Several modifiable lifestyles are said to be associated with cardiovascular diseases. For instance, cigarette smoking was well evaluated, and previous studies demonstrated that those who smoked more than 20 pack-years had a three-fold to six-fold higher risk of myocardial infarction than did those who had never smoked [1,2]. Similarly, low physical activity was associated with a higher incidence of cardiovascular diseases [3,4] through weight gain , increased cholesterol [6,7], blood pressure , or impaired glucose tolerance. [7,9] Evidence is mixed in terms of alcohol consumption. A previous systematic review/meta-analysis showed that alcohol drinkers had a 25% reduction in cardiovascular diseases compared to nonalcohol drinkers . However, other systematic reviews showed neither an increased nor decreased risk of cardiovascular disease among alcohol drinkers compared to nondrinkers [11,12]. Although the conclusions for some lifestyles were controversial, major lifestyles were well evaluated for their associations with cardiovascular diseases.
As with other modifiable lifestyles related to cardiovascular risk, a limited number of studies have evaluated the association between the frequency of tooth brushing and cardiovascular risk factors. A previous study in Japan reported that the risk of metabolic syndrome has decreased as the frequency of daily tooth brushing increased by 40–50% among the middle-aged population [13,14]. Adolescents who brushed their teeth at least once a day were reported to have lower low-density lipoprotein (LDL) cholesterol and higher high-density lipoprotein (HDL) cholesterol compared to those who reported a lower frequency of brushing . As a result, a low frequency of tooth brushing was associated with endothelial dysfunction . Although the current large-scale population-based study showed an inverse association between the frequency of tooth brushing and cardiovascular risk factors , additional studies are still needed on the association between the frequency of tooth brushing and cardiovascular events.
The aim of this study was to evaluate the association between the frequency of daily tooth brushing and subsequent cardiovascular events in a large dataset.
A retrospective longitudinal study was conducted at St. Luke’s International Hospital, a large teaching hospital in Tokyo, Japan. We included all participants who underwent health check-ups at the Center for Preventive Medicine in the hospital from 2005 to 2011 and followed up to 31 December 2018. We excluded those who had a history of cardiovascular events at their first visits. In addition, participants were excluded if they did not provide consent for the use of their anonymized data in this study. The frequency of daily tooth brushing was obtained as a part of the questionnaire in the check-ups. Our primary outcome was the development of cardiovascular events, and our secondary outcomes were the development of acute coronary syndrome and stroke. These outcomes were compared based on the frequency of daily tooth brushing, with adjustments made for potential confounders.
The Ethics Committee Institutional Review Board at St. Luke’s International Hospital approved this study (18-R203).
We defined cardiovascular events as the composite events of any acute coronary syndrome and stroke. The cardiovascular events were clinically diagnosed by each physician in the hospital, and the information was extracted from electronic medical records according to the International Classification of Disease (ICD)-10 . In addition, information about the outcomes diagnosed outside of the hospital was obtained based on participants’ self-reports. Outcome data were obtained from participants’ first visit through 31 December 2018. When participants developed outcomes two or more times, we only used the data from the outcome of the first episode.
Frequency of daily tooth brushing
All participants were asked about frequency of daily tooth brushing as a part of questionnaire in the health check-ups from 2005 to 2012 [translated from Japanese: ‘How many times do you brush your teeth in a typical day? (not every day, once a day, once to twice a day, and after every meal.)’]. In this questionnaire, ‘once a day’ meant that participants brushed their teeth once a day in most days, whereas ‘once to twice a day’ meant that participants brushed their teeth once or twice depending on the day. We classified the participants into four groups based on their answers. Among them, we excluded those who brushed their teeth not every day at baseline, because very limited number of them were observed [only 200 (0.3%) participants]. We defined those who brushed their teeth after every meal as the reference group.
We obtained information about participants’ demographics, social history, physical examinations, and comorbidities as part of the health check-ups at baseline and at the follow-up visits, as these variables could be potential confounders between the exposure and the outcomes. Age and gender were obtained as demographic data. Social history included self-reports of alcohol consumption (abstainer, occasional drinker, and regular drinker), cigarette smoking (never smoker, former smoker, and current smoker), and exercise habits (almost none, 1–2 times a week, 3–5 times a week, and almost every day) at each visit. A history of hypertension, diabetes, and dyslipidemia was taken, as these conditions may be cardiovascular disease-related comorbidities. BMI was calculated based on height and weight measurements performed by trained staff; BMI measurements were then classified into three groups based on the WHO criteria for the Asian population [underweight (<18.5 kg/m2), normal (18.5–24.9 kg/m2), and obese/overweight (25.0 kg/m2 or more)] . All of these data were treated as time-dependent variables to account for changes in conditions, lifestyles, and comorbidities.
First, we compared baseline participants’ characteristics and outcomes according to the frequency of tooth brushing. As bivariable analyses for characteristics by frequency of tooth brushing, analysis of variance and chi-square tests were used. Then, we performed longitudinal analyses with follow-up data for outcomes using the generalized estimating equation (binominal family, logit link function, and unstructured working correlation). Adjusted odds ratios (ORs) were calculated, with those who brushed their teeth after every meal as the reference group. Different models included different covariates to examine the consistency of the findings through the models [20–24]: model 1 included the frequency of daily tooth brushing and the time variable; model 2 included the participant’s age and gender in addition to model 1; model 3 included social histories and BMI in addition to model 2; and model 4 included comorbidities in addition to model 3.
All analyses were performed using STATA 14 (STATA Corp., College Station, Texas, USA).
A total of 71 221 participants were included in our study. The mean age was 45.6 (SD 12.2) years and 35 842 (50.3%) participants were male. Baseline participant characteristics by frequency of tooth brushing are shown in Table 1. Those who brushed their teeth less often tended to be male and obese/overweight. In terms of social history, those who brushed their teeth less often tended to have unfavorable habits, such as more regular alcohol consumption and current smoking and less frequent exercise. Similarly, unfavorable trends were observed in all comorbidities and their related measures.
During median follow-up of 2061(interquartile range: 933–3311) days, 1905 participants (1030 were based on ICD-10 code, 875 were based on participants’ self-report) developed cardiovascular events (acute coronary syndrome: 1149; stroke: 761; both: 5). Table 2 shows the adjusted ORs of outcomes for each tooth brushing frequency group. The adjusted ORs of cardiovascular events increased in a dose-dependent manner as the frequency of tooth brushing decreased compared to those who brushed their teeth after every meal. Specifically, those who brushed their teeth once a day had significantly higher adjusted ORs compared to those who brushed their teeth after every meal in model 1, but not in model 4 (the adjusted OR, 1.28; 95% confidence interval (CI), 1.23–1.56 in the model 1; the adjusted OR, 1.11; 95% CI, 0.98–1.26 in the model 4). Although the group comprised of those who brushed their teeth once a day showed trends of higher ORs for secondary outcomes than did the group comprised of those who brushed their teeth after every meal, this finding was more obvious for stroke than for acute coronary syndrome (the adjusted OR, 1.22; 95% CI, 1.01–1.48 for stroke in model 4).
Our longitudinal study showed a dose-dependent inverse association between the frequency of tooth brushing and subsequent cardiovascular events. Statistically higher adjusted ORs of cardiovascular events were observed only in the less adjusted model, but not in the full adjusted model among those who brushes their teeth once a day compared to those who brushed their teeth after every meal. Participants who brushed their teeth once a day may have an increased risk only for stroke, but not for acute coronary syndrome, compared to those who brushed their teeth after every meal.
We hypothesized two potential mechanisms in the inverse association. One of the mechanisms was that cardiovascular events had increased among people who brushed their teeth less frequently, mediating periodontal diseases . A previous systematic review demonstrated that patients with periodontal diseases had a relative risk of coronary heart diseases that was 1.24–1.35 times higher than that of those without periodontal diseases . It was said that periodontal diseases caused chronic inflammation and increased several inflammation markers, such as C-reactive protein , resulting in coronary heart diseases [27–29]. However, it may be insufficient to explain the inverse association between the frequency of tooth brushing and cardiovascular events by only the mediation of periodontal diseases because most people have periodontal diseases (more than 80% of those aged 35 or older in Japan  and 75% of adults in the USA ) in the general population. In addition, the magnitude of risk for cardiovascular events in our study was different from that in previous studies of periodontal diseases . Therefore, we cannot determine whether the inverse association can be attributed only to periodontal diseases.
Another potential mechanism was that people who brushed their teeth frequently may have advanced health awareness, resulting in the prevention of cardiovascular events. Favorable dental health awareness and oral hygiene behavior have been found to be related to high socioeconomic status, including better health-related habits . Another previous community cluster randomized trial demonstrated that a population-level health awareness program improved cardiovascular health awareness and reduced cardiovascular morbidity . Therefore, people who have advanced health awareness may prefer to engage in both frequent tooth brushing and behavior that promotes cardiovascular health. In other words, frequency of tooth brushing may be considered as the potential marker of cardiovascular disease and coronary heart disease. In fact, our study found non-significant increased OR for cardiovascular disease and coronary heart disease among participants who brushed their teeth once a day compared to those who did after every meal in the fully adjusted model, although they were significant in the model adjusted only for demographic data.
Our study had a unique categorization of the frequency of tooth brushing compared to previous studies. One unique characteristic in our sample was that approximately 45% of participants brushed their teeth after every meal. Most previous study populations were composed of people who brushed their teeth less frequently than our study population (e.g. the maximum frequency of tooth brushing was twice daily in a Scottish study ). Given that there were very few significant differences in outcomes between brushing one’s teeth after every meal and brushing one’s teeth once or twice a day, the additional benefits may be limited even if people brush their teeth three times a day. In other words, at least once to twice a day tooth brushing depending on the day, but more than once a day would be recommended to be favorable conditions in cardiovascular disease.
It was unclear why the development of stroke was more obvious than that of acute coronary syndrome in its association with the frequency of tooth brushing, even though the number of events was greater in acute coronary syndrome than in stroke. The risk factors may differ somewhat between acute coronary syndrome and stroke , differentiating the magnitude of the impact of the frequency of tooth brushing on each secondary outcome. Given that a previous large-scale study also reported that the estimated incidence of stroke was higher than that of acute coronary syndrome , this finding may indicate the true association.
Our study had some limitations. First, unrecognized covariates related to both the frequency of tooth brushing and cardiovascular events may exist, although we adjusted for potential covariates related to cardiovascular events as much as possible in our study. Another limitation was that we lacked information about periodontal diseases. However, as we discussed above, most Japanese individuals have been shown to have periodontal diseases, and the bias from the diseases may not be critical. Our data involved only the frequency of tooth brushing, not the quality of tooth brushing or the duration of tooth brushing. Given that a previous study reported that the duration of tooth brushing was also associated with increased risk factors , the lack of this information in the present study may bias the results.
Frequent tooth brushing was inversely associated with subsequent cardiovascular events in a dose-dependent manner. Even brushing one’s teeth once a day may be related to an increased likelihood of stroke than brushing one’s teeth after every meal. Less frequent tooth brushing may be considered to be a marker for subsequent cardiovascular disease and coronary heart disease, rather than a risk factor.
Conflicts of interest
There are no conflicts of interest.
1. Prescott E, Hippe M, Schnohr P, Hein HO, Vestbo J. Smoking and risk of myocardial infarction in women and men: longitudinal population study. BMJ. 1998; 316:1043–1047
2. Njølstad I, Arnesen E, Lund-Larsen PG. Smoking, serum lipids, blood pressure, and sex differences in myocardial infarction. A 12-year follow-up of the Finnmark study. Circulation. 1996; 93:450–456
3. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al.; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004; 364:937–952
4. Leon AS, Connett J, Jacobs DR Jr, Rauramaa R. Leisure-time physical activity levels and risk of coronary heart disease and death. The multiple risk factor intervention trial. JAMA. 1987; 258:2388–2395
5. Swift DL, Johannsen NM, Lavie CJ, Earnest CP, Church TS. The role of exercise and physical activity in weight loss and maintenance. Prog Cardiovasc Dis. 2014; 56:441–447
6. O’Donovan G, Stensel D, Hamer M, Stamatakis E. The association between leisure-time physical activity, low HDL-cholesterol and mortality
in a pooled analysis of nine population-based cohorts. Eur J Epidemiol. 2017; 32:559–566
7. Barlow CE, Defina LF, Radford NB, Berry JD, Cooper KH, Haskell WL, et al. Cardiorespiratory fitness and long-term survival in “low-risk” adults. J Am Heart Assoc. 2012; 1:e001354
8. Pal S, Radavelli-Bagatini S, Ho S. Potential benefits of exercise on blood pressure and vascular function. J Am Soc Hypertens. 2013; 7:494–506
9. Balk EM, Earley A, Raman G, Avendano EA, Pittas AG, Remington PL. Combined diet and physical activity promotion programs to prevent type 2 diabetes among persons at increased risk: a systematic review for the community preventive services task force. Ann Intern Med. 2015; 163:437–451
10. Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA. Association of alcohol consumption with selected cardiovascular disease
outcomes: a systematic review and meta-analysis. BMJ. 2011; 342:d671
11. Collaborators GBDA. Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2018; 392:1015–1035
12. Wood AM, Kaptoge S, Butterworth AS, Willeit P, Warnakula S, Bolton T, et al.; Emerging Risk Factors Collaboration/EPIC-CVD/UK Biobank Alcohol Study Group. Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. Lancet. 2018; 391:1513–1523
13. Tsutsumi C, Kakuma T. Regular tooth brushing
is associated with a decreased risk of metabolic syndrome according to a medical check-up database. Kurume Med J. 2015; 61:43–52
14. Tanaka A, Takeuchi K, Furuta M, Takeshita T, Suma S, Shinagawa T, et al. Relationship of toothbrushing to metabolic syndrome in middle-aged adults. J Clin Periodontol. 2018; 45:538–547
15. Kelishadi R, Mirmoghtadaee P, Qorbani M, Motlagh ME, Heshmat R, Taslimi M, et al. Tooth brushing
and cardiometabolic risk factors in adolescents: is there an association? The CASPIAN-III study. Int J Prev Med. 2013; 4:271–278
16. Matsui S, Kajikawa M, Maruhashi T, Iwamoto Y, Iwamoto A, Oda N, et al. Decreased frequency and duration of tooth brushing
is a risk factor for endothelial dysfunction. Int J Cardiol. 2017; 241:30–34
17. Park SY, Kim SH, Kang SH, Yoon CH, Lee HJ, Yun PY, et al. Improved oral hygiene care attenuates the cardiovascular risk of oral health disease: a population-based study from Korea. Eur Heart J. 2019; 40:1138–1145
18. World Health Organization. The International Classification of Diseases. 2016. http://www.who.int/classifications/icd/icdonlineversions/en/
. [Accessed 26 March 2019]
19. Consultation WHOE. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004; 363:157–163
20. Sotos-Prieto M, Bhupathiraju SN, Mattei J, Fung TT, Li Y, Pan A, et al. Association of changes in diet quality with total and cause-specific mortality
. N Engl J Med. 2017; 377:143–153
21. Gauderman WJ, Avol E, Gilliland F, Vora H, Thomas D, Berhane K, et al. The effect of air pollution on lung development from 10 to 18 years of age. N Engl J Med. 2004; 351:1057–1067
22. Lee D, Choi WJ, Oh JS, Yi MK, Han SW, Yun JW, Han SH. The relevance of hyperuricemia and metabolic syndrome and the effect of blood lead level on uric acid concentration in steelmaking workers. Ann Occup Environ Med. 2013; 25:27
23. Zelle DM, Corpeleijn E, Deinum J, Stolk RP, Gans RO, Navis G, Bakker SJ. Pancreatic β-cell dysfunction and risk of new-onset diabetes after kidney transplantation. Diabetes Care. 2013; 36:1926–1932
24. Mallamaci F, Minutolo R, Leonardis D, D’Arrigo G, Tripepi G, Rapisarda F, et al. Long-term visit-to-visit office blood pressure variability increases the risk of adverse cardiovascular outcomes in patients with chronic kidney disease. Kidney Int. 2013; 84:381–389
25. Humphrey LL, Fu R, Buckley DI, Freeman M, Helfand M. Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis. J Gen Intern Med. 2008; 23:2079–2086
26. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease
in women. N Engl J Med. 2000; 342:836–843
27. Wu T, Trevisan M, Genco RJ, Falkner KL, Dorn JP, Sempos CT. Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. Am J Epidemiol. 2000; 151:273–282
28. Kweider M, Lowe GD, Murray GD, Kinane DF, McGowan DA. Dental disease, fibrinogen and white cell count; links with myocardial infarction? Scott Med J. 1993; 38:73–74
29. 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
30. Japanese Ministry of Health, Labour and Welfare. Survey of Dental Diseases (2011). 2011. https://www.mhlw.go.jp/toukei/list/dl/62-17c23-1.pdf
. [Accessed 31 March 2019]
31. Brown LJ, Brunelle JA, Kingman A. Periodontal status in the United States, 1988–1991: prevalence, extent, and demographic variation. J Dent Res. 1996; 75:672–683
32. Shekar BC, Reddy C, Manjunath B, Suma S. Dental health awareness, attitude, oral health-related habits, and behaviors in relation to socio-economic factors among the municipal employees of Mysore city. Annals of Tropical Medicine and Public Health. 2011; 4:99–99
33. Kaczorowski J, Chambers LW, Dolovich L, Paterson JM, Karwalajtys T, Gierman T, et al. Improving cardiovascular health at population level: 39 community cluster randomised trial of cardiovascular health awareness program (CHAP). BMJ. 2011; 342:d442
34. de Oliveira C, Watt R, Hamer M. Toothbrushing, inflammation, and risk of cardiovascular disease
: results from Scottish Health Survey. BMJ. 2010; 340:c2451
35. Naito R, Miyauchi K, Nojiri S, Suzuki N, Daida H; PACIFIC Investigators and the EVEREST Investigators. Differences in clinical features in patients with acute coronary syndrome and stroke: Japanese multicenter registry results. Intern Med. 2018; 57:3233–3240