coronary artery disease
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TRANSCRIPT
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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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sePeriodontal 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
CoronaryArtery Disease
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Epidemiological connection between
coronary artery disease and
periodontal disease
Epidemiological connection between
coronary artery disease and
periodontal disease
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6.9 Million people have coronary heart
disease in USA
6.9 Million people have coronary heart
disease in USA
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Atherosclerosis Leading Cause of
Death in USA
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
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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se Periodontal Disease in the United StatesPeriodontal 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
• 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
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se Association between
dental health and acute myocardial infarction
Association between dental health and acute
myocardial infarction
Matilla KJ et alBrit. Med. J. 1989 298: 774
Matilla KJ et alBrit. Med. J. 1989 298: 774
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se Used index based on caries,
periodontal disease, periapical lesions, pericoronitis.
Patients admitted for acute myocardial infarction had higher scores than matched controls.
Used index based on caries, periodontal disease, periapical lesions, pericoronitis.
Patients admitted for acute myocardial infarction had higher scores than matched controls.
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sePatients above the upper quartile had
twice the risk of acute myocardial
infarction than did thosewith a score of zero.
Patients above the upper quartile had
twice the risk of acute myocardial
infarction than did thosewith a score of zero.
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This was comparable to risk of cigarette smoking, hypercholesterolemia and
hypertension.
This was comparable to risk of cigarette smoking, hypercholesterolemia and
hypertension.
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Dental Disease and Risk of Coronary Heart Disease and Mortality
Dental Disease and Risk of Coronary Heart Disease and Mortality
De Stefano F et alBrit. Med. J. 1993, 306: 688
De Stefano F et alBrit. Med. J. 1993, 306: 688
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se 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.
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.
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seExcluded 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)
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
Admitted for Coronary Artery Disease or died of Coronary Artery Disease as indicators of disease
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se Dental evaluation at baseline
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.
• 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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sePercentage of subjectsPercentage of subjects
death from CHD 2.6 4.1 8.411.9
admission for CHD 6.5 7.4 14.419.2
death from CHD 2.6 4.1 8.411.9
admission for CHD 6.5 7.4 14.419.2
No NoDisease Gingivitis Periodontitis ToothNo NoDisease Gingivitis Periodontitis Tooth
De stefano
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seODDS RatiosODDS Ratios
Risk Women MenFactors 25-49 Mortality 25-49
No disease 1.00 1.00 1.00 1.00Gingivitis 1.05 0.98 1.23 1.42Periodontitis 1.25 1.72 1.46 2.12No teeth 1.23 1.71 1.46 2.60Periodontal index 1.04 1.09 1.09 1.11Oral hygiene index 1.12 1.11 1.15 1.23
Risk Women MenFactors 25-49 Mortality 25-49
No disease 1.00 1.00 1.00 1.00Gingivitis 1.05 0.98 1.23 1.42Periodontitis 1.25 1.72 1.46 2.12No teeth 1.23 1.71 1.46 2.60Periodontal index 1.04 1.09 1.09 1.11Oral 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
adjusted for age, sex education, poverty level, marital status, blood pressure, cholesterol, diabetes, weight, physical activity, alcohol, smoking
De StefanoDe Stefano
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Analysis of these with data on
smoking showed the same pattern.
Analysis of these with data on
smoking showed the same pattern.
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No association between active caries and CHD
No association between active caries and CHD
Cor
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sePeriodontal Disease and Coronary Heart
Disease Risk
Periodontal Disease and Coronary Heart
Disease Risk
Hujoel P.P., et alJ.A.M.A. 2000, 284:1406
Hujoel P.P., et alJ.A.M.A. 2000, 284:1406
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seUsed 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.
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.
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At follow up 1265 subjects had at least 1 coronary heart disease event, either death, hospitalization or coronary revascularization therapy.
At follow up 1265 subjects had at least 1 coronary heart disease event, either death, hospitalization or coronary revascularization therapy.
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Periodontal Disease and Myocardial Disease have common risk factors, age, smoking, stress, social economics status, body fat, and so potential for confounding is substantial.
Periodontal Disease and Myocardial Disease have common risk factors, age, smoking, stress, social economics status, body fat, and so potential for confounding is substantial.
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Diabetes 5.2% 2.7% 2.0%Alcohol glass per day 0.81 0.73 0.55Pack years smoking 15.9 10.4 8.8Total cholesterol 222.1 215.4 212.74Age 52.4 43.0 42.0Male 50.4% 38.4% 30.5%White 70.2% 77.5% 88.7%African American 28.0% 21.1% 10.4%Education years 9.6 11.1 12.4
Diabetes 5.2% 2.7% 2.0%Alcohol glass per day 0.81 0.73 0.55Pack years smoking 15.9 10.4 8.8Total cholesterol 222.1 215.4 212.74Age 52.4 43.0 42.0Male 50.4% 38.4% 30.5%White 70.2% 77.5% 88.7%African American 28.0% 21.1% 10.4%Education years 9.6 11.1 12.4
Periodontitis Gingivitis HealthyPeriodontitis Gingivitis Healthy
Hujoel et al.Hujoel et al.
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seHazard Ratios
Compared to Healthy Hazard Ratios
Compared to Healthy
Unadjusted Adjusted for
Confoundersperiodontitis 2.66 1.14gingivitis 1.20 1.05
Unadjusted Adjusted for
Confoundersperiodontitis 2.66 1.14gingivitis 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.”
“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.”
Cor
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seOral Health and Systemic
Disease: Periodontitis and Cardiovascular
Disease
Oral Health and Systemic Disease: Periodontitis
and Cardiovascular Disease
Beck J.D. Offenbacher S.J. Dent. Edu. 1998, 62:859
Beck J.D. Offenbacher S.J. Dent. Edu. 1998, 62:859
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se Odds ratio with more or less
sites p.d > 3mm Odds ratio with more or less
sites p.d > 3mm
CHD Fatal Stroke CHD
3·1 2·8 1·9
CHD Fatal Stroke CHD
3·1 2·8 1·9
1147 Male Veterans from Boston1147 Male Veterans from Boston
BeckBeck
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se Number of sites with 20%
or more bone loss Number of sites with 20%
or more bone loss
ODDS Ratio for CHD
1-2 0.83-5 1.46-10 1.911-20 2.1
ODDS Ratio for CHD
1-2 0.83-5 1.46-10 1.911-20 2.1
Beck et alBeck et al
Cor
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sePeriodontal Disease and prevalent Coronary Heart Disease in the ARIC study
Periodontal Disease and prevalent Coronary Heart Disease in the ARIC study
Beck J.D et alJ. Dent. Res. 2000. 79. abst. #2269
Beck J.D et alJ. Dent. Res. 2000. 79. abst. #2269
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seODDS Ratio for C.H.D. ODDS Ratio for C.H.D.
per cent sites with attachment loss 3mm or more Males Females
0 – 6.4 1.0 1.06.5 – 15.1 1.7 0.715.2 – 31.0 1.5 0.831.1 – 100 1.7 0.9
per cent sites with attachment loss 3mm or more Males Females
0 – 6.4 1.0 1.06.5 – 15.1 1.7 0.715.2 – 31.0 1.5 0.831.1 – 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
Atherosclerosis Risk in Communities study
13.6% of males 5.5% of females had coronary
heart disease
Cor
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se Investigation of the Association Between
Angiographically Defined Coronary Artery Disease and
Periodontal Disease
Investigation of the Association Between
Angiographically Defined Coronary Artery Disease and
Periodontal Disease
Matthaner, S. S. et al.J. Periodontol 73:1169 2002
Matthaner, S. S. et al.J. Periodontol 73:1169 2002
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se 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
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 years47 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 yearsCAD -ve 24.4% former smokers 4.5 pack years
53 CAD +ve 83% male average 65.3 years47 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 yearsCAD -ve 24.4% former smokers 4.5 pack years
Matthaner,
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se CAD +ve CAD -veSites with CAL>6mm 6.85 3.32Radiographic bone loss 3.60mm 3.18mmMean probing depth 2.67mm 2.59mmTooth loss 8.9 9.1
When corrected for age previous smoking historyOdds ratio 1.06 Mean CALOdds ratio 1.03 CAL>6mmOdds ratio 1.31 Radiographic bone lossOdds ratio 2.54 Mean probing depth
These patients had minimal periodontal disease so CAL may be recession or pocket related
CAD +ve CAD -veSites with CAL>6mm 6.85 3.32Radiographic bone loss 3.60mm 3.18mmMean probing depth 2.67mm 2.59mmTooth loss 8.9 9.1
When corrected for age previous smoking historyOdds ratio 1.06 Mean CALOdds ratio 1.03 CAL>6mmOdds ratio 1.31 Radiographic bone lossOdds ratio 2.54 Mean probing depth
These patients had minimal periodontal disease so CAL may be recession or pocket related
Matthaner,
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seRatio of Cigarette Smoking in the Association Between Periodontal Disease and Coronary Heart Disease
Ratio of Cigarette Smoking in the Association Between Periodontal Disease and Coronary Heart Disease
Hyman, J. J. et al.J. Periodontol 73:988 2002
Hyman, J. J. et al.J. Periodontol 73:988 2002
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se5285 Subjects from NHANES 1988-94,
40 years or older5285 Subjects from NHANES 1988-94,
40 years or older
Loss of Attachment Odds ratio for heart attack history2.00 - 2.99mm 2.643.00-3.99mm 3.844mm or more 5.87
Loss of Attachment Odds ratio for heart attack history2.00 - 2.99mm 2.643.00-3.99mm 3.844mm or more 5.87
Hyman,
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se Oral Health and Peripheral Arterial Disease
Oral Health and Peripheral Arterial Disease
• Hung, H.C. et al• Circulation 2003:107:1152• 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
• Hung, H.C. et al• Circulation 2003:107:1152• 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
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se Odds RatioPeripheral Cardiovascular Disease
And
Odds RatioPeripheral Cardiovascular Disease
And • Periodontal Disease 1.41• Tooth Loss 1.39• Periodontal Disease & Tooth Loss 1.88• No Periodontal Disease and Tooth Loss 0.92
Controlled for traditional risk factors for cardiovascular disease.
• Periodontal Disease 1.41• Tooth Loss 1.39• Periodontal Disease & Tooth Loss 1.88• No Periodontal Disease and Tooth Loss 0.92
Controlled for traditional risk factors for cardiovascular disease.
Hung, H.C. et alHung, H.C. et al
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se 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.
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: 1173Holmlund. A. et al J. Periodontol 2006 77: 1173
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se Odds Ratio Periodontal bone loss
And Myocardial InfarctionOdds Ratio Periodontal bone loss
And 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.
• 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.
Cor
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seTREATMENT OF PERIODONTITIS AND
ENDOTHELIAL FUNCTION. TONETTI M S et al NEJMED.356:911, 2007
TREATMENT OF PERIODONTITIS AND ENDOTHELIAL FUNCTION. TONETTI M S et al
NEJMED.356:911, 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
Cor
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seCORRELATIONS BETWEEN CLINICAL
MEASUREMENTS OF PERIODONTAL DISEASE AND PRESENCE OF BACTERIAL ANTIGENS IN
HUMAN ATHEROSCLEROSIS. PUCAR A KENNEY EB etal 2007
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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se10 ARTERIES --VE, 14 +VE FOR 1 PERIO
BACTERIA. 10 +VE FOR 2, 2+VE FOR 3 20 HAD C.M.V 10 HAD CHLAMYDIA
10 ARTERIES --VE, 14 +VE FOR 1 PERIO
BACTERIA. 10 +VE FOR 2, 2+VE 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
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Coronary Artery Disease
In Women
Coronary Artery Disease
In Women
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se Lipid managementand control of other
coronary risk factors inpost menopausal women
Lipid managementand control of other
coronary risk factors inpost menopausal women
J. Women’s Health and Gender related Med. 9:235,2000J. Women’s Health and Gender related Med. 9:235,2000
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seStroke and
myocardial infarction
Number one killer of women with 500,000
deaths per year
Stroke and myocardial infarction
Number one killer of women with 500,000
deaths per year
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African American and Hispanic women at
greater risk than Caucasian women
African American and Hispanic women at
greater risk than Caucasian women
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This is more than the next 16 causes of death combined
This is more than the next 16 causes of death combined
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Risk of Myocardial infarction lower in women than men
Risk of Myocardial infarction lower in women than men
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First myocardial infarction in women is more severe and
more lethal than they are in men
First myocardial infarction in women is more severe and
more lethal than they are in men
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Women’s mortality rate at 6 months post myocardial infarction double that of men
Women’s mortality rate at 6 months post myocardial infarction double that of men
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Analysis of 350,000 patients after fibrinolytic
therapy for infarction.
Mortality for women 9.3%, men 4.5%
Analysis of 350,000 patients after fibrinolytic
therapy for infarction.
Mortality for women 9.3%, men 4.5%
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seWithout fibrinolytic therapyWithout fibrinolytic therapy
• 16% mortality for women• 10.9% for men
• 16% mortality for women• 10.9% for men
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Coronary artery bypass surgery
operative mortality 4.5% women,
2.6% men
Coronary artery bypass surgery
operative mortality 4.5% women,
2.6% men
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Menopause often causes
increase in total cholesterol and LDL
Menopause often causes
increase in total cholesterol and LDL
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Estrogen increase HDL levels
Estrogen increase HDL levels
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Post menopausal hormonal therapy
gave 53% reduction in death from CHD in
study using 121,700 registered nurses
Post menopausal hormonal therapy
gave 53% reduction in death from CHD in
study using 121,700 registered nurses
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Framingham Study. Risk of coronary artery disease doubles with onset of menopause
Framingham Study. Risk of coronary artery disease doubles with onset of menopause
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se Cardiovascular Disease During 6.9 Years of Hormone TherapyCardiovascular 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
• 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 controlsGrady, D. et al JAMA 2002, 288:49Grady, D. et al JAMA 2002, 288:49
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se 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
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Periodontal flap surgery to treat periodontitis. Note loss of crestal bone.Periodontal flap surgery to treat periodontitis. Note loss of crestal bone.
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Periodontitis.Histopathologyof intrabony defect showing bone resorption (yellow), inflammation (green) and epithelial proliferation (white).
Periodontitis.Histopathologyof intrabony defect showing bone resorption (yellow), inflammation (green) and epithelial proliferation (white).
Cor
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sePathogenesis of
AtheromaPathogenesis of
Atheroma
1. Fatty streak development
2. Atheromatous plaque development
3. Thrombus development
1. Fatty streak development
2. Atheromatous plaque development
3. Thrombus development
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Fatty streak developmentFatty streak development
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seDr. Enos and Holmes reported on autopsis of 2000 dead soldiers in Korean War average age 22.
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
• 35% had fatty streaks in coronary arteries• 42% had had established atheroma
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Average adult Aorta, mild fatty streaks, early atheroma.
Average adult Aorta, mild fatty streaks, early atheroma.
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Aorta. Arrow at prominent fatty streak
Aorta. Arrow at prominent fatty streak
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Initiation of atheroma by damage to endothelium which becomes more porous to lipids and
monocytes
Initiation of atheroma by damage to endothelium which becomes more porous to lipids and
monocytes
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Monocytes from blood stream pass through
endothelium into blood vessel wall
Monocytes from blood stream pass through
endothelium into blood vessel wall
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Healthy Coronary Artery cross sectionHealthy Coronary Artery cross section
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Hypertension
Homocysteine
Bacteria
Smoking
Diabetes
Initiators of Endothelial DysfunctionInitiators of Endothelial Dysfunction
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Oxidized LDL
Cytokines
Glycolatedend products
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Initiation of Monocyte attachment with activation of endothelial transcription nuclear factor K (TNF-K) by oxidized low density lipids, cytokines, and glycolated end products seen in diabetes.
Initiation of Monocyte attachment with activation of endothelial transcription nuclear factor K (TNF-K) by oxidized low density lipids, cytokines, and glycolated end products seen in diabetes.
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Vascular cell wall adhesion molecule (VCAM-1) Vascular cell wall adhesion molecule (VCAM-1) is induced by TNF-Kis induced by TNF-K
Vascular cell wall adhesion molecule (VCAM-1) Vascular cell wall adhesion molecule (VCAM-1) is induced by TNF-Kis induced by TNF-K
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Vascular cell wall adhesion molecule (VCAM-1) Vascular cell wall adhesion molecule (VCAM-1) is induced by TNF-Kis induced by TNF-K
Vascular cell wall adhesion molecule (VCAM-1) Vascular cell wall adhesion molecule (VCAM-1) is induced by TNF-Kis induced by TNF-K
VACM-1
VACM-1
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VCAM-1 and chemokine monocytic chemotactic protein I localizes monocytes in vessel wall.
VCAM-1 and chemokine monocytic chemotactic protein I localizes monocytes in vessel wall.
VACM-1
VACM-1
MCP1
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Low Density Lipids (LDL) pass through
damaged endothelium into blood vessel wall
Low Density Lipids (LDL) pass through
damaged endothelium into blood vessel wall
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LDL
LDL
LDL
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Low density lipids (LDL) oxidized in vessel wallLow density lipids (LDL) oxidized in vessel wall
O
O
OLDLO
LDLO
LDLO
LDLO
LDLO
LDLO
LDLO
LDLO
LDLO
LDLO
LDLO
LDLO
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seLDL’s 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.
LDL’s 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.
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MMP
MMP
Cytokines
Cytokines
Prostaglandins
LDLO
LDLO
LDLO
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Monocytes transform to
macrophages and take up LDL to form foam cells
Monocytes transform to
macrophages and take up LDL to form foam cells
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seMonocytes trigger
chronic inflammatory reaction with
lymphocytes andthis results in tissue necrosis and fibrosis
Monocytes trigger chronic inflammatory
reaction with lymphocytes and
this results in tissue necrosis and fibrosis
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MMP
MMP
Cytokines
Cytokines
Prostaglandins
LDLO
LDLO
LDLO
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Bacteria
Cytokines
Circulating bacteria and cytokines add to inflammation. This leads to Atheromatous plaque formation
Circulating bacteria and cytokines add to inflammation. This leads to Atheromatous plaque formation
MMP
MMP
Cytokines
Cytokines
Prostaglandins
LDLO
LDLO
LDLO
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High Density Lipids (HDL) inhibit
oxidation of LDL
High Density Lipids (HDL) inhibit
oxidation of LDL
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seHigh Density Lipids (HDL)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 hydrolase
Apolipoprotein A-1 stabilizes paraoxonase
• 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 hydrolase
Apolipoprotein A-1 stabilizes paraoxonase
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Enzymes associated with HDL apolipoproptein (apoAL)
and para-oxenase (PON) protect by destroying the oxidized pro-inflammatory
lipids from LDL
Enzymes associated with HDL apolipoproptein (apoAL)
and para-oxenase (PON) protect by destroying the oxidized pro-inflammatory
lipids from LDL
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sePON also inhibits
LDL induced Monocyte Migration.Periodontitis may cause reduction in Apo AI and PON and so increasethe level of oxidized lipidsand monocytes in blood
vessels walls.
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.
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HDL
HDL
HDL
LDL
LDL
LDL
O
O
O
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HDL
HDL
HDL
LDL
LDL
LDL
O
O
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ATHEROMATOUS PLAQUE
DEVELOPMENT
ATHEROMATOUS PLAQUE
DEVELOPMENT
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Blood vessel wall becomes distended and continues to accumulate cholesterol, some areas
become calcified
Blood vessel wall becomes distended and continues to accumulate cholesterol, some areas
become calcified
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Coronary artery with atheromatous plaques (arrows) Coronary artery with atheromatous plaques (arrows)
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THROMBUS DEVELOPMENT
THROMBUS DEVELOPMENT
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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)
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)
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MMP
MMP
MMP
MMP s from macrophages and proteases from circulating bacteria can destroy collagen to
form an unstable atheromatous plaque
MMP s from macrophages and proteases from circulating bacteria can destroy collagen to
form an unstable atheromatous plaque
Bacterial Proteases
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
MMP
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Blood vessel wall can rupture and then get thrombus formed at region of ulceration
Blood vessel wall can rupture and then get thrombus formed at region of ulceration
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Endothelium is destroyed with exposure of collagen and plaque to arterial blood.
Endothelium is destroyed with exposure of collagen and plaque to arterial blood.
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Platelets aggregate on exposedcollagen to form a thrombus.
Platelets aggregate on exposedcollagen to form a thrombus.C
oron
ary
Art
ery
Dis
ease
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Thrombus formationThrombus formation
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Oral BacteriaOral Bacteria
Circulating oral bacteria have peptides that cause platelet aggregation
Circulating oral bacteria have peptides that cause platelet aggregation
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Increase thrombosis can lead to suddenocclusion of vessel
Increase thrombosis can lead to suddenocclusion of vessel
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Coronary Artery occluded by thrombosisCoronary Artery occluded by thrombosis
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Thrombus formation on atheromataous plaque. Slits of cholesterol crystals seen in vessel wall.Thrombus formation on atheromataous plaque. Slits of cholesterol crystals seen in vessel wall.
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Coronary artery with narrowed lumen and thrombosis (arrows)
Coronary artery with narrowed lumen and thrombosis (arrows)
Narrowed Lumen
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Oral BacteriaOral Bacteria
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seThrombosis can give occlusion of vessel.
This is responsible for 50% of cases of myocardial infarction
Thrombosis can give occlusion of vessel.
This is responsible for 50% of cases of myocardial infarction
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Calcification (blue area) and distended vessel wall with narrowed lumen of Coronary Artery.
Calcification (blue area) and distended vessel wall with narrowed lumen of Coronary Artery.
lumen
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Ultrafast CAT Scanof Thorax Showing
Cross-Section of Heart.Calcified Tissues Stained Pink.
Note: Calcified Atheromatous Plaques in Coronary Arteries
Ultrafast CAT Scanof Thorax Showing
Cross-Section of Heart.Calcified Tissues Stained Pink.
Note: Calcified Atheromatous Plaques in Coronary Arteries
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BACTERIABACTERIA
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seBacteriaBacteria
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.
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.
Cor
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seGram negative bacteria or LPS given systemically can give following changes in major blood vessels
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
• inflammatory cell infiltrate• smooth muscle proliferation • fatty degeneration • intravascular coagulation
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se Gram Negative Bacterial InfectionsGram Negative Bacterial Infections
Chlamydia pneumonie CHD risk factor 2.3Heliobactor pylori MI risk factor 1.3
Chlamydia also seen in fatty streaks and atheroma plaques at autopsy
Chlamydia pneumonie CHD risk factor 2.3Heliobactor pylori MI risk factor 1.3
Chlamydia also seen in fatty streaks and atheroma plaques at autopsy
Cor
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seCORRELATION BETWEEN ATHEROSCLEROSIS AND PERIODONTAL PUTATIVE
PATHOGENIC BACTERIA IN CORONARY AND INTRENAL
MAMMARY ARTERIES
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.
PUCAR A M ILASIN J LEKOVIC V KENNEY E B ET AL . IN PRESS J.
PERIODONTOL.
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15 PATIENTS AT SURGERY TOOK CORONARY AND INTERNAL
MAMMARY ARTERY SECTIONS
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
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
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Identificationof Pathogens in
Atheromatous Plaques
Identificationof Pathogens in
Atheromatous Plaques
Haraszthy V.I et al J. Dent. Res. 1998: 71. 666.
Haraszthy V.I et al J. Dent. Res. 1998: 71. 666.
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seLooked at bacterial DNA in 27 Atheromatous Coronary Vessels obtained during endarterectomy19 were positive.
Looked at bacterial DNA in 27 Atheromatous Coronary Vessels obtained during endarterectomy19 were positive.
A. actinomycetemcomitans 6 casesP. Gingivalis 6 casesP. Intermedia 7 cases
A. actinomycetemcomitans 6 casesP. Gingivalis 6 casesP. Intermedia 7 cases
Cor
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seFrequency and Distribution of Periodontal Pathogens
in the Atheromas of Coronary Arteries.
Frequency and Distribution of Periodontal Pathogens
in the Atheromas of Coronary Arteries.
Meyers G.S.Balint Orban Competition
AAP Annual Meeting September 2000
Meyers G.S.Balint Orban Competition
AAP Annual Meeting September 2000
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seUsed 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.
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.
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seFrequencyFrequency
A. actinomycetemcomitans 29%B. Forsythus 24%P. Gingivalis 0%P. Intermedia 2%F. Nucleatum 29%
A. actinomycetemcomitans 29%B. Forsythus 24%P. Gingivalis 0%P. Intermedia 2%F. Nucleatum 29%
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CAROTID ARTERY.POSITIVE FOR P. GINGIVALIS
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ELECTRO N MICROGRAPH OF MACROPHAGE
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GRAM NEGATIVE BACTERIA IN MACROPHAGE
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seOther periodontalbacteria such as,
Porphyromonas gingivalis have also been shown to infect endothelial cells.
Other periodontalbacteria such as,
Porphyromonas gingivalis have also been shown to infect endothelial cells.
Progulske-Fox, A. et.al.J. Dent. Res. 1999, 34:393
Progulske-Fox, A. et.al.J. Dent. Res. 1999, 34:393
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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.)
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.)
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se Bacterial Involvementin Atheroma
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 67:5792
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
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 67:5792
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
Cor
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se CORRELATION BETWEEN ATHEROSCLEROSIS AND PERIODONTAL PUTATIVE PATHOGENIC BACTERIAL INFECTIONS IN CORONARY AND INTRNAL MAMMARY ARTERIES . PUCAR A , KENNEY EB et al J. PERIODONT. 2007 78:677
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.
Cor
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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
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seEstablishment
of a mouse model of infective induced
atheroma formation
Establishmentof a mouse model of
infective induced atheroma formation
Chung H.J. et al J. Dent. Res. 2000 79: #1356
Chung H.J. et al J. Dent. Res. 2000 79: #1356
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seUsed 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
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
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Chung et alChung et alChung et alChung et al
Mean area ofatheroma after 3 weeks
Mean area ofatheroma after 3 weeks
P. Gingivalis 162.1Mm2Control broth 88.6Mm2P. Gingivalis 162.1Mm2Control broth 88.6Mm2
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seTNF and PGE levels
in chamber were correlated with area of
atheroma TNF associated with serum cholesterol. Cholesterol associated with area of atheroma.
TNF and PGE levels in chamber were
correlated with area of atheroma TNF associated with serum cholesterol. Cholesterol associated with area of atheroma.
Cor
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seBacterial induced
periodontal disease increases circulating cytokines which can
accentuate inflammation in atheromatous vessels.
Bacterial induced periodontal disease increases circulating cytokines which can
accentuate inflammation in atheromatous vessels.
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Early gingivitis with margin of gingiva showing edema, redness and bleeding on probing.Early gingivitis with margin of gingiva showing edema, redness and bleeding on probing.
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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.
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.
Cytokines in Periodontal Inflammation
Cytokines in Periodontal Inflammation
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seCircukating and local Interleukin 1- levels
(Lemus, C., & Haake, S.)
Circukating and local Interleukin 1- levels
(Lemus, C., & Haake, S.)
Periodontitis Group Health GroupSerum IL-1 2,55pg/ml 0.76 pg/mlGingival fluid 5.96 pg/ml` 0.42 pg/ml
Periodontitis Group Health GroupSerum IL-1 2,55pg/ml 0.76 pg/mlGingival fluid 5.96 pg/ml` 0.42 pg/ml
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Chronic bacterial infections including
periodontal disease also increase circulating C Reactive Substance
Chronic bacterial infections including
periodontal disease also increase circulating C Reactive Substance
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seC 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.
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.
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se543 Healthy men who developed MI or
stroke compared to controls
C Reactive protein
MI or stroke 1.51 mg/lControls 1.13 mg/l
High versus lowest quartile of C-Reactive protein had risk factor for MI 2.9
543 Healthy men who developed MI or stroke compared to controls
C Reactive protein
MI or stroke 1.51 mg/lControls 1.13 mg/l
High versus lowest quartile of C-Reactive protein had risk factor for MI 2.9
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Bacteria from the oral cavity and dental plaque
can stimulate platelet aggregation.
Bacteria from the oral cavity and dental plaque
can stimulate platelet aggregation.
Cor
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seStreptococcus 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 268:1646
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 268:1646
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seStrep 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
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
Song K.E., Ouyang T., Herzberg M.C.Infect. Immun. 1998, 66: 5388
Cor
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seEffects of
oral flora on platelets:Possible consequences in
cardiovascular disease
Effects oforal flora on platelets:
Possible consequences incardiovascular disease
Herzberg, M. Mayer, M. W.J. Periodont. 1996 67:1138
Herzberg, M. Mayer, M. W.J. Periodont. 1996 67:1138
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seIn 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.
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.
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seHyperlipedemia caused
increased cardiac effects ofS. Sanguis. Also have seen similar effects in
platelets with P. Gingivalis.
Hyperlipedemia caused increased cardiac effects ofS. Sanguis. Also have seen similar effects in
platelets with P. Gingivalis.
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Inoculation of Strep Sanguis Strain 133-79 caused cardiac contractility to fall 60%
Strep Sanguis Strain L47 does not affect platelets gave no cardiac changes when inoculated into rabbits
Inoculation of Strep Sanguis Strain 133-79 caused cardiac contractility to fall 60%
Strep Sanguis Strain L47 does not affect platelets gave no cardiac changes when inoculated into rabbits
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Rabbits on high fat diet with hypercholesterolemia In vitro platelet aggregation response to strain 133-79 accelerated over that seen
on normal diet
Rabbits on high fat diet with hypercholesterolemia In vitro platelet aggregation response to strain 133-79 accelerated over that seen
on normal diet
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Hypertension
Homocysteine
Bacteria
Smoking
Diabetes
Initiators of Endothelial DysfunctionInitiators of Endothelial Dysfunction
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HYPERTENSIONHYPERTENSION
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Hypertensionincrease chance of endothelial injury
Hypertensionincrease chance of endothelial injury
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Hypertension
Homocysteine
Bacteria
Smoking
Diabetes
Initiators of Endothelial DysfunctionInitiators of Endothelial Dysfunction
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HOMOCYSTEINEHOMOCYSTEINE
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High levels of the Amino acid homocysteine
increase risk of coronary artery disease by being
toxic to endothelium.
High levels of the Amino acid homocysteine
increase risk of coronary artery disease by being
toxic to endothelium.
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Folic acid vitamin B6, B12 reduce levels of
homocysteine
Folic acid vitamin B6, B12 reduce levels of
homocysteine
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seHyperhomocysteinema odds ratio CHD 1.7
In 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, 2g vit B6 vit B12
Hyperhomocysteinema odds ratio CHD 1.7
In 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, 2g vit B6 vit B12
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Hypertension
Homocysteine
Bacteria
Smoking
Diabetes
Initiators of Endothelial DysfunctionInitiators of Endothelial Dysfunction
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SMOKINGSMOKING
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Toxic factors in cigarette smoke
increase risk endothelial injury
Toxic factors in cigarette smoke
increase risk endothelial injury
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Smokers 2.5 times more likely to have
heart attack
Smokers 2.5 times more likely to have
heart attack
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Hypertension
Homocysteine
Bacteria
Smoking
Diabetes
Initiators of Endothelial DysfunctionInitiators of Endothelial Dysfunction
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DIABETESDIABETES
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seHyperglycemia
causes endothelial dysfunction by a number of mechanisms
including inhibition of endothelial derived nitric oxide which
reduces the ability of vessel to respond with vasodilation
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 3:s54.
Consentino, F. et. al. Cardiovasc. Pharmacol. 1998 32 suppl 3:s54.
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Diabetes increase risk of atheroma because
of hyperlipemia
Diabetes increase risk of atheroma because
of hyperlipemia
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Diabetes has high triglycerides And low HDL
Diabetes has high triglycerides And low HDL
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Low density lipidscan initiate endothelial
dysfunction and monocyte attachment. LDL’s also interact with periodontal
inflammation.
Low density lipidscan initiate endothelial
dysfunction and monocyte attachment. LDL’s also interact with periodontal
inflammation.
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Antioxidants increase resistance of LDL to oxidation. Vitamin E
reduces risks of atheroma production
Antioxidants increase resistance of LDL to oxidation. Vitamin E
reduces risks of atheroma production
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Risk of CVD and MI reduced 77% with 800 IU tocopherol
400 IU gave a 47% reduction
Risk of CVD and MI reduced 77% with 800 IU tocopherol
400 IU gave a 47% reduction
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Vitamin E has little or no effect on established
atheroma
Vitamin E has little or no effect on established
atheroma
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seAssociation between
Periodontitis and Hyperlipidemia: Cause or Effect?
Association between Periodontitis and Hyperlipidemia: Cause or Effect?
Cutler C.W et alPeriodontol 1999 12:1429
Cutler C.W et alPeriodontol 1999 12:1429
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se51 subjects, 26 with chronic
adult periodontitis,25 healthy controls looked at
triglycerides, cholesterol, antibodies against
P. Gingivalis and L.P.S.and periodontal status.
51 subjects, 26 with chronic adult periodontitis,
25 healthy controls looked at triglycerides, cholesterol,
antibodies againstP. Gingivalis and L.P.S.and periodontal status.
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seRelationship with Periodontal Disease and other variables Relationship with Periodontal Disease and other variables
odds ratioAge > 50 years 3.5Serum triglyceride > 100mg/dl 8.6Serum cholesterol > 200mg/dl 7.0LPS Reactivity > 2 bands 40.8Elisa titre > 60 Eu 35.0
odds ratioAge > 50 years 3.5Serum triglyceride > 100mg/dl 8.6Serum cholesterol > 200mg/dl 7.0LPS Reactivity > 2 bands 40.8Elisa titre > 60 Eu 35.0
Cutler et alCutler et al
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Also did in vitro study to see effect of triglycerides
on release of IL1 beta from p.m.n.s.
Also did in vitro study to see effect of triglycerides
on release of IL1 beta from p.m.n.s.
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seInterleukin 1 beta secretion
by PMNS from healthy patients Interleukin 1 beta secretion
by PMNS from healthy patients
PMN 2.0PMN + P.g. L.P.S 24PMN+ triglycerides 2.3PMN +LPS + TG 35
PMN 2.0PMN + P.g. L.P.S 24PMN+ triglycerides 2.3PMN +LPS + TG 35
Cutler et al.Cutler et al.
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seShort term high fat diet impairs antibacterial function of p.m.n.s
hyperlipidemia can modulate release of cytokines and growth factor from rat macrophages and monocytes.
Cytokines IL1 beta and TNF alpha promote hyperlipidemia.
Short term high fat diet impairs antibacterial function of p.m.n.s
hyperlipidemia can modulate release of cytokines and growth factor from rat macrophages and monocytes.
Cytokines IL1 beta and TNF alpha promote hyperlipidemia.
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sePathophysiological
relationships between periodontitis and systemic disease: Recent concepts
involving serum lipids
Pathophysiological relationships between
periodontitis and systemic disease: Recent concepts
involving serum lipids
Iacopino A.M, Cutler C.W.J. Periodont. 2000. 71:1375
Iacopino A.M, Cutler C.W.J. Periodont. 2000. 71:1375
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sePeriodontitis induced
changes in immune cell functions causes metabolic
dysregulation of lipid metabolism involving
cytokines.
Periodontitis induced changes in immune cell
functions causes metabolic dysregulation of lipid metabolism involving
cytokines.
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From periodontitis elevated serum IL-1ß and
TNF change lipid metabolism so get
hyperlipidemia.
From periodontitis elevated serum IL-1ß and
TNF change lipid metabolism so get
hyperlipidemia.
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seThe elevated lipids in
diabetes and periodontitis also increases monocytic responsiveness and pmn activity so get increased cytokine production and
further periodontal disease.
The elevated lipids in diabetes and periodontitis also increases monocytic responsiveness and pmn activity so get increased cytokine production and
further periodontal disease.
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seRecommended levels of LDLRecommended levels of LDL
• 1 or more risk factor < 160mg / ml• 2 or more risk factor < 130mg / ml• Presence of atherosclerosis or
Diabetes < 100 mg /ml
• 1 or more risk factor < 160mg / ml• 2 or more risk factor < 130mg / ml• Presence of atherosclerosis or
Diabetes < 100 mg /ml
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Recommendedlevels of HDL
>35 mg/ml
Recommendedlevels of HDL
>35 mg/ml
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High cholesterol >200mg/ml with LDL
>130 mg/ml increases risk of heart attack 2.4 times
High cholesterol >200mg/ml with LDL
>130 mg/ml increases risk of heart attack 2.4 times
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seHarvard Study, Dr. W.C. Taylor
Used 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.”
Harvard Study, Dr. W.C. Taylor
Used 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.”
Cor
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seDr 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 years202mg/dl or less 97.8203 to 244mg/dl 97.3
245mg/dl or more 96.2
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 years202mg/dl or less 97.8203 to 244mg/dl 97.3
245mg/dl or more 96.2
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seCholesterol Reducing DrugsInhibit Synthesis of Cholesterol. Up-Regulate Nitric Oxide Sinthetase
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
• LIPITOR ( ATORVASTATIN) • MEVACOR( LOVASTATIN) • ZOCOR (SIMVASTATIN)• PRAVACHOL( PRAVASTATIN)• REDUCTION OF MI AND GENERAL MORTALITY.• ALSO IMPROVE VESSEL NARROWING
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LOVASTATIN MEVACORLOVASTATIN MEVACOR
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se Dr A Gotto Cornell UniversityAm. J. Cardiol., Dec. 2000 pg. 1176
6,605 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% diabetic
Average Total Cholesterol 221mg/dlLDL 150mg/dlHDL 37mg/dl
Total Cholesterol fell 18.4%LDL fell 25%HDL fell 15%
Reduction in sudden death, heart attack, unstable angina 36%Reduction in need for angioplasty 33%Reduction in hospitalization for angina 34%
Dr A Gotto Cornell UniversityAm. J. Cardiol., Dec. 2000 pg. 1176
6,605 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% diabetic
Average Total Cholesterol 221mg/dlLDL 150mg/dlHDL 37mg/dl
Total Cholesterol fell 18.4%LDL fell 25%HDL fell 15%
Reduction in sudden death, heart attack, unstable angina 36%Reduction in need for angioplasty 33%Reduction in hospitalization for angina 34%
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Alcohol 1 to 2 glasses a day reduces cholesterol,
reduces clotting
Alcohol 1 to 2 glasses a day reduces cholesterol,
reduces clotting
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One to two drinks ofalcohol per day gives
30-50 percent reduction in CHD in men. Maybe due to increase levels of HDL, or to blood clotting reduction
One to two drinks ofalcohol per day gives
30-50 percent reduction in CHD in men. Maybe due to increase levels of HDL, or to blood clotting reduction
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Aspirin inhibitsplatelet aggregation
Aspirin inhibitsplatelet aggregation
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seAspirin 325 mg every other day for 4.5 years 22000 male MDs
Aspirin 325 mg every other day for 4.5 years 22000 male MDs
Aspirin 194 MI 5 deaths Controls 189 MI 18 deaths
Aspirin 194 MI 5 deaths Controls 189 MI 18 deaths
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se2418 Israeli women 100 to 500 mg Aspirin every other day for 3 years
2418 Israeli women 100 to 500 mg Aspirin every other day for 3 years
• 40% less MI mortality • 34% less general mortality
• 40% less MI mortality • 34% less general mortality
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Early infarct affecting left ventricleEarly infarct affecting left ventricle
thrombus
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Cross section of heart with area of necrosisCross section of heart with area of necrosis
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Infarct in ventricular wall with loss of muscle and scarringInfarct in ventricular wall with loss of muscle and scarring
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Area of previous infarct with rupture of ventricular wallArea of previous infarct with rupture of ventricular wall
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Histology of Myocardial Infarction
Histology of Myocardial Infarction
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Normal heart muscleNormal heart muscle
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Beginning of infarct, loss of striations and nuclei of cardiac muscleBeginning of infarct, loss of striations and nuclei of cardiac muscle
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Continued loss of cellular vitality of myocardiumContinued loss of cellular vitality of myocardium
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Myocardial infarct with replacement of necrotic myocardium with inflammatory cells and fibroblastsMyocardial infarct with replacement of necrotic myocardium with inflammatory cells and fibroblasts
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Established infarct with fibrotic scarring in myocardiumEstablished infarct with fibrotic scarring in myocardium
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seSystematic review of
the association between respiratory diseases
and oral heaith. Azarpazhooh. A. J.
PERIODONT.2006.77:1465.
Systematic review of the association between
respiratory diseases and oral heaith.
Azarpazhooh. A. J. PERIODONT.2006.77:1
465.
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seAssociation 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.
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.
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FURTHER READING CLINICAL PERIODONTOLOGY
10 th EDITION CHAPTER 18
FURTHER READING CLINICAL PERIODONTOLOGY
10 th EDITION CHAPTER 18