ABSTRACT
Oral diseases and masticatory dysfunction are more prevalent in hypertensive patients and may hinder blood pressure (BP) control during pharmacological treatment. However, the effect of the oral function on cardiovascular outcomes in patients with poorly controlled hypertension remains unclear. A total of 5 484 middle‐aged and older hypertensive patients receiving antihypertensive medications without prior cardiovascular diseases (CVD) (mean age: 67.5 ± 8.0 years) were followed to investigate incident CVD. Cox proportional hazards models were used to examine associations between the baseline oral status (number of remaining teeth and denture use) and the risk of developing CVD, stratified by BP control status. Poorly controlled BP was defined as systolic BP (SBP) ≥ 130 mmHg or diastolic BP ≥ 80 mmHg. Over a mean follow‐up period of 9.9 ± 2.7 years, 567 individuals (10.3%) experienced CVD events. In the poorly controlled BP group, tooth loss and non‐use of dentures were significantly associated with an increased risk of CVD; the hazard ratios (95% confidence intervals) were 1.79 (1.28–2.48) for 10–19 teeth, 1.37 (0.97–1.94) for 1–9 teeth with denture use, 1.56 (1.13–2.17) for no teeth with denture use, and 2.17 (1.30–3.64) for 0–9 teeth with non‐use of dentures, compared with ≥20 teeth. This association differed significantly between the poorly controlled and well‐controlled BP groups (P for interaction = 0.016). In conclusion, tooth loss and non‐use of dentures are associated with a higher risk of CVD among adults with poorly controlled hypertension, suggesting that BP control status under treatment modifies this association.
Keywords: blood pressure, cardiovascular, denture use, hypertension, tooth loss
1. Introduction
Oral diseases represent a major global public health challenge, with a rising prevalence particularly in low‐ and middle‐income communities [1]. Despite being largely preventable, they affect over 3.5 billion people worldwide [2]. Approximately 22% of middle‐aged and older adults (≥45 years) have lost their teeth [3], with periodontitis being the primary cause [2].
Previous cross‐sectional and longitudinal studies have demonstrated associations of periodontal disease and tooth loss with elevated blood pressure (BP) [4, 5]. Meta‐analyses indicate that individuals with greater tooth loss tend to have higher SBP and a higher incidence of hypertension than those with fewer missing teeth [6]. Recent evidence suggests that oral diseases may contribute to unsuccessful antihypertensive management. For example, treated hypertensive adults with periodontitis exhibit approximately 2.3–3.0 mmHg higher mean SBP [7]. Additionally, the association between oral diseases and cardiovascular disease (CVD) risk, previously reported in the general population and in patients with type 2 diabetes or established CVD, has recently been confirmed in hypertensive individuals [8, 9, 10, 11, 12, 13, 14, 15]. Furthermore, interventions targeting oral diseases significantly reduced BP and improved CVD risk markers, including systemic inflammation, left ventricular mass, and arterial stiffness, in patients with resistant hypertension [16].
Based on these observations, we hypothesized that oral diseases are associated with an increased risk of CVD among individuals with poorly controlled BP despite antihypertensive therapy. Clarifying this hypothesis may help identify hypertensive patients who would benefit most from oral health interventions. It may also promote medical‐dental collaboration to extend healthy life expectancy. Therefore, we conducted this study to investigate the association between oral status and incident CVD in patients receiving antihypertensive medication.
2. Methods
2.1. Study Participants
The Iwate–Kenpoku cohort (Iwate–KENCO) study was a population‐based prospective study conducted in the Ninohe, Kuji, and Miyako districts of northern Iwate Prefecture, located in northeastern Honshu, Japan. Participants were recruited through a government‐regulated health checkup program conducted between April 2002 and January 2005 [17].
Of the 26 469 individuals who consented to participate, 5 484 were included in the analysis after applying the following exclusion criteria: age under 40 years (n = 1 100); non‐use of antihypertensive medication (n = 17 118); a history of CVD (myocardial infarction or stroke; n = 937); or missing data for key covariates (n = 1 888). This study protocol was approved by the institutional ethics committee, and written informed consent was obtained from all participants.
2.2. Data Collection and Measurements
BP was measured twice using an automatic digital sphygmomanometer after the participants had rested for 5 min in a seated position. The mean of the two measurements was used for the subsequent analysis. Body mass index (BMI) was calculated as weight (kg) divided by height squared (m2). Participants completed a self‐administered questionnaire documenting their medical history, including the number of remaining natural teeth, current medications, and lifestyle factors such as smoking and alcohol consumption. Information on the number of natural teeth and denture use was obtained through structured interviews conducted by trained investigators at baseline. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation, modified by a Japanese coefficient [18]. Serum high‐sensitivity C‐reactive protein (hsCRP) levels were measured using the Behring latex‐enhanced CRP assay on a Behring nephelometer BN‐100 (Dade Behring, Deerfield, IL, USA). The detection limit for hsCRP was 0.1 mg/L; values below this threshold were set to 0.1 mg/L.
2.3. Risk Factor Definitions
Participants were classified into five groups based on the number of remaining teeth and denture use at baseline: (1) 0–9 teeth without dentures; (2) edentulous with dentures; (3) 1–9 teeth with dentures; (4) 10–19 teeth; and (5) ≥20 teeth. Furthermore, as a sensitivity analysis, participants were classified into four groups based solely on the number of remaining teeth: (1) edentulous; (2) 1–9 teeth; (3) 10–19 teeth; and (4) ≥20 teeth. According to the American College of Cardiology (ACC)/American Heart Association (AHA) guideline for the prevention, detection, evaluation, and management of high BP in adults [19], participants were categorized into two BP control groups: well‐controlled BP (SBP < 130 mmHg and DBP < 80 mmHg) and poorly controlled BP (SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg). Diabetes mellitus was defined as a random blood glucose level ≥ 200 mg/dL, a fasting blood glucose level ≥ 126 mg/dL, a glycosylated hemoglobin (HbA1c, NGSP‐equivalent) level ≥ 6.5%, and/or current use of antidiabetic medication. Dyslipidemia was defined as total cholesterol ≥240 mg/dL, high‐density lipoprotein cholesterol (HDL‐C) < 40 mg/dL, and/or current use of lipid‐lowering therapy. Smoking and drinking habits were defined as current smoking and alcohol consumption, respectively. Physical activity was assessed using a self‐reported questionnaire and categorized based on the participant's ability to walk 1 km, as previously described [20]. Education level was classified into two categories (≤9 and >9 years) according to a previous report [21].
2.4. Outcomes
Patients newly diagnosed with stroke, acute myocardial infarction, or sudden cardiac and unexpected death (SCUD) were registered until December 2014. Initial registration was performed by attending physicians at each hospital. To ensure comprehensive case ascertainment, investigators (including physicians and trained research nurses) visited referred hospitals in the study area to review medical charts and/or discharge summaries. The primary endpoint was time to the first occurrence of a composite CVD event, defined as stroke, acute myocardial infarction, or SCUD. Stroke cases were identified from a local stroke registry [22]. Acute myocardial infarction was diagnosed based on the Monitoring of Trends and Determinants in CVD criteria [23]. SCUD was defined according to World Health Organization criteria as sudden unexpected death occurring within 24 h of the individual being observed alive and symptom‐free [24].
2.5. Statistical Analyses
Baseline data of the study participants, categorized by the number of remaining teeth, were presented as mean ± standard deviation or percentage, except for hsCRP levels, which were presented as the median with interquartile range. Continuous and categorical variables at baseline were compared among tooth categories using a one‐way analysis of variance and the chi‐square (χ 2) test, respectively. The Kruskal–Wallis test was used to compare hsCRP levels among the categories.
To analyze the association between tooth category and the incidence of overall CVD, stroke, and acute myocardial infarction/SCUD, multivariable Cox proportional hazards models were constructed. Model 1 was adjusted for age and sex, while Model 2 was adjusted for age, sex, BMI, eGFR (≥60 or <60 mL/min/1.73 m2), diabetes mellitus (yes or no), dyslipidemia (yes or no), smoking and alcohol consumption (yes or no), SBP, physical activity (high or low), and years of education (≤ 9 years or >9 years).
Because hsCRP reflects systemic inflammation that may lie on the causal pathway between oral frailty and cardiovascular outcomes, its inclusion in the main model could result in potential overadjustment. Therefore, we conducted a sensitivity analysis by additionally adjusting for hsCRP (Model 3) to assess the robustness of our findings.
After verifying the proportional hazards assumption using log–log survival plots and Schoenfeld residual–based tests (GLOBAL p = 0.34), hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated for the development of CVD across each tooth categories, with participants having ≥20 remaining teeth serving as the reference group.
In those with poorly controlled BP, subgroup analyses were also conducted according to age (≥65 or <65 years), sex, diabetes mellitus (yes or no), physical activity (high or low), years of education (≤9 or >9 years), and the following BP categories at baseline based on the ACC/AHA guideline [19]: stage 1 hypertension (SBP ≥ 130 mmHg but <140 mmHg and/or DBP ≥ 80 mmHg but <90 mmHg); and stage 2 or above hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg).
All statistical analyses were performed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA). Two‐sided p‐values of <0.05 were considered statistically significant.
3. Results
Among the 1 713 participants in the well‐controlled BP group, 56.7% had 0–9 teeth, 19.5% had 10–19 teeth, and 23.8% had ≥20 teeth. In the poorly controlled BP group (n = 3 771), the corresponding proportions were 55.4%, 21.2%, and 23.4%, respectively (Table 1). Among those with 0–9 teeth, denture use was reported by 93.4% in the well‐controlled BP group and 94.3% in the poorly controlled BP group. In both BP groups, the number of remaining teeth was inversely correlated with age and positively correlated with physical activity and education level.
TABLE 1.
Baseline characteristics of study participants stratified by number of remaining teeth and denture use.
|
Well‐controlled blood pressure (n = 1713) Number of remaining teeth |
Poorly controlled blood pressure (n = 3771) Number of remaining teeth |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| All participants | 20+ | 10–19 | 1‐9 with denture use | 0 with denture use | 0‐9 without denture use | p value | 20+ | 10–19 | 1‐9 with denture use | 0 with denture use | 0‐9 without denture use | p value | |
| Number | 5484 | 408 | 334 | 366 | 541 | 64 | 881 | 799 | 804 | 1168 | 119 | ||
| Age (years) | 67.5 ± 8.0 | 63.2 ± 7.7 | 66.1 ± 7.8 | 68.7 ± 7.4 | 71.3 ± 6.0 | 70.3 ± 6.3 | <0.001 | 63.2 ± 8.4 | 65.1 ± 8.2 | 67.8 ± 7.2 | 71.5 ± 6.4 | 68.4 ± 7.4 | <0.001 |
| Sex (men) | 34.2% | 35.8% | 29.9% | 30.6% | 18.9% | 40.6% | <0.001 | 48.0% | 40.7% | 35.2% | 27.2% | 36.1% | <0.001 |
| Body mass index (kg/m2) | 25.2 ± 3.4 | 24.9 ± 3.2 | 24.8 ± 3.3 | 24.5 ± 3.1 | 24.6 ± 3.3 | 25.9 ± 4.0 | 0.057 | 25.5 ± 3.4 | 25.5 ± 3.4 | 25.4 ± 3.5 | 25.4 ± 3.4 | 25.6 ± 3.8 | 0.820 |
| Estimated GFR ≥ 60 (ml/min/1.73 m2) | 88.7% | 91.7% | 89.5% | 88.5% | 85.2% | 82.8% | 0.019 | 91.1% | 91.2% | 88.7% | 86.1% | 85.7% | 0.001 |
| Diabetes mellitus | 10.2% | 9.8% | 9.9% | 8.7% | 9.1% | 9.4% | 0.980 | 9.6% | 10.8% | 9.6% | 11.6% | 14.3% | 0.310 |
| Dyslipidemia | 24.1% | 25.0% | 25.4% | 22.4% | 23.1% | 23.4% | 0.851 | 25.0% | 23.5% | 23.5% | 24.5% | 26.9% | 0.878 |
| Current drinker | 28.0% | 30.4% | 28.1% | 26.2% | 13.9% | 29.7% | <0.001 | 41.5% | 34.5% | 26.9% | 20.5% | 26.9% | <0.001 |
| Current smoker | 8.6% | 6.9% | 9.6% | 9.3% | 6.1% | 12.5% | 0.128 | 10.6% | 10.1% | 8.1% | 7.1% | 10.1% | 0.040 |
| Systolic blood pressure (mmHg) | 136.7 ± 18.2 | 117.3 ± 8.6 | 117.4 ± 8.8 | 117.8 ± 8.1 | 117.4 ± 8.3 | 118.8 ± 9.1 | 0.716 | 145.5 ± 15.2 | 144.1 ± 13.7 | 144.1 ± 13.7 | 146.0 ± 14.1 | 145.7 ± 14.9 | 0.047 |
| Diastolic blood pressure (mmHg) | 79.3 ± 10.2 | 70.4 ± 6.9 | 69.7 ± 6.4 | 69.5 ± 6.1 | 68.7 ± 6.3 | 68.8 ± 5.7 | 0.002 | 85.8 ± 8.3 | 84.3 ± 8.3 | 84.3 ± 8.0 | 82.0 ± 8.5 | 83.5 ± 7.7 | <0.001 |
| HsCRP (mg/L) | 0.6 (0.3‐1.1) | 0.5 (0.3‐1.0) | 0.5 (0.3‐1.1) | 0.5 (0.3‐1.1) | 0.5 (0.3‐1.1) | 0.5 (0.2‐1.2) | 0.693 | 0.6 (0.3‐1.1) | 0.6 (0.3‐1.2) | 0.6 (0.3‐1.2) | 0.6 (0.3‐1.2) | 0.6 (0.3‐1.2) | 0.874 |
| Physical activity (1‐km walking feasibility) | 67.4% | 75.5% | 71.3% | 68.6% | 55.8% | 40.6% | <0.001 | 79.5% | 73.5% | 66.9% | 57.8% | 59.7% | <0.001 |
| Years of education ≤ 9 (years) | 69.8% | 54.7% | 61.7% | 68.6% | 84.7% | 81.3% | <0.001 | 52.0% | 62.5% | 73.1% | 86.2% | 73.9% | <0.001 |
Note: Data are presented as the mean with standard deviation or percentage.
Abbreviations: GFR, glomerular filtration rate; HsCRP, high sensitivity C‐reactive protein.
During a mean follow‐up period of 9.9 ± 2.7 years, 567 individuals (10.3%) experienced their first CVD event, consisting of stroke (84.7%) and acute myocardial infarction/SCUD (15.3%). Among all participants, the multivariable‐adjusted HRs for the development of total CVD and stroke increased significantly with a decreasing number of teeth (p for trend = 0.028 and 0.024, respectively; Table 2). In the poorly controlled BP group, compared with participants having ≥ 20 teeth, the fully adjusted HRs (95%CIs) for total CVD were 1.79 (1.28–2.48) for those with 10–19 teeth, 1.37 (0.97–1.94) for those with 1–9 teeth and denture use, 1.56 (1.13–2.17) for those with no teeth and denture use, and 2.17 (1.30–3.64) for those with 0–9 teeth and non‐use of dentures. In contrast, no such association was observed in the well‐controlled BP group, with a significant interaction between BP control status and tooth category (P for interaction = 0.016). A similar pattern was observed for stroke, with higher risks among participants with poorly controlled BP and tooth loss, especially those with no denture use (Table 2). In contrast, no significant association was observed for acute myocardial infarction/SCUD, regardless of BP control status, likely due to the small number of events. Similar associations of tooth category with total CVD, stroke, and acute myocardial infarction/SCUD were observed after further adjustment for hsCRP (Table S1). As a sensitivity analysis, participants with poorly controlled BP were categorized into four groups based solely on the number of remaining teeth (0, 1–9, 10–19, and ≥ 20 teeth), and this alternative classification yielded a similar trend of increasing risk of total CVD and stroke with decreasing tooth count (Table S2). Conversely, in participants with well‐controlled BP, no significant associations were observed between tooth category and the incidence of total CVD, with a significant interaction between BP control status and tooth category (P for interaction = 0.010; Tables S2).
TABLE 2.
Association of the number of remaining teeth and denture use with the incidence of cardiovascular events.
| Number of remaining teeth and denture use | No./1 000 person years | Model 1 a | Model 2 b | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Blood pressure group | No. of individuals | No. of events | Person years | HR | 95%CI | P value | P for trend | HR | 95%CI | P value | P for trend | P for interaction c | |||||||
| All CVD | Total | 0–9 without denture use | 183 | 31 | 1 692 | 18.3 | 2.08 | 1.38 | — | 3.15 | 0.001 | 1.94 | 1.28 | — | 2.94 | 0.002 | |||
| 0 with denture use | 1 709 | 209 | 16 620 | 12.6 | 1.37 | 1.05 | — | 1.79 | 0.019 | 1.26 | 0.96 | — | 1.65 | 0.091 | |||||
| 1–9 with denture use | 1 170 | 121 | 11 515 | 10.5 | 1.29 | 0.98 | — | 1.71 | 0.070 | 1.23 | 0.93 | — | 1.63 | 0.141 | |||||
| 10–19 | 1 133 | 116 | 11 276 | 10.3 | 1.41 | 1.07 | — | 1.85 | 0.016 | 1.36 | 1.03 | — | 1.79 | 0.031 | |||||
| 20+ | 1 289 | 90 | 13 224 | 6.8 | 1.00 | 0.009 | 1.00 | 0.028 | |||||||||||
| Stroke | 0–9 without denture use | 183 | 28 | 1 704 | 16.4 | 2.30 | 1.48 | — | 3.57 | <0.001 | 2.12 | 1.36 | — | 3.31 | 0.001 | ||||
| 0 with denture use | 1 709 | 180 | 16 705 | 10.8 | 1.43 | 1.07 | — | 1.91 | 0.017 | 1.29 | 0.96 | — | 1.74 | 0.089 | |||||
| 1–9 with denture use | 1 170 | 106 | 11 562 | 9.2 | 1.39 | 1.02 | — | 1.88 | 0.035 | 1.31 | 0.96 | — | 1.78 | 0.085 | |||||
| 10–19 | 1 133 | 93 | 11 347 | 8.2 | 1.38 | 1.01 | — | 1.88 | 0.041 | 1.33 | 0.97 | — | 1.81 | 0.074 | |||||
| 20+ | 1 289 | 73 | 13 293 | 5.5 | 1.00 | 0.007 | 1.00 | 0.024 | |||||||||||
| AMI/SCUD | 0–9 without denture use | 183 | 3 | 1 818 | 1.7 | 1.06 | 0.31 | — | 3.65 | 0.925 | 1.06 | 0.31 | — | 3.69 | 0.922 | ||||
| 0 with denture use | 1 709 | 29 | 17 354 | 1.7 | 1.11 | 0.59 | — | 2.11 | 0.748 | 1.10 | 0.57 | — | 2.11 | 0.785 | |||||
| 1–9 with denture use | 1 170 | 15 | 11 943 | 1.3 | 0.88 | 0.43 | — | 1.77 | 0.710 | 0.90 | 0.44 | — | 1.84 | 0.780 | |||||
| 10–19 | 1 133 | 23 | 11 645 | 2.0 | 1.52 | 0.81 | — | 2.86 | 0.192 | 1.53 | 0.81 | — | 2.88 | 0.191 | |||||
| 20+ | 1 289 | 17 | 13 560 | 1.3 | 1.00 | 0.512 | 1.00 | 0.543 | |||||||||||
| All CVD | Poorly controlled blood pressure | 0–9 without denture use | 119 | 20 | 1 130 | 17.7 | 2.31 | 1.38 | — | 3.86 | 0.001 | 2.17 | 1.30 | — | 3.64 | 0.003 | 0.016 | ||
| 0 with denture use | 1 168 | 157 | 11 245 | 14.0 | 1.69 | 1.23 | — | 2.34 | 0.001 | 1.56 | 1.13 | — | 2.17 | 0.008 | |||||
| 1–9 with denture use | 804 | 83 | 7 970 | 10.4 | 1.43 | 1.02 | — | 2.02 | 0.040 | 1.37 | 0.97 | — | 1.94 | 0.071 | |||||
| 10–19 | 799 | 96 | 7 868 | 12.2 | 1.85 | 1.33 | — | 2.57 | <0.001 | 1.79 | 1.28 | — | 2.48 | 0.001 | |||||
| 20+ | 881 | 57 | 8 999 | 6.3 | 1.00 | 0.001 | 1.00 | 0.004 | |||||||||||
| Well‐controlled blood pressure | 0–9 without denture use | 64 | 11 | 562 | 19.6 | 1.51 | 0.75 | — | 3.05 | 0.245 | 1.41 | 0.69 | — | 2.88 | 0.341 | ||||
| 0 with denture use | 541 | 52 | 5 375 | 9.7 | 0.79 | 0.49 | — | 1.28 | 0.337 | 0.71 | 0.43 | — | 1.15 | 0.160 | |||||
| 1–9 with denture use | 366 | 38 | 3 545 | 10.7 | 0.97 | 0.60 | — | 1.58 | 0.912 | 0.91 | 0.56 | — | 1.49 | 0.714 | |||||
| 10–19 | 334 | 20 | 3 408 | 5.9 | 0.60 | 0.34 | — | 1.06 | 0.078 | 0.57 | 0.33 | — | 1.01 | 0.054 | |||||
| 20+ | 408 | 33 | 4 225 | 7.8 | 1.00 | 0.111 | 1.00 | 0.083 | |||||||||||
| Stroke | Poorly controlled blood pressure | 0–9 without denture use | 119 | 19 | 1 130 | 16.8 | 2.59 | 1.51 | — | 4.42 | 0.001 | 2.40 | 1.40 | — | 4.12 | 0.001 | 0.116 | ||
| 0 with denture use | 1 168 | 135 | 11 318 | 11.9 | 1.68 | 1.19 | — | 2.39 | 0.004 | 1.52 | 1.07 | — | 2.17 | 0.021 | |||||
| 1–9 with denture use | 804 | 74 | 8 012 | 9.2 | 1.49 | 1.03 | — | 2.16 | 0.034 | 1.41 | 0.98 | — | 2.05 | 0.068 | |||||
| 10–19 | 799 | 77 | 7 929 | 9.7 | 1.74 | 1.21 | — | 2.50 | 0.003 | 1.66 | 1.16 | — | 2.39 | 0.006 | |||||
| 20+ | 881 | 48 | 9 044 | 5.3 | 1.00 | 0.004 | 1.00 | 0.014 | |||||||||||
| Well‐controlled blood pressure | 0–9 without denture use | 64 | 9 | 574 | 15.7 | 1.62 | 0.74 | — | 3.53 | 0.229 | 1.54 | 0.70 | — | 3.41 | 0.285 | ||||
| 0 with denture use | 541 | 45 | 5 387 | 8.4 | 0.89 | 0.52 | — | 1.52 | 0.671 | 0.79 | 0.45 | — | 1.36 | 0.384 | |||||
| 1–9 with denture use | 366 | 32 | 3 550 | 9.0 | 1.09 | 0.64 | — | 1.88 | 0.744 | 1.02 | 0.59 | — | 1.76 | 0.951 | |||||
| 10–19 | 334 | 16 | 3 418 | 4.7 | 0.64 | 0.34 | — | 1.21 | 0.173 | 0.61 | 0.32 | — | 1.16 | 0.131 | |||||
| 20+ | 408 | 25 | 4 250 | 5.9 | 1.00 | 0.213 | 1.00 | 0.175 | |||||||||||
| AMI/SCUD | Poorly controlled blood pressure | 0–9 without denture use | 119 | 1 | 1 195 | 0.8 | 0.77 | 0.10 | — | 6.13 | 0.806 | 0.82 | 0.10 | — | 6.55 | 0.853 | 0.165 | ||
| 0 with denture use | 1 168 | 22 | 11 813 | 1.9 | 1.69 | 0.74 | — | 3.84 | 0.213 | 1.73 | 0.75 | — | 4.00 | 0.198 | |||||
| 1–9 with denture use | 804 | 9 | 8 271 | 1.1 | 1.05 | 0.41 | — | 2.68 | 0.917 | 1.11 | 0.43 | — | 2.86 | 0.823 | |||||
| 10–19 | 799 | 19 | 8 179 | 2.3 | 2.42 | 1.09 | — | 5.37 | 0.030 | 2.55 | 1.15 | — | 5.69 | 0.022 | |||||
| 20+ | 881 | 9 | 9 248 | 1.0 | 1.00 | 0.115 | 1.00 | 0.101 | |||||||||||
| Well‐controlled blood pressure | 0–9 without denture use | 64 | 2 | 623 | 3.2 | 1.03 | 0.21 | — | 4.98 | 0.975 | 0.80 | 0.16 | — | 4.03 | 0.789 | ||||
| 0 with denture use | 541 | 7 | 5 541 | 1.3 | 0.48 | 0.16 | — | 1.45 | 0.192 | 0.46 | 0.15 | — | 1.43 | 0.180 | |||||
| 1–9 with denture use | 366 | 6 | 3 672 | 1.6 | 0.60 | 0.20 | — | 1.82 | 0.368 | 0.62 | 0.20 | — | 1.89 | 0.399 | |||||
| 10–19 | 334 | 4 | 3 466 | 1.2 | 0.49 | 0.15 | — | 1.67 | 0.255 | 0.47 | 0.14 | — | 1.59 | 0.223 | |||||
| 20+ | 408 | 8 | 4 312 | 1.9 | 1.00 | 0.631 | 1.00 | 0.657 | |||||||||||
Abbreviations: AMI, acute myocardial infarction; CI, confidence interval; CVD, cardiovascular disease; HR, hazard ratio; SCUD, sudden cardiac and unexpected death.
Model 1 was constructed for age, sex.
Model 2 was constructed for age, sex, body mass index, estimated glomerular filtration rate ≥60 or <60 ml/min/1.73 m2, diabetes mellitus (yes or no), dyslipidemia (yes or no), smoking consumption (yes or no), drinking consumption (yes or no), systolic blood pressure, physical activity (high or low), and years of education (≤9 or >9 years).
P for interaction between tooth category and blood pressure control status.
As shown in Table 3, baseline covariates (including age, sex, diabetes mellitus, physical activity, and BP category) did not modify the association between tooth category and CVD risk within the poorly controlled BP group (Table 3). This association differed significantly by education level (≤ 9 or >9 years) within the poorly controlled BP group (P for interaction = 0.047; Table 3).
TABLE 3.
Association of the number of remaining teeth and denture use with the incidence of all cardiovascular events according to the blood pressure group.
| Well‐controlled blood pressure | P for interaction b | Poorly controlled blood pressure | P for interaction b | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HR a | 95%CI | p value | HR a | 95%CI | p value | ||||||||
| Age | |||||||||||||
| <65 years (n = 1 765) | 0.60 | 0.369 | — | 0.96 | 0.033 | 0.015 | 1.12 | 0.91 | — | 1.37 | 0.281 | 0.936 | |
| ≥ 65 years (n = 3 719) | 1.09 | 0.93 | — | 1.28 | 0.298 | 1.10 | 1.00 | — | 1.22 | 0.056 | |||
| Sex | |||||||||||||
| Men (n = 1 878) | 1.15 | 0.93 | — | 1.412 | 0.204 | 0.130 | 1.18 | 1.04 | — | 1.34 | 0.012 | 0.690 | |
| Women (n = 3 606) | 0.88 | 0.72 | — | 1.07 | 0.206 | 1.05 | 0.93 | — | 1.19 | 0.414 | |||
| Diabetes mellitus | |||||||||||||
| No (n = 4 923) | 0.99 | 0.85 | — | 1.16 | 0.917 | 0.728 | 1.07 | 0.98 | — | 1.18 | 0.147 | 0.509 | |
| Yes (n = 561) | 1.07 | 0.63 | — | 1.81 | 0.800 | 1.29 | 1.02 | — | 1.64 | 0.034 | |||
| Physical activity (1‐km walking feasibility) | |||||||||||||
| No (n = 1 788) | 1.02 | 0.82 | — | 1.27 | 0.861 | 0.667 | 1.06 | 0.91 | — | 1.24 | 0.435 | 0.230 | |
| Yes (n = 3 696) | 0.97 | 0.80 | — | 1.17 | 0.722 | 1.13 | 1.01 | — | 1.26 | 0.028 | |||
| Years of education | |||||||||||||
| ≤ 9 years (n = 3 830) | 1.03 | 0.872 | — | 1.21 | 0.746 | 0.827 | 1.06 | 0.95 | — | 1.17 | 0.304 | 0.047 | |
| > 9 years (n = 1 654) | 0.93 | 0.67 | — | 1.30 | 0.685 | 1.28 | 1.07 | — | 1.53 | 0.006 | |||
| Blood pressure category | |||||||||||||
| Stage 1 hypertension (n = 1 382) | 1.13 | 0.963 | — | 1.324 | 0.136 | 0.493 | |||||||
| Stage 2 hypertension or higher (n =2 389) | 1.10 | 0.986 | — | 1.224 | 0.089 | ||||||||
Abbreviations: CI, confidence interval; HR, hazard ratio.
The hazard ratio for all cardiovascular events associated with a single decrease in the tooth categories, with 20 or more teeth regarded as the reference category. Model was constructed for age, sex, body mass index, estimated glomerular filtration rate ≥60 or <60 ml/min/1.73 m2, diabetes mellitus (yes or no), dyslipidemia (yes or no), smoking consumption (yes or no), drinking consumption (yes or no), systolic blood pressure, physical activity (high or low), and years of education (≤9 or >9 years).
P for interaction between tooth category (per one‐category decrease) and risk category.
4. Discussion
This study demonstrated several important findings concerning the association between oral status and cardiovascular risk in middle‐aged and older adults receiving antihypertensive medication. First, the risk of developing CVD increased significantly with fewer remaining teeth and lack of dentures, but only in individuals with poorly controlled BP (SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg). This association showed a significant interaction with BP control status. Second, within the poorly controlled BP group, the highest risk was observed in individuals with 0–9 remaining teeth who did not use dentures, suggesting a critical role for functional oral status in this high‐risk population. In contrast, no significant association was observed in participants with well‐controlled BP.
Recently, epidemiological studies targeting participants with hypertension have reported an inverse association between the number of remaining teeth and incident CVD (including stroke), all‐cause mortality, and CVD mortality [9, 14, 25]. However, this association has been less clear in the specific context of treated hypertension, especially when considering the degree of BP control. Our study is the first to elucidate a significant modification of the CVD risk associated with oral status in a community‐based prospective cohort, depending on whether BP targets are achieved among individuals receiving antihypertensive medication. Furthermore, by incorporating denture use status into the remaining tooth count classification, we provided a measure reflecting functional oral capacity, which was shown to be a powerful stratifier of CVD risk among participants with poorly controlled BP.
Several mechanisms have been proposed to explain the association between a lower number of remaining teeth and an increased risk of developing CVD. Tooth loss may be linked to three key pathways: long‐term exposure to periodontitis, lower socioeconomic status (SES), and an impaired masticatory function. We argue that the amplification of CVD risk only in the poorly controlled BP group suggests a synergy between two major vulnerabilities: systemic disease mismanagement and oral frailty/vulnerability. First, tooth loss and elevated BP may share a chronic inflammatory state, which could synergistically promote the development of CVD. Periodontitis, which is the leading cause of tooth loss, can induce low‐grade bacteremia and endotoxemia, promoting oxidative stress, coagulation activation, and systemic inflammation [2, 26, 27]. These processes contribute to endothelial dysfunction, arterial stiffness, and subclinical organ damage, increasing CVD risk [2, 28, 29]. In the present study, only a single hsCRP measurement was available and other key inflammatory markers were not assessed; therefore, we could not establish inflammation as a mediator of the association between tooth loss and CVD. Nevertheless, the failure to achieve BP control (i.e., BP ≥ 130/80 mmHg) despite antihypertensive treatment may indicate a higher baseline systemic inflammatory burden and greater vascular damage, rendering such patients particularly vulnerable to the added burden of oral disease [30]. Second, participants with severe tooth loss or not using dentures tended to have fewer years of education, a proxy for lower SES, within the study population. Low SES, characterized by reduced income, limited education, and poor access to healthcare, is generally associated with higher CVD risk [8, 31]. However, in our study, the association between tooth status and CVD risk was stronger among participants with higher educational attainment, suggesting possible effect modification by education. As education level represents only one dimension of socioeconomic status, our data do not allow us to formally evaluate the mediating effects of SES. Nevertheless, residual socioeconomic pathways may partly mediate the relationship between tooth status and CVD risk. Third, dietary modifications resulting from a decreased masticatory function due to tooth loss may have influenced the risk of CVD [32]. Individuals with a poor oral status, particularly those with complete tooth loss who do not use dentures, may restrict their diet, leading to a reduced intake of essential nutrients such as dietary fiber, fruits, and vitamins [26, 33, 34]. Although not directly assessed in the present study, this nutritional inadequacy, together with the established vascular risks of uncontrolled hypertension [35], likely contributed to the heightened CVD risk observed in such high‐risk individuals.
This study had several limitations. First, the number of remaining teeth and denture use were assessed using a self‐administered questionnaire, consistent with previous epidemiological methods [10, 11, 12, 13]. Although self‐reported measures may be subject to reporting bias, prior research has shown moderate to high agreement with clinical assessments [36]. In addition, periodontal disease severity was not assessed, and tooth count served only as a crude proxy for cumulative oral health [8]. This limitation may result in residual confounding, and future studies should incorporate standardized periodontal evaluations. Second, the etiology of tooth loss was not determined in this study, as in previous studies. Consequently, external factors, such as physical trauma or prosthetic use (including dental implants), may have contributed to the tooth loss. Nevertheless, tooth loss is primarily attributed to periodontal disease and dental caries [37]. Third, details on antihypertensive medication use, changes, adherence, and follow‐up clinical data were not collected, which may have influenced the outcomes. Fourth, BP was assessed at a single time point, which may have led to misclassification of poorly controlled BP status. However, as such misclassification is generally considered non‐differential, it would tend to bias the associations toward the null, indicating that our findings should be interpreted as conservative estimates [38]. Finally, in this Japanese population‐based study, the cumulative incidence of acute myocardial infarction/SCUD was much lower than that of stroke (1.05 vs. 5.48 per 1 000 person‐years), which is consistent with previous Japanese epidemiological reports [39, 40]. This may partly explain the lack of a relationship between the number of remaining teeth and the development of acute myocardial infarction/SCUD, suggesting that further verification is required to clarify this relationship.
This study has several crucial clinical implications. The AHA/ACC guidelines recommend maintaining BP < 130/80 mmHg and managing comorbidities [19], while the Italian Society of Hypertension and the Italian Society of Periodontology and Implantology recommend oral health management in hypertensive patients [41]. However, BP control remains suboptimal; for instance, only 39.9% of U.S. adults and 26.7% of Japanese adults achieve BP targets [42, 43]. Our findings highlight the importance of assessing oral status in treated hypertensive patients, particularly those with poorly controlled BP. Such assessment is easy to implement in clinical practice and may help physicians identify a highly vulnerable subgroup, potentially promoting denture use among edentulous individuals, a measure known to reduce the risk of hypertension incidence [41], CVD mortality [25], and all‐cause mortality [25]. Furthermore, our results underscore the need for dentists to consider BP control status, ultimately fostering essential medical‐dental collaboration to improve CVD outcomes. Collaboration with dental researchers will be considered to broaden the scope of this research.
In conclusion, tooth loss and non‐use of dentures are associated with an elevated risk of CVD in middle‐aged and older adults receiving antihypertensive treatment, with this association being particularly pronounced in individuals with poorly controlled BP. These findings underscore the importance of incorporating the oral functional status into risk stratification strategies for this vulnerable population.
Conflicts of Interest
The authors declare no conflicts of interest.
Disclosures
The authors have nothing to report.
Supporting information
Supporting file 1: jch70224‐sup‐0001‐Table.xlsx
Acknowledgments
This research was supported in part by grants‐in‐aid from the Scientific Research Fund of the Ministry of Education, Science, and Culture of Japan (24K20118, 22K11706, and 24K14755), Tokyo, and the Ministry of Health, Labour and Welfare, Health and Labor Sciences research grants, Japan (H23‐Junkankitou [Seishuu]‐lppan‐005; H26‐Junkankitou [Seisaku]‐lppan‐001; H29‐Junkankitou [Seisaku]‐lppan‐003, 20FA1002, and 23FA1006).
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Supplementary Materials
Supporting file 1: jch70224‐sup‐0001‐Table.xlsx