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Localized Oral Infections and Systemic Inflammation The Oral

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					Localized Oral Infections and Systemic
Inflammation: The Oral Infections and
Vascular Disease Epidemiology Study




                     Ryan Demmer, MPH
                     Pre-doctoral Fellow
      Division of Epidemiology, School of Public Health
                   University of Minnesota
    No disclosures to make
Coauthors:
Moïse Desvarieux, MD, PhD
Panos Papapanou, DDS, PhD
Bernadette Boden-Albala, DrPH, MPH
David Jacobs, PhD
Ralph Sacco, MD, MS
       Scientific Question:

  How might infection influence
       atherosclerosis?

  Are current local oral infections
associated with elevated markers of
      systemic inflammation?
METHODS
           INVEST Design

• Prospective cohort study
  investigating the relationship
  between oral infection and
  atherosclerotic progression
• Cross-sectional results presented
  here
  – Addressing potential mechanism by
    which infections and atherosclerosis
    might be related
              Methods:
           INVEST Eligibility
• Hispanic, Black or White
• Age 55 or older
• No baseline history of stroke, MI, or other
  chronic inflammatory conditions
• Living in a defined geographic area of
  Northern Manhattan
• Ability to come to clinic for in-person
  assessment
               Methods:
      Clinical Oral Examination

• Pocket (probing) depth (PD) measures
  were made at six locations per tooth using
  a UNC-15 manual probe
  – Measured in mm
  – Measured in up to 192 sites per mouth
• PD is a strong correlate of current
  infection
probe
          Methods:
  Summary Exposure Definition

• Periodontal disease is defined by
  severity and extent of infection
• Severity (depth of pocket)
  – 4 mm selected as cutpoint
• Extent (# or % of infected sites per
  mouth)
          Methods:
  Summary Exposure Definition

• Number of sites per mouth with PD ≥
  4 mm
  – Burden of infection
• Percent of sites per mouth with PD ≥
  4 mm
  – Intensity of infection
            Methods:
  White Blood Cell Count (WBC)
• Fasting blood samples
• Whole blood collected in 5-cm3 EDTA-
  anticoagulated tubes
• White Blood Cell Count (WBC) (# cells x
  109/L) assessed with automated cell
  counter using standardized laboratory
  techniques
  –   Coulter STK-R and Coulter STK-S, Coulter Electronics, and Sysmex SE-9500,
      TOA Medical Electronics
    Methods: Risk Factor Assessment
     (The following conventional CVD risk factors were
               included in adjusted analyses)
• In person interviews
  – Age on last birthday
  – Race/ethnicity
  – Smoking (current, former or never)
     • pack-years added no additional information
  – Gender
  – Education (completed high school)
• Diabetes (yes/no via interview)
  – Or fasting glucose > 126
• Blood pressure (continuous mm Hg)
  – Assessed in person by trained research
    assistants
Results
            General Characteristics
                    n = 911
Variable         %     Variable          Mean +/- SD
Female           60%   Age               66 ± 8
Race/Ethnicity         # missing teeth   14 ± 8
 Hispanic        63%   SBP               142 ± 20
 Black           21%   DBP               81 +/- 12
 White           16%
Smoking
 Ever            53%
 Current         15%
Edentulous       19%
              White Blood Cells Distribution
                     140


                     120


                     100
Number of Subjects




                     80


                     60


                     40


                     20


                      0
                           1.

                                  2.

                                         3.

                                                4.

                                                       5.

                                                              6.

                                                                     7.

                                                                            8.

                                                                                   9.

                                                                                          10

                                                                                          11

                                                                                          12

                                                                                          13

                                                                                          14
                             50

                                    50

                                           50

                                                  50

                                                         50

                                                                50

                                                                       50

                                                                              50

                                                                                     50

                                                                                            .5

                                                                                            .5

                                                                                            .5

                                                                                            .5

                                                                                            .5
                                                                                              0

                                                                                              0

                                                                                              0

                                                                                              0

                                                                                              0
                                          White Blood Count (Cells x 10^9/L)


Mean = 6.20 ± 1.90;                                                            Median = 5.90
                                  Mean WBC values across quartiles of
                                   % PD≥4 mm: Intensity of infection
                                         n = 911; p for trend across quartiles = 0.27;
                                           p for trend including edentulous = 0.52
                        6.60

                        6.40
  WB C (cells x 10^9)




                        6.20

                        6.00

                        5.80

                        5.60

                        5.40
                               0% - 2%     3% - 10%    11% - 25%     gt 25%              edentulous (n =
                               (n=176)      (n=180)     (n=195)       (n=185)                 175)
            Unadjusted                           Percent of sites with PD >= 4mm
            Adjusted
Adjusted model includes: age, gender, smoking, diabetes, race/ethn., education and SBP
                                             Mean WBC values across quartiles
                                             of # PD≥4 mm: Burden of infection
                                             n = 911; p for trend across quartiles = 0.25;
                                               p for trend including edentulous = 0.06
                      6.60



                      6.40
 WBC (cells x 10^9)




                      6.20



                      6.00


                      5.80


                      5.60


                      5.40
                             0 - 2 (n=175)    2 - 8 (n=185)   9 - 26 (n=184)   gt 26 (n=188)   edentulous
                                                                                                (n=175)
                 Unadjusted                              Number of sites with PD >= 4 mm
                 Adjusted
Adjusted model includes: age, gender, smoking, diabetes, race/ethn., education and SBP
                   Red line = Mean tooth loss across quartiles
                           of quartiles of # PD ≥ 4 mm
                               Unadjusted WBC
                               Adjusted WBC
                               # Missing Teeth
        6.60                                                                              20

                                                                                          18
        6.40
                                                                                          16

                                                                                          14
        6.20




                                                                                               # M issing Teeth
                                                                                          12
  WBC




        6.00                                                                              10

                                                                                          8
        5.80
                                                                                          6

                                                                                          4
        5.60
                                                                                          2
        5.40                                                                              0
               0 - 2 (n=175)   2 - 8 (n=185) 9 - 26 (n=184) gt 26 (n=188)    edentulous
                                           Number of sites with PD >= 4 mm    (n=175)

Adjusted model includes: age, gender, smoking, diabetes, race/ethn., education and SBP
                Conclusions

• WBC appears to be positively related to
  extent of periodontal infection – although
  not in a monotonic fashion
• Relationship between periodontal status
  and WBC may be random in these data
  – Weak relationship relative to literature
  – Relationship may vary with age
• Burden (# of sites) of infection may be
  more important than intensity of infection
                Limitations

• Cross-sectional
• Use of pocket depth alone as exposure
  – misclassification
• No neutrophil data
  – Other studies have shown neutrophils to be
    explanatory
• CRP, IL-6 and Fibrinogen results
  unavailable at this time
                 Discussion
• Tooth loss may distort overall periodontal
  health
• WBC in edentulous difficult to interpret
  – Potential for infection is reduced
  – History of severe infection likely
• Edentulous have elevated levels of carotid
  artery plaque
  – After careful adjustment for health behaviors
    and other life style factors
  – Implication: removal of infection may alleviate
    periodontal disease but not eliminate CVD
    risk?
                    Moïse Desvarieux, M.D., Ph.D.
                        Principal Investigator
•   Project Coordinator
     – George T. Loo, MPA, MPH
                                     Co-Investigators and Consultants
•   Research Assistants
                                     • Columbia University
     – Mariana Cukier, DDS
                                          – Panos Papapanou, DDS, PhD
     – Palma Gervasi, BA
                                          – Ralph L. Sacco MD, MS
     – Giselle Santivanez, BS
                                          – Ira Lamster, DDS, MS
•   Core Laboratory (CALM)
                                     • University of Minnesota
     – Daniel J. Fink, MD, MPH
                                          – Aaron Folsom, MD
     – Kihn M. Kiu, BS
                                          – Mark Herzberg, DDS, PhD
•   Ultrasound Specialists
                                          – David Jacobs, PhD
     – Tanja Rundek, MD, PhD
                                          – Russell Luepker, MD, MS
•   NOMASS Research Director
                                     • University of Paris
     – Bernadette Boden-Albala,
                                          – Pierre-Jean Touboul, MD
        DrPH, MPH
                                     • Wake Forest University
•   NOMASS Project Coordinator
                                          – Ward Riley, PhD
     – Janet de Rosa, MPH
•   Periodontal Laboratory
    Technicians
     – Miriam S. Herrera-Abreu, BS
     – Romanita S. Celenti, MS
•   Predoctoral Fellow
     – Ryan Demmer, MPH

				
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