Approx 30% of adults have periodontitis 8-13% have severe - PDF document

1/26/2011 Periodontal Disease and Cardiovascular Health: What we know and how it applies to your patients Ken Kornman DDS, PhD Interleukin Genetics Waltham, MA K. S. Kornman is a fulltime employee and shareholder of Interleukin Genetics, Inc. Interleukin Genetics has patents issued and pending on the use of the genetic variations for various diseases. Sixth Annual Women’s Cardiac Health Conference Massachusetts Medical Society February 4, 2011 Early 1900’s: Connections between infected teeth and gums and multiple systemic diseases were wrong WD Miller, late 1800’s Robert Koch, late 1800’s WD Miller, 1891; The Human Mouth as a Focus of Infection. Dental Cosmos 33:689-706 WD Hunter, 1900; Oral sepsis as a cause of disease. British Medical Journal 2:215-216 WD Hunter 1911; The role of sepsis and antisepsis in medicine and the importance of oral sepsis as its chief cause. Lancet 1:79-86; and Dental Register 44:579-611. 1

1/26/2011 Periodontitis: Bacterially- induced chronic inflammatory disease, that destroys connective tissue and bone that support the teeth Approx 30% of adults have periodontitis • 8-13% have severe generalized disease Bacterial accumulations on the teeth initiate periodontal inflammation Photos courtesy of Michael McGuire Disease modifiers--- e.g....diet, smoking, diabetes, genetics 2

1/26/2011 Patients with periodontitis are on different paths • 480 male Sri Lankan tea plantation workers • 15 yr longitudinal monitoring q 3yrs • No treatment Number of Number of Loe et al. 1986 8% Missing Teeth 35 30 25 20 15 81% 10 5 11% 0 15 20 25 30 35 40 45 Age in Years Periodontitis progression and severity is primarily a function of host modifying factors Genetic risk factors Connective Host tissue and immuno- Microbial bone inflammatory y Challenge Challenge metabolism response Environmental and acquired risk factors Page and Kornman 1997 ---i.e. smoking, diabetes, diet 3

1/26/2011 Periodontitis, Inflammation, and the health of your patients The chronic diseases of aging are connected through common inflammatory mechanisms through common inflammatory mechanisms Inflammation levels differ among individuals and are mostly controllable Treatment of periodontitis reduces systemic Treatment of periodontitis reduces systemic inflammation---and may improve diseases influenced by inflammation. Inflammation, your health, and the health of your patients The chronic diseases of aging are connected through common inflammatory mechanisms through common inflammatory mechanisms 4

1/26/2011 Dissick et al. 2010 J Periodontology Moderate to Severe periodontitis is associated with Rheumatoid arthritis N= 69 RA; 35 OA % with mod-severe periodontitis periodontitis 60 51 50 40 30 26 20 p=0.03 10 0 Rheumatoid arthritis Osteoarthritis Patients with recent acute myocardial infarction had worse dental problems than control subjects with no MI history Mattila et al 1989 • 100 patients with acute MI • 104 community controls; no history of MI • S ignificant association between MI and severity of dental disease history DeS DeS tefano et al 1993 tefano et al. 1993 Offenbacher et al. 1996 5

1/26/2011 Key Findings from Selected Observational Studies on Relationship of Periodontitis and Cardiovascular Disease Study N Country Age Outcom e Odds 95% Confidence ratio ratio i t interval l Holmlund et 4,254 Sweden 20-70 CHD 2.69 1.12, 6.46 al. 2006 Dietrich et 1,203 USA 21-59 CHD 2.12 1.26, 3.60 al. 2008 Senba et al. 23,088 Japan <66 CHD 1.68 1.08, 2.61 2008 You et al. 22,862 USA >44 Stroke 1.27 1.09, 1.49 2009 Choe et al. 867,256 Korea >29 Stroke 1.3 1.2. 1.4 2009 • Periodontitis effect is greater in young vs >60 yo; • Effect on stroke is greater than effect on CHD. • Effect also seen in multiple Asian studies and in never-smokers. Periodontitis is independently associated with atherosclerotic cardiovascular disease Increased prevalence and Periodontal disease is a risk incidence of CAD in patients factor for CHD that is with periodontitis, an independent of traditional independent risk factor for independent risk factor for CHD risk factor i k f CAD • Humphrey et al 2008; meta- • Humphrey et al 2008; meta- • Bahekar et al. 2007; meta- • Bahekar et al. 2007; meta- analysis analysis analysis analysis • Risk 1.24 to 1.35 • Risk 1.24 to 1.35 • 5 prospective studies (86,092 • 5 prospective studies (86,092 patients) Periodontitis: 1.14 patients) Periodontitis: 1.14 risk for CHD; p<0.001 risk for CHD; p<0.001 • Case –control studies (1,423 • Case –control studies (1,423 ( ,4 3 ( ,4 3 patients) Periodontitis: 2.22 patients) Periodontitis: 2.22 risk for CHD; p<0.001 risk for CHD; p<0.001 6

1/26/2011 Potential explanations for periodontitis association with CHD • Periodontitis raises • Diabetes, smoking, • Periodontal bacteria: bl blood CRP d CRP ma complicate may complicate • can be found in the statistical analysis blood • Higher CRP associated • can be found in • Some studies with MI risk atheromas adequately sized to • Various properly adjust • Periodontitis treatment microorganisms reduces CRP levels associated with CVD • Common genetics risk • Antibiotic studies show no benefit h b fit Major risk factors Periodontitis raises Chronic are common to systemic bacteremia inflammatory burden both diseases Inflammation, your health, and the health of your patients The chronic diseases of aging are connected through common inflammatory mechanisms through common inflammatory mechanisms Inflammation levels differ among individuals and are mostly controllable 7

1/26/2011 Inflammation levels differ among individuals Kelley-Hedgepath 2008 CRP mg/L • NHANES 1999-2002; 8,335 adults • CRP mg/L • Male: 3.38 + 0.12 • Female 4.88 + 0.17 • p<0.01 Ethnicity Gender Inflammation levels differ among individuals • NHANES 1999-2002; 8,335 adults •NHANES 1999-2002; 8,335 adults BMI CRP mg/L p-value Smoking CRP mg/L p-value <20 2.31 + 0.30 No 3.90 + 0.14 <0.01 20- 24.9 2.59 + 0.13 Yes 4.47 + 0.15 <0.01 25- 29 9 25 29.9 3 80 + 0 15 3.80 + 0.15 >30 6.29 + 0.24 Smoking Body Fat 8

1/26/2011 Moderate to severe periodontitis increases systemic inflammation Generalized Meta-analysis of Periodontitis patients periodontitis raises periodontitis and blood have higher CRP systemic inflammation y CRP • N=40 adult • N=53 localized • 18 suitable papers periodontitis (AP); periodontitis; N=54 • CRP higher in N=35 controls generalized; N=43 periodontitis than controls healthy • CRP • Median CRP p=0.030 • Often >2.1 mg/ L in • higher in AP • 1.45 mg/ L periodontitis cases (p<0.001) generalized • Weighted mean • Associated with • 1.30 mg/ L localized difference (WMD) number of active between • 0.90 mg/ L controls 9 g/ sites over 6 mos periodontitis and d d • Leukocytes elevated controls = 1.56 in generalized vs. mg/ L; p=0.00001 • Ebersole et al. 1997 localized and controls (p=0.002) • Paraskevas et al. 2008 • Loos et al. 2000 Severe periodontitis is associated with increase in “high” CRP levels Generalized Severe Severe periodontitis is periodontitis is associated associated with CRP> 3mg/ L with CRP> 3mg/ L • N=59 moderate •Thai population periodontitis • N=62 localized chronic periodontitis • N=50 severe periodontitis •N= 21 generalized severe • N=65 healthy periodontitis •N=38 healthy • Subjects with CRP > 3mg/ L •Lower CRP than • Severe: 38% Severe: 38% Caucasians Caucasians • Moderate: 23.7% • Subjects with CRP > 3mg/ L • Healthy: 16.9% Generalized: 28.6% Localized: 17.7% Healthy: 2.6% • Noack, Genco, et al. 2001 •Pitiphat et al. 2008 9

1/26/2011 Inflammation, your health, and the health of your patients The chronic diseases of aging are connected through common inflammatory mechanisms through common inflammatory mechanisms Inflammation levels differ among individuals and are mostly controllable Treatment of periodontitis reduces systemic Treatment of periodontitis reduces systemic inflammation---and may improve diseases influenced by inflammation. Treatment of moderate to severe periodontitis decreases systemic inflammation---with time Meta-analysis of Acute periodontal treatment periodontitis treatment and increases systemic blood CRP inflammatory mediators • Aggressive non-surgical • 6 tx studies treatment increases systemic inflammatory mediators for • Weighted mean difference up to 1 month; then lower = 0.5 mg/ L; p=0.02 mediators after 6 mos • D’Aiuto et al. 2004; 2007 • Paraskevas et al. 2008 • Graziani et al. 2010 • 14 severe chronic periodontitis cases • Scaling & root planing • 24 hrs post-treatment increased CRP to mean > 12mg/ L 10