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    1 Comment for this article
    Definitions and Categorization
    Kehinde Umeizudike 1, Solomon Nwhator 2, Anna-Maria Heikkinen 3, Timo Sorsa 3 | 1 Prev. Dentistry, Univ. of Lagos, Nigeria; 2 Prev. & Com. Dent. OAU, Ile-Ife, Nigeria; 3, Helsinki University, Finland
    We read with keen interest the recently published article by Pussinen et al(1) ‘Association of Childhood Oral Infections with Cardiovascular Risk Factors and Subclinical Atherosclerosis in Adulthood’ in which a significant association was reported between an increasing number of oral infections in childhood and increased carotid intima-media thickness (CIMT) in adulthood. We however, have some concerns.

    First, how did they periodontal health/disease? The authors defined periodontal disease as ‘gingival bleeding on probing and periodontal probing pocket depths’. The new case definition of periodontal disease by Trombelli et al(2) diagnosed a gingivitis case as BOP score ≥ 10% as
    % BOP sites helps to differentiate between a healthy and gingivitis patient.(3) Furthermore, Nwhator et al(4) demonstrated the high sensitivity of BOP sites with aMMP-8 assay. Their patients appeared to be periodontally healthy with little or no deepened pockets but mainly BOP. The main oral problem may therefore be oral health behaviour, including ineffective oral hygiene habits.

    Secondly, the authors categorized periodontal probing pocket depth into shallow (2-5.9 mm) and deep pockets (6 mm). What was their basis for this categorization? Their data did not clearly demonstrate the presence of deep periodontal pockets. It therefore seems that the subclinical atherosclerosis may be associated predominantly with weak oral hygiene instructions rather than oral infections/periodontal diseases. In the latest classification of periodontitis, staging and grading are essential components includes tooth loss.(5) A clear staging might give a better association between periodontal disease and CIMT.

    Thirdly, no infections and/or infectious agents were identified, neither did they consider the role of proinflammatory biomarkers. Using an oral hygiene index would have helped to elucidate the direct effect of plaque biofilms on subclinical atherosclerosis. A direct correlation has already been established between poor oral hygiene and periodontal inflammation (4) using aMMP-8 immunoassay (96% sensitive for poor oral hygiene) an important trigger in oral inflections and in oral-systemic link. We propose the use of a validated, simple salivary aMMP-8 assay as a more sensitive marker for subclinical atherosclerosis (CIMT) in oral infections.

    The authors received no financial support and declare no potential conflicts of interest with respect to the authorship and/or publication of this article. Timo Sorsa is an inventor of US-patents 5652227, 5736341, 5866432, and 6143476. Timo Sorsa and Dirk-Rolf Gieselmann are inventors of patent 20170023571.

    1.Pussinen PJ, Paju S, Koponen J, Viikari JSA, Taittonen L, Laitinen T, Burgner DP, Kähönen M, Hutri-Kähönen N, Raitakari OT, Juonala M. Association of Childhood Oral Infections with Cardiovascular Risk Factors and Subclinical Atherosclerosis in Adulthood. JAMA Netw Open. 2019;2(4):e192523.
    2.Trombelli L, Farina R, Silva CO, Tatakis DN. Plaque-induced gingivitis: Case definition and diagnostic considerations. J Clin Periodontol. 2018;45 Suppl 20:S44-S67.
    3.Lang NP, Bartold PM. Periodontal health. J Periodontol. 2018;89 Suppl 1:S9–S16.
    4.Nwhator SO, Ayanbadejo PO, Umeizudike KA, Opeodu OI, Agbelusi GA, Olamijulo JA, Arowojolu MO, Sorsa T, Babajide BS, Opedun DO. Clinical Correlates of A Lateral Flow Immunoassay Oral Risk Indicator. J Periodontol. 2014:85(1):188-194.
    5. Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Periodontol. 2018;89 Suppl 1:S159-S172.
    Original Investigation
    April 26, 2019

    Association of Childhood Oral Infections With Cardiovascular Risk Factors and Subclinical Atherosclerosis in Adulthood

    Author Affiliations
    • 1Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
    • 2Department of Medicine, University of Turku, Turku, Finland
    • 3Division of Medicine, Turku University Hospital, Turku, Finland
    • 4Vaasa Central Hospital, Vaasa, Finland
    • 5Department of Clinical Physiology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
    • 6Royal Children’s Hospital, Parkville, Victoria, Australia
    • 7Murdoch Childrens Research Institute, Parkville, Victoria, Australia
    • 8Department of Clinical Physiology, Tampere University Hospital and University of Tampere, Tampere, Finland
    • 9Department of Pediatrics, University of Tampere and Tampere University Hospital, Tampere, Finland
    • 10Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
    • 11Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
    JAMA Netw Open. 2019;2(4):e192523. doi:10.1001/jamanetworkopen.2019.2523
    Key Points español 中文 (chinese)

    Question  Are childhood oral infections or inflammatory conditions associated with the risk of adulthood subclinical atherosclerosis?

    Findings  In this cohort study of 755 participants followed up for 27 years into adulthood, a number of clinical signs of oral infections in childhood were associated with both cumulative exposure to cardiovascular risk factors during the follow-up and subclinical atherosclerosis in adulthood.

    Meaning  Childhood oral infections may be a modifiable risk factor for adult cardiovascular disease.


    Importance  Severe forms of common chronic oral infections or inflammations are associated with increased cardiovascular risk in adults. To date, the role of childhood oral infections in cardiovascular risk is not known because no long-term studies have been conducted.

    Objective  To investigate whether signs of oral infections in childhood are associated with cardiovascular risk factors and subclinical atherosclerosis in adulthood.

    Design, Setting, and Participants  The cohort study (n = 755) was derived from the Cardiovascular Risk in Young Finns Study, an ongoing prospective cohort study in Finland initiated in 1980. Participants underwent clinical oral examinations during childhood, when they were aged 6, 9, or 12 years and a clinical cardiovascular follow-up in adulthood in 2001 at age 27, 30, or 33 years and/or in 2007 at age 33, 36, or 39 years. Cardiovascular risk factors were measured at baseline and during the follow-up until the end of 2007. Final statistical analyses were completed on February 19, 2019.

    Main Outcomes and Measures  Four signs of oral infections (bleeding on probing, periodontal probing pocket depth, caries, and dental fillings) were documented. Cumulative lifetime exposure to 6 cardiovascular risk factors was calculated from dichotomized variables obtained by using the area-under-the-curve method. Subclinical atherosclerosis (ie, carotid artery intima-media thickness [IMT]) was quantified in 2001 (n = 468) and 2007 (n = 489).

    Results  This study included 755 participants, of whom 371 (49.1%) were male; the mean (SD) age at baseline examination was 8.07 (2.00) years. In this cohort, 33 children (4.5%) had no sign of oral infections, whereas 41 (5.6%) had 1 sign, 127 (17.4%) had 2 signs, 278 (38.3%) had 3 signs, and 248 (34.1%) had 4 signs. The cumulative exposure to risk factors increased with the increasing number of oral infections both in childhood and adulthood. In multiple linear regression models, childhood oral infections, including signs of either periodontal disease (R2 = 0.018; P = .01), caries (R2 = 0.022; P = .008), or both (R2 = 0.024; P = .004), were associated with adulthood IMT. The presence of any sign of oral infection in childhood was associated with increased IMT (third tertile vs tertiles 1 and 2) with a relative risk of 1.87 (95% CI, 1.25-2.79), whereas the presence of all 4 signs produced a relative risk of 1.95 (95% CI, 1.28-3.00). The associations were more obvious in boys: if periodontal disease were present, the corresponding estimate was 1.69 (95% CI, 1.21-2.36); if caries, 1.46 (95% CI, 1.04-2.05); and if all 4 signs of oral infections, 2.25 (95% CI, 1.30-3.89). The associations were independent of cardiovascular risk factors.

    Conclusions and Relevance  Oral infections in childhood appear to be associated with the subclinical carotid atherosclerosis seen in adulthood.