© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
J Periodont Res 2015; 50: 173–179 All rights reserved
JOURNAL OF PERIODONTAL RESEARCH doi:10.1111/jre.12190
Original Article
Relationship between metabolic syndrome and periodontitis in 80-year-old Japanese subjects
K. Minagawa1, M. Iwasaki1, H. Ogawa1, A. Yoshihara2, H. Miyazaki1 1
Division of Preventive Dentistry, Department of Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan and 2Division of Oral Science for Health Promotion, Department of Oral Health and Welfare Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Minagawa K, Iwasaki M, Ogawa H, Yoshihara A, Miyazaki H. Relationship between metabolic syndrome and periodontitis in 80-year-old Japanese subjects. J Periodont Res 2015; 50: 173–179. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Background and Objective: Potentially significant associations between metabolic syndrome (MetS) and periodontitis have been reported in recent studies; however, there are limited data on their association in the very old. The aim of this cross-sectional study was to investigate the association between MetS and periodontitis among 80-year-old Japanese subjects. Material and Methods: The subjects were 234 Japanese aged 80 years old who participated in a health and periodontal examination in June 2008 in Niigata city, Japan, and were classified into three groups: (i) severe periodontitis: having six or more interproximal sites with clinical attachment level ≥ 6 mm and three or more interproximal sites with probing pocket depth (PPD) ≥ 5 mm (not on the same tooth) (n = 19); (ii) moderate periodontitis: having six or more interproximal sites with clinical attachment level ≥ 4 mm or six or more interproximal sites with PPD ≥ 5 mm (not on the same tooth) (n = 162); and (iii) no or mild periodontitis: neither “moderate” nor “severe” periodontitis (n = 53). MetS was defined using the modified criteria of the guidelines for the diagnosis of MetS in Japan. An ordinal logistic regression model was used to evaluate the association between MetS and periodontitis. Adjustments for gender, income, education, smoking status, dental visiting patterns, brushing frequency, exercise habits and dietary energy and food intake were considered. Results: Overall, 57 individuals (24.4%) were diagnosed as having MetS. MetS was associated with the presence and severity of periodontitis (crude odds ratio = 2.24, 95% confidence interval = 1.14–4.41). This association remained statistically significant after multivariate adjustments (adjusted odds ratio = 2.10, 95% confidence interval = 1.03–4.28). Conclusion: Our findings provide evidence of an association between MetS and periodontitis in elderly Japanese.
Metabolic syndrome (MetS) is characterized as a clustering of metabolic disorders: abdominal obesity, hyper-
glycemia, elevated blood pressure (BP) and dyslipidemia. It is associated with a high risk for the development of
Kumiko Minagawa, DDS, Department of Oral Health Science, Division of Preventive Dentistry, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-Dori, Chuo-Ku, Niigata, 951-8514, Japan Tel: +81 25 227 2858 Fax: +81 25 227 0807 e-mail: [email protected] Key words: elderly; epidemiology; metabolic
syndrome; periodontitis Accepted for publication March 11, 2014
cardiovascular disease (CVD) and type 2 diabetes mellitus (1); therefore, it has attracted attention from many fields.
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Individual components of MetS have been reported as risk factors for periodontitis (2–5). Potentially significant associations between MetS and periodontitis have been also reported in recent studies. Individuals with MetS had a higher risk for a poor periodontal status (6–9). However, these previous studies targeted the age group of 40–75 years and, to the best of our knowledge, no study has looked at the relationship between periodontitis and the MetS, in the older elderly over 75 years old. Japan has become a super-aged society. In 2010, there were 14,220,000 people (11.2% of the total population) over the age of 75. Increasing age is an important risk factor for both MetS and periodontitis (10). In the National Health and Nutrition Survey Japan 2011 of people aged 75 years or over, the prevalence of MetS was 28.7% (11). In the Survey of Dental Diseases 2011 of people aged 75 years or over, the prevalence of periodontitis was 44.9% (12). In view of these observations, we considered that it is important to investigate the relationship between periodontitis and MetS in older Japanese. This may lead to better understanding of the relationship between periodontitis and systemic disease in the elderly. The aim of this crosssectional study was to investigate the association between MetS and periodontitis among 80-year-old Japanese subjects. Specifically, the present study investigated whether the prevalence of periodontitis is found to be more frequent and severe in individuals with MetS than in individuals without it.
Material and methods Study population
Cross-sectional data in June 2008 were derived from the Niigata Study. Briefly, the Niigata Study is a community-based cohort study initiated in 1998 to evaluate relationships between systemic health and oral health. In April 1998, all 4542 Niigata (Japan) citizens aged 70 years (2099 men and 2443 women) were sent a written
request to participate in the survey. The invitation was mailed again to non-respondents 3 wk later and, consequently, 81.4% (n = 3695) responded positively to participate in the survey. Considering the availability of resources, examination appointments could be arranged for 600 individuals. The final study sample was randomly recruited from several areas of Niigata to have an approximately equal number of men (n = 306) and women (n = 294). Participants had undergone annual follow-up examinations during 1999–2008 (13). During 1998–2008, 241 of the 600 original participants were not available for the current study due to the following reasons: (i) 122 refused, (ii) 31 were hospitalized, (iii) 80 had died and (iv) eight had moved out of Niigata City. Therefore, 359 individuals who turned 70 in 1998 and were 80 years of age in 2008 were enrolled in to the current study. They underwent dental and medical examinations, anthropometric evaluations, dietary intake assessment and interviews. Eight subjects who did not submit complete data were excluded, leaving 351 subjects; 234 (111 men and 123 women) with at least 10 teeth (6,14) of these 351 subjects were selected for participation in the analyses. The participants in the study agreed to undergo medical and dental examinations, and signed informed consent forms regarding the protocol, which was reviewed and approved by the Ethics Committee of the Faculty of Dentistry, Niigata University.
Hospital. As determined by replicate examinations of 10 patients, the percentage agreement (1 mm) ranged from 87.5% to 100% for PPD and from 83.3% to 100% for clinical attachment level. The j ranged from 0.81 to 1.00 for PPD and from 0.74 to 1.00 for the clinical attachment level. Following the American Academy of Periodontology/Centers for Disease Control and Prevention (AAP/CDC) definition for periodontitis (15) with modification, the subjects were classified into three groups: (i) severe periodontitis: having six or more interproximal sites with clinical attachment level ≥ 6 mm and three or more interproximal sites with PPD ≥ 5 mm (not on the same tooth) (n = 19); (ii) moderate periodontitis: having six or more interproximal sites with clinical attachment level ≥ 4 mm or six or more interproximal sites with PPD ≥ 5 mm (not on the same tooth) (n = 162); and (iii) no or mild periodontitis: neither “moderate” nor “severe” periodontitis (n = 53). Because increasing age is a major risk factor for periodontal disease, we decided not to apply the original AAP/CDC definition to this very old study population. Preliminary analysis revealed that the prevalence of moderate or severe periodontitis based on the original AAP/CDC definition was over 92%. A nationwide survey in Japan reported that the prevalence of moderate or severe periodontitis in people 80–84 years of age was 56.9% (12).
Dental examination
Medical examination, anthropometric evaluation, dietary intake assessment and interview
The periodontal examination included the assessment of probing pocket depth (PPD) and clinical attachment level at six sites around each tooth. Probing was performed using a pressure constant probe (Vivacare TPS Probe; Vivacare, Schaan, Liechtenstein) at a probing force of 20 g and rounded to the nearest whole millimeter. The periodontal examination was carried out by four trained dentists under sufficient illumination using artificial light. Calibration of the examiners was carried out using volunteer patients at the Faculty
Fasting blood samples were drawn for the measurement of hemoglobin A1c (HbA1c), total cholesterol, highdensity lipoprotein cholesterol and triglyceride. BP recordings were obtained from the right arm of the participants in a sitting position after 5 min of rest. Waist circumference was measured with a soft tape on standing participants midway between the lowest rib and the iliac crest. Dietary habits during the preceding month were assessed with a validated
Metabolic syndrome and periodontitis food frequency questionnaire (16). Estimates of dietary intakes of total energy and food groups (rice, fruit and vegetables) were calculated using an ad hoc computer algorithm for the food frequency questionnaire, which was based on the Standard Tables of Food Composition in Japan (17). A standardized questionnaire was completed, covering the participants’ current and previous medication, exercise habits, smoking status, with those reporting any smoking history classified as smokers, socio-economic status (household income and years of school attendance) and oral health-related behavior (brushing frequency [< 2 times/d or ≥ 2 times/d], pattern of visits to a dentist [regularly or episodically]). Participants who currently exercise (> 30 min per session, two times per week and prolonged duration for 3 mo) were classified as participants taking regular exercise (18). Lower income was defined as annual household income < 2,000,000 Japanese Yen, and lower education was defined as school attendance ≤ 8 years. MetS was defined using the modified criteria of the guidelines for the diagnosis of MetS in Japan (19): defined by the presence of central obesity for which waist circumference of ≥ 85 cm for men and ≥ 90 cm for women is an essential component, accompanied by the presence of at least two of the following three risk factors: hyperglycemia, elevated BP and dyslipidemia. Hyperglycemia was defined as HbA1c ≥6.0% and/or the current use of antidiabetic medications. HbA1c was used as a surrogate for fasting plasma glucose to define hyperglycemia (20). Elevated BP was defined as systolic/diastolic BPs of 130/85 mm Hg and/or the current use of antihypertensive medications (21). Dyslipidemia was defined as triglycerides ≥ 150 mg/dL and/or high-density lipoprotein-cholesterol < 40 mg/dL and/or the current use of antidyslipidemic medications. Statistical analyses
The participants’ variables were described using frequency distribution
for categorical variables and the mean SD for continuous variables. The chi-squared test for categorical variables and analysis of variance for continuous variables were used to test differences in the percentages and the means of selected characteristics among different study groups. Tests of the study’s principal hypothesis – that MetS is associated with periodontitis – included ordinal logistic regression modeling. The primary outcome of the analyses was the three-category periodontitis variable with no or mild periodontitis as the reference category. The principal exposure variable included MetS coded as a binary variable. We added gender, income, education, smoking status, pattern of visits to a dentist, brushing frequency, exercise habits and dietary energy and food intake as covariates in multivariate analyses based on previous studies (6,7,22). Ordinal regression analysis was conducted according to the cumulative
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proportionality method. The proportional odds assumption was tested using Brant’s test (23). As a part of the sensitivity analysis, linear regression analyses were performed, including average PPD and average clinical attachment level as secondary outcome measures (6,24). Tests of normality using the Shapiro– Wilk test revealed that PPD and clinical attachment level outcome variables were not normally distributed; therefore, log10 transformed variables were used to achieve a distribution that is more symmetric. The level of significance for predictor variables was set at p < 0.05. All calculations and statistical analyses were performed with the STATA software package (Stata Corp., College Station, TX, USA).
Results The selected characteristics of the participants were classified by MetS
Table 1. Selected characteristics of the study participants with and without MetS MetS No 177 (75.6%) Dental conditions No. of teeth 21.2 5.9 Demographic and socio-economic status 80 Ageb Gender Men 74 (66.7) Women 103 (83.7) Lower income 23 (74.2) Lower education 69 (76.7) Health behavior Smoking status Non-smoker 125 (79.6) Previous smoker 44 (68.8) Current smoker 8 (61.5) Toothbrushing ≥ 2 times/d 130 (77.8) Visit dentist regularly 108 (77.7) Exercise regularly 54 (71.1) Dietary intake Energy (kcal/d) 2077.5 643.9 Rice (g/d) 248.2 126.5 Vegetables (g/d) 402.1 217.7 Fruit (g/d) 160.3 99.5
Yes 57 (24.4%)
pa
21.2 5.4
0.959
80
–
37 20 8 21
(33.3) (16.3) (25.8) (23.3)
0.002
32 20 5 37 31 22
(20.4) (31.2) (38.5) (22.2) (22.3) (29.0)
0.111
1992.9 237.9 376.3 135.0
0.84 0.773
0.215 0.375 0.257
582.9 125.1 170.9 96.5
0.379 0.591 0.416 0.086
Continuous variables are expressed as the mean standard division; categorical variables, as n (percentage). Bold text highlights statistically significant findings. a P value for the comparison of selected characteristics by the status of MetS. b All participants were 80 years of age. MetS, metabolic syndrome.
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Table 2. Relationships of MetS and its components with periodontitis in the ordinal regression analyses Periodontitis No or mild n = 53
Moderate n = 162
MetS No 26.0 67.2 Yes 12.3 75.4 MetS components Abdominal obesity No 26.3 66.7 Yes 19.2 71.7 Hyperglycemia or medication use No 23.3 70.0 Yes 20.3 66.7 Elevated BP or medication use No 25.4 64.4 Yes 21.7 70.8 Dyslipidemia or medication use No 26.2 65.8 Yes 16.5 75.3
Severe n = 19
ORcrude (95% CI)
ORadjusteda (95% CI)
6.8 12.3
Referent group 2.24 (1.14–4.41)
Referent group 2.10 (1.03–4.28)
7.0 9.2
Referent group 1.46 (0.84–2.53)
Referent group 1.12 (0.62–2.06)
6.7 13.0
Referent group 1.44 (0.73–2.81)
Referent group 1.42 (0.71–2.84)
10.2 7.4
Referent group 1.06 (0.56–2.00)
Referent group 1.10 (0.55–2.15)
8.1 8.2
Referent group 1.52 (0.85–2.71)
Referent group 1.61 (0.88–2.96)
Proportional odds assumption statistics: Brant’s test, p = 0.274 for MetS, 0.274 for abdominal obesity, 0.221 for hyperglycemia, 0.217 for elevated BP and 0.224 for dyslipidemia, respectively. Frequency distribution of periodontitis in relation to MetS and its components’ status is expressed as a percentage. Bold text highlights statistically significant findings. a Adjusted for gender, income, education, smoking status, pattern of visits to a dentist, brushing frequency, exercise habits and dietary energy and food intake. BP, blood pressure; CI, confidence interval; MetS, metabolic syndrome; OR, odds ratio.
status (Table 1). The prevalence of MetS was 24.4%. Men had a higher prevalence of MetS than women did (33.3% vs. 16.3%; p = 0.002). Table 2 shows the results of ordinal regression analyses. In the univariate model, MetS was associated with the level of periodontitis (odds ratio [OR] = 2.24, 95% confidence interval [CI] = 1. 14–4.41]. This statistically significant association remained after adjustment for possible confounders. In the multivariate model, the adjusted OR for participants with MetS was 2.10 (95% CI = 1.03–4.28). There were no significant associations of each MetS components with the level of periodontitis. The overall average PPD and clinical attachment level values were 2.07 (SD = 0.41) and 3.14 (SD = 0.79), respectively. Table 3 shows the results of linear regression analyses. MetS was significantly associated with periodontitis assessed as average PPD. After adjusting for possible confounders, the study participants with MetS showed a
significantly higher average PPD (b coefficients = 0.027, p = 0.028) than those without MetS (Table 3). In unadjusted analyses, MetS was associated significantly with average clinical attachment level (b coefficients = 0.034, p = 0.030); however, this significant association disappeared after adjustment for confounders. There were no significant associations of each MetS component with average PPD or clinical attachment level.
Discussion In this study, an association was found between MetS and periodontitis among 80-year-old Japanese subjects after adjusting for their socioeconomic status and health behavior. This finding concurs with recent studies, although early epidemiologic studies included very few elderly participants. Shimazaki et al. (6) conducted a survey of 584 men and women (mean age = 55.7) among the Japan population. Kushiyama et al.
(7) investigated this relationship among 1070 Japanese aged 40– 70 years old in Miyazaki city. Fukui et al. (9) performed a survey targeting 6421 people aged 34–77 years in Japan. These studies reported that MetS had a significant association with periodontitis. The present study confirms previous findings and contributes additional evidence that suggests the association between MetS and periodontitis among the older age group. When the components of MetS were examined separately, there were no significant associations of each MetS component with the level of periodontitis, which was partly explained by the fact that each individual component includes a variety of conditions, ranging from mild to severe, resulting in underestimation of the observed association between MetS components and periodontitis. A combination of multiple risk factors (abdominal obesity, hyperglycemia, elevated BP and dyslipidemia) can lead to periodontitis. Recent studies have suggested that MetS can increase the risk of adverse outcomes significantly, even in the elderly (25–28). Butler et al. and He et al. found a higher risk of developing CVD in older subjects with MetS than in those without MetS. Wang et al. recently observed that MetS predicted congestive heart failure independent of interim myocardial infarction in the elderly (29). Additionally, MetS correlated with CVD in elderly diabetics (27). As the present study focused on the “older-elderly,” defined as those aged 80 years, the results convey the important message that MetS is associated with oral health even among the “very old” elderly population, and thus highlight that preventing MetS is important across the entire lifespan. We chose not to apply the original AAP/CDC definition to this very old study population because preliminary analysis revealed that the prevalence of moderate or severe periodontitis based on the original AAP/CDC definition was over 92%. A nationwide survey in Japan reported that the prevalence of moderate or severe periodontitis in people 80–84 years of age was 56.9% (12). This divergence may
Metabolic syndrome and periodontitis
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Table 3. Relationships of MetS and its components with PPD and CAL in linear regression analyses Average PPDa
Average CALa Adjustedb
Crude B MetS (yes vs. no) MetS components (yes vs. no) Abdominal obesity Hyperglycemia or medication use Elevated BP or medication use Dyslipidemia or medication use
SE
p
0.030
0.012
0.012
0.018 0.022 0.013 0.013
0.010 0.012 0.012 0.011
0.087 0.078 0.297 0.240
B
Adjustedb
Crude SE
p
B
SE
p
0.027
0.012
0.028
0.034
0.016
0.030
0.015 0.024 0.015 0.008
0.011 0.012 0.012 0.011
0.173 0.081 0.221 0.449
0.011 0.012 0.009 0.009
0.014 0.016 0.016 0.016
0.398 0.442 0.578 0.578
B
SE
p
0.024
0.016
0.126
0.007 0.011 0.010 0.012
0.014 0.016 0.016 0.014
0.625 0.492 0.533 0.410
Bold text highlights statistically significant findings. a Values were log10 transformed before analyses. b Adjusted for gender, income, education, smoking status, pattern of visits to a dentist brushing frequency, exercise habits and dietary energy and food intake. B, difference in the adjusted means of periodontal parameters between one group and the reference group; BP, blood pressure; CAL, clinical attachment level; MetS, metabolic syndrome; PPD, probing pocket depth; SE, standard error of the estimate (b).
be explained by the fact that increasing age is a major risk factor for periodontal disease (30). According to the periodontitis criteria used in this study, more than nine teeth are needed to define periodontitis. In addition, the current study included average PPD and clinical attachment level as secondary outcome measures. In the previous study using average PPD as the major outcome (31), researchers stated that they excluded subjects with fewer than 10 teeth from the study because of the inherent difficulties in properly assessing periodontal health in these patients. Among the elderly, not only periodontal disease, but also dental caries are the major reasons for tooth loss (32). As the history of dental treatment was not collected in this study, it was difficult to include subjects with experience of tooth loss due to periodontal disease in the analyses. Based on the above, we decided not to include individuals with fewer than 10 teeth in the current study. A previous study investigating the association of periodontitis and MetS (6) also excluded subjects with < 10 teeth from the analyses. There are several possible explanations for the finding of the current study. High-sensitivity C-reactive protein and proinflammatory cytokines, such as tumor necrosis factor alpha and interleukins 6 and 1, have been reported as elevated in patients with MetS (33–37). At a local level, these
mediators are also known to contribute to periodontal tissue destruction and bone resorption (38). Therefore, individuals with MetS may tend to be hyperresponsive to inflammation and hence more susceptible to periodontitis in the presence of periodontal pathogens. Oxidative stress could add evidence to elucidate the mechanism of the link between MetS and periodontitis. It is generally accepted that the origin of MetS is in a “proinflammatory” state derived from excessive caloric intake, overnutrition and other chronic inflammatory conditions (39–41). The proinflammatory status leads to an increase in oxidative stress, which may contribute to periodontal tissue destruction by damaging DNA and proteins, causing lipid peroxidation and oxidation of other enzymes (e.g. antiproteases), and stimulating proinflammatory mediators through activation of the transcription factors nuclear factor-jb and activator protein 1 (42–44). Several studies have demonstrated an increase in the products of oxidative damage in peripheral blood from persons with periodontitis (45,46). On the other hand, reduced antioxidant capacity was found in those with periodontitis (47). Periodontal conditions are significantly associated with the frequency of toothbrushing, regular dental visits and smoking history (48–51). Thus, negative lifestyle habits may aggravate periodontal disease as well as health
conditions such as abdominal obesity, dyslipidemia, hypertension and hyperglycemia. The strengths of this study include the examination of a homogeneous group of Japanese elderly, which eliminated the influences of variations in race and gender on our results. On the other hand, there were several limitations of our study. First, the subjects were from a convenient cohort who participated in this survey voluntarily and may not fully represent the general Japanese population. During 1998–2008, 241 of the 600 original participants were not available for the current study; therefore, 359 individuals who turned 70 in 1998 and were 80 years of age in 2008 were enrolled in the current study. Of these 351 subjects, 234 with at least 10 teeth were selected for participation in the analyses. Therefore, the subjects who were included in this study may be biased. Generally, the individuals that responded positively and participated long term tended to be healthier than the general population (52). Although our study has important implications for the association between MetS and periodontitis, the results based on this single study should be interpreted with some caution, as this selection bias may lead to over- or underestimation of the true association. Second, we analyzed only subjects with ≥ 10 teeth; thus, the relationship between MetS and periodontitis among subjects with few teeth,
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including edentulous subjects, was unclear. Third, at the beginning of the Niigata study (when the participants were 70 years old), we did not collect information that was necessary to diagnose MetS, such as waist circumstance and serum lipid profile. Therefore, we could not design a longitudinal study to evaluate the association between periodontitis and MetS using Niigata study data. The cross-sectional design prevented us from assessing the temporal relationship and establishing causality. Fourth, only 19 participants were defined as having severe periodontitis. Two types of errors have to be considered; however, this would not lead to overestimation of the observed associations. Finally, because other information regarding participants’ oral health status (e.g. dental plaque scores, subgingival biofilm and history of dental treatment) and the diagnosis of diseases previously recognized as relevant to MetS were not collected, a number of other potentially important confounders could not be included in the analyses. Residual confounding remains a risk. In summary, the findings of the present study suggest that MetS is significantly associated with periodontitis among 80-year-old Japanese subjects. Additional longitudinal epidemiological studies with larger, more diversified samples and more complete information are needed to further evaluate the relationship between these two diseases.
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Acknowledgements This work was supported by a grantin-aid from the Ministry of Health and Welfare of Japan (H10-Iryo-001, H13-Iryo-001 and H16-Iryo-020) and a grant-in-aid for Young Scientists (B) (23792504). The authors declare no conflicts of interest in the publication of this paper.
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J Periodont Res 2015; 50: 173–179 All rights reserved
JOURNAL OF PERIODONTAL RESEARCH doi:10.1111/jre.12190
Original Article
Relationship between metabolic syndrome and periodontitis in 80-year-old Japanese subjects
K. Minagawa1, M. Iwasaki1, H. Ogawa1, A. Yoshihara2, H. Miyazaki1 1
Division of Preventive Dentistry, Department of Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan and 2Division of Oral Science for Health Promotion, Department of Oral Health and Welfare Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Minagawa K, Iwasaki M, Ogawa H, Yoshihara A, Miyazaki H. Relationship between metabolic syndrome and periodontitis in 80-year-old Japanese subjects. J Periodont Res 2015; 50: 173–179. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Background and Objective: Potentially significant associations between metabolic syndrome (MetS) and periodontitis have been reported in recent studies; however, there are limited data on their association in the very old. The aim of this cross-sectional study was to investigate the association between MetS and periodontitis among 80-year-old Japanese subjects. Material and Methods: The subjects were 234 Japanese aged 80 years old who participated in a health and periodontal examination in June 2008 in Niigata city, Japan, and were classified into three groups: (i) severe periodontitis: having six or more interproximal sites with clinical attachment level ≥ 6 mm and three or more interproximal sites with probing pocket depth (PPD) ≥ 5 mm (not on the same tooth) (n = 19); (ii) moderate periodontitis: having six or more interproximal sites with clinical attachment level ≥ 4 mm or six or more interproximal sites with PPD ≥ 5 mm (not on the same tooth) (n = 162); and (iii) no or mild periodontitis: neither “moderate” nor “severe” periodontitis (n = 53). MetS was defined using the modified criteria of the guidelines for the diagnosis of MetS in Japan. An ordinal logistic regression model was used to evaluate the association between MetS and periodontitis. Adjustments for gender, income, education, smoking status, dental visiting patterns, brushing frequency, exercise habits and dietary energy and food intake were considered. Results: Overall, 57 individuals (24.4%) were diagnosed as having MetS. MetS was associated with the presence and severity of periodontitis (crude odds ratio = 2.24, 95% confidence interval = 1.14–4.41). This association remained statistically significant after multivariate adjustments (adjusted odds ratio = 2.10, 95% confidence interval = 1.03–4.28). Conclusion: Our findings provide evidence of an association between MetS and periodontitis in elderly Japanese.
Metabolic syndrome (MetS) is characterized as a clustering of metabolic disorders: abdominal obesity, hyper-
glycemia, elevated blood pressure (BP) and dyslipidemia. It is associated with a high risk for the development of
Kumiko Minagawa, DDS, Department of Oral Health Science, Division of Preventive Dentistry, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-Dori, Chuo-Ku, Niigata, 951-8514, Japan Tel: +81 25 227 2858 Fax: +81 25 227 0807 e-mail: [email protected] Key words: elderly; epidemiology; metabolic
syndrome; periodontitis Accepted for publication March 11, 2014
cardiovascular disease (CVD) and type 2 diabetes mellitus (1); therefore, it has attracted attention from many fields.
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Individual components of MetS have been reported as risk factors for periodontitis (2–5). Potentially significant associations between MetS and periodontitis have been also reported in recent studies. Individuals with MetS had a higher risk for a poor periodontal status (6–9). However, these previous studies targeted the age group of 40–75 years and, to the best of our knowledge, no study has looked at the relationship between periodontitis and the MetS, in the older elderly over 75 years old. Japan has become a super-aged society. In 2010, there were 14,220,000 people (11.2% of the total population) over the age of 75. Increasing age is an important risk factor for both MetS and periodontitis (10). In the National Health and Nutrition Survey Japan 2011 of people aged 75 years or over, the prevalence of MetS was 28.7% (11). In the Survey of Dental Diseases 2011 of people aged 75 years or over, the prevalence of periodontitis was 44.9% (12). In view of these observations, we considered that it is important to investigate the relationship between periodontitis and MetS in older Japanese. This may lead to better understanding of the relationship between periodontitis and systemic disease in the elderly. The aim of this crosssectional study was to investigate the association between MetS and periodontitis among 80-year-old Japanese subjects. Specifically, the present study investigated whether the prevalence of periodontitis is found to be more frequent and severe in individuals with MetS than in individuals without it.
Material and methods Study population
Cross-sectional data in June 2008 were derived from the Niigata Study. Briefly, the Niigata Study is a community-based cohort study initiated in 1998 to evaluate relationships between systemic health and oral health. In April 1998, all 4542 Niigata (Japan) citizens aged 70 years (2099 men and 2443 women) were sent a written
request to participate in the survey. The invitation was mailed again to non-respondents 3 wk later and, consequently, 81.4% (n = 3695) responded positively to participate in the survey. Considering the availability of resources, examination appointments could be arranged for 600 individuals. The final study sample was randomly recruited from several areas of Niigata to have an approximately equal number of men (n = 306) and women (n = 294). Participants had undergone annual follow-up examinations during 1999–2008 (13). During 1998–2008, 241 of the 600 original participants were not available for the current study due to the following reasons: (i) 122 refused, (ii) 31 were hospitalized, (iii) 80 had died and (iv) eight had moved out of Niigata City. Therefore, 359 individuals who turned 70 in 1998 and were 80 years of age in 2008 were enrolled in to the current study. They underwent dental and medical examinations, anthropometric evaluations, dietary intake assessment and interviews. Eight subjects who did not submit complete data were excluded, leaving 351 subjects; 234 (111 men and 123 women) with at least 10 teeth (6,14) of these 351 subjects were selected for participation in the analyses. The participants in the study agreed to undergo medical and dental examinations, and signed informed consent forms regarding the protocol, which was reviewed and approved by the Ethics Committee of the Faculty of Dentistry, Niigata University.
Hospital. As determined by replicate examinations of 10 patients, the percentage agreement (1 mm) ranged from 87.5% to 100% for PPD and from 83.3% to 100% for clinical attachment level. The j ranged from 0.81 to 1.00 for PPD and from 0.74 to 1.00 for the clinical attachment level. Following the American Academy of Periodontology/Centers for Disease Control and Prevention (AAP/CDC) definition for periodontitis (15) with modification, the subjects were classified into three groups: (i) severe periodontitis: having six or more interproximal sites with clinical attachment level ≥ 6 mm and three or more interproximal sites with PPD ≥ 5 mm (not on the same tooth) (n = 19); (ii) moderate periodontitis: having six or more interproximal sites with clinical attachment level ≥ 4 mm or six or more interproximal sites with PPD ≥ 5 mm (not on the same tooth) (n = 162); and (iii) no or mild periodontitis: neither “moderate” nor “severe” periodontitis (n = 53). Because increasing age is a major risk factor for periodontal disease, we decided not to apply the original AAP/CDC definition to this very old study population. Preliminary analysis revealed that the prevalence of moderate or severe periodontitis based on the original AAP/CDC definition was over 92%. A nationwide survey in Japan reported that the prevalence of moderate or severe periodontitis in people 80–84 years of age was 56.9% (12).
Dental examination
Medical examination, anthropometric evaluation, dietary intake assessment and interview
The periodontal examination included the assessment of probing pocket depth (PPD) and clinical attachment level at six sites around each tooth. Probing was performed using a pressure constant probe (Vivacare TPS Probe; Vivacare, Schaan, Liechtenstein) at a probing force of 20 g and rounded to the nearest whole millimeter. The periodontal examination was carried out by four trained dentists under sufficient illumination using artificial light. Calibration of the examiners was carried out using volunteer patients at the Faculty
Fasting blood samples were drawn for the measurement of hemoglobin A1c (HbA1c), total cholesterol, highdensity lipoprotein cholesterol and triglyceride. BP recordings were obtained from the right arm of the participants in a sitting position after 5 min of rest. Waist circumference was measured with a soft tape on standing participants midway between the lowest rib and the iliac crest. Dietary habits during the preceding month were assessed with a validated
Metabolic syndrome and periodontitis food frequency questionnaire (16). Estimates of dietary intakes of total energy and food groups (rice, fruit and vegetables) were calculated using an ad hoc computer algorithm for the food frequency questionnaire, which was based on the Standard Tables of Food Composition in Japan (17). A standardized questionnaire was completed, covering the participants’ current and previous medication, exercise habits, smoking status, with those reporting any smoking history classified as smokers, socio-economic status (household income and years of school attendance) and oral health-related behavior (brushing frequency [< 2 times/d or ≥ 2 times/d], pattern of visits to a dentist [regularly or episodically]). Participants who currently exercise (> 30 min per session, two times per week and prolonged duration for 3 mo) were classified as participants taking regular exercise (18). Lower income was defined as annual household income < 2,000,000 Japanese Yen, and lower education was defined as school attendance ≤ 8 years. MetS was defined using the modified criteria of the guidelines for the diagnosis of MetS in Japan (19): defined by the presence of central obesity for which waist circumference of ≥ 85 cm for men and ≥ 90 cm for women is an essential component, accompanied by the presence of at least two of the following three risk factors: hyperglycemia, elevated BP and dyslipidemia. Hyperglycemia was defined as HbA1c ≥6.0% and/or the current use of antidiabetic medications. HbA1c was used as a surrogate for fasting plasma glucose to define hyperglycemia (20). Elevated BP was defined as systolic/diastolic BPs of 130/85 mm Hg and/or the current use of antihypertensive medications (21). Dyslipidemia was defined as triglycerides ≥ 150 mg/dL and/or high-density lipoprotein-cholesterol < 40 mg/dL and/or the current use of antidyslipidemic medications. Statistical analyses
The participants’ variables were described using frequency distribution
for categorical variables and the mean SD for continuous variables. The chi-squared test for categorical variables and analysis of variance for continuous variables were used to test differences in the percentages and the means of selected characteristics among different study groups. Tests of the study’s principal hypothesis – that MetS is associated with periodontitis – included ordinal logistic regression modeling. The primary outcome of the analyses was the three-category periodontitis variable with no or mild periodontitis as the reference category. The principal exposure variable included MetS coded as a binary variable. We added gender, income, education, smoking status, pattern of visits to a dentist, brushing frequency, exercise habits and dietary energy and food intake as covariates in multivariate analyses based on previous studies (6,7,22). Ordinal regression analysis was conducted according to the cumulative
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proportionality method. The proportional odds assumption was tested using Brant’s test (23). As a part of the sensitivity analysis, linear regression analyses were performed, including average PPD and average clinical attachment level as secondary outcome measures (6,24). Tests of normality using the Shapiro– Wilk test revealed that PPD and clinical attachment level outcome variables were not normally distributed; therefore, log10 transformed variables were used to achieve a distribution that is more symmetric. The level of significance for predictor variables was set at p < 0.05. All calculations and statistical analyses were performed with the STATA software package (Stata Corp., College Station, TX, USA).
Results The selected characteristics of the participants were classified by MetS
Table 1. Selected characteristics of the study participants with and without MetS MetS No 177 (75.6%) Dental conditions No. of teeth 21.2 5.9 Demographic and socio-economic status 80 Ageb Gender Men 74 (66.7) Women 103 (83.7) Lower income 23 (74.2) Lower education 69 (76.7) Health behavior Smoking status Non-smoker 125 (79.6) Previous smoker 44 (68.8) Current smoker 8 (61.5) Toothbrushing ≥ 2 times/d 130 (77.8) Visit dentist regularly 108 (77.7) Exercise regularly 54 (71.1) Dietary intake Energy (kcal/d) 2077.5 643.9 Rice (g/d) 248.2 126.5 Vegetables (g/d) 402.1 217.7 Fruit (g/d) 160.3 99.5
Yes 57 (24.4%)
pa
21.2 5.4
0.959
80
–
37 20 8 21
(33.3) (16.3) (25.8) (23.3)
0.002
32 20 5 37 31 22
(20.4) (31.2) (38.5) (22.2) (22.3) (29.0)
0.111
1992.9 237.9 376.3 135.0
0.84 0.773
0.215 0.375 0.257
582.9 125.1 170.9 96.5
0.379 0.591 0.416 0.086
Continuous variables are expressed as the mean standard division; categorical variables, as n (percentage). Bold text highlights statistically significant findings. a P value for the comparison of selected characteristics by the status of MetS. b All participants were 80 years of age. MetS, metabolic syndrome.
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Table 2. Relationships of MetS and its components with periodontitis in the ordinal regression analyses Periodontitis No or mild n = 53
Moderate n = 162
MetS No 26.0 67.2 Yes 12.3 75.4 MetS components Abdominal obesity No 26.3 66.7 Yes 19.2 71.7 Hyperglycemia or medication use No 23.3 70.0 Yes 20.3 66.7 Elevated BP or medication use No 25.4 64.4 Yes 21.7 70.8 Dyslipidemia or medication use No 26.2 65.8 Yes 16.5 75.3
Severe n = 19
ORcrude (95% CI)
ORadjusteda (95% CI)
6.8 12.3
Referent group 2.24 (1.14–4.41)
Referent group 2.10 (1.03–4.28)
7.0 9.2
Referent group 1.46 (0.84–2.53)
Referent group 1.12 (0.62–2.06)
6.7 13.0
Referent group 1.44 (0.73–2.81)
Referent group 1.42 (0.71–2.84)
10.2 7.4
Referent group 1.06 (0.56–2.00)
Referent group 1.10 (0.55–2.15)
8.1 8.2
Referent group 1.52 (0.85–2.71)
Referent group 1.61 (0.88–2.96)
Proportional odds assumption statistics: Brant’s test, p = 0.274 for MetS, 0.274 for abdominal obesity, 0.221 for hyperglycemia, 0.217 for elevated BP and 0.224 for dyslipidemia, respectively. Frequency distribution of periodontitis in relation to MetS and its components’ status is expressed as a percentage. Bold text highlights statistically significant findings. a Adjusted for gender, income, education, smoking status, pattern of visits to a dentist, brushing frequency, exercise habits and dietary energy and food intake. BP, blood pressure; CI, confidence interval; MetS, metabolic syndrome; OR, odds ratio.
status (Table 1). The prevalence of MetS was 24.4%. Men had a higher prevalence of MetS than women did (33.3% vs. 16.3%; p = 0.002). Table 2 shows the results of ordinal regression analyses. In the univariate model, MetS was associated with the level of periodontitis (odds ratio [OR] = 2.24, 95% confidence interval [CI] = 1. 14–4.41]. This statistically significant association remained after adjustment for possible confounders. In the multivariate model, the adjusted OR for participants with MetS was 2.10 (95% CI = 1.03–4.28). There were no significant associations of each MetS components with the level of periodontitis. The overall average PPD and clinical attachment level values were 2.07 (SD = 0.41) and 3.14 (SD = 0.79), respectively. Table 3 shows the results of linear regression analyses. MetS was significantly associated with periodontitis assessed as average PPD. After adjusting for possible confounders, the study participants with MetS showed a
significantly higher average PPD (b coefficients = 0.027, p = 0.028) than those without MetS (Table 3). In unadjusted analyses, MetS was associated significantly with average clinical attachment level (b coefficients = 0.034, p = 0.030); however, this significant association disappeared after adjustment for confounders. There were no significant associations of each MetS component with average PPD or clinical attachment level.
Discussion In this study, an association was found between MetS and periodontitis among 80-year-old Japanese subjects after adjusting for their socioeconomic status and health behavior. This finding concurs with recent studies, although early epidemiologic studies included very few elderly participants. Shimazaki et al. (6) conducted a survey of 584 men and women (mean age = 55.7) among the Japan population. Kushiyama et al.
(7) investigated this relationship among 1070 Japanese aged 40– 70 years old in Miyazaki city. Fukui et al. (9) performed a survey targeting 6421 people aged 34–77 years in Japan. These studies reported that MetS had a significant association with periodontitis. The present study confirms previous findings and contributes additional evidence that suggests the association between MetS and periodontitis among the older age group. When the components of MetS were examined separately, there were no significant associations of each MetS component with the level of periodontitis, which was partly explained by the fact that each individual component includes a variety of conditions, ranging from mild to severe, resulting in underestimation of the observed association between MetS components and periodontitis. A combination of multiple risk factors (abdominal obesity, hyperglycemia, elevated BP and dyslipidemia) can lead to periodontitis. Recent studies have suggested that MetS can increase the risk of adverse outcomes significantly, even in the elderly (25–28). Butler et al. and He et al. found a higher risk of developing CVD in older subjects with MetS than in those without MetS. Wang et al. recently observed that MetS predicted congestive heart failure independent of interim myocardial infarction in the elderly (29). Additionally, MetS correlated with CVD in elderly diabetics (27). As the present study focused on the “older-elderly,” defined as those aged 80 years, the results convey the important message that MetS is associated with oral health even among the “very old” elderly population, and thus highlight that preventing MetS is important across the entire lifespan. We chose not to apply the original AAP/CDC definition to this very old study population because preliminary analysis revealed that the prevalence of moderate or severe periodontitis based on the original AAP/CDC definition was over 92%. A nationwide survey in Japan reported that the prevalence of moderate or severe periodontitis in people 80–84 years of age was 56.9% (12). This divergence may
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Table 3. Relationships of MetS and its components with PPD and CAL in linear regression analyses Average PPDa
Average CALa Adjustedb
Crude B MetS (yes vs. no) MetS components (yes vs. no) Abdominal obesity Hyperglycemia or medication use Elevated BP or medication use Dyslipidemia or medication use
SE
p
0.030
0.012
0.012
0.018 0.022 0.013 0.013
0.010 0.012 0.012 0.011
0.087 0.078 0.297 0.240
B
Adjustedb
Crude SE
p
B
SE
p
0.027
0.012
0.028
0.034
0.016
0.030
0.015 0.024 0.015 0.008
0.011 0.012 0.012 0.011
0.173 0.081 0.221 0.449
0.011 0.012 0.009 0.009
0.014 0.016 0.016 0.016
0.398 0.442 0.578 0.578
B
SE
p
0.024
0.016
0.126
0.007 0.011 0.010 0.012
0.014 0.016 0.016 0.014
0.625 0.492 0.533 0.410
Bold text highlights statistically significant findings. a Values were log10 transformed before analyses. b Adjusted for gender, income, education, smoking status, pattern of visits to a dentist brushing frequency, exercise habits and dietary energy and food intake. B, difference in the adjusted means of periodontal parameters between one group and the reference group; BP, blood pressure; CAL, clinical attachment level; MetS, metabolic syndrome; PPD, probing pocket depth; SE, standard error of the estimate (b).
be explained by the fact that increasing age is a major risk factor for periodontal disease (30). According to the periodontitis criteria used in this study, more than nine teeth are needed to define periodontitis. In addition, the current study included average PPD and clinical attachment level as secondary outcome measures. In the previous study using average PPD as the major outcome (31), researchers stated that they excluded subjects with fewer than 10 teeth from the study because of the inherent difficulties in properly assessing periodontal health in these patients. Among the elderly, not only periodontal disease, but also dental caries are the major reasons for tooth loss (32). As the history of dental treatment was not collected in this study, it was difficult to include subjects with experience of tooth loss due to periodontal disease in the analyses. Based on the above, we decided not to include individuals with fewer than 10 teeth in the current study. A previous study investigating the association of periodontitis and MetS (6) also excluded subjects with < 10 teeth from the analyses. There are several possible explanations for the finding of the current study. High-sensitivity C-reactive protein and proinflammatory cytokines, such as tumor necrosis factor alpha and interleukins 6 and 1, have been reported as elevated in patients with MetS (33–37). At a local level, these
mediators are also known to contribute to periodontal tissue destruction and bone resorption (38). Therefore, individuals with MetS may tend to be hyperresponsive to inflammation and hence more susceptible to periodontitis in the presence of periodontal pathogens. Oxidative stress could add evidence to elucidate the mechanism of the link between MetS and periodontitis. It is generally accepted that the origin of MetS is in a “proinflammatory” state derived from excessive caloric intake, overnutrition and other chronic inflammatory conditions (39–41). The proinflammatory status leads to an increase in oxidative stress, which may contribute to periodontal tissue destruction by damaging DNA and proteins, causing lipid peroxidation and oxidation of other enzymes (e.g. antiproteases), and stimulating proinflammatory mediators through activation of the transcription factors nuclear factor-jb and activator protein 1 (42–44). Several studies have demonstrated an increase in the products of oxidative damage in peripheral blood from persons with periodontitis (45,46). On the other hand, reduced antioxidant capacity was found in those with periodontitis (47). Periodontal conditions are significantly associated with the frequency of toothbrushing, regular dental visits and smoking history (48–51). Thus, negative lifestyle habits may aggravate periodontal disease as well as health
conditions such as abdominal obesity, dyslipidemia, hypertension and hyperglycemia. The strengths of this study include the examination of a homogeneous group of Japanese elderly, which eliminated the influences of variations in race and gender on our results. On the other hand, there were several limitations of our study. First, the subjects were from a convenient cohort who participated in this survey voluntarily and may not fully represent the general Japanese population. During 1998–2008, 241 of the 600 original participants were not available for the current study; therefore, 359 individuals who turned 70 in 1998 and were 80 years of age in 2008 were enrolled in the current study. Of these 351 subjects, 234 with at least 10 teeth were selected for participation in the analyses. Therefore, the subjects who were included in this study may be biased. Generally, the individuals that responded positively and participated long term tended to be healthier than the general population (52). Although our study has important implications for the association between MetS and periodontitis, the results based on this single study should be interpreted with some caution, as this selection bias may lead to over- or underestimation of the true association. Second, we analyzed only subjects with ≥ 10 teeth; thus, the relationship between MetS and periodontitis among subjects with few teeth,
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including edentulous subjects, was unclear. Third, at the beginning of the Niigata study (when the participants were 70 years old), we did not collect information that was necessary to diagnose MetS, such as waist circumstance and serum lipid profile. Therefore, we could not design a longitudinal study to evaluate the association between periodontitis and MetS using Niigata study data. The cross-sectional design prevented us from assessing the temporal relationship and establishing causality. Fourth, only 19 participants were defined as having severe periodontitis. Two types of errors have to be considered; however, this would not lead to overestimation of the observed associations. Finally, because other information regarding participants’ oral health status (e.g. dental plaque scores, subgingival biofilm and history of dental treatment) and the diagnosis of diseases previously recognized as relevant to MetS were not collected, a number of other potentially important confounders could not be included in the analyses. Residual confounding remains a risk. In summary, the findings of the present study suggest that MetS is significantly associated with periodontitis among 80-year-old Japanese subjects. Additional longitudinal epidemiological studies with larger, more diversified samples and more complete information are needed to further evaluate the relationship between these two diseases.
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Acknowledgements This work was supported by a grantin-aid from the Ministry of Health and Welfare of Japan (H10-Iryo-001, H13-Iryo-001 and H16-Iryo-020) and a grant-in-aid for Young Scientists (B) (23792504). The authors declare no conflicts of interest in the publication of this paper.
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