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

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.

[1]  Sarabjeet Singh,et al.  The prevalence and incidence of coronary heart disease is significantly increased in periodontitis: a meta-analysis. , 2007, American heart journal.

[2]  Jianhui Zhu,et al.  Infection and atherosclerosis: emerging mechanistic paradigms. , 1999, Circulation.

[3]  Y. Kokubo,et al.  Impact of High-Normal Blood Pressure on the Risk of Cardiovascular Disease in a Japanese Urban Cohort: The Suita Study , 2008, Hypertension.

[4]  Craig S. Miller,et al.  Salivary biomarkers of periodontal disease in response to treatment. , 2011, Journal of clinical periodontology.

[5]  O. Nóbrega,et al.  Association of systemic inflammatory activity with coronary and carotid atherosclerosis in the very elderly. , 2011, Atherosclerosis.

[6]  F. Lu,et al.  Correlation of peripheral Th17 cells and Th17-associated cytokines to the severity of carotid artery plaque and its clinical implication. , 2012, Atherosclerosis.

[7]  T. Braun,et al.  Bacterial and salivary biomarkers predict the gingival inflammatory profile. , 2012, Journal of periodontology.

[8]  S. Sakoda,et al.  Association of Inflammatory Markers and Carotid Intima-Media Thickness with the Risk of Cardiovascular Events in High-Risk Patients , 2010, Cerebrovascular Diseases.

[9]  Edit Nagy,et al.  Inflammatory mediators in saliva associated with arterial stiffness and subclinical atherosclerosis , 2013, Journal of hypertension.

[10]  V. Mohan,et al.  Association of high sensitivity C-reactive protein (hsCRP) and tumour necrosis factor-alpha (TNF-alpha) with carotid intimal medial thickness in subjects with different grades of glucose intolerance--the Chennai Urban Rural Epidemiology Study (CURES-31). , 2008, Clinical biochemistry.

[11]  A. Alibrandi,et al.  Biglycan expression in hypertensive subjects with normal or increased carotid intima-media wall thickness. , 2009, Clinica chimica acta; international journal of clinical chemistry.

[12]  Subclinical atherosclerosis and fetuin-A plasma levels in essential hypertensive patients , 2013, Hypertension Research.

[13]  I. Lamster,et al.  Inflammatory biomarkers in saliva: assessing the strength of association of diabetes mellitus and periodontal status with the oral inflammatory burden. , 2012, Journal of clinical periodontology.

[14]  I. Heyligers,et al.  Estrogen enhances mechanical stress-induced prostaglandin production by bone cells from elderly women. , 2001, American journal of physiology. Endocrinology and metabolism.

[15]  L. Manzoli,et al.  Autonomic nervous system, inflammation and preclinical carotid atherosclerosis in depressed subjects with coronary risk factors. , 2010, Atherosclerosis.

[16]  N. Anstey,et al.  Effect of Periodontal Therapy on Arterial Structure and Function Among Aboriginal Australians: A Randomized, Controlled Trial , 2014, Hypertension.

[17]  R. Genco,et al.  Periodontal disease and cardiovascular disease: epidemiology and possible mechanisms. , 2002, Journal of the American Dental Association.

[18]  J. Paramo,et al.  Monocyte cyclooxygenase-2 overactivity: a new marker of subclinical atherosclerosis in asymptomatic subjects with cardiovascular risk factors? , 2005, European heart journal.

[19]  K. Chayama,et al.  Periodontal Infection Is Associated With Endothelial Dysfunction in Healthy Subjects and Hypertensive Patients , 2008, Hypertension.

[20]  D. Schlessinger,et al.  Independent and additive effects of cytokine patterns and the metabolic syndrome on arterial aging in the SardiNIA Study. , 2011, Atherosclerosis.

[21]  P. López‐Jornet,et al.  Measurement of atherosclerosis markers in patients with periodontitis: a case-control study. , 2012, Journal of periodontology.

[22]  J. Tongren,et al.  Cytokine production in rhesus monkeys infected with Plasmodium coatneyi. , 1999, The American journal of tropical medicine and hygiene.

[23]  Yutaka Imai,et al.  The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2014) , 2014, Hypertension Research.

[24]  Y. Nomura,et al.  Salivary biomarkers for predicting the progression of chronic periodontitis. , 2012, Archives of oral biology.

[25]  A. Nakashima,et al.  Different risk factors for the maximum and the mean carotid intima-media thickness in hemodialysis patients. , 2003, Internal medicine.

[26]  T. Ogihara,et al.  The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009) , 2009, Hypertension Research.

[27]  T. Cutress,et al.  Development of the World Health Organization (WHO) community periodontal index of treatment needs (CPITN). , 1982, International dental journal.

[28]  Y. Kokubo,et al.  Impact of Chronic Kidney Disease on Carotid Atherosclerosis According to Blood Pressure Category: The Suita Study , 2013, Stroke.

[29]  L. Chow,et al.  Comparative Evaluation of Cytokines in Gingival Crevicular Fluid and Saliva of Patients with Aggressive Periodontitis , 2013, The International journal of biological markers.

[30]  J. Loscalzo,et al.  Shouldering the risk factor burden: infection, atherosclerosis, and the vascular endothelium. , 2002, Circulation.