Periodontitis, Dental Procedures, and Young-Onset Cryptogenic Stroke.

Periodontitis is associated with an increased risk of ischemic stroke, and the risk may be particularly high among young people with unexplained stroke etiology. Thus, we investigated in a case-control study whether periodontitis or recent invasive dental treatments are associated with young-onset cryptogenic ischemic stroke (CIS). We enrolled participants from a multicenter case-control SECRETO study including adults aged 18 to 49 y presenting with an imaging-positive first-ever CIS and stroke-free age- and sex-matched controls. Thorough clinical and radiographic oral examination was performed. Furthermore, we measured serum lipopolysaccharide (LPS) and lipotechoic acid (LTA) levels. Multivariate conditional regression models were adjusted for stroke risk factors, regular dentist visits, and patent foramen ovale (PFO) status. We enrolled 146 case-control pairs (median age 41.9 y; 58.2% males). Periodontitis was diagnosed in 27.5% of CIS patients and 20.1% of controls (P < 0.001). In the fully adjusted models, CIS was associated with high periodontal inflammation burden (odds ratio [OR], 95% confidence interval) with an OR of 10.48 (3.18-34.5) and severe periodontitis with an OR of 7.48 (1.24-44.9). Stroke severity increased with the severity of periodontitis, having an OR of 6.43 (1.87-23.0) in stage III to IV, grade C. Invasive dental treatments performed within 3 mo prestroke were associated with CIS, with an OR of 2.54 (1.01-6.39). Association between CIS and invasive dental treatments was especially strong among those with PFO showing an OR of 6.26 (1.72-40.2). LPS/LTA did not differ between CIS patients and controls but displayed an increasing trend with periodontitis severity. Periodontitis and recent invasive dental procedures were associated with CIS after controlling for multiple confounders. However, the role of bacteremia as a mediator of this risk was not confirmed.

Systemic Metabolic Signatures of Oral Diseases.

Systemic metabolic signatures of oral diseases have been rarely investigated, and prospective studies do not exist. We analyzed whether signs of current or past infectious/inflammatory oral diseases are associated with circulating metabolites. Two study populations were included: the population-based Health-2000 (n = 6,229) and Parogene (n = 452), a cohort of patients with an indication to coronary angiography. Health-2000 participants (n = 4,116) provided follow-up serum samples 11 y after the baseline. Serum concentrations of 157 metabolites were determined with a nuclear magnetic resonance spectroscopy-based method. The associations between oral parameters and metabolite concentrations were analyzed using linear regression models adjusted for age, sex, number of teeth, smoking, presence of diabetes, and education (in Health-2000 only). The number of decayed teeth presented positive associations with low-density lipoprotein diameter and the concentrations of pyruvate and citrate. Negative associations were found between caries and the unsaturation degree of fatty acids (FA) and relative proportions of docosahexaenoic and omega-3 FAs. The number of root canal fillings was positively associated with very low-density lipoprotein parameters, such as diameter, cholesterol, triglycerides, and number of particles. Deepened periodontal pockets were positively associated with concentrations of cholesterol, triglycerides, pyruvate, leucine, valine, phenylalanine, and glycoprotein acetyls and negatively associated with high-density lipoprotein (HDL) diameter, FA unsaturation degree, and relative proportions of omega-6 and polyunsaturated FAs. Bleeding on probing (BOP) was associated with increased concentrations of triglycerides and glycoprotein acetyls, as well as decreased proportions of omega-3 and omega-6 FAs. Caries at baseline predicted alterations in apolipoprotein B-containing lipoproteins and HDL-related metabolites in the follow-up, and both caries and BOP were associated with changes in HDL-related metabolites and omega-3 FAs in the follow-up. Signs of current or past infectious/inflammatory oral diseases, especially periodontitis, were associated with metabolic profiles typical for inflammation. Oral diseases may represent a modifiable risk factor for systemic chronic inflammation and thus cardiometabolic disorders.

Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium.

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.

Carotid artery calcification in panoramic radiographs associates with oral infections and mortality.

AIM: To study the prevalence of carotid artery calcification (CAC) in relation to apical and marginal periodontitis, subgingival dysbiotic bacterial species and serum and saliva immune responses against them. In addition, the aim was to analyse the association of CAC with angiographically verified coronary artery disease (CAD) and mortality. METHODOLOGY: In the present random Parogene cohort, the patients had an indication for coronary angiography. Apical and marginal periodontitis were diagnosed during clinical and radiographic oral examinations, and CAC on panoramic radiographs (n = 492). Presence and severity of CAD were registered from angiography. Subgingival dysbiotic bacterial species were quantitated using checkerboard DNA-DNA-hybridization, and serum and saliva antibody levels were determined by immunoassays. The cohort was followed-up for 10 years or until death (median 9.9, range 0.21-10.4) via linkage to the national death register. The statistical models were adjusted for age, gender, smoking, hypertension, diabetes and dyslipidemia. RESULTS: A total of 102 (20.7%) patients had detectable CAC, which was moderate in 81 (16.4%) and severe in 21 (4.3%). CAC was associated (OR, 95% CI) with severe apical periodontitis (2.25, 1.15-4.41), root canal fillings (1.15, 1.04-1.26), alveolar bone loss (2.66, 1.21-5.84), severe periodontal inflammation (2.23, 1.11-4.47), high level of gram-negative subgingival species (2.73, 1.34-5.50), saliva IgG against dysbiotic species (1.05, 1.01-1.10/unit) and severe (2.58, 1.36-4.90) and chronic (2.13, 1.15-3.93) CAD. A total of 105 (20.7%) patients died during the follow-up and 53 (10.4%) deaths were because of cardiovascular diseases (CVD). Severe CAC predicted worse survival with HRs (95% CI) of 3.08 (1.58-6.06) for all-cause and 3.43 (1.42-8.25) for CVD death. CONCLUSIONS: CAC on panoramic tomography was associated with (i) apical and marginal periodontitis and dysbiotic bacterial species giving rise to an immunological response, and with (ii) severe, chronic CAD and increased mortality. The results further emphasize the role of oral infections in CAD and the importance of referring a patient with CAC for a cardiovascular evaluation.

Association between dental factors and mortality.

AIM: To study whether oral parameters such as endodontic infections, root canal fillings, number of teeth or wearing removable dentures at baseline are associated with cardiovascular- and all-cause mortality in a follow-up of approximately 8 years. METHODOLOGY: The Finnish Parogene cohort consists of 508 Finnish adults (mean age 63.3 years, SD 9.1) with cardiac symptoms, all of whom had undergone coronary angiography for accurate baseline coronary status. Extensive clinical and radiographic oral examinations were performed, and additional data were acquired from medical records and questionnaires. Root canal fillings and endodontic lesions, as well as their co-occurrence, were determined from panoramic radiographs. The mortality data were assessed via record linkage with the Finnish Causes of Death register (mean follow-up time 7.81 years, SD 1.45 years). A total of n = 471 dentate patients were included in the statistical analyses. RESULTS: A total of n = 69 deaths were recorded, of which n = 41 were due to cardiovascular diseases (CVDs, ICD-10 I00-I99). The deceased had fewer root canal fillings (mean 1.57; SD 1.64 vs. mean 2.30; SD 2.34, P = 0.03) than the survivors. The number of missing teeth was associated with smoking, occluded coronary arteries and diabetes. Cox regression with Firth's penalized maximum-likelihood method using age as timescale revealed an inverse association (HR; 95%CI) between mortality and number of teeth (all-cause 0.91; 0.86-0.96, CVD mortality 0.89; 0.83-0.96), use of removable dentures (all-cause 0.24; 0.09-0.62, CVD mortality 0.20; 0.06-0.72), root canal fillings (all-cause 0.82; 0.70-0.94, CVD mortality 0.79; 0.63-0.96) and having root canal fillings in all teeth with apical rarefactions (all-cause 0.27; 0.06-0.79, CVD mortality 0.09; 0.01-0.63), when gender, smoking, occluded coronary arteries, periodontal inflammatory burden index and the number of teeth were adjusted for. CONCLUSIONS: The number of missing teeth appeared to be the strongest predictor of mortality in this study, whereas endodontic infections per se had no independent association. Nevertheless, signs of professional intervention in these problems, such as root canal fillings and removable dentures, appeared to be associated with improved survival, which might partly be explained by the utilization of healthcare services.

Childhood Oral Infections Associate with Adulthood Metabolic Syndrome: A Longitudinal Cohort Study.

Chronic oral infection/inflammation is cross-sectionally associated with metabolic syndrome (MetS) in adults, but there are few longitudinal studies and studies on childhood oral infections and adult MetS risk. We investigated whether childhood clinical parameters indicative of oral infection/inflammation were associated with adulthood MetS and its components. A total of 755 children aged 6, 9, and 12 y underwent a clinical oral examination in 1980 as part of the Cardiovascular Risk in Young Finns Study. Oral health measures included bleeding on probing (BOP), periodontal probing pocket depth, caries, fillings, and visible plaque. Metabolic parameters were determined at baseline and during follow-up. MetS was diagnosed (n = 588, 77.9%) in the adulthood at 21 y (in 2001), 27 y (in 2007), and 31 y (in 2011) after the oral assessment, when the participants were 27 to 43 y old. Regression analyses were adjusted for childhood age, sex, body mass index, and family income, as well as adulthood smoking and education level. In adulthood, MetS was diagnosed in 11.9% (2001), 18.7% (2007), and 20.7% (2011) of participants at the 3 follow-ups. Childhood caries and fillings were associated with increased risk of adult MetS (risk ratio [95% CI], 1.25 [0.90 to 2.45] and 1.27 [1.02 to 1.99]) and with increased systolic blood pressure (1.78 [1.01 to 4.26] and 2.48 [1.11 to 4.12]) and waist circumference (2.25 [1.02 to 4.99] and 1.56 [1.01 to 3.25]), whereas BOP and visible plaque were associated with plasma glucose (1.97 [1.08 to 3.60] and 1.88 [1.00 to 3.53]). Severity of BOP (P = 0.015) and caries (P = 0.005) and teeth with plaque (P = 0.027) were associated with number of MetS components. No such trends were seen with probing pocket depth. Childhood oral infection/inflammation was associated with adverse metabolic parameters and MetS in adulthood.

Salivary IgA to MAA-LDL and Oral Pathogens Are Linked to Coronary Disease.

A large body of literature has established the link between periodontal disease and cardiovascular disease. Oxidized low-density lipoproteins (OxLDLs) have a crucial role in atherosclerosis progression through initiation of immunological response. Monoclonal IgM antibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and to malondialdehyde acetaldehyde-modified low-density lipoprotein (MAA-LDL) have been shown to cross-react with the key virulence factors of periodontal pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We have previously shown that salivary IgA antibodies to MAA-LDL cross-react with P. gingivalis in healthy humans. In this study, we aim to assess whether oral mucosal immune response represented by salivary IgA to MAA-LDL and oral pathogens is associated with coronary artery disease (CAD). Also, the molecular mimicry through antibody cross-reaction between salivary IgA to MAA-LDL and oral pathogens was evaluated. The study subjects consisted of 451 patients who underwent a coronary angiography with no CAD ( n = 133), stable CAD ( n = 169), and acute coronary syndrome (ACS, n = 149). Elevated salivary IgA antibody levels to MAA-LDL, Rgp44 (gingipain A hemagglutinin domain of P. gingivalis), and Aa-HSP60 (heat shock protein 60 of A. actinomycetemcomitans) were discovered in stable-CAD and ACS patients when compared to no-CAD patients. In a multinomial regression model adjusted for known cardiovascular risk factors, stable CAD and ACS were associated with IgA to MAA-LDL ( P = 0.016, P = 0.043), Rgp44 ( P = 0.012, P = 0.004), Aa-HSP60 ( P = 0.032, P = 0.030), Tannerella forsythia ( P = 0.002, P = 0.004), Porphyromonas endodontalis ( P = 0.016, P = 0.020), Prevotella intermedia ( P = 0.038, P = 0.005), and with total IgA antibody concentration ( P = 0.002, P = 0.016). Salivary IgA to MAA-LDL showed cross-reactivity with the oral pathogens tested in the study patients. The study highlights an association between salivary IgA to MAA-LDL and atherosclerosis. However, whether salivary IgA to MAA-LDL and the related oral humoral responses play a causal role in the development in the CAD should be elucidated in the future.

Oral health and systemic inflammatory, cardiac and nitroxid biomarkers in hemodialysis patients.

BACKGROUND: Periodontal diseases have systemic inflammatory effects and have been adversely associated with cardiovascular diseases, which are also the most frequent cause of death in the end-stage renal disease. The aim of this cross-sectional study was to investigate the oral health and serum biomarkers among the hemodialysis (HD) patients in Slovenia. MATERIAL AND METHODS: 111 HD patients were periodontally examined and their sera were assayed for C reactive protein (CRP), cardiac troponin T (TnT), nitrite/nitrate (NOx) and antibody levels to A. actinomycetemcomitans and P. gingivalis. The association of oral health with systemic response was analyzed with Kruskal-Wallis test, Fisher's exact test and multivariate linear regression. RESULTS: Bleeding on probing without periodontal pockets was present in 5.2%, calculus without periodontal pockets in 42.1%, shallow periodontal pockets in 39.5% and deep periodontal pockets in 13.2% of dentate patients. There were 28.8% edentulous participants. 63.1% of the patients had CRP levels higher than 3 mg/L and 34.2% higher than 10 mg/L. TnT was detectable in all participants, with 25.2% exhibiting levels higher than 100 ng/L. The median level of NOx was 43.1 µmol/L. Participants with higher CRP were more likely to be edentulous and have higher TnT levels. A direct association of oral health with TnT or NOx was not detected. CONCLUSIONS: HD patients in Slovenia have compromised oral health and increased serum inflammatory and cardiac biomarkers. Edentulousness was an independent predictor for the increased CRP, indicating a need for improved dental care to retain the teeth as long as possible.

Intestinal alkaline phosphatase at the crossroad of intestinal health and disease - a putative role in type 1 diabetes.

BACKGROUND: Patients with type 1 diabetes have shown an increase in circulating cytokines, altered lipoprotein metabolism and signs of vascular dysfunction in response to high-fat meals. Intestinal alkaline phosphatase (IAP) regulates lipid transport and inflammatory responses in the gastrointestinal tract. We therefore hypothesized that changes in IAP activity could have profound effects on gut metabolic homeostasis in patients with type 1 diabetes. METHODS: Faecal samples of 41 nondiabetic controls and 46 patients with type 1 diabetes were analysed for IAP activity, calprotectin, immunoglobulins and short-chain fatty acids (SCFAs). The impact of oral IAP supplementation on intestinal immunoglobulin levels was evaluated in C57BL/6 mice exposed to high-fat diet for 11 weeks. RESULTS: Patients with type 1 diabetes exhibited signs of intestinal inflammation. Compared to controls, patients with diabetes had higher faecal calprotectin levels, lower faecal IAP activities accompanied by lower propionate and butyrate concentrations. Moreover, the amount of faecal IgA and the level of antibodies binding to oxidized LDL were decreased in patients with type 1 diabetes. In mice, oral IAP supplementation increased intestinal IgA levels markedly. CONCLUSION: Deprivation of protective intestinal factors may increase the risk of inflammation in the gut - a phenomenon that seems to be present already in patients with uncomplicated type 1 diabetes. Low levels of intestinal IgA and antibodies to oxidized lipid epitopes may predispose such patients to inflammation-driven complications such as cardiovascular disease and diabetic nephropathy. Importantly, oral IAP supplementation could have beneficial therapeutic effects on gut metabolic homeostasis, possibly through stimulation of intestinal IgA secretion.

Mannose-binding lectin gene polymorphism in relation to periodontal infection.

BACKGROUND AND OBJECTIVE: Mannose-binding lectin (MBL) plays an important role in innate immunity. MBL deficiency is usually caused by mutations in exon 1 of the MBL structural gene (MBL2). Our aim was to investigate MBL2 polymorphisms and their relation to salivary levels of periodontal inflammatory/tissue destruction markers and two major periodontitis-associated bacteria. MATERIAL AND METHODS: Salivary samples from 222 subjects were available for genotyping by pyrosequencing. The subjects between 40 and 60 years of age and having a minimum of 20 teeth were divided into three periodontal groups: 80 had generalized periodontitis, 65 had localized periodontitis and 77 were periodontitis-free. A comparison between their MBL2 genotypes and salivary detection rates and levels of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis as well as interleukin -1ß, matrix metalloproteinase -8, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 was performed. RESULTS: The frequencies of the MBL2 wild-type (A/A), heterozygote variants (A/O) and homozygote variants (O/O) were 69.4%, 26.6% and 4%, respectively. In A. actinomycetemcomitans-positive subjects having homozygote or heterozygote MBL2 variants, the salivary concentrations of IL-1ß (p = 0.010) were elevated and those of TIMP-1 (p = 0.001) were decreased. In addition their matrix metalloproteinase -8/TIMP-1 ratio was higher (p < 0.001) and they had more pocket teeth (p = 0.012) than subjects negative for A. actinomycetemcomitans. CONCLUSION: Our findings indicate that the carriage of A. actinomycetemcomitans may facilitate extended periodontal inflammation and destruction in subjects with a variant form of human MBL2.

Association of Endodontic Lesions with Coronary Artery Disease.

An endodontic lesion (EL) is a common manifestation of endodontic infection where Porphyromonas endodontalis is frequently encountered. EL may associate with increased risk for coronary artery disease (CAD) via similar pathways as marginal periodontitis. The aim of this cross-sectional study was to delineate the associations between EL and CAD. Subgingival P. endodontalis, its immune response, and serum lipopolysaccharide were examined as potential mediators between these 2 diseases. The Finnish Parogene study consists of 508 patients (mean age, 62 y) who underwent coronary angiography and extensive clinical and radiographic oral examination. The cardiovascular outcomes included no significant CAD ( n = 123), stable CAD ( n = 184), and acute coronary syndrome (ACS; n = 169). EL was determined from a panoramic tomography. We combined data of widened periapical spaces (WPSs) and apical rarefactions to a score of EL: 1, no EL ( n = 210); 2, ≥1 WPS per 1 apical rarefaction ( n = 222); 3, ≥2 apical rarefactions ( n = 76). Subgingival P. endodontalis was defined by checkerboard DNA-DNA hybridization analysis, and corresponding serum antibodies were determined by ELISA. In our population, 50.4% had WPSs, and 22.8% apical rarefactions. A total of 51.2% of all teeth with apical rarefactions had received endodontic procedures. Subgingival P. endodontalis levels and serum immunoglobulin G were associated with a higher EL score. In the multiadjusted model (age, sex, smoking, diabetes, body mass index, alveolar bone loss, and number of teeth), having WPSs associated with stable CAD (odds ratio [OR] = 1.94, 95% confidence interval [95% CI] = 1.13 to 3.32, P = 0.016) and highest EL score were associated with ACS (OR = 2.46, 95% CI = 1.09 to 5.54, P = 0.030). This association was especially notable in subjects with untreated teeth with apical rarefactions ( n = 59, OR = 2.72, 95% CI = 1.16 to 6.40, P = 0.022). Our findings support the hypothesis that ELs are independently associated with CAD and in particular with ACS. This is of high interest from a public health perspective, considering the high prevalence of ELs and CAD.

Missing Teeth Predict Incident Cardiovascular Events, Diabetes, and Death.

Periodontitis, the main cause of tooth loss in the middle-aged and elderly, associates with the risk of atherosclerotic vascular disease. The objective was to study the capability of the number of missing teeth in predicting incident cardiovascular diseases (CVDs), diabetes, and all-cause death. The National FINRISK 1997 Study is a Finnish population-based survey of 8,446 subjects with 13 y of follow-up. Dental status was recorded at baseline in a clinical examination by a trained nurse, and information on incident CVD events, diabetes, and death was obtained via national registers. The registered CVD events included coronary heart disease events, acute myocardial infarction, and stroke. In Cox regression analyses, having ≥5 teeth missing was associated with 60% to 140% increased hazard for incident coronary heart disease events (P < 0.020) and acute myocardial infarction (P < 0.010). Incident CVD (P < 0.043), diabetes (P < 0.040), and death of any cause (P < 0.019) were associated with ≥9 missing teeth. No association with stroke was observed. Adding information on missing teeth to established risk factors improved risk discrimination of death (P = 0.0128) and provided a statistically significant net reclassification improvement for all studied end points. Even a few missing teeth may indicate an increased risk of CVD, diabetes, or all-cause mortality. When individual risk factors for chronic diseases are assessed, the number of missing teeth could be a useful additional indicator for general medical practitioners.

Systemic exposure to a common periodontal pathogen and missing teeth are associated with metabolic syndrome.

Periodontitis is a common chronic infection of tooth-supporting tissues leading to tooth loss. Two of the major periodontal pathogens are Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Clinically diagnosed periodontitis has been associated with metabolic syndrome (MetS). The aim of the study was to investigate the association of serum antibody levels against A. actinomycetemcomitans and P. gingivalis and the number of missing teeth with MetS. The population was the PAIS subcohort of the FINRISK '97 study (n = 1,354). The subjects were men aged 45-74 years, and they participated in this cardiovascular risk factor survey in Finland. A total of 534 (39 %) subjects had MetS defined according to the guidelines of the International Diabetes Federation. Serum antibody levels against the pathogens were measured by multiserotype ELISA. A. actinomycetemcomitans antibody levels and the number of missing teeth were significantly higher in subjects with a large waist circumference or with low serum high-density lipoprotein cholesterol. The number of missing teeth was also higher among subjects with a high serum triglyceride concentration or high plasma glucose concentration. Seropositivity for A. actinomycetemcomitans was significantly associated with MetS with an odds ratio (OR) 1.42 (95 % confidence interval 1.09-1.85, p = 0.009). More than four missing teeth and complete edentulousness were also significantly associated with MetS with ORs 1.69 (1.26-2.27, p < 0.001) and 1.93 (1.30-2.86, p = 0.001), respectively. Missing teeth and systemic exposure to A. actinomycetemcomitans were associated with several components of Mets. Infection with this common pathogen or the host response against it is associated with the presence of MetS.

Acute myocardial infarction elevates serine protease activity in saliva of patients with periodontitis.

BACKGROUND AND OBJECTIVE: There are indications that acute myocardial infarction (AMI) may have an effect on the oral environment, which is reflected in the expression of salivary and gingival proteinases. According to our knowledge, no studies have been carried out to investigate the effect of AMI on the activities of two major tissue-destructive serine protease and microbial effectors, elastase and cathepsin G, produced by oral fluid polymorphonuclear granulocytes (PMN). Therefore, we compared the activities of elastase and cathepsin G in saliva from patients with AMI and from systemically healthy subjects (non-AMI) with similar periodontal conditions. MATERIAL AND METHODS: A total of 92 patients (47 AMI and 28 non-AMI patients with gingivitis or periodontitis, and 17 systemically and periodontally healthy subjects as a control group) were recruited. Clinical periodontal measurements were recorded, and stimulated whole-saliva samples were collected. The patients with AMI were clinically examined within 3-4 d after admission to the coronary care unit. The activities of saliva neutrophil elastase and cathepsin G were measured after collection, at specific time-points during incubation (from baseline to 23 h) by specific synthetic peptide substrate assays. RESULTS: The saliva of patients with AMI and periodontitis had a significant trend for the highest elastase activities among the study groups. Elastase and cathepsin G activities correlated significantly with each other in the AMI periodontitis group (r = 0.8, p < 0.01). In a logistic regression analysis, the level of salivary elastase activity associated significantly with periodontitis. CONCLUSION: AMI may be reflected in PMN serine protease elastase activity in saliva, despite its strong association with periodontitis.

Periodontopathogen- and host-derived immune response in acute coronary syndrome.

Owing to molecular mimicry, periodontal pathogen carriage may result in a systemic cross-reactive immune response with the host. The analyses were performed to investigate if serum antibody levels to human heat shock protein 60 (HSP60) are associated with the antibody levels and salivary carriage of two periodontal pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, as well as with the dental status in patients with acute coronary syndrome (ACS). ACS patients (n = 141) were monitored at baseline when entering to hospital, and after 1 week, 3 months and 1 year. Periodontal status was recorded by dental radiographs, and A. actinomycetemcomitans and P. gingivalis were detected by PCR from saliva at baseline. Serum IgG and IgA antibody levels were determined at all time points. All antibody levels remained quite stable during the follow-up. Serum IgG-class antibody levels to A. actinomycetemcomitans and HSP60 had a strong positive correlation with each other at all time points (r∼0.4, P < 0.05). Mean serum IgG antibody levels to HSP60 were significantly higher in the A. actinomycetemcomitans IgG- and IgA-seropositive than in the seronegative patients, but did not differ between the pathogen carriers compared to the non-carriers. HSP60 antibody levels did not differ significantly between the edentulous, non-periodontitis and periodontitis patients. Despite the observed cross-reactivity in the systemic IgG-class antibody response to HSP60 and A. actinomycetemcomitans, the pathogen carriage in saliva or the periodontal status did not affect the HSP60 antibody levels in ACS patients.

Elevated MMP-8 and decreased myeloperoxidase concentrations associate significantly with the risk for peripheral atherosclerosis disease and abdominal aortic aneurysm.

Matrix metalloproteinases are responsible for degradation and remodelling of extracellular matrix and exert important roles in initiation and progression of inflammatory diseases. We aimed to examine the role of Matrix metalloproteinases (MMPs) and their regulators in degenerative arterial diseases. Serum samples were collected from patients with arterial disease (n = 126), who underwent surgery because of symptomatic aorto-occlusive disease (AOD, n = 18), carotid artery stenosis (n = 67) or abdominal arotic aneurysm (n = 41). Serum MMP-1, MMP-8, MMP-13, TIMP-1, myeloperoxidase (MPO) and neutrophil elastase (HNE) concentrations were determined by ELISA, and the molar ratio of MMP-8 and TIMP-1 was calculated. To get reference values, the determinations were done on samples of healthy blood donors (n = 100). In univariate analyses, the patients had higher MMP-8 (P < 0.001), TIMP-1 (P = 0.045), and MMP-8/TIMP-1 (P < 0.001), and lower MPO (P < 0.001) when compared with the blood donors. All three subgroups had higher MMP-8 (P < 0.001) and MMP-8/TIMP-1 (P < 0.001), and lower MPO (P < 0.01, except AOD) levels when compared with the references. In multiple logistic regression analyses, the male gender (P < 0.01), age (P < 0.001), elevated MMP-8 (P < 0.001) and decreased MPO (P < 0.001) concentrations associated significantly with the risk for arterial disease, and provided an area under curve (AUC) of 0.97 in the Receiver operating characteristics analyses. In multiple linear regression analyses, HNE correlated with both MMP-8 (P < 0.001) and MPO (P = 0.008) concentrations. Combination of high MMP-8 and low MPO level in serum eventually reflecting selectively modified neutrophil degranulation may indicate increased risk for arterial disease.

Lymphotoxin alpha LTA+496C allele is a risk factor for periodontitis in patients with coronary artery disease.

Periodontitis and coronary artery disease (CAD) are inflammatory diseases and associated with each other. The major histocompatibility complex (MHC) region carries genes involved in immune response and inflammation. We investigated whether the MHC genes correlate with the presence of periodontitis or with the occurrence of periodontal pathogens in patients with CAD. Blood and saliva samples from CAD patients (n = 106) were collected at the time of hospitalization. Nine MHC genetic markers [human leukocyte antigen (HLA)-A, HLA-B, HLA-DRB1, lymphotoxin alpha (LTA) +253(a/g), +496(C/T), +633(c/g), +724(C/A), C4A and C4B)] were typed. Based on panoramic tomography, patients were categorized into nonperiodontitis and periodontitis groups. Two major periodontal pathogens, Aggregatibacter (Actinobacillus) actinomycetemcomitans and Porphyromonas gingivalis, were cultivated and polymerase chain reaction-amplified from salivary samples. Serum immunoglobulin (Ig)A and IgG antibody levels to these pathogens were measured. In the univariate analysis, LTA+496C allele (OR = 5.29; 95% CI = 2.07-13.51, P = 0.00027), and the occurrence of P. gingivalis in saliva (OR = 4.74; 95% CI = 1.64-13.70; P = 0.002) were more frequent in periodontitis when compared with nonperiodontitis. Similarly, serum IgA antibody level against the pathogen was increased in periodontitis (P = 0.048). In the multiple logistic regression analysis, when a wide range of covariates was included, the LTA+496C allele (OR = 10.87; 95% CI = 3.23-36.60; P = 0.00012) and the elevated serum IgA antibody level against P. gingivalis (OR = 1.56; 95% CI = 1.05-2.30; P = 0.026) remained as significant risk factors for periodontitis. In conclusion, the major finding of this study is that the LTA+496C allele is associated with periodontitis in patients with CAD.