS Reactivity gt 2 bands 40.8
• Elisa titre gt 60 Eu 35.0

Cutler et al
186
Also did in vitro study to see effect of
triglycerides on release of IL1 beta from p.m.n.s.
187
Interleukin 1 beta secretion by PMNS from
healthy patients

• PMN 2.0
• PMN P.g. L.P.S 24
• PMN triglycerides 2.3
• PMN LPS TG 35

Cutler et al.
188
Short term high fat diet impairs antibacterial
function of p.m.n.shyperlipidemia can modulate
release of cytokines and growth factor from rat
macrophages and monocytes.Cytokines IL1 beta
and TNF alpha promote hyperlipidemia.
189
Pathophysiological relationships between
periodontitis and systemic disease Recent
concepts involving serum lipids

• Iacopino A.M, Cutler C.W.
• J. Periodont. 2000. 711375

190
Periodontitis induced changes in immune cell
functions causes metabolic dysregulation of lipid
metabolism involving cytokines.
191
From periodontitis elevated serum IL-1ß and TNF
change lipid metabolism so get hyperlipidemia.
192
The elevated lipids in diabetes and periodontitis
also increases monocytic responsiveness and pmn
activity so get increased cytokine production and
further periodontal disease.
193
Recommended levels of LDL

• 1 or more risk factor lt 160mg / ml
• 2 or more risk factor lt 130mg / ml
• Presence of atherosclerosis or
• Diabetes lt 100 mg /ml

194
Recommendedlevels of HDLgt35 mg/ml
195
High cholesterol gt200mg/ml with LDL gt130 mg/ml
increases risk of heart attack 2.4 times
196
Harvard Study, Dr. W.C. TaylorUsed data from MR
FIT trail for persons without risk factors such
as smoking or hypertension. We calculate a
gain in life expectancy of 3 days to 3 months
from a lifelong program of cholesterol
reduction.
197
Dr J. Stamler NorthwesternUniversity Study of
361,662 young and middle aged men.Top 20 of
cholesterol levels three times more likely to die
of coronary artery disease than lowest 20 but
general mortality not so dramatic. Cholesterol
level living at 7 years 202mg/dl or
less 97.8 203 to 244mg/dl 97.3 245mg/dl or more
96.2
198
Cholesterol Reducing DrugsInhibit Synthesis of
Cholesterol. Up-Regulate Nitric Oxide Sinthetase

• LIPITOR ( ATORVASTATIN)
• MEVACOR( LOVASTATIN)
• ZOCOR (SIMVASTATIN)
• PRAVACHOL( PRAVASTATIN)
• REDUCTION OF MI AND GENERAL MORTALITY.
• ALSO IMPROVE VESSEL NARROWING

199
LOVASTATIN MEVACOR
200
Dr A Gotto Cornell UniversityAm. J. Cardiol.,
Dec. 2000 pg. 11766,605 healthy adults aged 47
to 73, 5,608 men, 997women, Lovastatin or Placebo
plus low saturated fat low cholesterol diet
followed for 5-2 years.LDL 130-190 mg/dlHDL
less than 45 mg/dltriglycerides less than
400mg/dl12 smokers, 22 hypertensive, 2
diabeticAverage Total Cholesterol
221mg/dl LDL 150mg/dl HDL 37mg/dlTotal
Cholesterol fell 18.4 LDL fell 25 HDL fell
15Reduction in sudden death, heart attack,
unstable angina 36Reduction in need for
angioplasty 33Reduction in hospitalization
for angina 34
201
Alcohol 1 to 2 glasses a day reduces cholesterol,
reduces clotting
202
One to two drinks ofalcohol per day gives30-50
percent reduction in CHD in men. Maybe due to
increase levels of HDL, or to blood clotting
reduction
203
Aspirin inhibitsplatelet aggregation
204
Aspirin 325 mg every other day for 4.5 years
22000 male MDs

• Aspirin 194 MI 5 deaths
• Controls 189 MI 18 deaths

205
2418 Israeli women 100 to 500 mg Aspirin every
other day for 3 years

• 40 less MI mortality
• 34 less general mortality

206
thrombus
Early infarct affecting left ventricle
207
Cross section of heart with area of necrosis
208
Infarct in ventricular wall with loss of muscle
and scarring
209
Area of previous infarct with rupture of
ventricular wall
210
Histology of Myocardial Infarction
211
Normal heart muscle
212
Beginning of infarct, loss of striations and
nuclei of cardiac muscle
213
Continued loss of cellular vitality of myocardium
214
Myocardial infarct with replacement of necrotic
myocardium with inflammatory cells and fibroblasts
215
Established infarct with fibrotic scarring in
myocardium
216
Systematic review of the association between
respiratory diseases and oral heaith.
Azarpazhooh. A. J. PERIODONT.2006.771465.
217
Association between oral health and pneumonia
odds ratio 1.2 to 9.6. Good evidence of value of
periodontal initial therapy in treatment of
respiratory diseases in high risk elderly.
218
FURTHER READING CLINICAL PERIODONTOLOGY 10 th
EDITION CHAPTER 18