Composition of subgingival microbiota associated with periodontitis and diagnosis of malignancy-a cross-sectional study.

Periodontitis is one of the world's most prevalent infectious conditions, affecting between 25 and 40% of the adult population. It is a consequence of the complex interactions between periodontal pathogens and their products, which trigger the host inflammatory response, chronic inflammation, and tissue destruction. Chronic systemic low-grade inflammation is involved in numerous diseases, and it is also known that long-lasting inflammation and chronic infections predispose one to cancer. Here, we characterized and compared the subgingival microbiota associated with periodontitis and diagnosis of malignancy in a longitudinal 10-year follow-up study. The study was conducted on 50 patients with periodontitis and 40 periodontally healthy individuals. The recorded clinical oral health parameters were periodontal attachment loss (AL), bleeding on probing (BOP), gingival index (GI), probing depth (PD), and plaque index (PI). Subgingival plaque was collected from each participant, from which DNA was extracted, and 16S rRNA gene amplicon sequencing performed. Cancer diagnoses data were collected between the years 2008-2018 from the Swedish Cancer Registry. The participants were categorized based on having cancer at the time of sample collection (CSC), having developed cancer later (DCL), and controls without any cancer. The most abundant phyla across all 90 samples were Actinobacteria, Proteobacteria, Firmicutes, Bacteroidetes, and Fusobacteria. At the genus level, Treponema, Fretibacterium, and Prevotella were significantly more abundant in samples of periodontitis patients compared to non-periodontitis individuals. With regard to samples of cancer patients, Corynebacterium and Streptococcus were more abundant in the CSC group; Prevotella were more abundant in the DCL group; and Rothia, Neisseria, and Capnocytophaga were more abundant in the control group. In the CSC group, we also found that the presence of periodontal inflammation, in terms of BOP, GI, and PLI, significantly correlated with species belonging to the genera Prevotella, Treponema, and Mycoplasma. Our results revealed that several subgingival genera were differentially enriched among the studied groups. These findings underscore the need for further research to fully understand the role that oral pathogens may play in the development of cancer.

Periodontitis may predict the use of prescription medicines later in life, a database study.

Medications used for the treatment of diseases also affect oral health. We investigated how having/not having periodontitis at baseline in 1985 was associated with purchases of medicines in the long term. The study paradigm is in the oral health-systemic health connections. We hypothesized that periodontitis links to purchases of medicines later in life. The study cohort consisted of 3,276 individuals from the greater Stockholm area, Sweden. Of them, 1,655 were clinically examined at baseline. Patients were followed-up for >35 years, using the national population and patient registers. The burden of systemic diseases and purchases of medicines were statistically analyzed comparing patients with (n = 285) and without (n = 1,370) periodontitis. The results showed that patients with periodontitis had purchased more of certain medications than non-periodontitis patients. Periodontitis patients purchased significantly more drugs used in diabetes (p = 0.035), calcium channel blockers (p = 0.016), drugs acting on the renin-angiotensin system (p = 0.024), and nervous system drugs (p = 0.001). Hence, patients with periodontitis indeed had purchased specific medications statistically significantly more than the periodontally healthy ones. This indicates that periodontitis, over time, might increase the risk for systemic diseases with the subsequent need for medication.

Prevalence of cancer in relation to signs of periodontal inflammation.

We investigated the associations between periodontal inflammation (gingivitis and periodontitis) and all-kind malignancies, specifically breast and prostate cancer, in a cohort followed-up for 30 years. The study hypothesis was based on the oral inflammation vs. systemic health paradigm. A sample of 2,168 subjects from an original cohort of 105,718 individuals from the greater Stockholm area in Sweden that had been followed since 1985 was investigated. Swedish national health registers were used in the study. Chi-square tests and logistic multiple regression analyses were conducted. The results showed that periodontitis was significantly associated with any cancer after adjusting for gender, age, income, and education (p = 0.015). The probability of getting cancer increased on average by 38% if the patient had periodontitis vs. had not; the odds ratio was 1.380 (95% confidence interval l.066-1.786). No significant association was observed between periodontitis and breast cancer (p = 0.608), while the association between periodontitis and prostate cancer tended towards significance (p = 0.082). However, no statistically significant difference was found between the observed and the calculated distribution of any cancer in gingivitis groups (p = 0.079). Thus, the study hypothesis was partly confirmed by showing a statistically significant association between periodontitis and any cancer.

The Stockholm Study: Over 30 years' Observation of the Effect of Oral Infections on Systemic Health.

The Stockholm Studies are a series of investigations started in 1985 and still ongoing. Out of 105,798 inhabitants, aged 30 and 40 years and living in the greater Stockholm area in Sweden, 3273 subjects were randomly selected. Of them, 1676 were clinically examined focusing on oral health. The subjects were then followed up using national population and health registers in order to study associations between oral health parameters and systemic health outcomes and finally death. The 35 years of observation provides unique possibilities to analyze, for example, how periodontitis links to a number of systemic health issues. The results have consequently provided numerous new associations and confirmed earlier observations on how poor oral health is associated with heart diseases and cancer.

Periodontal microorganisms and diagnosis of malignancy: A cross-sectional study.

BACKGROUND: Oral infections associate statistically with cancer. OBJECTIVE: We hypothesized that certain periodontal microorganisms might specifically link to malignancies in general and set out to investigate this in our ongoing cohort study. METHODS: A sample of 99 clinically examined patients from our cohort of 1676 subjects was used to statistically investigate the associations between harboring periodontal microorganisms Aggregatibacter actinomycetemcomitans (A.a), Porphyromonas gingivalis (P.g), Prevotella intermedia (P.i), Tannerella forsythia (T.f) and Treponema denticola (T.d). We used oral infection indexes and the incidence figures of malignancies as registered in 2008-2016 in the Swedish National Cancer Register. RESULTS: The pathogen A.a showed strong association with malignancy in 32 out of the 99 patients while P.g and P.i were more prevalent among patients without malignancy. In principal component analyses, A.a appeared in the strongest component while the second strongest component consisted of a combination of T.f and T.d. The third component consisted of a combination of P.g and P.i, respectively. Of basic and oral health variables, gingival index appeared to be the strongest expression of inflammation (Eigen value 4.11 and Explained Variance 68.44 percent). CONCLUSIONS: The results partly confirmed our hypothesis by showing that harboring certain periodontal bacteria might link to malignancy. However, the associations are statistical and no conclusions can be drawn about causality.

Tobacco Products, Periodontal Health and Education Level: Cohort Study from Sweden.

BACKGROUND: The aim of this study is to investigate if using tobacco products (including snuff, smoking tobacco and dual-using) associates with periodontal health, education level and mortality in a Swedish cohort, hypothesizing that tobacco products affect periodontal health, associate with lower education and increase the risk of death. METHOD: Study cohort of 1080 subjects aged 31-40 years (528 men, 552 women) was clinically examined and interviewed in 1985 and followed for mortality until 2015. Subjects were classified into two groups: "tobacco users" and "non-users". Associations between periodontal health parameters, tobacco products, education level and age of death were analysed. SPSS was used for analyses. RESULTS: Tobacco products, as well as education level associated, with poor periodontal health. Tobacco users and lower education was linked to higher plaque-, calculus- and gingival-index scores than non-users (p < 0.001). They also had significantly higher prevalence of deep periodontal pockets (≥5 mm) (p < 0.001 and 0.010, respectively), missing teeth (p = 0.010 and 0.003, respectively) and lower education level (p < 0.001) compared with non-users. However, tobacco product users did not die significantly earlier than non-users. CONCLUSION: Tobacco products had a negative impact on periodontal health. Tobacco product users were less educated. However, using tobacco products may not cause premature death.

Apical periodontitis associates with cardiovascular diseases: a cross-sectional study from Sweden.

BACKGROUND: Periodontal disease associates with systemic diseases but corresponding links regarding apical periodontitis (AP) are not so clear. Hence our aim was to study association between AP and the prevalence of systemic diseases in a study population from Sweden. METHODS: The subjects were 150 patients from a randomly selected epidemiological sample of 1676 individuals. 120 accepted to participate and their basic and clinical examination data were available for these secondary analyses where dental radiographs were used to record signs for endodontic treatments and AP. Periapical Index and modified Total Dental Index scores were calculated from the x-rays to classify the severity of AP and dental infection burden, respectively. Demographic and hospital record data were collected from the Swedish National Statistics Center. T-test, chi-square and univariate analysis of covariance (ANCOVA) and regressions analyses were used for statistics. RESULTS: Of the 120 patients 41% had AP and 61% had received endodontic treatments of which 52% were radiographically unsatisfactory. AP patients were older and half of them were smokers. AP and periodontitis often appeared in the same patient (32.5%). From all hospital diagnoses, cardiovascular diseases (CVD) were most common, showing 20.4% prevalence in AP patients. Regression analyses, controlled for age, gender, income, smoking and periodontitis, showed AP to associate with CVD with odds ratio 3.83 (95% confidence interval 1.18-12.40; p = 0.025). CONCLUSIONS: The results confirmed our hypothesis by showing that AP statistically associated with cardiovascular diseases. The finding that subjects with AP also often had periodontitis indicates an increased oral inflammatory burden.

Autoimmune Diseases and Oral Health: 30-Year Follow-Up of a Swedish Cohort.

Oral infections up-regulate a number of systemic inflammatory reactions that, in turn, play a role in the development of systemic diseases. We investigated the association between oral health and autoimmune diseases in a cohort of Swedish adults. Hypothesis was that poor oral health associates with incidence of autoimmune diseases. Overall 1676 subjects aged 30-40 years old from Stockholm County (Sweden) participated in this study in 1985. Subjects were randomly selected from the registry file of Stockholm region and were followed-up for 30 years. Their hospital and open health care admissions (World Health Organization ICD 9 and 10 codes) were recorded from the Swedish national health registers. The association between the diagnosed autoimmune disease and the oral health variables were statistically analyzed. In all, 50 patients with autoimmune diagnoses were detected from the data. Plaque index was significantly higher in the autoimmune disease group (≥median 35 (70%) vs. ˂median 872 (54%), p = 0.030). No statistical difference was found in gingival index, calculus index, missing teeth, periodontal pockets, smoking or snuff use between patients with and without autoimmune disease. Our study hypothesis was partly confirmed. The result showed that subjects with a higher plaque index, marker of poor oral hygiene, were more likely to develop autoimmune diseases in 30 years.

Salivary MMP-13 gender differences in periodontitis: A cross-sectional study from Sweden.

We investigated serum and saliva concentrations of matrix metalloproteinases, MMP-8, MMP-9, and MMP-13, and their tissue inhibitor TIMP-1, in a group of patients with and without periodontitis from Sweden. The hypothesis was that these biomarkers are higher in the periodontitis patients. Ninety patients participated in this cross-sectional study. Fifty-one patients had periodontitis whereas 39 were periodontally healthy. Saliva and serum samples were analyzed with immunofluorometric, enzyme-linked immunosorbent assay and western blot. Results were statistically analyzed with independent t test, Mann-Whitney U test, Bonferroni corrections, and regression analyses. MMP-13 was not detected in serum, but in saliva, higher values were found among the periodontally healthy compared with periodontitis subjects (0.32 ± 0.26 vs. 0.21 ± 0.23 ng/ml, p < .05). Female gender and clinical attachment loss were the explanatory factors for higher salivary MMP-13 values with odds ratio 3.08 (95% confidence interval [1.17, 8.11]) and 3.57 (95% confidence interval [1.08, 11.82]), respectively. No statistically significant differences between groups were found in serum and saliva values of MMP-8, MMP-9, and TIMP-1. Contrary to our hypothesis, no statistically significant differences between patients with and without periodontitis were seen in MMP-8, MMP-9, and TIMP-1 values. However, higher MMP-13 concentrations in saliva were associated with female gender and higher clinical attachment loss. Metabolism of MMP-13 may thus have some gender implications in periodontitis.

Dental Calculus Links Statistically to Angina Pectoris: 26-Year Observational Study.

OBJECTIVES: Dental infections, such as periodontitis, associate with atherosclerosis and its complications. We studied a cohort followed-up since 1985 for incidence of angina pectoris with the hypothesis that calculus accumulation, proxy for poor oral hygiene, links to this symptom. METHODS: In our Swedish prospective cohort study of 1676 randomly selected subjects followed-up for 26 years. In 1985 all subjects underwent clinical oral examination and answered a questionnaire assessing background variables such as socio-economic status and pack-years of smoking. By using data from the Center of Epidemiology, Swedish National Board of Health and Welfare, Sweden we analyzed the association of oral health parameters with the prevalence of in-hospital verified angina pectoris classified according to the WHO International Classification of Diseases, using descriptive statistics and logistic regression analysis. RESULTS: Of the 1676 subjects, 51 (28 women/23 men) had been diagnosed with angina pectoris at a mean age of 59.8 ± 2.9 years. No difference was observed in age and gender between patients with angina pectoris and subjects without. Neither was there any difference in education level and smoking habits (in pack years), Gingival index and Plaque index between the groups. Angina pectoris patients had significantly more often their first maxillary molar tooth extracted (d. 16) than the other subjects (p = 0.02). Patients also showed significantly higher dental calculus index values than the subjects without angina pectoris (p = 0.01). Multiple regression analysis showed odds ratio 2.21 (95% confidence interval 1.17-4.17) in the association between high calculus index and angina pectoris (p = 0.015). CONCLUSION: Our study hypothesis was confirmed by showing for the first time that high dental calculus score indeed associated with the incidence of angina pectoris in this cohort study.

Gingival Inflammation Associates with Stroke--A Role for Oral Health Personnel in Prevention: A Database Study.

OBJECTIVES: Gingival inflammation is the physiological response to poor oral hygiene. If gingivitis is not resolved the response will become an established lesion.We studied whether gingivitis associates with elevated risk for stroke. The hypothesis was based on the periodontitis-atherosclerosis paradigm. METHODS: In our prospective cohort study from Sweden 1676 randomly selected subjects were followed up from 1985 to 2012. All subjects underwent clinical oral examination and answered a questionnaire assessing background variables such as socio-economic status and pack-years of smoking. Cases with stroke were recorded from the Center of Epidemiology, Swedish National Board of Health and Welfare, Sweden, and classified according to the WHO International Classification of Diseases. Unpaired t-test, chi-square tests, and multiple logistic regression analyses were used. RESULTS: Of the 1676 participants, 39 subjects (2.3%) had been diagnosed with stroke. There were significant differences between the patients with stroke and subjects without in pack-years of smoking (p = 0.01), prevalence of gingival inflammation (GI) (p = 0.03), and dental calculus (p = 0.017). In a multiple regression analysis the association between GI, confounders and stroke, GI showed odds ratio 2.20 (95% confidence interval 1.02-4.74) for stroke. CONCLUSION: Our present findings showed that gingival inflammation clearly associated with stroke in this 26-year cohort study. The results emphasize the role of oral health personnel in prevention.

Unique database study linking gingival inflammation and smoking in carcinogenesis.

We investigated statistical association between gingival inflammation and cancer in a group of patients followed up for 26 years with the hypothesis that gingival inflammation affects carcinogenesis. Altogether, 1676 30- to 40-year-old subjects from Stockholm were clinically examined in 1985. In 2011, we compared the baseline oral examination and follow-up data with cancer diagnoses sourced from the Swedish national hospital register databases. Of 1676 individuals, 89 (55 women, 34 men) had got cancer by the year 2011. Women were found to be at higher risk for cancer than men. Smoking (expressed in pack-years) had been more prevalent in the cancer group than in those with no cancer diagnosis. Gingival index, marker of gingival inflammation, was higher in the cancer group than in subjects with no cancer. There were no significant differences between the groups regarding age, education, dental plaque and calculus index scores, or in the number of missing teeth. In multiple logistic regression analysis with cancer as the dependent variable and several independent variables, pack-years of smoking appeared to be a principal independent predictor with odds ratio (OR) 1.32 while gingival inflammation showed OR 1.29. Hence, our present findings showed that together with smoking, gingival inflammation indeed associated with the incidence of cancer in this cohort.

Dental calculus is associated with death from heart infarction.

OBJECTIVES: We studied whether the amount of dental calculus is associated with death from heart infarction in the dental infection-atherosclerosis paradigm. MATERIALS: Participants were 1676 healthy young Swedes followed up from 1985 to 2011. At the beginning of the study all subjects underwent oral clinical examination including dental calculus registration scored with calculus index (CI). Outcome measure was cause of death classified according to WHO International Classification of Diseases. Unpaired t-test, Chi-square tests, and multiple logistic regressions were used. RESULTS: Of the 1676 participants, 2.8% had died during follow-up. Women died at a mean age of 61.5 years and men at 61.7 years. The difference in the CI index score between the survivors versus deceased patients was significant by the year 2009 (P < 0.01). In multiple regression analysis of the relationship between death from heart infarction as a dependent variable and CI as independent variable with controlling for age, gender, dental visits, dental plaque, periodontal pockets, education, income, socioeconomic status, and pack-years of smoking, CI score appeared to be associated with 2.3 times the odds ratio for cardiac death. CONCLUSIONS: The results confirmed our study hypothesis by showing that dental calculus indeed associated statistically with cardiac death due to infarction.

History of dental infections associates with cancer in periodontally healthy subjects: a 24-year follow-up study from sweden.

BACKGROUND: Infections of teeth are highly prevalent, often leading to tooth extractions. Missing teeth can thus be considered as proxy for chronic dental infections, caries or periodontitis. We followed-up a cohort for 24 years investigating the association between missing teeth and the incidence of cancer with the hypothesis that dental chronic inflammation links to cancer. METHODS: WHO ICD-7-9-10 malignant diagnoses were recorded from the Swedish Cancer Registry from 1985 to 2009 in 1 390 individuals who had underwent clinical oral examination in 1985. The subjects appeared periodontally healthy and thus the probable reason for tooth extractions was deep caries. Using Fisher's exact t-test and multiple logistic regression analysis the results were analysed for the association between cancer incidence and baseline oral health parameters and a number of other explanatory factors. RESULTS: Of the 1 390 subjects 71 had got cancer by year 2009. The results of the multiple regression analysis showed that between any type of cancer as a dependent variable, and several independent explanatory variables, missing second molar in the right mandible and age appeared as the principle independent predictors significantly associating with cancer, with an odds ratio (95% confidence interval) of 2.62 (1.18-5.78) and 1.91 (1.06-3.43), respectively. CONCLUSIONS: In periodontally healthy subjects extracted molars, proxy for past dental infections, seemed to predict cancer risk in the studied age group - hence supporting a role of chronic dental infection/inflammation in carcinogenesis.

The association of dental plaque with cancer mortality in Sweden. A longitudinal study.

OBJECTIVES: To study whether the amount of dental plaque, which indicates poor oral hygiene and is potential source of oral infections, associates with premature death from cancer. DESIGN: Prospective cohort study. PARTICIPANTS: 1390 randomly selected healthy young Swedes followed up from 1985 to 2009. All subjects underwent oral clinical examination and answered a questionnaire assessing background variables such as socioeconomic status and smoking. OUTCOME MEASURES: Causes of death were recorded from national statistics and classified according to the WHO International Classification of Diseases. Unpaired t test, χ(2) tests and multiple logistic regressions were used. RESULTS: Of the 1390 participants, 4.2% had died during the follow-up. Women had died at a mean age of 61.0 (±2.6 SD) years and men at the age of 60.2 (±2.9 SD) years. The amount of dental plaque between those who had died versus survived was statistically significant (p<0.001). In multiple logistic regression analysis, dental plaque appeared to be a significant independent predictor associated with 1.79 times the OR of death (p<0.05). Age increased the risk with an OR of 1.98 (p<0.05) and gender (men) with an OR of 1.91 (p<0.05). The malignancies were more widely scattered in men, while breast cancer was the most frequent cause of death in women. CONCLUSIONS: This study hypothesis was confirmed by showing that poor oral hygiene, as reflected in the amount of dental plaque, was associated with increased cancer mortality.

C-reactive protein in relation to early atherosclerosis and periodontitis.

Periodontitis may affect atherosclerosis via the chronic inflammation. We investigated high-sensitivity C-reactive protein (hsCRP) in relation to early vascular atherosclerotic changes in non-symptomatic subjects with and without long-term periodontitis. Carotid ultrasonography with calculation of common carotid artery intima-media area (cIMA) was performed, and hsCRP and atherosclerosis risk factors were analysed in randomly chosen 93 patients with periodontitis and 41 controls. The relationship between hsCRP, cIMA and atherosclerosis risk factors was evaluated with multiple logistic regression analysis. Women displayed lower hsCRP (p < 0.05) and higher serum HDL (p < 0.001) than men. In all patients with periodontitis, cIMA values were higher than in controls. Periodontitis appeared to be a major predictor for increased cIMA (odds ratio, 3.82; 95% confidence interval, 1.19-12.26). Neither of these factors was significantly associated with hsCRP which thus appeared not sensitive enough to be a marker for periodontitis or atherosclerosis. Hence, irrespective of low hsCRP levels, periodontitis appeared to increase the risk for atherosclerosis.

Associations of periodontal microorganisms with salivary proteins and MMP-8 in gingival crevicular fluid.

OBJECTIVE: We investigated in subjects with and without periodontitis, the levels of certain salivary proteins and matrix metalloproteinase-8 (MMP-8) in gingival crevicular fluid (GCF), in relation to the presence of specific periodontal pathogens. METHODS: Clinical parameters were recorded at baseline, in 1985 and in 2009 from 99 subjects; 56 with and 43 without periodontitis (mean age 59.2 ± SD 2.9). Saliva samples collected in 2009 were analysed for salivary albumin, total protein and immunoglobulins A, G and M. GCF was collected for analysis of MMP-8 levels and for the PCR-analysis of the microorganisms Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola and Tannerella forsythia. RESULTS: Periodontitis patients were more often infected by P. gingivalis (p < 0.05), P. intermedia and T. denticola (p = 0.01) than controls. Salivary albumin and protein concentrations were significantly higher in subjects with T. denticola (p < 0.05). MMP-8 levels were significantly higher in subjects with T. denticola (p < 0.001) and T. forsythia (p < 0.01). No corresponding results were found in salivary immunoglobulin concentrations. CONCLUSION: The presence of T. denticola seemed to increase salivary albumin and total protein concentrations, and GCF levels of MMP-8. Both T. denticola and T. forsythia seemed to induce a cascade of host response with increased MMP-8 in GCF.

Periodontal disease may associate with breast cancer.

The main purpose was to evaluate the association between periodontal disease and the incidence of breast cancer in a prospective study of 3273 randomly selected subjects aged 30-40 years at baseline. Breast cancer incidence was registered from 1985 to 2001 according to the WHO International Classification of Diseases criteria. At baseline, 1676 individuals also underwent a clinical oral examination (Group A) whereas 1597 subjects were not clinically examined but were registered (Group B). The associations between breast cancer, periodontal disease, and missing molars were determined using multiple logistic regression models with several background variables and known risk factors for cancer. In total 26 subjects in group A and 15 subjects in group B had breast cancer. The incidence of breast cancer was 1.75% in subjects who had periodontal disease and/or any missing molars, and 0 in subjects who had periodontal disease but had no missing molars. For periodontally healthy subjects with no missing teeth the breast cancer incidence was 1%. For group B the respective incidence was 0.94%. Female gender (odds ratio (OR) 13.08) and missing any molar in the mandible (OR 2.36) were explanatory variables for breast cancer. Of the subjects with periodontal disease and any missing molars in the mandible 5.5% had breast cancer in comparison to 0.5% of the subjects who had periodontal disease but no missing molars in the mandible (P < 0.02). Chronic periodontal disease indicated by missing molars seemed to associate statistically with breast cancer.

Increased leukotriene concentrations in gingival crevicular fluid from subjects with periodontal disease and atherosclerosis.

Recent studies indicate that periodontal disease is associated with the development of early atherosclerotic lesions in the carotid artery. Since inflammation is a key feature in both atherosclerosis and periodontal disease, a common mediator of the two diseases could be anticipated. Leukotrienes are lipid-derived inflammatory mediators recently implicated in the pathogenesis of atherosclerosis and previously shown to be produced in periodontitis. The aim of the present study was to detect leukotrienes in gingival crevicular fluid (GCF) from subjects with atherosclerosis. Carotid ultrasonography and oral clinical examination were performed in 19 periodontitis patients and 16 healthy subjects. Atherosclerotic plaques were detected on ultrasound examination in 13 subjects with periodontis, and in 5 of the healthy subjects. Elevated concentrations of leukotriene B(4) and cysteinyl-leukotrienes were detected in GCF from subjects with a high dental plaque index (PLI>0.3), supporting an increased leukotriene formation in periodontitis. In addition, subjects with atherosclerotic plaques had significantly elevated concentrations of cysteinyl-leukotrienes in their GCF as compared with subjects without a visible plaque. Finally, the increased cysteinyl-leukotriene concentrations in GCF from atherosclerotic subjects were observed also when sub groups of periodontis patients and healthy subjects were compared separately. In summary, increased GCF concentrations of cysteinyl-leukotrienes were correlated to measures of both periodontitis and atherosclerosis. These results suggest that increased leukotriene formation may represent a possible link between periodontitis and atherosclerosis and a risk factor marker for both diseases.