Oral inflammation, such as periodontitis, can lead to endothelial dysfunction, accelerated atherosclerosis, and vascular dysfunction. The relationship between vascular dysfunction and other common forms of oral infections such as denture-related stomatitis (DRS) is unknown. Similar risk factors predispose to both conditions including smoking, diabetes, age, and obesity. Accordingly, we aimed to investigate endothelial function and major vascular disease risk factors in 44 consecutive patients with dentures with clinical and microbiological features of DRS (
Oral inflammation is an important element in the pathogenesis of vascular disease. In particular, large body of evidence has accumulated recently that chronic periodontitis is a potential novel risk factor for atherosclerosis and endothelial dysfunction [
While numerous studies have focused on the links between periodontitis and endothelial dysfunction, little is known about the links between other forms of oral infection and inflammation in the context of cardiovascular risk. In particular, denture-related stomatitis (DRS) is an inflammatory process of the oral mucosa in contact with a denture and is one of the most common diseases in elderly patients, affecting up to 70% of patients in the course of life [
While in periodontitis systemic activation of the immune system is very important in mediating increased cardiovascular risk, the extent of systemic response to DRS is poorly characterized. Systemic inflammation may affect vascular dysfunction in number of ways, which include activation of monocytes and T cells with overproduction of cytokines such as interferon
Using 44 consecutive patients with dental prostheses for at least 6 months were included in this study. Their oral mucosa was examined by the dentist to clinically identify inflammation and DRS. The clinical signs of oral mucosa inflammation in DRS include erythema and swelling of palatal mucosa, sometimes combined with subjective symptoms, such as dysgeusia or burning sensation. These observations were confirmed by routine microbiological laboratory diagnostic tests for
Swabs were taken from the hard palate (between the second and third palatal fold). Samples were collected after an overnight fast and after at least 6 hours of continous denture usage, without the use of adhesives or rinsing the mouth with disinfectants. The material was collected in accordance with the general principles of microbial material collection.
Patients’ blood pressure (systolic, diastolic) was monitored for 24 hours using ambulatory blood pressure monitoring system (ABPM; SpaceLabs 90217, Ultralite device). Systolic diastolic and mean arterial pressures were recorded every 20 minutes for 24 hours. Day and night averages were calculated. One patient in control group did not agree to wear the ABPM monitor. Major risk factors for both atherosclerosis and DRS were recorded based on patient medical records and detailed patient history. Clinical risk factors were defined as follows: hyperlipidemia (total plasma cholesterol level > 5 mmol/L and/or triglycerides level > 1,7 mmol/L), diabetes (fasting glucose level ≥ 7 mmol/L or HbA1c > 6.5% or current treatment with insulin or oral hypoglycemic agents), hypertension (blood pressure ≥ 140/90 mmHg or current treatment with antihypertensive agents), and smoking (current or within last 6 months) based on [
Flow-mediated dilatation (FMD) method was used to determine the vascular endothelial function and NMD (nitroglycerine-mediated dilatation) for measuring endothelial-independent vasodilatation. Measurements were conducted using Toshiba Xario Diagnostic Ultrasound System after 1, 2, and 4-5 minutes after manometer cuff deflation or sublingual administration of nitroglycerine and presented as percentage of the diameter of the artery before intervention. Method validation in our laboratory has been described elsewhere [
The measurements of intima-media thickness were performed in 12 different points (2 cm below common carotid arteries bulbs, ca. every 1 cm, omitting visible coronary plaques), on right and left common carotid artery, measuring the distance between the border between artery lumen and carotid artery intima and second bright line-m (border between media and adventitia) as described previously [
Analysis was performed using Statsoft Statistica software. Compliance of the distribution of variables with normal distribution was tested by Shapiro-Wilk test. Most of the variables did not have normal distributions, and therefore the results are presented as medians and 25th (
Both groups were balanced in terms of age, sex, body mass index (BMI) value, and antihypertensive treatment. There were more smokers and patients with diabetes mellitus (DM) in DRS group than in control group, although these differences were not statistically significant. Higher prevalence of DM and smoking in DRS group is consistent with epidemiologic data and is understandable, as both are recognized as a risk factor for developing DRS [
Patient clinical characteristics.
DRS group |
Control group |
||
---|---|---|---|
Gender (M : F) | 2 : 18 |
|
6 : 18 |
Age |
63,9 (6,6) |
|
65,9 (10,3) |
BMI |
28,5 (24,9; 33,6) |
|
27,8 (24,3; 29,3) |
Smoking (%) | 6 (30%) |
|
3 (12,5%) |
Diabetes mellitus (%) | 6 (30%) |
|
2 (8,3%) |
Hypertension (%) | 17 (85%) |
|
19 (79,2%) |
Hyperlipidemia (%) | 13 (65%) |
|
12 (50%) |
Medications (%) | |||
ACE inhibitor | 7 (35%) |
|
12 (50%) |
Acetylsalicylic acid | 3 (15%) |
|
4 (17%) |
|
7 (35%) |
|
10 (42%) |
Ca antagonist | 3 (15%) |
|
8 (34%) |
Diuretic | 7 (35%) |
|
6 (25%) |
Statin | 6 (30%) |
|
5 (21%) |
Insulin | 2 (10%) |
|
2 (8,3%) |
Oral antidiabetic agents | 2 (10%) |
|
2 (8,3%) |
ACE: angiotensin converting enzyme, BMI: body mass index, DM: diabetes mellitus, SD: standard deviation.
Ambulatory blood pressure monitoring has shown no significant differences in both mean systolic and mean diastolic blood pressure in DRS and control non-DRS group (Figure
Ambulatory blood pressure parameters in control and DRS patients. Blood pressure parameters were assessed by 24 h measurement with ambulatory blood pressure monitoring system. Results are presented as mean (SD);
Flow-mediated dilatation measurements showed a significantly reduced median percentage of arterial dilation in response to flow in the DRS group in comparison with control patients (Figure
Vascular dysfunction in control and DRS. Vascular endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent nitroglycerin-mediated dilatation (NMD) parameters were assessed by ultrasonography. Results presented as median (
Intima-media thickness evaluation showed no significant differences in either maximal or mean IMT in studied groups. It is important to point out that neither of the groups showed very high values of mean IMT (Figure
IMT measurements in DRS and control group. (a) Mean common carotid artery intima-media thickness. Results are presented as mean (SD); (b) maximal common carotid artery intima-media thickness. Results presented as median (
As the elevated blood triglycerides, LDL and total cholesterol levels and low HDL cholesterol levels are recognized as cardiovascular risk factors; we compared their concentrations in blood samples collected from patients with oral fungal infection and with healthy oral mucosa. We found that plasma levels of total, LDL, and HDL cholesterol were similar in both groups; however, triglycerides levels were significantly elevated in DRS group (Figure
Plasma lipid profile and C-reactive protein levels in control and DRS patients. (a) Comparison of lipid profiles. Results are presented as median (
Spearman correlation between parameters of vascular function parameters and triglycerides levels. (a) Spearman correlation between FMD and triglycerides levels:
As there was a much lower proportion of males in our study population, we performed an additional subgroup analysis in female population. It revealed that all studied vascular phenomena were observed to the same extent as in total studied population, including the difference in endothelium derived vasorelaxations (FMD (mean ± SD):
The oral health impact on the general health is evident. Oral infections and inflammation have been implicated in many disease entities, such as rheumatoid arthritis [
While numerous previous studies have shown increased cardiovascular risk in subjects with oral inflammatory conditions such as periodontitis [
Previous studies focused on a positive association between periodontitis and vascular endothelial dysfunction. Amar et al. and Blum et al. observed that subjects with advanced periodontal disease exhibit worse endothelial function when compared to the healthy controls [
The mechanisms of increased cardiovascular risk in oral inflammatory conditions are multifactorial and range from chronic systemic inflammation (periodontitis) to the effects of risk factors such as diabetes, hyperlipidemia, smoking, and age which predispose to both cardiovascular diseases and oral disorders, such as periodontitis [
The role of systemic inflammation, very well defined in periodontitis, is not known in DRS. The mechanisms through which DRS could affect endothelial dysfunction are unclear. In periodontitis, bacteria lead to the activation of the local immune response, leading to systemic inflammation. Similarly, immune stimulation of T cells and monocytes has been reported in response to fungal
De Oliveira et al. and Rodriguez-Archilla et al. have found that oral
However our results may point us to the potential role of vascular risk factors such as diabetes, smoking, and hypertriglyceridemia in mediating vascular dysfunction. Although no relationship was found between triglyceride levels and endothelial dysfunction in a simple correlation analysis, when multivariate linear regression was introduced including diabetes, smoking, and/or triglyceride levels, the difference in endothelial function was no longer significant (data not shown). One has to however bear in mind that statistical power of such analysis in the studied group was relatively modest.
While the finding that classical risk factors may be main mediators of endothelial dysfunction may not sound exceptionally interesting, it is very important to show that this is the case in DRS subjects, and therefore this group of patients should be carefully studied in larger epidemiological trials. This is particularly important in the light of ageing population.
Despite the lack of differences in the levels of total, HDL, and LDL cholesterol in the blood of healthy subjects and DRS, we observed significantly higher levels of triglycerides in patients with DRS. Our surprising finding that DRS is associated with selective increase in triglyceride levels is quite intriguing and could be related to the fact that denture wearing can change dietary habits. It could also suggest that increased triglyceride levels could be a risk factor of DRS, although our study was not powered to answer this question. There are no studies looking at lipid parameters in DRS, while conflicting data are available regarding periodontitis. Sandi et al. and Penumarthy et al. observed higher concentrations of total cholesterol and LDL cholesterol in the blood of patients with periodontal disease than in healthy group, but the differences in the levels of triglycerides and HDL cholesterol were shown only by Penumarthy et al., despite the smaller sample sizes [
We did not observe the tendency towards elevated blood pressure in patients with DRS as compared to healthy subjects. This shows potential important difference in oral inflammatory conditions as periodontitis is potentially associated with elevated blood pressure, which was frequently observed [
In conclusion, our study shows that patients with denture-related stomatitis are characterized by more pronounced systemic endothelial dysfunction than denture subjects without stomatitis. This difference in vascular function is likely linked with increased cardiovascular risk in DRS and indicates that such patients should be carefully monitored for cardiovascular disease. While our study identifies certain very interesting and potentially very important cardiovascular aspects of denture-related stomatitis, a larger study is warranted to finally confirm these observations. This may be very important for clinical practice considering ageing population.
C-reactive protein
Diabetes mellitus
Denture-related stomatitis
Flow-mediated dilatation
High density lipoprotein cholesterol
Low density lipoprotein cholesterol
Nitroglycerine-mediated dilatation
25th (
tandard deviation.
The authors declare that there is no conflict of interests regarding the publication of this paper.
Joanna Maciąg and Grzegorz Osmenda contributed equally to this study.
This study was supported by Public Funds for Science of Republic of Poland Grant no. 2997/B/P01/2009/36 and the Foundation for Polish Science Welcome Grant (FNP/Welcome/02) (TJG, TM, GO, AS).