Primary apical periodontitis correlates to elevated levels of interleukin-8 in a Swedish population: A report from the PAROKRANK study.

AIM: To explore associations between root filled teeth, primary and secondary apical periodontitis, and levels of inflammatory markers in blood from patients with a first myocardial infarction and matched controls. METHODOLOGY: Between May 2010 and February 2014, 805 patients with a first myocardial infarction and 805 controls, matched for sex, age, and postal code area, were recruited to the multicentre case-control study PAROKRANK (periodontitis and its relation to coronary artery disease). All participants underwent a physical and oral examination, as well as blood sampling. Using panoramic radiography, root filled teeth, primary apical periodontitis, and secondary apical periodontitis were assessed by three independent observers. Blood samples were analysed with enzyme-linked immunosorbent assay method for the following inflammatory markers: interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-12p70, tumour necrosis factor-α, and high-sensitivity C-reactive protein (hsCRP). Additionally, white blood cell count and plasma-fibrinogen were analysed. Associations between endodontic variables and the levels of inflammatory markers were statistically analysed with Mann-Whitney U-test and Spearman correlation, adjusted for confounding effects of baseline factors (sex, age, myocardial infarction, current smoking, diabetes, family history of cardiovascular disease, education, marital status, and periodontal disease). RESULTS: Mean age of the cohort was 62 years, and 81% were males. Root fillings were present in 8.4% of the 39 978 examined teeth and were associated with higher levels of hsCRP, fibrinogen, and leukocyte count, but lower levels of IL-2 and IL-12p70. After adjusting for confounders, root filled teeth remained associated with higher levels of fibrinogen, but lower levels of IL-1ß, IL-2, IL-6, and IL-12p70. Primary apical periodontitis was found in 1.2% of non-root filled teeth and associated with higher levels of IL-8 (correlation 0.06, p = .025). Secondary apical periodontitis was found in 29.6% of root filled teeth but did not relate to the levels of any of the inflammatory markers. CONCLUSIONS: This study supports the notion that inflammation at the periapex is more than a local process and that systemic influences cannot be disregarded. Whether the observed alterations in plasma levels of inflammatory markers have any dismal effects on systemic health is presently unknown but, considering the present results, in demand of further investigation.

Endodontic inflammatory disease: A risk indicator for a first myocardial infarction.

AIM: To study the association between endodontic inflammatory disease and a first myocardial infarction (MI). METHODOLOGY: The study comprised 805 patients with recent experience of a first MI, each gender, age and geographically matched with a control. Panoramic radiographs were available for 797 patients and 796 controls. Endodontic inflammatory disease was assessed radiographically. The sum of decayed, missing and filled teeth (DMFT) was calculated, and the number of root filled teeth and teeth with periapical lesions were recorded. The associated risk of a first MI was expressed as odds ratios (OR) with 95% confidence intervals (CI), unadjusted and adjusted for confounders (family history of cardiovascular disease, smoking habits, marital status, education and diabetes). RESULTS: Patients who had suffered a first MI had higher DMFT (mean 22.5 vs. 21.9, p = .013) and more missing teeth (mean 7.5 vs. 6.3; p < .0001) than the healthy controls. The number of missing teeth was associated with an increased risk of a first MI (adjusted OR 1.04; CI 1.02-1.06). Conversely, decay-free, filled teeth were associated with decreased risk (adjusted OR 0.98; CI 0.96-1.00). Analysis based on age disclosed the following variables to be associated with an increased risk of a first MI: number of decayed teeth (adjusted OR 1.18; CI 1.02-1.37, in patients <60 years), any primary periapical lesion (adjusted OR 1.57; CI 1.08-2.29, in patients <65 years) and the proportion of root filled teeth (adjusted OR 1.18; CI 1.03-1.36, in patients ≥65 years). CONCLUSIONS: More missing teeth was independently associated with an increased risk of a first MI. In addition, endodontic inflammatory disease may contribute as an independent risk factor to cardiovascular disease since untreated caries, periapical lesions and root fillings, depending on age, were significantly associated with a first MI.

Attitudes and lifestyle factors in relation to oral health and dental care in Sweden: a cross-sectional study.

OBJECTIVE: The aim of the present study was to investigate attitudes to and perceptions of dental treatment and costs, self-assessed personal oral health status and dental self-care in an adult Swedish population, with special reference to potential associations between these factors and periodontal status. MATERIAL AND METHODS: The study population comprised 1577 subjects who had undergone radiographic dental examination. The subjects were grouped by severity of periodontitis, based on extent of bone loss, as none, mild/moderate or severe. Subjects answered a questionnaire about socioeconomic factors, oral care habits and attitudes to dental treatment. Other questions covered medical history, smoking and other life style factors. Associations were tested using the Chi-squared test and a logistic regression model. RESULTS: Compared to subjects with no periodontitis, those with mild/moderate or severe periodontitis were less likely to afford (p < .001), more often refrained from treatment due to costs (p < .001) and in the past year had experienced dental problems for which they had not sought treatment (p < .001). They also reported more anxiety in relation to dental appointments (p = .001). Regarding caries prevention, the severe periodontitis group used least fluoride products (p = .002). CONCLUSIONS: Swedish adults regard their oral health as important, those with periodontitis have a more negative perception of their oral health and are less prone to seek help. These discouraging findings suggest the need for targeted measures, which focus on improving the care of this group of patients.

Periodontitis Increases the Risk of a First Myocardial Infarction: A Report From the PAROKRANK Study.

BACKGROUND: The relationship between periodontitis (PD) and cardiovascular disease is debated. PD is common in patients with cardiovascular disease. It has been postulated that PD could be causally related to the risk for cardiovascular disease, a hypothesis tested in the Periodontitis and Its Relation to Coronary Artery Disease (PAROKRANK) study. METHODS AND RESULTS: Eight hundred five patients (<75 years of age) with a first myocardial infarction (MI) and 805 age- (mean 62±8), sex- (male 81%), and area-matched controls without MI underwent standardized dental examination including panoramic x-ray. The periodontal status was defined as healthy (≥80% remaining bone) or as mild-moderate (from 79% to 66%) or severe PD (<66%). Great efforts were made to collect information on possibly related confounders (≈100 variables). Statistical comparisons included the Student pairwise t test and the McNemar test in 2×2 contingency tables. Contingency tables exceeding 2×2 with ranked alternatives were tested by Wilcoxon signed rank test. Odds ratios (95% confidence intervals) were calculated by conditional logistic regression. PD was more common (43%) in patients than in controls (33%; P<0.001). There was an increased risk for MI among those with PD (odds ratio, 1.49; 95% confidence interval, 1.21-1.83), which remained significant (odds ratio, 1.28; 95% confidence interval, 1.03-1.60) after adjusting for variables that differed between patients and controls (smoking habits, diabetes mellitus, years of education, and marital status). CONCLUSIONS: In this large case-control study of PD, verified by radiographic bone loss and with a careful consideration of potential confounders, the risk of a first MI was significantly increased in patients with PD even after adjustment for confounding factors. These findings strengthen the possibility of an independent relationship between PD and MI.

Saliva and plasma levels of cardiac-related biomarkers in post-myocardial infarction patients.

AIM: To relate cardiac biomarkers, such as cystatin C and growth differentiation factor-15 (GDF-15) in saliva to myocardial infarction (MI) and to periodontal status, and to investigate the relation between salivary and plasma cardiac biomarkers. MATERIALS AND METHODS: Two hundred patients with MI admitted to coronary care units and 200 matched controls without MI were included. Dental examination and collection of blood and saliva samples was performed 6-10 weeks after the MI for patients and in close proximity thereafter for controls. Analysing methods: ARCHITECT i4000SR, Immulite 2000 XPi or ELISA. RESULTS: The mean age was 62 ± 8 years and 84% were male. Total probing pocket depth, fibrinogen, white blood cell counts and HbA1c were higher in patients than controls. GDF-15 levels correlated with most of the included clinical variables in both study groups. No correlation was found between plasma and saliva levels of cystatin C or GDF-15. CONCLUSION: Salivary cystatin C and GDF-15 could not differentiate between MI patients and controls.

[Periodontitis - an often neglected risk factor for several other diseases]. / Parodontit ­ en ofta förbisedd riskfaktor för en rad sjukdomar.

Periodontitis is a chronic inflammatory disease that degrades dental supporting tissues, including the alveolar bone. The global prevalence is 19%, in Sweden it is 11%. Left untreated, periodontitis can cause loss of teeth. The initial clinical manifestations of periodontitis usually start between 35 and 45 years of age. The underlying pathological mechanism is an aberrant inflammatory response to the bacteria colonizing the gingival crevice. Periodontitis has been associated with several other diseases, most prominently diabetes. The relation between periodontitis and diabetes is bidirectional in the sense that diabetes increases the risk for periodontitis and vice versa. Periodontitis also increases the risk for cardiovascular disease and cancer.

[Diabetes and periodontitis - common, important but often neglected]. / Diabetes och parodontit ­ viktig aspekt av diabetesvården.

Diabetes and periodontitis are two global epidemics. There is a two-way relationship between diabetes and periodontitis. Diabetes increases the risk of periodontitis and periodontitis increases the risk for deteriorating glucose levels, having undetected diabetes, and for future diabetes. A recent Cochrane report summarized that there is moderate-certainty evidence that periodontal treatment improves glycaemic control in people with both periodontitis and diabetes. The recent PAROKRANK study found that undetected dysglycaemia was independently associated to both myocardial infarction and to periodontitis. To increase awareness of oral health in people with diabetes this article summarizes recent evidence.

Endodontic Inflammatory Disease and Future Cardiovascular Events and Mortality: A Report from the PAROKRANK Study.

INTRODUCTION: Prospective studies assessing the relation between endodontic inflammatory disease and subsequent cardiovascular events are few. The present aim was to explore associations between endodontic variables and future cardiovascular events in patients with myocardial infarction and matched controls participating in the PAROKRANK (Periodontitis and Its Relation to Coronary Artery Disease) study. METHODS: Eight-hundred five patients hospitalized for a first myocardial infarction and 805 controls were recruited between 2010 and 2014. Signs of endodontic inflammatory disease were assessed in panoramic radiographs taken at baseline. Mortality and morbidity data during the approximately 8 years of follow up were obtained from national registries. The risk for future cardiovascular events (first of mortality and nonfatal myocardial infarction, stroke, or hospitalization for heart failure) was analyzed with the log-rank test and Cox proportional hazards regression adjusted for the following confounders: sex, age, smoking, myocardial infarction, diabetes, education, marital status, family history of cardiovascular disease, and marginal periodontitis. RESULTS: In total, 285 future events were observed during the follow-up period. Unadjusted analyses revealed that ≥1 root-filled tooth increased the risk of a future event. After adjustment, the number of remaining teeth and non-root-filled teeth decreased the risk of future events, whereas a higher Decayed, Missing and Filled Teeth score increased the risk and ≥1 primary apical periodontitis decreased the risk of suffering cardiovascular events. A higher Decayed, Missing and Filled Teeth score and decayed teeth increased the risk of all-cause mortality. CONCLUSIONS: Tooth loss is a strong indicator of an increased risk for future cardiovascular events. Root-filled teeth seem of limited value as a risk indicator when accounting for other risk factors. The potential effect of dental interventions on future events should be assessed in future research.

Association of high cardiovascular risk and diabetes with calcified carotid artery atheromas depicted on panoramic radiographs.

OBJECTIVE: To evaluate whether estimates of risk of future cardiovascular events and death and established or unknown diabetes are significantly associated with calcified carotid artery atheromas (CCAAs) on panoramic radiographs (PRs). The main focus was on men and women without previous myocardial infarction (MI). METHODS: The PAROKRANK (Periodontitis and its Relation to Coronary Artery Disease) study included patients with a first MI and matched control subjects. In this substudy, 738 patients (138 women) and 744 control subjects (144 women) with available PRs were assessed for CCAA. Cardiovascular risk estimates were determined according to the Framingham Risk Score (FRS) and Systematic COronary Risk Evaluation (SCORE). Established and previously unknown diabetes was also determined. RESULTS: CCAA was detected on PRs in 206 control subjects (28%) and 251 patients (34%). FRS was significantly associated with CCAA among control subjects (P = .04) and patients (P = .001). SCORE was associated with CCAA among control subjects (P < .01) but not patients (P = .07). Among men, FRS and SCORE were associated with CCAA in both control subjects and patients. Diabetes was not significantly associated with CCAA after adjustments. CONCLUSIONS: Elevated cardiovascular risk scores were associated with CCAA on PRs among control subjects. Diabetes was not independently associated with CCAA, possibly owing to selection bias.

Undetected Dysglycemia Is an Important Risk Factor for Two Common Diseases, Myocardial Infarction and Periodontitis: A Report From the PAROKRANK Study.

OBJECTIVE: Information on the relationship among dysglycemia (prediabetes or diabetes), myocardial infarction (MI), and periodontitis (PD) is limited. This study tests the hypothesis that undetected dysglycemia is associated with both conditions. RESEARCH DESIGN AND METHODS: The PAROKRANK (Periodontitis and Its Relation to Coronary Artery Disease) study included 805 patients with a first MI and 805 matched control subjects. All participants without diabetes (91%) were examined with an oral glucose tolerance test. Abnormal glucose tolerance (AGT) (impaired glucose tolerance or diabetes) was categorized according to the World Health Organization. Periodontal status was categorized from dental X-rays as healthy (≥80% remaining alveolar bone height), moderate (79-66%), or severe (<66%) PD. Odds ratios (ORs) and 95% CIs were calculated by logistic regression and were adjusted for age, sex, smoking, education, marital status, and explored associated risks of dysglycemia to PD and MI, respectively. RESULTS: AGT was more common in patients than in control subjects (32% vs. 19%; P < 0.001) and was associated with MI (OR 2.03; 95% CI 1.58-2.60). Undetected diabetes was associated with severe PD (2.50; 1.36-4.63) and more strongly in patients (2.35; 1.15-4.80) than in control subjects (1.80; 0.48-6.78), but not when categorized as AGT (total cohort: 1.07; 0.67-1.72). Severe PD was most frequent in subjects with undetected diabetes, and reversely undetected diabetes was most frequent in patients with severe PD. CONCLUSIONS: In this large case-control study previously undetected dysglycemia was independently associated to both MI and severe PD. In principal, it doubled the risk of a first MI and of severe PD. This supports the hypothesis that dysglycemia drives two common diseases, MI and PD.

Symptoms of depression and their relation to myocardial infarction and periodontitis.

BACKGROUND: Psychosocial stress and depression are established risk factors for cardiovascular disease and a relationship to periodontitis has been suggested. We studied symptoms of depression and their relation to myocardial infarction and periodontitis. METHODS: In a Swedish case-control study, 805 patients, <75 years with a first myocardial infarction and 805 controls without myocardial infarction were matched for age, gender and geographic area. Mean age was 62±8 years and 81% were male. Standardised physical examination and dental panoramic X-ray for grading of periodontal status was performed. Medical history including risk factors related to cardiovascular disease and periodontitis was collected as was detailed information on perceived stress at home and work, and symptoms of depression (Montgomery Åsberg Depression Scale). A Montgomery Åsberg Depression Scale score ⩾13 was considered clinically relevant. RESULTS: A family history of cardiovascular disease, smoking and divorce was more frequent among patients than controls. Patients had more symptoms of depression than controls (14 vs 7%; p<0.001) but received less anti-depressive treatment (16 vs 42%; p<0.001). Symptoms of depression doubled the risk for myocardial infarction (Montgomery Åsberg Depression Scale: odds ratio 2.17 (95% confidence interval 1.41-3.34)). There was no difference in symptoms of depression between study participants with and without periodontitis. CONCLUSION: Patients with a first myocardial infarction were more frequently depressed than matched controls without myocardial infarction, but received less anti-depressive treatment. A relationship between depression and periodontitis could not be confirmed.

Salivary Matrix Metalloproteinase-8 and -9 and Myeloperoxidase in Relation to Coronary Heart and Periodontal Diseases: A Subgroup Report from the PAROKRANK Study (Periodontitis and Its Relation to Coronary Artery Disease).

BACKGROUND AND OBJECTIVE: Matrix metalloproteinase (MMP) -8, -9 and myeloperoxidase (MPO) are inflammatory mediators. The potential associations between MMP-8, -9, MPO and their abilities to reflect cardiovascular risk remains to be evaluated in saliva. The objective of this study was to investigate the levels and associations of salivary MMP-8, -9, MPO and tissue inhibitors of metalloproteinase (TIMP)-1 in myocardial infarction (MI) patients and controls with or without periodontitis. MATERIALS AND METHODS: 200 patients with a first MI admitted to coronary care units in Sweden from May 2010 to December 2011 and 200 controls matched for age, gender, residential area and without previous MI were included. Dental examination and saliva sample collection was performed 6-10 weeks after the MI in patients and at baseline in controls. The biomarkers MMP -8, -9, MPO and TIMP-1 were analyzed by time-resolved immunofluorescence assay (IFMA), Western blot and Enzyme-Linked ImmunoSorbent Assay (ELISA). RESULTS: After compensation for gingivitis, gingival pockets and smoking, the mean salivary levels of MMP-8 (543 vs 440 ng/mL, p = 0.003) and MPO (1899 vs 1637 ng/mL, p = 0.02) were higher in non-MI subjects compared to MI patients. MMP-8, -9 and MPO correlated positively with clinical signs of gingival/periodontal inflammation while TIMP-1 correlated mainly negatively with these signs. The levels of latent and active forms of MMP-8 did not differ between the MI and non-MI groups. Additionally, MMP-8, MPO levels and MMP-8/TIMP-1 ratio were significantly higher in men compared to women with MI. CONCLUSIONS: This study shows that salivary levels of the analyzed biomarkers are associated with periodontal status. However, these biomarkers could not differentiate between patients with or without a MI. These findings illustrate the importance to consider the influence of oral conditions when analyzing levels of inflammatory salivary biomarkers.