Elsevier

Atherosclerosis

Volume 237, Issue 1, November 2014, Pages 123-128
Atherosclerosis

Salivary inflammatory cytokines may be novel markers of carotid atherosclerosis in a Japanese general population: The Suita study

https://doi.org/10.1016/j.atherosclerosis.2014.08.046Get rights and content

Highlights

  • Salivary inflammatory cytokines were associated with periodontal status.

  • IL-6 and TNF-α levels in saliva were associated with carotid atherosclerosis.

  • PGE2 in saliva was associated with carotid atherosclerosis only in women.

  • Mean- and Max-IMT have different risk factors, respectively.

Abstract

Objective

Salivary biomarkers have been recently useful of periodontal disease, which is also risk factor of atherosclerosis. However, there are few studies of the association between salivary inflammatory cytokines and carotid atherosclerosis. We aimed to clarify the association between salivary inflammatory cytokines and periodontal disease and carotid atherosclerosis in a general urban population.

Methods

We studied 608 Japanese men and women (mean age: 65.4 years) in the Suita study. Carotid atherosclerosis was evaluated by high-resolution ultrasonography with atherosclerotic indexes of intima-media thickness (IMT). Periodontal status was evaluated by the Community Periodontal Index (CPI). Salivary levels of interleukin-1β, interleukin-6, tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were measured by enzyme linked immunosorbent assay. The risks of carotid atherosclerosis (≥75th percentiles of mean- [0.88 mm] and Max-IMT [1.50 mm]) according to the quartiles of salivary inflammatory cytokines were compared using of adjusted-logistic regression models.

Results and conclusion

All salivary inflammatory cytokines were positively associated with CPI. The adjusted odds ratios for carotid atherosclerosis of mean-IMT in the highest quartile of interleukin-6 and TNF-α were higher than those in the lowest quartiles (OR = 2.32 and 2.88; 95% confidence intervals = 1.19–4.51 and 1.51–5.49, respectively). The adjusted odds ratio for carotid atherosclerosis of mean-IMT in the highest quartile of PGE2 was greater than those in the lowest quartile in women (OR = 2.78; 95% confidence intervals = 1.11–6.95). In conclusion, higher levels of salivary inflammatory cytokines were associated with both periodontal disease and carotid atherosclerosis. Selected salivary inflammatory cytokines may be useful screening markers for periodontal disease and carotid atherosclerosis.

Introduction

Inflammatory cytokines in plasma have associated with carotid atherosclerosis. Recent investigations have shown that plasma levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) were associated to the severity and progression of carotid artery plaques [1], [2], [3], [4], [5], [6], [7], [8]. Prostaglandin E2 (PGE2) in plasma was related to sub-clinical atherosclerosis in apparently healthy subjects exposed to cardiovascular risk factors [9].

On the other hand, previous studies have suggested that periodontal disease has associated with cardiovascular disease (CVD) [10], [11]. The findings from cross-sectional and longitudinal epidemiologic studies were supported by in vitro and animal studies describing plausible mechanisms linking periodontal infection to development of atherosclerotic diseases, to the triggering of clinical coronary events or to both [12]. One recent investigation has reported that carotid IMT regressed with moderate to severe periodontal disease after periodontal therapy in Aboriginal Australian adults, suggesting periodontal disease and atherosclerosis are positively associated [13].

Until now, periodontal pocket examination has been used typically for diagnosis of periodontal disease. However, recently it has been suggested that select salivary biomarkers could have utility for monitoring periodontal health [14], [15], [16], [17]. Saliva contains locally and systemically derived biomarkers of periodontal disease [18]. We focused on attention to saliva as a useful biological sample which reflects the oral health condition because saliva samples can be collected easily and non-invasively differently from blood samples. However, there is no study on the association between salivary inflammatory cytokines and carotid atherosclerosis, in Asia. The purpose of this study was therefore to investigate the association between not only salivary inflammatory cytokines and periodontal status but also those cytokines and carotid atherosclerosis. In this study, we assessed the hypothesis that selected inflammatory cytokines in saliva are related to periodontal disease and carotid atherosclerosis in a general urban Japanese population.

Section snippets

Study participants

We studied 608 Japanese (271 men and 337 women, mean age: 65.4 years) who underwent a medical check-up, dental examination, and carotid ultrasonography between June 2008 and March 2012 in the Suita study [19]. Before the study started, the study protocol was approved by the Ethics Committee of the National Cerebral and Cardiovascular Center (M19-62), and only individuals who provided informed consent after receiving a full explanation of the study purpose and methods both in writing and orally

Results

Detailed demographic data between 3 groups according to the periodontal status are summarized in Table 1. In the different CPI groups, salivary inflammatory cytokines and mean-IMT increased accordance with progression of periodontal disease. All salivary inflammatory cytokines were positively associated with CPI (IL-1β: r = 0.17, P < 0.001; IL-6: r = 0.15, P < 0.001; TNF-α: r = 0.17, P < 0.001; PGE2: r = 0.16, P < 0.001).

The multivariable-adjusted mean-IMT (Table 2) in subjects with the highest

Discussion

In this study, higher salivary IL-6 and TNF-α were associated with the periodontal status and carotid atherosclerosis. To our knowledge, this is the first population study to show the relationship between salivary inflammatory cytokines and periodontal disease and carotid atherosclerosis. Salivary IL-6 and TNF-α may indicate intensity of carotid IMT. Salivary inflammatory cytokines may be novel markers of intensities of carotid atherosclerosis, which may be useful screening markers for CVDs as

Sources of funding

This study was supported by the Intramural Research Fund of the National Cerebral and Cardiovascular Center (22-4-5), and Grants-in-Aid from the Ministry of Education Science and Culture of Japan (Nos. 20390489, 23390441 and 26293411).

Conflicts of interests

The authors declare that they have no conflict of interests.

Disclosures

Nothing to disclosures.

Acknowledgments

We thank all members of the Suita Medical Association, the Suita City Health Center, Satsuki-Junyukai, the Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, Dr. Joe Sakagami for establishing the dental examination database system, Drs. Yoko Yoshimuta and Kayoko Takemura for the contribution in oral examination.

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