J Periodontal Implant Sci.  2018 Dec;48(6):337-346. 10.5051/jpis.2018.48.6.337.

Accelerated inflammation in peripheral artery disease patients with periodontitis

  • 1Department of Periodontology, Tokyo Medical and Dental University, Tokyo, Japan.
  • 2Division of Periodontology, Department of Oral Interdisciplinary Medicine, Kanagawa Dental University Graduate School of Dentistry, Yokosuka, Japan. aoyama@kdu.ac.jp


Peripheral artery disease (PAD) is a form of arteriosclerosis that occurs in the extremities and involves ischemia. Previous studies have reported that patients with periodontitis are at high risk for PAD. However, the relationship between these 2 diseases has not yet been fully elucidated. In this cross-sectional study, we investigated this relationship by comparing patients with PAD to those with arrhythmia (ARR) as a control group.
A large-scale survey was conducted of patients with cardiovascular disease who visited Tokyo Medical and Dental University Hospital. We investigated their oral condition and dental clinical measurements, including probing pocket depth, bleeding on probing, clinical attachment level, and number of missing teeth; we also collected salivary and subgingival plaque samples and peripheral blood samples. All patients with PAD were extracted from the whole population (n = 25), and a matching number of patients with ARR were extracted (n = 25). Simultaneously, ARR patients were matched to PAD patients in terms of age, gender, prevalence of diabetes, hypertension, dyslipidemia, obesity, and the smoking rate (n = 25 in both groups). Real-time polymerase chain reaction was performed to measure the bacterial counts, while the enzyme-linked immunosorbent assay method was used to measure anti-bacterial antibody titers and proinflammatory cytokine levels in serum.
PAD patients had more missing teeth (18.4±2.0) and higher serum levels of C-reactive protein (1.57±0.85 mg/dL) and tumor necrosis factor-alpha (70.3±5.7 pg/mL) than ARR patients (12.0±1.7, 0.38±0.21 mg/dL, and 39.3±4.5 pg/mL, respectively). Meanwhile, no statistically significant differences were found in other dental clinical measurements, bacterial antibody titers, or bacterial counts between the 2 groups.
Our findings suggested that PAD patients had poorer oral and periodontal state with enhanced systemic inflammation.


Cross-sectional study; Inflammation; Periodontitis; Peripheral artery disease

MeSH Terms

Arrhythmias, Cardiac
Bacterial Load
C-Reactive Protein
Cardiovascular Diseases
Cross-Sectional Studies
Enzyme-Linked Immunosorbent Assay
Peripheral Arterial Disease*
Real-Time Polymerase Chain Reaction
Tumor Necrosis Factor-alpha
C-Reactive Protein
Tumor Necrosis Factor-alpha


  • Figure 1 Periodontal status. (A) mean PPD, (B) CAL, (C) BOP, and (D) number of missing teeth for each subject in both PAD (test) and ARR (control) groups were measured. The values are expressed as mean±standard error. PPD: probing pocket depth, CAL: clinical attachment level, BOP: bleeding on probing, PAD: peripheral artery disease, ARR: arrhythmia. a)P<0.05 compared with the ARR group.

  • Figure 2 The deepest PPD at front teeth and molars. PPD for all tested sites was calculated and we selected sites that had the deepest PPD and single roots at the front teeth area, and the PPD and multiple roots at the molars area, respectively, for each subject. The deepest PPDs for both PAD (test) and ARR (control) groups were averaged as the representative values per group. The values are expressed as mean±standard error. PPD: probing pocket depth, PAD: peripheral artery disease, ARR: arrhythmia. a)P<0.05 compared with the ARR group.

  • Figure 3 Comparison of serum levels. Peripheral blood was collected from all subjects in both PAD (test) and ARR (control) groups and the levels of (A) CRP, (B) IL-6, and (C) TNF-alpha in the serum were measured. The values are expressed as mean±standard error. PAD: peripheral artery disease, ARR: arrhythmia, CRP: C-reactive protein, IL-6: interleukin-6, TNF-alpha: tumor necrosis factor-alpha. a)P<0.05; b)P<0.01 compared with the ARR group.

  • Figure 4 IgG antibody titers of periodontal bacteria. IgG antibody titers of each periodontopathic antigens (A) P. gingivalis and (B) A. actinomycetemcomitans were analyzed with serum samples from all subjects in both PAD (test) and ARR (control) groups by ELISA. Box-and-whisker plot shows medians, 25th and 75th percentiles as boxes, and 10th and 90th percentiles as whiskers. IgG: immunoglobulin G, PAD: peripheral artery disease, ARR: arrhythmia, ELISA: enzyme-linked immunosorbent assay.

  • Figure 5 P. gingivalis counts in oral samples. Gingival crevicular fluid was collected from the deepest periodontal pocket and unstimulated saliva from each subject in both PAD (test) and ARR (control) groups, then bacterial counts by real-time PCR were measured. (A) P. gingivalis counts in saliva. (B) The counts in periodontal pocket. Box-and-whisker plot shows medians, 25th and 75th percentiles as boxes, and 10th and 90th percentiles as whiskers. PAD: peripheral artery disease, ARR: arrhythmia, PCR: polymerase chain reaction.


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