Salivary inflammatory cytokines may be novel markers of carotid atherosclerosis in a Japanese general population: The Suita study☆
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.
References (29)
- et al.
Association of high sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-alpha (TNF-alpha) with carotid intimal medial thickness in subjects with different grades of glucose intolerance- the Chennai Urban Rural Epidemiology Study (CURE-31)
Clin Biochem
(2008) - et al.
Biglycan expression in hypertensive subjects with normal or increased carotid intima-media wall thickness
Clin Chim Acta.
(2009) - et al.
Autonomic nervous system, inflammation and preclinical carotid atherosclerosis in depressed subjects with coronary risk factors
Atherosclerosis
(2010) - et al.
Independent and additive effects of cytokine patterns and the metabolic syndrome on arterial aging in the SardiNIA Study
Atherosclerosis
(2011) - et al.
Association of systemic inflammatory activity with coronary and carotid atherosclerosis in the very elderly
Atherosclerosis
(2011) - et al.
Correlation of peripheral Th17 cells and Th17-associated cytokines to the severity of carotid artery plaque and its clinical implication
Atherosclerosis
(2012) - et al.
The prevalence and incidence of coronary heart disease is significantly increased in periodontitis: a meta-analysis
Am Heart J
(2007) - et al.
Periodontal disease and cardiovascular disease: epidemiology and possible mechanisms
J Am Dent Assoc
(2002) - et al.
Salivary biomarkers for predicting the progression of chronic periodontitis
Arch Oral Biol
(2012) - et al.
Cerebrovasc Dis
(2010)
Subclinical atherosclerosis and fetuin-A plasma levels in essential hypertensive patients
Hypertens Res
Monocyte cyclooxygenase-2 overactivity: a new marker of subclinical atherosclerosis in asymptomatic subjects with cardiovascular risk factors?
Eur Heart J
Measurement of atherosclerosis markers in patients with periodontitis: a case-control study
J Periodontol
Effect of periodontal therapy on arterial structure and function among aboriginal Australians: a randomized, controlled trial
Hypertension
Cited by (30)
Protein-based salivary biomarkers for the diagnosis of periodontal diseases: Systematic review and meta-analysis
2023, Journal of Taibah University Medical SciencesInvestigation of the relationship between periodontal and systemic inflammation in children with Sickle Cell Disease: A case- control study
2022, CytokineCitation Excerpt :While expressing the relationship between periodontal diseases and systemic diseases, it is reported that especially the increase in HsCRP, IL-1β, IL-6 and oxidative stress markers levels in bloodstream and tissues exacerbate both periodontal and systemic diseases [40]. It has been suggested that salivary cytokine levels in patients with metabolic syndrome, cardiovascular disease and polycystic ovary syndrome, all of which are characterized by chronic systemic inflammation, are higher than those of systemically healthy subjects who have a similar periodontal status [41–43]. Sickle cell disease may increase local cytokine production in periodontal tissues in the same way as in systemic inflammatory diseases such as metabolic syndrome and cardiovascular disease.
Identification of the different salivary Interleukin-6 profiles in patients with periodontitis: A cross-sectional study
2021, Archives of Oral BiologyTracking the functional meaning of the human oral-microbiome protein-protein interactions
2020, Advances in Protein Chemistry and Structural BiologyPerceived discrimination is associated with the inflammatory response to acute laboratory stress in women at risk for cardiovascular disease
2018, Brain, Behavior, and ImmunityCitation Excerpt :Local mucosal production of IL-6 may relate to activation of a stress pathway that may be dysregulated by the adversity of discrimination. Furthermore, higher levels of salivary IL-6 have been associated with carotid atherosclerosis as measured by intima-media thickness (Kosaka et al., 2014). However, more investigation is need in that the relationship between salivary IL-6 and perceived discrimination may be bidirectional.
- ☆
This article encompasses the doctoral dissertation of Takayuki Kosaka.