Letter to the Editor
2006; Lippincott Williams & Wilkins; Volume: 26; Issue: 2 Linguagem: Inglês
10.1161/01.atv.0000198249.67996.e0
ISSN1524-4636
AutoresSok‐Ja Janket, Jukka H. Meurman, Pekka Nuutinen, Markku Qvarnström, Martha E. Nunn, Alison E. Baird, Thomas E. Van Dyke, Judith A. Jones,
Tópico(s)Iron Metabolism and Disorders
ResumoHomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 26, No. 2Letter to the Editor Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplementary MaterialsFree AccessLetterPDF/EPUBLetter to the EditorSalivary Lysozyme and Prevalent Coronary Heart Disease. Possible Effects of Oral Health on Endothelial Dysfunction Sok-Ja Janket, Jukka H. Meurman, Pekka Nuutinen, Markku Qvarnström, Martha E. Nunn, Alison E. Baird, Thomas E. Van Dyke and Judith A. Jones Sok-Ja JanketSok-Ja Janket From the Boston University School of Dental Medicine (S.-J.J., M.E.N., T.E.V.D., J.A.J.), Boston, Mass; the University of Helsinki Dental School (J.H.M., M.Q.), Helsinki, Finland; the Kuopio University Medical School (P.N.), Finland; and the National Institute of Neurological Disorders and Stroke (A.E.B.), National Institutes of Health, Bethesda, Maryland. , Jukka H. MeurmanJukka H. Meurman From the Boston University School of Dental Medicine (S.-J.J., M.E.N., T.E.V.D., J.A.J.), Boston, Mass; the University of Helsinki Dental School (J.H.M., M.Q.), Helsinki, Finland; the Kuopio University Medical School (P.N.), Finland; and the National Institute of Neurological Disorders and Stroke (A.E.B.), National Institutes of Health, Bethesda, Maryland. , Pekka NuutinenPekka Nuutinen From the Boston University School of Dental Medicine (S.-J.J., M.E.N., T.E.V.D., J.A.J.), Boston, Mass; the University of Helsinki Dental School (J.H.M., M.Q.), Helsinki, Finland; the Kuopio University Medical School (P.N.), Finland; and the National Institute of Neurological Disorders and Stroke (A.E.B.), National Institutes of Health, Bethesda, Maryland. , Markku QvarnströmMarkku Qvarnström From the Boston University School of Dental Medicine (S.-J.J., M.E.N., T.E.V.D., J.A.J.), Boston, Mass; the University of Helsinki Dental School (J.H.M., M.Q.), Helsinki, Finland; the Kuopio University Medical School (P.N.), Finland; and the National Institute of Neurological Disorders and Stroke (A.E.B.), National Institutes of Health, Bethesda, Maryland. , Martha E. NunnMartha E. Nunn From the Boston University School of Dental Medicine (S.-J.J., M.E.N., T.E.V.D., J.A.J.), Boston, Mass; the University of Helsinki Dental School (J.H.M., M.Q.), Helsinki, Finland; the Kuopio University Medical School (P.N.), Finland; and the National Institute of Neurological Disorders and Stroke (A.E.B.), National Institutes of Health, Bethesda, Maryland. , Alison E. BairdAlison E. Baird From the Boston University School of Dental Medicine (S.-J.J., M.E.N., T.E.V.D., J.A.J.), Boston, Mass; the University of Helsinki Dental School (J.H.M., M.Q.), Helsinki, Finland; the Kuopio University Medical School (P.N.), Finland; and the National Institute of Neurological Disorders and Stroke (A.E.B.), National Institutes of Health, Bethesda, Maryland. , Thomas E. Van DykeThomas E. Van Dyke From the Boston University School of Dental Medicine (S.-J.J., M.E.N., T.E.V.D., J.A.J.), Boston, Mass; the University of Helsinki Dental School (J.H.M., M.Q.), Helsinki, Finland; the Kuopio University Medical School (P.N.), Finland; and the National Institute of Neurological Disorders and Stroke (A.E.B.), National Institutes of Health, Bethesda, Maryland. and Judith A. JonesJudith A. Jones From the Boston University School of Dental Medicine (S.-J.J., M.E.N., T.E.V.D., J.A.J.), Boston, Mass; the University of Helsinki Dental School (J.H.M., M.Q.), Helsinki, Finland; the Kuopio University Medical School (P.N.), Finland; and the National Institute of Neurological Disorders and Stroke (A.E.B.), National Institutes of Health, Bethesda, Maryland. Originally published1 Feb 2006https://doi.org/10.1161/01.ATV.0000198249.67996.e0Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:433–434To the Editor:Total leukocyte count in the peripheral blood has been reported to be a significant predictor of future cardiac events and mortality.1 Leukocyte-derived salivary lysozyme has been associated with oral infection,2 and serum lysozyme has been implicated in impaired glucose metabolism,3 a contributory factor for endothelial dysfunction.4 We postulated that salivary lysozyme, therefore, would be associated with coronary heart disease (CHD).This study was approved by the joint ethical committee of the Kuopio University Hospital and the University of Kuopio. We investigated the relationship between the CHD and lysozyme levels in a case-control study of 250 angiographically confirmed CHD patients and 250 sex- and age-matched controls, adjusting for age, sex, smoking, body mass index (BMI), diabetes mellitus, total cholesterol/high-density lipoprotein (HDL) cholesterol, hyperten sion, and serum C-reactive protein (CRP) levels ≥10 mg/L or ≥3 mg/L using logistic regression analyses. To assess the specific contribution of oral health through impaired glucose metabolism, we controlled for the Asymptotic Dental Score (ADS), an estimate of oral infection burden, comprising 5 major oral pathologies, namely pericoronitis, gingivitis, dental caries, root remnants, and the edentulous state.5The basic characteristics of the cohort (Table I, available online at http://atvb.ahajournals.org) and cross-tabulation of lysozyme levels and other vascular risk factors are presented online (Table II, available online at http://atvb.ahajournals.org). After adjustment for established cardiac risk factors including age, sex, smoking, total cholesterol/HDL cholesterol, diabetes, hypertension, BMI, and CRP, odds ratios (ORs) with 95% CIs for the association between salivary lysozyme and CHD increased from 1.00 (the reference group) to 1.16 (0.51 to 2.63), 1.82 (0.83 to 4.01), and 3.62 (1.60 to 8.16) from the lowest to highest quartiles of salivary lysozyme (P value for linear trend <0.0001; Figure; Table III, available online at http://atvb.ahajournals.org). Models using log-transformed lysozyme or omitting the intermediate variables such as diabetes or hypertension generated similar results. When we adjusted for the ADS, the ORs (CI) decreased slightly to 1.00, 1.12 (0.48 to 2.62), 1.92 (0.85 to 4.34), and 3.45 (1.50 to7.93). When we adjusted for CRP using a threshold of 3 mg/L, the OR for the fourth quartile of lysozyme decreased to 2.73 (1.53 to 4.87) compared with the other 3 quartiles combined and the C-statistic also decreased, suggesting a reduced explanatory ability of CRP at 3 mg/L. Download figureDownload PowerPointOR for CHD according to the quartiles of lysosyme levels.Salivary lysozyme conferred a much stronger association with CHD than the ADS oral infection score. We hypothesize that this additional risk increase might be attributable to impaired glucose metabolism and subsequent accumulation of advanced glycation end products (AGE) as depicted in the conceptual model (Figure I, available online at http://atvb.ahajournals.org). However, this hypothesis calls for further prospective studies.Lysozyme is secreted locally, and there is no significant correlation between serum and salivary lysozyme.6 Salivary lysozyme may underscore dual pathways by which poor oral health may contribute to CHD pathogenesis.5 Poor dentition is a limiting factor for adequate intake of beneficial nutrients to prevent CHD (ie, fiber,7 antioxidants,8,9 and fruits and vegetables10). Moreover, edentulism encourages high fat and carbohydrate intake,11,12 thus, it may contribute to a higher level of AGE and subsequent CHD.13–15The conclusion of our meta-analysis,16 that persons with periodontal disease might be at a higher risk of developing cardiovascular disease, has been corroborated by several recent trials reporting that periodontal treatment decreased the level of systemic CRP17–19 and further by other immunologic studies that linked the periodontal pathogen Porphyromonas gingivalis to atherosclerosis.20–22Leukocytes may play a role in cardiopathogenesis, as Kowolik et al23 and Margolis et al24 concurred. Salivary lysozyme may be a marker for the dual contribution of oral leukocytes to cardiopathogenesis, via infection and elevated AGE deriving from an unhealthy diet.In conclusion, increased quartiles of salivary lysozyme, which may be a consequence of oral infection or impaired glucose metabolism, were associated with increasing ORs (1.00, 1.16, 1.82, and 3.62, respectively, P for trend <0.0001) for CHD after controlling for traditional CHD risk factors.Further prospective investigations are warranted to establish whether this is a causal relationship.FootnotesCorrespondence to Sok-Ja Janket, Boston University School of Dental Medicine, 100 East Newton St, Rm G-619, Boston, MA 02118. E-mail [email protected] References 1 Margolis KL, Manson JE, Greenland P, Rodabough RJ, Bray PF, Safford M, Grimm RHJ, Howard BV, Assaf AR, Prentice R. Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the Women's Health Initiative Observational Study. Arch Intern Med. 2005; 165: 500–508.CrossrefMedlineGoogle Scholar2 Suomalainen K, Saxen L, Vilja P, Tenovuo J. Peroxidases, lactoferrin and lysozyme in peripheral blood neutrophils, gingival crevicular fluid and whole saliva of patients with localized juvenile periodontitis. Oral Dis. 1996; 2: 129–134.MedlineGoogle Scholar3 Zheng F, Cai W, Mitsuhashi T, Vlassara H. Lysozyme enhances renal excretion of advanced glycation endproducts in vivo and suppresses adverse age-mediated cellular effects in vitro: a potential AGE sequestration therapy for diabetic nephropathy? Mol Med. 2001; 7: 737–747.CrossrefMedlineGoogle Scholar4 Eckel RH, Wassef M, Chait A, Sobel B, Barrett E, King G, Lopes-Virella M, Reusch J, Ruderman N, Steiner G, Vlassara H. Prevention Conference VI: Diabetes and Cardiovascular Disease: Writing Group II: pathogenesis of atherosclerosis in diabetes. Circulation. 2002; 105: e138–e143.LinkGoogle Scholar5 Janket SJ, Qvarnstrom M, Meurman JH, Baird AE, Nuutinen P, Jones JA. Asymptotic dental score and prevalent coronary heart disease. Circulation. 2004; 109: 1095–1100.LinkGoogle Scholar6 Wagner V, Wagnerova M. Lack of correlation between serum and salivary concentration levels of immunoglobulin A and lysozyme (muramidase). J Hyg Epidemiol Microbiol Immunol. 1989; 33: 353–356.MedlineGoogle Scholar7 Nowjack-Raymer RE, Sheiham A. Association of edentulism and diet and nutrition in US adults. J Dent Res. 2003; 82: 123–126.CrossrefMedlineGoogle Scholar8 Hung HC, Willett W, Ascherio A, Rosner BA, Rimm E, Joshipura KJ. Tooth loss and dietary intake. J Am Dent Assoc. 2003; 134: 1185–1192.CrossrefMedlineGoogle Scholar9 Lowe G, Woodward M, Rumley A, Morrison C, Tunstall-Pedoe H, Stephen K. Total tooth loss and prevalent cardiovascular disease in men and women: possible roles of citrus fruit consumption, vitamin C, and inflammatory and thrombotic variables. J Clin Epidemiol. 2003; 56: 694–700.CrossrefMedlineGoogle Scholar10 Joshipura KJ, Hu FB, Manson JE, Stampfer MJ, Rimm EB, Speizer FE, Colditz G, Ascherio A, Rosner B, Spiegelman D, Willett WC. The effect of fruit and vegetable intake on risk for coronary heart disease [see comment]. Ann Intern Med. 2001; 134: 1106–1114.CrossrefMedlineGoogle Scholar11 Johansson I, Tidehag P, Lundberg V, Hallmans G. Dental status, diet and cardiovascular risk factors in middle-aged people in northern Sweden. Community Dent Oral Epidemiol. 1994; 22: 431–436.CrossrefMedlineGoogle Scholar12 Janket S, Baird A, Chuang S, Jones J. Heart of the matter/a response letter to the article by Hujoel P et al. "Examining the link between coronary heart disease and the elimination of chronic dental infections." J Am Dent Assoc. 2001; 132: 1648–1650.Google Scholar13 Libby P, Plutzky J. Diabetic macrovascular disease: the glucose paradox? [comment]. Circulation. 2002; 106: 2760–2763.LinkGoogle Scholar14 Vlassara H. Recent progress in advanced glycation end products and diabetic complications. Diabetes. 1997; 46 (suppl 2): S19–S25.CrossrefMedlineGoogle Scholar15 Liu S, Willett WC. Dietary glycemic load and atherothrombotic risk. Curr Atheroscler Rep. 2002; 4: 454–461.CrossrefMedlineGoogle Scholar16 Janket S, Baird A, Chuang S, Jones JA. Meta-analysis of periodontal disease and risk of coronary heart disease and stroke. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003; 95: 559–569.CrossrefMedlineGoogle Scholar17 D'Aiuto F, Ready D, Tonetti MS. Periodontal disease and C-reactive protein-associated cardiovascular risk. J Periodontol. 2004; 39: 236–241.CrossrefGoogle Scholar18 D'Aiuto F, Parkar M, Andreou G, Brett PM, Ready D, Tonetti MS. Periodontitis and atherogenesis: causal association or simple coincidence? J Clin Periodontol. 2004; 31: 402–411.CrossrefMedlineGoogle Scholar19 Iwamoto Y, Nishimura F, Soga Y, Takeuchi K, Kurihara M, Takashiba S, Murayama Y. Antimicrobial periodontal treatment decreases serum C-reactive protein, tumor necrosis factor-alpha, but not adiponectin levels in patients with chronic periodontitis. J Periodontol. 2003; 74: 1231–1236.CrossrefMedlineGoogle Scholar20 Choi J, Chung S, Kang H, Rhim B, Kim S, Kim S. Establishment of porhyromonas gingivalis heat-shock-proteint specific T-cell line from atherosclerosis patients. J Dent Res. 2002; 81: 344–348.CrossrefMedlineGoogle Scholar21 Li L, Messas E, Batista EL Jr, Levine RA, Amar S. Porphyromonas gingivalis infection accelerates the progression of atherosclerosis in a heterozygous apolipoprotein E-deficient murine model.[erratum appears in Circulation 2002;105:1617]. Circulation. 2002; 105: 861–867.CrossrefMedlineGoogle Scholar22 Janket S, Meurman JH. Underlying chronic infection and leukocyte count [Comments/letter]. Arch Intern Med. 2005; 165: 1795.Google Scholar23 Kowolik MJ, Dowsett SA. Leukocyte response to dental plaque accumulation: a risk factor for heart disease? (letter/comments). Arch Intern Med. 2005; 165: 1795–1796.Google Scholar24 Margolis KL, Manson JE, Greenland P. Leukocyte response to dental plaque accumulation: a risk factor for heart disease? (In reply). Arch Intern Med. 2005; 165: 1796.MedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Mirza M, Sultan R, Choudhary M, Tahir M, Larsen M, Tariq S and Rahman S (2022) Label-free quantitation of the changes in salivary proteome associated with the chronic consumption of the betel nut ( Areca catechu ) , Molecular Omics, 10.1039/D1MO00391G, 18:2, (123-132) Zhang Y, Zhao Z, Kong P, Gao L, Yu Y, Liu J, Wang P, Li B, Zhang X, Yang L and Wang Z (2020) A comparative pharmacogenomic analysis of three classic TCM prescriptions for coronary heart disease based on molecular network modeling, Acta Pharmacologica Sinica, 10.1038/s41401-019-0352-3, 41:6, (735-744), Online publication date: 1-Jun-2020. Sun H, Chen Y, Zou X, Li Q, Li H, Shu Y, Li X, Li W, Han L and Ge C (2016) Salivary Secretory Immunoglobulin (SIgA) and Lysozyme in Malignant Tumor Patients, BioMed Research International, 10.1155/2016/8701423, 2016, (1-6), . 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Meurman J, Hämäläinen P and Janket S (2006) Oral infections in older adults, Aging Health, 10.2217/1745509X.2.6.1013, 2:6, (1013-1023), Online publication date: 1-Dec-2006. Jiang L, Li Y, Wang L, Guo J, Liu W, Meng G, Zhang L, Li M, Cong L and Sun M (2021) Recent Insights Into the Prognostic and Therapeutic Applications of Lysozymes, Frontiers in Pharmacology, 10.3389/fphar.2021.767642, 12 February 2006Vol 26, Issue 2 Advertisement Article InformationMetrics https://doi.org/10.1161/01.ATV.0000198249.67996.e0PMID: 16424364 Originally publishedFebruary 1, 2006 PDF download Advertisement
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