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ORIGINAL ARTICLE Periodontal and Systemic Diseases Among Swedish Dental School Patients – A Retrospective Register Stud...

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ORIGINAL ARTICLE

Periodontal and Systemic Diseases Among Swedish Dental School Patients – A Retrospective Register Study Marija Marjanovica,b/Kåre Buhlina Purpose: To investigate if patients with periodontitis attending the Dental School in Huddinge, Sweden presented with more signs of systemic diseases, such as cardiovascular disease, diabetes mellitus and respiratory diseases, compared to healthy and gingivitis patients. Materials and Methods: In this retrospective study, dental charts were examined where the periodontal diagnoses of patients were known. A total of 325 patients with severe periodontitis and 149 patients without periodontitis, born 1928 to 1968, were identified. Diagnosis regarding the systemic diseases was self-reported. Odds ratios for cardiovascular diseases, diabetes mellitus and respiratory diseases were calculated with a logistic regression model that was adjusted for age, gender and smoking. Results: It was observed that more cases of periodontitis were found in older individuals than the controls (61.7 vs 56.2 years; P < 0.001). A total of 44.3% of patients with severe periodontitis also suffered from cardiovascular diseases, 19.1% respiratory diseases and 21.2% from diabetes mellitus. Among the controls, 30.9% had cardiovascular disease, 23.5% suffered from respiratory diseases and 6.7% had diabetes mellitus. Across both groups, hypertension was the most frequent diagnosis. There was a significant association between periodontitis and cardiovascular disease (odds ratio [OR] = 1.79, confidence interval [CI] 1.12–2.86), but not between respiratory diseases and periodontitis (OR = 0.88, CI 0.53–1.47). The risk of diabetes mellitus was greater among those patients with periodontitis (OR = 2.95, CI 1.45– 6.01). Conclusion: This study found that patients with periodontitis presented with more systemic diseases, such as cardiovascular disease and diabetes mellitus than control patients. However, no association was found between periodontitis and respiratory diseases. At the present time, the reasons for the associations or lack of association are unknown. Key words: register study, risk factor, periodontal disease, Sweden, systemic diseases Oral Health Prev Dent 2013; 11: 49-55

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eriodontitis, a common chronic, tissue destructive inflammatory state, has been associated with various systemic diseases during the early decades of the last century. However, it was not until the 1980s that carefully designed Finnish studies focused again on these relationships (Mattila et al, 1989, Syrjänen et al, 1989). As a result, a renewed interest in this area has led to studies that have tried to investigate whether there is a

a

Associate Professor, Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.

b

Dentist, General Dental Clinic, The Public Dental Health Office in Halland, County of Halland, Hyltebruk, Sweden.

Correspondence: Dr. Kåre Buhlin, Department of Periodontology, Karolinska Institutet, Alfred Nobels Allé 8, Box 4064, 141 04, Huddinge, Sweden. Tel/Fax: +46-8-711-8343. Email: [email protected]

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Submitted for publication: 18.08.11; accepted for publication: 30.04.12

connection between periodontitis and a number of systemic diseases. The common trait and connection between them is thought to be of an inflammatory origin. Many studies have focused on cardiovascular disease (CVD) but associations have also been found between diabetes mellitus and respiratory diseases. The most common risk factors for these diseases are hypercholesterolemia, obesity and smoking, although other inflammatory diseases have been discussed as risk factors or potential risk indicators (Buhlin et al, 2009). Epidemiological and clinical studies have shown that patients with periodontitis are at a significantly increased risk of developing CVD, diabetes mellitus and respiratory diseases (Scannapieco et al, 1998; Beck et al, 2001; Mealey and Rethman, 2003). Altered sero-

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logical risk marker profiles in patients with periodontitis might result from an invasion of bacteria, bacterial products or cytokines (IL-1, IL-6, TNF_ and PGE2) from the periodontal lesion into the blood stream, contributing to the induction and maintenance of a chronic inflammatory state (Ridker, 1999; Pizzo et al, 2010). Dyslipidemia and insulin resistance have been reported to be elevated in patients with periodontitis (Rader, 2007). In addition, a Finnish study has shown that serum antibody levels of periodontal bacteria Aggregatibacter actinomycetemcomitans predict coronary heart events (Pussinen et al, 2005). However, the contribution of these bacteria to atherosclerotic plaque formation is still unknown. The release of host-derived inflammatory mediators such as cytokines from chronically inflamed periodontal tissues into the circulation or respiratory tracts might provide a link between periodontal and these chronic inflammatory diseases, since chronic infection and inflammation predispose individuals to develop them (Scannapieco et al, 1998; Fox et al, 2007; Rader, 2007; Lamster et al, 2008). The association between periodontitis and respiratory inflammatory diseases such as asthma could have several explanations. Oral pathogens could be aspirated down to the lungs and/or the epithelium could be changed by the oral pathogens, enzymes or cytokines, thus creating a susceptibility to other infections (Scannapieco et al, 2001). However, even though data were adjusted for known risk factors, such as smoking and socioeconomic factors, other aggravating factors may still explain or at least contribute to the association between systemic disease and periodontitis; lifestyle factors, including diet and health awareness, are often not included in the statistical modelling. The aim of this chart register study was to investigate if patients with the diagnosis of severe periodontitis also had more signs of cardiovascular disease, respiratory diseases and diabetes mellitus compared to those with healthy periodontia.

MATERIALS AND METHODS Data selection and analysis This retrospective register study was performed at the Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden, using their EFFICA database, a computerised dental chart system (Tieto; Helsinki, Finland), for anamnestic, dental status and daily notes for every patient attending the De-

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partment. From this chart register, 474 charts were identified that contained a periodontal diagnosis in the status sheet, and these patients had received dental treatment from 2002 to 2008. Most of these patients had been referred to the Department of Dental Hygiene to receive oral hygiene and mechanical root debridement. 2002 was selected as it was the year that the EFFICA system was implemented at the Department of Dental Medicine, making this data set a convenience sample, and only valid for this specific population. Therefore, the resulting conclusions need to be interpreted with this in mind. Years of birth were selected from 1928 to 1968, and 1968 was selected as the end year since very few people develop CVD before 40 years of age (Arbes Jr et al, 1999). A total of 329 patients were selected from the 474 as they were diagnosed with different kinds of severe chronic generalised periodontitis (at least 30% of the present teeth had gingival bleeding, gingival pockets and had lost 33% of the bone support or more) or chronic generalised moderate periodontitis, localised severe (88.0% [43.0% generalised severe periodontitis]) (less than 30% of the present sites had gingival bleeding, gingival pockets and had lost 33% of the bone support or more) (Armitage, 1999). The others had chronic generalised slight periodontitis, localised severe (12.0%). Anamnestic data regarding age, gender, tobacco use, periodontal disease diagnosis and the patient’s medical records were obtained from the dental charts. The self-reported medical information regarding CVD (yes/no and type), respiratory diseases (yes/no and type) and diabetes mellitus (yes/no and type), as well as the disease severity were obtained from the dental charts. Smokers were considered to be those who were current smokers according to the charts. Nonsmokers were also those who had stopped smoking at least 5 years previously. The student obtained the medical information orally from the patient, and an instructor, who also discussed general health with the patient, subsequently confirmed it. The oral questions posed by the therapists regarding the patient’s general health were not standardised. In addition, due to the nature of the study, the examiners were not calibrated. Four charts were excluded due to missing data, therefore 325 charts were included in the severe periodontitis group. In the control group, the periodontal diagnosis healthy (n = 61) and gingivitis (n = 104) were selected. Sixteen cases of missing data were found in the gingivitis group, which is why

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88 were chosen. In total, 149 patients were included as controls. The CVD diagnoses identified in the dental charts were myocardial infarction, angina pectoris, atherosclerosis, heart failure, tachycardia, hypertension or other (heart murmur, heart valve problems). If the patients had received several CVD diagnoses, as identified in the same chart, the most severe was selected. Diabetes mellitus and respiratory diseases (asthma and chronic obstructive respiratory disease or other) were divided separately into two groups (yes/no). All data were first collected by a dental student and then corroborated by an experienced dentist, often a specialist or a dental hygiene instructor.

Table 1 Mean age (years) of the participants and smoking frequency (%) regarding periodontitis, CVD, respiratory diseases and diabetes mellitus

Peridontitis Yes No CVD Yes No Respiratory diseases Yes No

Age (years)

Smoking (%)

61.7 [SD 9.27] 56.2 [SD 9.34] P < 0.001

55.1 33.6 P < 0.001

64.2 [SD 9.31] 57.2 [SD 8.78] P < 0.001

28.4 51.0 P < 0.001

60.4 [SD 9.85] 59.9 [SD 9.58]

13.5 26.5 P < 0.001

62.9 [SD 9.11] 59.4 [SD 9.62] P < 0.001

15.7 17.6

Statistical analysis The Statistica 8 software programme (Statsoft; Tulsa, OK, USA) was used to perform statistical analysis. Parametric and nonparametric data were analysed, using the Student’s t-test or Mann-Whitney U-test, respectively. They were evaluated using the chi-square independent test or Fisher’s exact test in those cases where the expected values were less than 5. Odds ratios for CVD, respiratory diseases and diabetes mellitus were calculated with a stepwise logistic regression analysis adjusted for age, gender and smoking. The level of significance was set at 0.05 and the confidence interval (CI) at 95%. CIs were calculated using Wald’s method. The study was performed in accordance with the Regional Ethics Committee of the Karolinska Institute and was also conducted in accordance with the Helsinki Declaration.

RESULTS Our data analysis demonstrated that the patients with periodontitis were on average 5 years older than the controls without periodontal disease (61.7 vs 56.2; P < 0.001, Table 1). Both groups consisted of men and women; among those who suffered from periodontitis there was a relatively even gender distribution. However, within the control group there was a higher number of female cases (63.8%, data not shown). There were also significantly more smokers among those with periodontitis 55.1% vs 33.6% in the control group (P < 0.001, Table 1). In addition, there was also evidence that those who suffered from both severe periodontitis and CVD, respiratory diseases or diabetes mellitus were also

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Diabetes Yes No

SD: standard deviation. Significant differences in italics.

smokers to a greater number than the controls. Hypertension was the most common CVD diagnosis across both groups, and myocardial infarction was twice as common in the periodontitis group compared to the periodontally healthier ones (Table 2). The main finding of the study was that those patients with severe periodontitis also claimed that they suffered from more CVD and diabetes mellitus. The number of patients exhibiting respiratory diseases (mostly asthma) was the same between the groups, and those who claimed that they did not suffer from any diseases were fewer in the severe periodontitis group (37.2% vs 46.3%). Those who suffered from CVD were significantly older than those who did not (P < 0.001, Table 1) and their periodontitis status was also more prominent (44.3% vs 30.9%; P = 0.006, Table 3). Patients born before 1950 had significantly more CVD than the younger ones (54% vs 25%; P < 0.001). There were also fewer smokers in the CVD group compared to those without (28% vs 51%; P < 0.001), and women had more CVD diagnoses than men (44% vs 35%; P < 0.049, Table 3). With regard to respiratory diseases, the most common diagnosis was asthma, in over 90% of patients, and the remainder had chronic obstructive pulmonary disease. However, no association was found between respiratory diseases and periodonti-

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Table 2 Prevalence in % and (n) of healthy patients and those with different cardiovascular diagnoses in different age subgroups Severe periodontitis % (n)

Periondontally healthy % (n)

Born 1928-1939 Severe periodontitis % (n)

Born 1928-1939 Periondontally healthy % (n)

Born 1940-1959 Severe periodontitis % (n)

Born 1940-1959 Periondontally healthy % (n)

Born 1960-1968 Severe periodontitis % (n)

Born 1960-1968 Periondontally healthy % (n)

(149)

(87)

(19)

(204)

(93)

(34)

(37)

69.1 (103)

29.9 (26)

36.9 (7)

62.3 (127)

68.9 (64)

82.3 (28)

86.4 (32)

Myocardial infarction, angina pectoris, atherosclerosis 12.3 (40) 6.7 (10) 21.8 (19) 10.5 (2)

9.3 (19)

8.6 (8)

5.9 (2)

0 (0)

Heart failure, tachycardia and others 8.3 (27) 12.1 (18) 16.1 (14)

26.3 (5)

5.9 (12)

10.8 (10)

2.9 (1)

8.1 (3)

Hypertension 23.7 (77)

26.3 (5)

22.5 (46)

11.8 (11)

8.8 (3)

5.4 (2)

Total (325) Healthy 55.6 (181)

12.1 (18)

32.2 (28)

Table 3 Frequencies in % and (n) for CVD, respiratory diseases and diabetes mellitus for various subgroups Women % (n)

Men % (n)

Smokers % (n)

Non-smokers % (n)

Born before 1950 Yes % (n)

Born before 1950 No % (n)

Periodontitis Yes % (n)

Periodontitis No % (n)

CVD 43.9 (119) P < 0.04

35.0 (71)

28.4 (65) P < 0.001

51.0 (125)

53.6 (135) P < 0.001

24.8 (55)

44.3 (144) P = 0.006

30.9 (46)

13.5 (31)

26.5 (65) P < 0.001

21.0 (53)

19.4 (43)

18.8 (61)

23.5 (35)

15.7 (36)

17.6 (43)

22.2 (56) P < 0.001

10.4 (23)

21.2 (69) P < 0.001

6.7 (10)

Respiratory diseases 20.7 (56) 19.7 (40) Diabetes mellitus 13.7 (37) 20.7(42) P < 0.042

tis (P = 0.24), or between age and respiratory diseases (P = 0.65). Among those patients with respiratory diseases, there were significantly fewer smokers who had periodontitis (27% vs 14%; P < 0.001, Table 3). Diabetes mellitus was more prevalent in men than in women (21% vs 14%; P < 0.042) and patients with diabetes were older than those without the disease (P < 0.001, Table 1). Diabetes was also more common among those with periodontitis (P < 0.001) (Table 3). Of note, the charts gave no information as to what type of diabetes the patients had.

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Stepwise logistic regression analysis Using stepwise logistic regression analysis (periodontitis, gender, smoking and born in 1950 or before), we found an association between periodontitis and all CVDs in general, with an odds ratio (OR) of 1.79 (CI 1.12–2.86). There was also an association between those born in 1950 or before, and CVD (OR 2.90) and diabetes (OR 2.19) (Table 4). No interactions were detected between CVD and age, although there was an interaction between age and smoking. Interestingly, smoking was negatively associated with CVD (OR = 0.36, CI 0.24–0.54), diabetes (OR = 0.88, CI 0.27–0.70) and respirato-

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Table 4 Odds ratios, OR, and 95% confidence interval (CI) for the relationship between periodontal health, CVD, respiratory diseases and diabetes mellitus

1

CVD OR (CI)

Respiratory diseases OR (CI)

Diabetes mellitus OR (CI)

Periodontitis OR (CI)

Periodontitis1

1.79 (1.12–2.86)

0.88 (0.53–1.47)

2.95 (1.45–6.01)

_

Women

1.38 (0.92–2.09)

1.05 (0.66–1.67)

0.58 (0.35–0.95)

0.61 (0.40–0.93)

Smoking2

0.36 (0.24–0.54)

0.44 (0.27–0.70)

0.87 (0.54–1.42)

3.80 (2.39–6.06)

Born before 1950

2.90 (1.91–4.38)

1.11 (0.71–1.74)

2.19 (1.27–3.79)

3.08 (2.02–4.69)

The patient has periodontitis. 2 The patient smokes. The associations are shown for all participants. Significant differences in italics.

ry diseases (OR = 0.43, CI 2.39–6.06)), but not for periodontitis (OR =3.8, CI 0.54–1.42). Women had a lower risk for periodontitis (OR = 0.61), as well as suffering from diabetes (OR = 0.58). Associations were also found between periodontitis and diabetes (OR = 2.95, CI 1.45–6.01), but no association was found with respiratory diseases (OR = 0.88, CI 0.53–1.47). No interactions were detected between diabetes or respiratory diseases and gender, smoking or age.

DISCUSSION This retrospective study found an association between periodontitis, CVD and diabetes mellitus respectively, but not with respiratory diseases when adjusted for age, gender and smoking. However, the population examined in this study was not randomised from a general Swedish population since we selected patients receiving dental care at a Dental School. The patients had been treated by different dental students and had been subjected to different kinds of treatments at various intervals, indicating that some patients only sought dental treatment if it was an emergency. In general, those who received care at the Dental School tended to have a worse periodontal status than the general population; therefore the results due to sampling should be carefully evaluated. In this study, self-reported anamnestic information was also used for medical status and tobacco use. Several studies have been performed to investigate the validity of

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self-reported medical questionnaires in dental care and they show a good degree of validity (Loesche and Lopatin, 1998; Buhlin et al, 2002). The association between self-reported medical information, such as stroke, in relation to the prevalence of diagnosed stroke, has also shown a good measure of accuracy (Engstad et al, 2000). With regard to stroke and myocardial infarction, 75% of the selfreported information was known to be correct (Psaty et al, 1995). However, self-reporting could lead to validity problems, since some patients do not want to answer correctly and the patients could also have diseases that they do not know about (Thompson et al, 1999). One problem with the current study was that dental students had done all the periodontal examinations, although an experienced dentist corroborated all patients and diagnostics and the diagnostic criteria followed the guidelines from Armitage 1999. In this study, the patients in the periodontitis group were older than the controls; furthermore, if the patient was born before 1950 the ORs were higher for CVD. This highlights the importance of performing a stepwise logistic regression adjusted for age, smoking and gender. Smoking is a well-known risk factor for periodontitis, respiratory diseases and CVD. This study also found a strong relationship between smoking and periodontitis. However, it was surprising and confusing that smokers in this study had significantly less CVD and respiratory diseases compared to nonsmokers. One reason could be that the population was not representative, for instance, there

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were more smokers in this study compared to the general Swedish population. Another reason could be that those with CVD or asthma had stopped smoking to a greater extent than those without any diagnosis. The prevalence of CVD among the patients with periodontitis was 44.3% and 38.2% across all participants. These numbers were very high compared to other studies. In a study by Lagervall et al (2003) the prevalence was 10.1%. There could be several reasons explaining the difference: the population may have been sicker and probably socioeconomically weaker; one of the reasons why someone becomes a patient at the Dental School are the low prices. This study showed an association between CVD and periodontitis, although the association could be temporal and due to circumstantial events for this specific group, since we do not know how long the patient may have suffered from the systemic disease. If periodontitis increased the risk for CVD, periodontal treatment would therefore decrease proatherogenic markers in the blood. In a Swedish intervention study, patients who received periodontal treatment were found to have elevated cholesterol and inflammatory markers 12 months after treatment (Buhlin et al, 2009). In this study, the most important finding was yielded by the multiple logistic regression analysis, since it was adjusted for age, periodontitis, smoking and gender. There was a strong association between periodontitis and diabetes (OR = 3.0). This is in line with previous studies, particularly the American study by Tsai et al (2002) (OR = 2.9). It is known that patients with poorly controlled diabetes have a greater risk of having periodontitis, since they are more prone to infections. Furthermore, studies have indicated that periodontitis has an effect on glycemic control and influences the metabolic syndrome (Grossi and Genco 1998; Taylor, 2001, Holmlund et al, 2007). The association between well-maintained diabetes and periodontitis was not very strong, and in the present study it is unknown if the diabetes was well controlled. Therefore, the magnitude of the association in this study between periodontitis and diabetes remains uncertain. Furthermore, this study found no association between periodontitis and respiratory diseases, which is interesting since other studies have indicated a bacterial association (Scannapieco et al, 1998; Gomes-Filho et al, 2009; Mehta et al, 2009). This study concluded that periodontal disease may have a reverse association with asthma problems, which

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is in line with findings from a North American study (Arbes et al, 2006). One hypothesis for this reverse relationship could be that infections and inflammations, like periodontitis, might immunise the individual against asthma. A risk group are those who have a lower respiratory tract infection and are older. Since the population was relatively young and healthy, this might be one reason why there was no association in the current investigation. The most common respiratory diagnosis was asthma and the previous links with periodontitis have mostly been reported to be associated with pneumonia and chronic obstructive respiratory disease (Scannapieco et al, 1998; 2001). Some studies reported that children with asthma had more gingivitis than children without (McDerra et al, 1998), and otherstudies suggested a similar relationship in the adult population (Laurikainen and Kuusisto, 1998). However, to date asthma has not been clearly associated with periodontitis in adults.

CONCLUSION This study found that there was an association in this population between periodontitis and certain systemic diseases, such as CVD and diabetes mellitus, but not with respiratory diseases such as asthma. The mechanisms regarding the relationships between the diseases remain largely unknown and warrant further investigation. In the future, this might lead to closer co-operation between the dental and medical professions.

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