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Background In our recent genome-wide association study, we found that genetic polymorphisms in the complement factor H (CFH) gene and S100A gene region are strongly associated with serum matrix metalloproteinase 8 (MMP-8) concentration and the release of MMP-8 from neutrophils. As MMP-8 is centrally involved in the pathogenesis of periodontitis, we aimed to evaluate the presence of genetic polymorphisms of S100A8/A9/A12, MMP8, and CFH in periodontitis. In addition, we studied whether polymorphisms of these genes affect the concentrations of S100A8, S100A12, MMP-8, or complement activation marker in saliva. Methods We genotyped four single-nucleotide polymorphisms (SNPs, rs1560833 in S100A8/A9/A12, rs11225395 in MMP8, rs800292 in CFH, and rs1061170 in CFH) and measured salivary concentrations of S100A8, S100A12, MMP-8, and terminal complement complex (TCC) in the Parogene cohort (n = 508). The cohort was composed of patients with an indication to coronary angiography and all underwent a clinical and radiographic oral examination. Results CFH polymorphisms rs800292 and rs1061170 were associated with periodontal parameters. None of the polymorphisms showed association with salivary proteins. However, salivary concentrations of S100A8, S100A12, MMP-8, and TCC were strongly associated with the number of periodontal pockets and alveolar bone loss. Conclusion Interestingly, genetic variants of CFH, MMP8, and S100A8/A9/A12 gene regions did not affect salivary levels of measured proteins. However, saliva levels of S100A8, S100A12, MMP-8, and TCC, and CFH polymorphisms were associated with clinical and radiographic signs of periodontitis. Our study further supports the observations that any dysregulation of complement may increase the risk of inflammatory disorders, such as periodontitis.

Funding Information: Open Access funding provided by University of Helsinki. The study has been supported by The Finnish Dental Society Apollonia (grant for MP and LL), the Helsinki and Uusimaa Hospital District (HUS, grant for LL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The data of this study has not been presented elsewhere. Publisher Copyright: © 2022, The Author(s). We examined the usefulness of dried spot blood and saliva samples in SARS-CoV-2 antibody analyses. We analyzed 1231 self-collected dried spot blood and saliva samples from healthcare workers. Participants filled in a questionnaire on their COVID-19 exposures, infections, and vaccinations. Anti-SARS-CoV-2 IgG, IgA, and IgM levels were determined from both samples using the GSP/DELFIA method. The level of exposure was the strongest determinant of all blood antibody classes and saliva IgG, increasing as follows: (1) no exposure (healthy, non-vaccinated), (2) exposed, (3) former COVID-19 infection, (4) one vaccination, (5) two vaccinations, and (6) vaccination and former infection. While the blood IgG assay had a 99.5% sensitivity and 75.3% specificity to distinguish participants with two vaccinations from all other types of exposure, the corresponding percentages for saliva IgG were 85.3% and 65.7%. Both blood and saliva IgG-seropositivity proportions followed similar trends to the exposures reported in the questionnaires. Self-collected dry blood and saliva spot samples combined with the GSP/DELFIA technique comprise a valuable tool to investigate an individual’s immune response to SARS-CoV-2 exposure or vaccination. Saliva IgG has high potential to monitor vaccination response wane, since the sample is non-invasive and easy to collect.

Lipopolysaccharide is a virulence factor of gram-negative bacteria with a crucial importance to the bacterial surface integrity. From the host's perspective, lipopolysaccharide plays a role in both local and systemic inflammation, activates both innate and adaptive immunity, and can trigger inflammation either directly (as a microbe-associated molecular pattern) or indirectly (by inducing the generation of nonmicrobial, danger-associated molecular patterns). Translocation of lipopolysaccharide into the circulation causes endotoxemia, which is typically measured as the biological activity of lipopolysaccharide to induce coagulation of an aqueous extract of blood cells of the assay. Apparently healthy subjects have a low circulating lipopolysaccharide activity, since it is neutralized and cleared rapidly. However, chronic endotoxemia is involved in the pathogenesis of many inflammation-driven conditions, especially cardiometabolic disorders. These include atherosclerotic cardiovascular diseases, obesity, liver diseases, diabetes, and metabolic syndrome, where endotoxemia has been recognized as a risk factor. The main source of endotoxemia is thought to be the gut microbiota. However, the oral dysbiosis in periodontitis, which is typically enriched with gram-negative bacterial species, may also contribute to endotoxemia. As endotoxemia is associated with an increased risk of cardiometabolic disorders, lipopolysaccharide could be considered as a molecular link between periodontal microbiota and cardiometabolic diseases.

Saliva is an alternative sample material to nasopharyngeal swab in SARS-CoV-2 diagnostics. We investigated possible aspects to improve the reliability of SARS-CoV-2 detection from saliva. Saliva was collected from asymptomatic healthy subjects (n=133) and COVID-19 patients (n=9). SARS-CoV-2 detection was performed with quantitative reverse-transcriptase PCR (RT-qPCR) with two viral and one host target serving as an internal control. The use of internal control revealed that in the first RT-qPCR run 25–30 % of assays failed. The failure is associated with poor RNA quality. When the amount of RNA was cut down to half from the original amount, the performance of RT-qPCR was greatly enhanced (95 % of the assays succeeded). The quality of RNA was not affected by the use of different nucleic acid stabilizing buffers. Our study showed that saliva is suitable material for RT-qPCR based SARS-CoV-2 diagnostics, but the use of internal control is essential to distinguish the true negative samples from failed assays.

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.

During the COVID-19 pandemic, healthcare workers (HCWs) have faced unprecedented workloads and personal health risks leading to mental disorders and surges in sickness absence. Previous work has shown that interindividual differences in psychological resilience might explain why only some individuals are vulnerable to these consequences. However, no prognostic tools to predict individual HCW resilience during the pandemic have been developed. We deployed machine learning (ML) to predict psychological resilience during the pandemic. The models were trained in HCWs of the largest Finnish hospital, Helsinki University Hospital (HUS, N = 487), with a six-month follow-up, and prognostic generalizability was evaluated in two independent HCW validation samples (Social and Health Services in Kymenlaakso: Kymsote, N = 77 and the City of Helsinki, N = 322) with similar follow-ups never used for training the models. Using the most predictive items to predict future psychological resilience resulted in a balanced accuracy (BAC) of 72.7–74.3% in the HUS sample. Similar performances (BAC = 67–77%) were observed in the two independent validation samples. The models' predictions translated to a high probability of sickness absence during the pandemic. Our results provide the first evidence that ML techniques could be harnessed for the early detection of COVID-19-related distress among HCWs, thereby providing an avenue for potential targeted interventions.

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.

BACKGROUND Smoking is a risk factor for periodontal disease because of its complex impact on the inflammatory response in the periodontium. We investigated the effect of smoking on salivary periodontal biomarkers, matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and myeloperoxidase (MPO). METHODS Saliva biomarkers were analyzed in the Parogene population (n = 480) comprising a random cohort of patients that have undergone coronary angiography and oral examination. The effect of time since cessation and pack years of smoking on biomarkers were investigated. RESULTS Saliva MMP-8, MMP-9, TIMP-1, and MPO concentrations distinguished periodontitis patients significantly from patients without periodontitis. When the time since cessation was considered, the area-under-the-curve values (p-value) for periodontitis were 0.76 (

Objective Oxidized epitopes such as malondialdehyde-acetaldehyde (MAA) play a crucial role in the progression of atherosclerosis through activation of the humoral immune response. The exact mechanism of the association between atherosclerosis and periodontal diseases is not fully understood. The aim of the current study is to evaluate the association of oral humoral immune response to oxidized epitopes with parameters of periodontal disease. Materials and methods The Parogene cohort consist of patients who have undergone coronary angiography due to cardiac symptoms. In this study, 423 patients were randomly selected for an extensive oral examination. Salivary Immunoglobulin A to oxidized epitopes and bacterial antigens was determined by chemiluminescence immunoassay. Results In a binary logistic regression model adjusted with periodontal disease confounders, periodontal pocket depth (PPD) 4-5 mm associated with salivary IgA antibodies to MAA-LDL (p = 0.034), heat shock protein 60 of Aggregatibacter actinomycetemcomitans (p = 0.045), Porphyromonas gingivalis (p = 0.045), A. actinomycetemcomitans (p = 0.005), P. intermedia (p = 0.020), and total IgA (p = 0.003). Conclusions The current study shows the association of salivary IgA to MAA-LDL with PPD 4-5 mm in a cohort of patients with chronic coronary artery disease. Humoral immune cross-reactivation to oxidized epitopes such MAA-LDL could partly explain the link of periodontitis with systemic diseases.

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.

Headlines Chronic oral infections are associated with cardiovascular diseases via direct and indirect mechanisms Inflammation is an important link between oral infections and CVD Oral infections and CVD share many common risk factors Periodontal treatment has been proven to be beneficial for general health in addition to oral health

Genetic factors play a role in periodontitis. Here we examined whether the risk haplotype of MHC class III region BAT1-NFKBIL1-LTA and lymphotoxin-α polymorphisms associate with salivary biomarkers of periodontal disease. A total of 455 individuals with detailed clinical and radiographic periodontal health data were included in the study. A 610 K genotyping chip and a Sequenom platform were used in genotyping analyses. Phospholipid transfer protein activity, concentrations of lymphotoxin-α, IL-8 and myeloperoxidase, and a cumulative risk score (combining Porphyromonas gingivalis, IL-1β and matrix metalloproteinase-8) were examined in saliva samples. Elevated IL-8 and myeloperoxidase concentrations and cumulative risk scores associated with advanced tooth loss, deepened periodontal pockets and signs of periodontal inflammation. In multiple logistic regression models adjusted for periodontal parameters and risk factors, myeloperoxidase concentration (odds ratio (OR); 1.37, P = 0.007) associated with increased odds for having the risk haplotype and lymphotoxin-α concentration with its genetic variants rs2857708, rs2009658 and rs2844482. In conclusion, salivary levels of IL-8, myeloperoxidase and cumulative risk scores associate with periodontal inflammation and tissue destruction, while those of myeloperoxidase and lymphotoxin-α associate with genetic factors as well.

Aim We investigated the association between the Aggregatibacter actinomycetemcomitans serotypes, periodontal status and coronary artery disease (CAD). Materials and methods The study population included 497 patients who underwent coronary angiography, and clinical oral examination. Quantitative polymerase chain reaction assays were designed to identify the serotypes from saliva samples. Results Aggregatibacter actinomycetemcomitans serotype frequencies were as follows: serotype "c" 35.7%, "b" 28.6%, "a" 26.2%, "e" 7.1%, "d" 2.4% and "f" 0%. The subjects with a detectable serotype had less teeth and higher bleeding on probing than those with no serotype. Serotypes "b" and "c" associated with periodontal probing depths and periodontal inflammatory burden. The saliva and subgingival bacterium quantities and serum antibody levels against A. actinomycetemcomitans were highest in patients harbouring serotype "c." Serotypes "b" and "c" were most frequent (59.3%) in patients with CAD (p = .040), and they associated with the risk of stable CAD with an odds ratio of 2.67 (95% confidence interval 1.06-7.44). Also, the severity of CAD (p = .018) associated with serotypes "b" and "c." Conclusions Aggregatibacter actinomycetemcomitans serotypes "b" and "c" associate with both periodontal and CAD status. Detectable serotypes associate with the quantity and the serology of the bacterium emphasizing both local and systemic effect of the A. actinomycetemcomitans serotypes.

Periodontitis, a common polymicrobial inflammatory disease in the tooth supporting tissues, is a risk factor for coronary artery disease. One of the proposed underlying mechanisms is the systemic immune response to periodontal infection. We studied how serum antibodies against seven periodontal pathogens and their subgingival levels associate with each other, periodontitis, and coronary artery disease.The Parogene cohort included 505 Finnish patients (mean age 63 y) who underwent coronary angiography, and clinical and radiographic oral examinations. Coronary diagnosis was defined as no significant coronary artery disease (50% stenosis, n = 152), stable coronary artery disease (≥50% stenosis, n = 184) and acute coronary syndrome (n = 169). Levels of subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Tannerella forsythia, Campylobacter rectus, and Fusobacterium nucleatum were determined by checkerboard DNA-DNA hybridization. Serum antibody (IgA/IgG) levels were analyzed with enzyme-linked immunosorbent assay (ELISA). Aggregate IgA/IgG burdens were calculated by summing and standardizing the serum antibody levels.Patients with active periodontitis were characterized by higher levels of subgingival bacteria and corresponding IgA/IgG response. Quartiles 2-4 of serum IgA/IgG burden indicated higher risk for acute coronary syndrome (OR 1.84, 95%CI 1.01-3.35 for IgA; OR 1.87, 95%CI 1.01-3.46 for IgG) independently of established cardiovascular risk factors, body mass index, number of teeth, subgingival bacterial levels and periodontal diagnosis.Our findings support the hypothesis that the association between periodontitis and cardiovascular diseases is partly mediated by the immunologic response for periodontal pathogens.

Aim We aimed to study how lipopolysaccharide (LPS) in saliva and serum associates with each other, periodontal microbial burden, periodontitis and coronary artery disease (CAD). Materials and methods The used Parogene cohort comprised N = 505 Finnish adults. Coronary diagnosis was acquired by coronary angiography, and the main outcomes were as follows: no significant CAD (n = 123), stable CAD (n = 184) and acute coronary syndrome (n = 169). Periodontitis was defined according to clinical and radiographic examinations. Levels for 75 strains of subgingival bacteria were determined by checkerboard DNA–DNA hybridization. Saliva and serum LPS activity was analysed by Limulus amebocyte lysate assay. Results The level of 11 bacterial strains, which were mainly oral and respiratory Gram-negative species, associated with salivary LPS levels in an age- and gender-adjusted linear regression. A total of 4.9% of the serum LPS, that is endotoxemia, variation was explainable by saliva LPS among patients with periodontitis (n = 247, R2 = .049, Pearson's r = .222, p

Apical periodontitis is an inflammatory reaction at the apex of an infected tooth. Its microbiota resembles that of marginal periodontitis and may induce local and systemic antibodies binding to bacteria- and host-derived epitopes. Our aim was to investigate the features of the adaptive immune response in apical periodontitis. The present Parogene cohort (n = 453) comprises patients with cardiac symptoms. Clinical and radiographic oral examination was performed to diagnose apical and marginal periodontitis. A three-category endodontic lesion score was designed. Antibodies binding to the bacteria- and host-derived epitopes were determined from saliva and serum, and bacterial compositions were examined from saliva and subgingival samples. The significant ORs (95% CI) for the highest endodontic scores were observed for saliva IgA and IgG to bacterial antigens (2.90 (1.01&ndash, 8.33) and 4.91 (2.48&ndash, 9.71)/log10 unit), saliva cross-reacting IgG (2.10 (1.48&ndash, 2.97)), serum IgG to bacterial antigens (4.66 (1.22&ndash, 10.1)), and Gram-negative subgingival species (1.98 (1.16&ndash, 3.37)). In a subgroup without marginal periodontitis, only saliva IgG against bacterial antigens associated with untreated apical periodontitis (4.77 (1.05&ndash, 21.7)). Apical periodontitis associates with versatile adaptive immune responses against both bacterial- and host-derived epitopes independently of marginal periodontitis. Saliva immunoglobulins could be useful biomarkers of oral infections including apical periodontitis&mdash, a putative risk factor for systemic diseases.

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.

AIM Matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and myeloperoxidase (MPO) participate in extracellular matrix breakdown both in periodontium and atherosclerotic plaques. We investigated the diagnostic value of serum and saliva biomarkers in periodontitis and acute coronary syndrome (ACS). MATERIALS AND METHODS The population was PAROGENE (n = 481), a random cohort of patients with an indication for coronary angiography. All patients underwent a clinical and radiographic oral examination. Groups consisting of periodontitis versus non-periodontitis, and ACS versus non-ACS patients were compared. RESULTS Saliva MMP-8, MMP-9 and MPO provided significant area-under-curve (AUC) values for periodontitis, 0.69 (

To study antibody responses associated with molecular mimicry in periodontitis.Fifty-four periodontitis cases (mean age 54.0 years) and 44 controls (53.6 years) were examined, after which cases received periodontal treatment. Established immunoassays were used to analyse levels of antibodies against two pathogens, Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg), heat shock proteins (Hsp), Hsp60, Hsp65, and Hsp70, and epitopes of oxidized low-density lipoprotein (oxLDL) (CuOx-LDL and MDA-LDL) in plasma samples that were collected at baseline and after 3 (n = 48) and 6 (n = 30) months.When age, sex, smoking habit, and the number of teeth were considered in multivariate logistic regressions, Aa and Pg IgG, Hsp65-IgA, CuOx-LDL-IgG and -IgM, and MDA-LDL-IgG antibody levels were associated with periodontitis, whereas Hsp60-IgG2 antibody levels were inversely associated. The Aa antibody levels significantly correlated with the levels of IgA antibodies to Hsp65 and Hsp70, and both OxLDL IgA antibody levels. The levels of antibodies to Pg correlated with IgG antibodies to Hsp60, Hsp70, and both oxLDL antibody epitopes. None of the antibody levels changed significantly after treatment.Periodontitis is associated with persistently high levels of circulating antibodies that are reactive with pathogen- and host-derived antigens.

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.

Background Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged Key hypotheses/aims (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.

Aim Chronic periodontitis has an episodic and multifactorial character, with fluctuations in bacterial burden, inflammatory response, and tissue destruction. We investigated the association of selected salivary biomarkers with periodontal parameters and validated the use of a novel salivary diagnostic approach, the cumulative risk score (CRS), in detection of periodontitis in subjects with angiographically verified coronary artery disease diagnosis. Materials and methods The concentrations of matrix metalloproteinase (MMP)-8, interleukin (IL)-1β, and Porphyromonas gingivalis were analysed from saliva of 493 subjects. The subjects participated in a detailed clinical and radiographic oral examination. The CRS index, combining the three salivary biomarkers, was calculated for each subject. Results High salivary concentrations of MMP-8, IL-1β, and P. gingivalis were associated with deepened periodontal pockets and alveolar bone loss, and MMP-8 and IL-1β with bleeding on probing. The CRS index had a stronger association with moderate to severe periodontitis (OR 6.13; 95% CI 3.11-12.09) than any of the markers alone. Conclusions Salivary concentrations of MMP-8, IL-1β, and P. gingivalis are associated with various clinical and radiographic measures of periodontitis. The CRS index, combining the three salivary biomarkers, is associated with periodontitis more strongly than any of the markers alone regardless of the coronary artery disease status of the patients.

IMPORTANCE Severe forms of common chronic oral infections or inflammations are associated with increased cardiovascular risk in adults. To date, the role of childhood oral infections in cardiovascular risk is not known because no long-term studies have been conducted. OBJECTIVE To investigate whether signs of oral infections in childhood are associated with cardiovascular risk factors and subclinical atherosclerosis in adulthood. DESIGN, SETTING, AND PARTICIPANTS The cohort study (n = 755) was derived from the Cardiovascular Risk in Young Finns Study, an ongoing prospective cohort study in Finland initiated in 1980. Participants underwent clinical oral examinations during childhood, when they were aged 6, 9, or 12 years and a clinical cardiovascular follow-up in adulthood in 2001 at age 27, 30, or 33 years and/or in 2007 at age 33, 36, or 39 years. Cardiovascular risk factors were measured at baseline and during the follow-up until the end of 2007. Final statistical analyses were completed on February 19, 2019. MAIN OUTCOMES AND MEASURES Four signs of oral infections (bleeding on probing, periodontal probing pocket depth, caries, and dental fillings) were documented. Cumulative lifetime exposure to 6 cardiovascular risk factors was calculated from dichotomized variables obtained by using the area-under-the-curve method. Subclinical atherosclerosis (ie, carotid artery intima-media thickness [IMT]) was quantified in 2001 (n = 468) and 2007 (n = 489). RESULTS This study included 755 participants, of whom 371 (49.1%) were male; the mean (SD) age at baseline examination was 8.07 (2.00) years. In this cohort, 33 children (4.5%) had no sign of oral infections, whereas 41 (5.6%) had 1 sign, 127 (17.4%) had 2 signs, 278 (38.3%) had 3 signs, and 248 (34.1%) had 4 signs. The cumulative exposure to risk factors increased with the increasing number of oral infections both in childhood and adulthood. In multiple linear regression models, childhood oral infections, including signs of either periodontal disease (R-2 = 0.018; P = .01), caries (R-2 = 0.022; P = .008), or both (R-2 = 0.024; P = .004), were associated with adulthood IMT. The presence of any sign of oral infection in childhood was associated with increased IMT (third tertile vs tertiles 1 and 2) with a relative risk of 1.87 (95% CI, 1.25-2.79), whereas the presence of all 4 signs produced a relative risk of 1.95 (95% CI, 1.28-3.00). The associations were more obvious in boys: if periodontal disease were present, the corresponding estimate was 1.69 (95% CI, 1.21-2.36); if caries, 1.46 (95% CI, 1.04-20.05); and if all 4 signs of oral infections, 2.25 (95% CI, 1.30-3.89). The associations were independent of cardiovascular risk factors. CONCLUSIONS AND RELEVANCE Oral infections in childhood appear to be associated with the subclinical carotid atherosclerosis seen in adulthood.

This cross-sectional study characterizes the association between subgingival bacterial profile and periodontal parameters in patients assigned to coronary angiography because of cardiologic problems, which may affect the oral microbiota.Pooled subgingival bacterial samples were collected from 477 dentate individuals during the oral examinations, along with periodontal probing depth (PD) and assessments of bleeding on probing (BOP) and radiographic alveolar bone loss (ABL). The checkerboard DNA-DNA hybridization assay was used to determine the levels of 29 oral bacteria, which were divided into three bacterial complexes.All bacterial combinations from the etiologic bacterial group and each species from the red complex were significantly associated (P0.001) with grade of ABL. The prevalence of the etiologic bacterial group and the level of each species were also associated strongly with the proportion of sites with PD 4 to 5 mm and ≥ 6 mm, BOP, and ABL, except Aggregatibacter actinomycetemcomitans. Levels of Gram-negative oral bacteria correlated significantly with those of Gram-positive species (r = 0.840, P0.001). In multiple logistic regression analysis, the prevalence of the etiologic bacterial group, levels of Gram-negative bacteria and Treponema denticola, and the prevalence of Porphyromonas gingivalis and T. denticola associated significantly with ABL, whereas other bacterial complexes and levels of Gram-positive species did not.Although levels of Gram-negative and -positive species paralleled periodontal parameters, only the species considered etiologic were associated with ABL.

We investigated the association between angiographically verified coronary artery disease (CAD) and subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola.The cross-sectional study population (n = 445) comprised 171 (38.4%) patients with Stable CAD, 158 (35.5%) with acute coronary syndrome (ACS) and 116 (26.1%) with no significant CAD (No CAD). All patients participated in clinical and radiological oral health examinations. Pooled subgingival bacterial samples were analysed by checkerboard DNA-DNA hybridization assays.In all study groups, the presence of P. gingivalis, T. forsythia and T. denticola indicated a significant (p ≤ 0.001) linear association with the extent of alveolar bone loss (ABL), but A. actinomycetemcomitans did not (p = 0.074). With a threshold level of bacterial cells 1 × 10(5) A. actinomycetemcomitans was significantly more prevalent in the Stable CAD group (42.1%) compared to the No CAD group (30.2%) (p = 0.040). In a multi-adjusted logistic regression analysis using this threshold, A. actinomycetemcomitans positivity associated with Stable CAD (OR 1.83, 95% CI 1.00-3.35, p = 0.049), but its level or levels of other bacteria did not.The presence of subgingival A. actinomycetemcomitans associates with an almost twofold risk of Stable CAD independently of alveolar bone loss.

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.

Objective The aim of this study was to investigate the association between angiographically verified coronary artery disease (CAD) and salivary levels of four major periodontal pathogens. Methods The study population ( n = 492) was composed of 179 (36.4%) patients with stable CAD, 166 (33.7%) with acute coronary syndrome (ACS), and 119 (24.2%) showing no pathological findings by coronary angiography. All patients were subjected to a detailed oral health examination. The saliva samples were analyzed for lipopolysaccharide activity as well as for Aggregatibacter actinomycetemcomitans , Porphyromonas gingivalis , Prevotella intermedia , and Tannerella forsythia by quantitative PCR. Serum antibodies levels against A. actinomycetemcomitans were analyzed. Results The level of bacterial burden was linearly associated with alveolar bone loss ( p p = 0.015). The median salivary levels of A. actinomycetemcomitans in pathogen-positive patients were significantly higher in the “Stable CAD” ( p = 0.014) and the “ACS” ( p = 0.044) groups when compared to “No significant CAD” patients. In logistic regression models, a 10-fold increase in the salivary A. actinomycetemcomitans levels was associated with a risk for stable CAD and ACS with odds ratios (ORs) of 7.47 (95% confidence interval [CI]: 1.57–35.5, p = 0.012) and 4.31 (95% CI: 1.06–17.5, p = 0.041), respectively. The OR for the association of IgA-class antibody levels against A. actinomycetemcomitans with ACS risk was 3.13 (95% CI: 1.38–7.12, p = 0.006)/log 10 unit increase. Conclusions High salivary levels of A. actinomycetemcomitans and systemic exposure to the bacterium were associated with increased risk for CAD. These findings emphasize the importance of oral microbiota in cardiovascular risk assessment and therapeutics.

An association exists between chronic infection-induced inflammation, such as periodontitis, and acute coronary syndrome (ACS). We studied the association of serum neutrophil markers, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-8, tissue inhibitor of metalloproteinase (TIMP)-1 concentrations and MMP-8 ⁄TIMP-1 ratio, with the risk of recurrent ACS. Radiographic periodontal status was recorded from 141 patients with acute non-Q-wave infarction or unstable angina pectoris, who participated in a double-blind, placebo-controlled study with clarithromycin for 3 months. Serum samples were collected within arrival to the hospital, at 1 week, 3 months and 1 year. Recurrent ACS events were registered during the 1-year follow-up. In the whole population, high serum MPO concentrations at 1 week (fourth quartile versus quartiles 1‐3) were associated with the risk of recurrent ACS with a relative risk (RR) of 2.52 (95% CI, 1.277‐4.980; P = 0.008). In patients without periodontal disease, high MPO concentration at 1 week and 1 year predicted recurrent ACS with RRs of 3.54 (1.600‐7.831; P = 0.002) and 2.87 (1.171‐7.038; P = 0.021), respectively. In the placebo group, but not in the clarithromycin group, high serum MMP-8 ⁄TIMP-1 ratio at 1 week predicted recurrent ACS with an RR of 3.23 (1.295‐8.063; P = 0.012). Our results suggest that high serum neutrophil markers reflect increased risk of recurrent ACS, especially in patients without periodontal disease and not receiving antimicrobial medication.

INTRODUCTION We investigated the association of periodontitis and severity of coronary artery disease (CAD) as verified using coronary angiography. MATERIAL AND METHODS Participants were recruited among those attending coronary angiography at Helsinki University Central Hospital, Finland, in 2007 and 2008. Detailed clinical periodontal examination [number of teeth, bleeding on probing, periodontal probing depth (PPD)] and oral panoramic radiographs [alveolar bone loss (ABL), angular bone defects] were performed. RESULTS Of 506 patients, 123 (24.3%) had no significant CAD, whereas 184 (36.4%) had stable CAD and 169 (33.4%) acute coronary syndrome (ACS). Both stable CAD and ACS were associated with 8-17 missing teeth with ORs 4.33 (1.61-11.7, p = 0.020) and 5.24 (1.90-14.5, p = 0.014), and more than seven teeth with PPD ≥6 mm with ORs 2.44 (1.01-6.07, p = 0.049) and 2.75 (1.16-6.53, p = 0.022) respectively. Severe ABL was associated with ACS with an OR 5.39 (1.23-23.6, p = 0.025). Number of stenosed arteries was linearly associated with ABL (p for trend

AIM We investigated in a nationally representative sample, how periodontitis modifies the association between the carriage of periodontal pathogens and serology. MATERIALS AND METHODS The population comprised 1586 dentate subjects who participated in an interview, clinical and radiological oral health examination, and saliva collection. Serum immunoglobulin A (IgA)- and IgG-class antibody levels against Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis and their salivary occurrence were determined in the whole population. The quantity of the pathogens was measured in a subpopulation. RESULTS In the univariate analyses, the corresponding antibody levels were higher in the pathogen carriers compared with the non-carriers, and clearly higher in the carriers with periodontal pockets compared with the carriers without. In the multi-variate analyses, however, all antibody levels associated strongly with age (p

The oral commensal bacterium Streptococcus gordonii interacts with salivary amylase via two amylase-binding proteins, AbpA and AbpB. Based on sequence analysis, the 20-kDa AbpA protein is unique to S. gordonii , whereas the 82-kDa AbpB protein appears to share sequence homology with other bacterial dipeptidases. The aim of this study was to verify the peptidase activity of AbpB and further explore its potential functions. The abpB gene was cloned, and histidine-tagged AbpB (His-AbpB) was expressed in Escherichia coli and purified. Its amylase-binding activity was verified in an amylase ligand binding assay, and its cross-reactivity was verified with an anti-AbpB antibody. Both recombinant His-AbpB and partially purified native AbpB displayed dipeptidase activity and degraded human type VI collagen and fibrinogen, but not salivary amylase. Salivary amylase precipitates not only AbpA and AbpB but also glucosyltransferase G (Gtf-G) from S. gordonii supernatants. Since Streptococcus mutans also releases Gtf enzymes that could also be involved in multispecies plaque interactions, the effect of S. gordonii AbpB on S. mutans Gtf-B activity was also tested. Salivary amylase and/or His-AbpB caused a 1.4- to 2-fold increase of S. mutans Gtf-B sucrase activity and a 3- to 6-fold increase in transferase activity. An enzyme-linked immunosorbent assay verified the interaction of His-AbpB and amylase with Gtf-B. In summary, AbpB demonstrates proteolytic activity and interacts with and modulates Gtf activity. These activities may help explain the crucial role AbpB appears to play in S. gordonii oral colonization.

The present study comprised 101 (48 men) employees of the Finnish Broadcasting Company with or without irregular shift work, but all with a work week of five shifts in a row followed by 2 days off. The mean age of the subjects was 41.0 years (SD = 9.9). The BiteStrip, a single-use disposable EMG device was used for one night during the work week to detect sleep bruxism. The Actiwatch Plus actigraph was worn on the non-dominant wrist for the entire week to evaluate sleep. Total sleep time and fragmentation index, the latter as a measure of sleep efficiency was calculated for the present study. The BiteStrip scores among the participants were: 0- no bruxism: 52.2% (according to the manufacturer, comparable to a sleep laboratory bruxism count of up to 39 over 5 h), 1- mild: 29.3% (40-74 counts), 2- moderate: 12.0%: (75-124 counts) and 3- severe: 6.5% (>125 counts). Severe bruxers slept less during the work week than non-bruxers (P = 0.009), but severe bruxers slept slightly more than non-bruxers during days off. The group means of the sleep fragmentation index decreased from start towards the middle of the work week and increased during days off (P = 0.016). The levels of the fragmentation indices were consistently higher in accordance with bruxism severity (P = 0.013). It was concluded that bruxism has a coherent relationship with sleep efficiency and it can be detected at home with a low cost device.

Periodontitis increases the atherosclerosis risk, but information on the role of periodontal pathogens in atherogenesis is limited. In the present study we have investigated, whether the major periodontal pathogen, Aggregatibacter (Actinobacillus) actinomycetemcomitans, induces development of atherosclerosis in apolipoprotein E-deficient mice. The mice received 4, 6, or 8 weekly i.v. injections of live pathogen (10(7)CFU/50 microl/mouse) or saline as control, and were killed 1 week after the last injection. The atherosclerotic lesion formation was examined from whole aortas and aortic sinus cryosections after lipid staining. Neither the lesion area in the aortas or en face analyses, nor their immunoreactivity to the macrophage-marker CD68 differed significantly between the infected and the control mice. However, the pathogen administration increased serum C-reactive protein (CRP) concentrations, and induced proatherogenic lipoprotein profiles with smaller particle sizes in very-low density (VLDL), low density (LDL), and high density (HDL) lipoprotein fractions. It also caused elevated matrix metalloproteinase-9 expression in the aortas and increased serum gelatinase level. Lipopolysaccharide deriving from the pathogen was associated with proatherogenic lipoprotein fractions: VLDL and especially LDL. The results indicate that A. actinomycetemcomitans contributes to disturbed lipoprotein profiles, inflammatory reaction, and matrix remodelling which are known to promote the development of atherosclerosis.

Periodontitis is bacterial infection of tooth-supporting tissues leading to inflammation and, subsequently, to loss of teeth. It is one of the most common infections worldwide. Recent studies have shown that periodontal infection may pose a threat to general health by increasing the risk of cardiovascular and lung diseases, and preterm labour. Thus, useful markers of systemic exposure to periodontitis are needed. Markers of periodontitis in serum include those derived directly from periodontopathic pathogens and those originating from the host defence and immune mechanisms. Periodontitis is associated with endotoxemia, which can be directly measured as elevated concentrations of lipopolysaccharide (LPS) in periodontitis patients compared with healthy subjects. Also indirect methods determining endotoxemia, such as elevated concentrations of serum LPS binding protein, soluble CD14, and antibodies to LPS of periodontal pathogens have been reported. Surrogate measures of the host response against periodontal infection, such as matrix metalloproteinases, cytokines, chemokines, inflammation markers, antiphospholipid antibodies, and antibodies to periodontal pathogens, have been used. Of these, however, only antibodies to periodontal pathogens may be seen as specific markers of systemic exposure to periodontopathic pathogens. In this paper we describe and discuss serum markers of periodontitis that have been used for research purposes and/or to support diagnostics. Based on literature review, we encourage research and development of serum screening methods for periodontitis that could be used by general physicians.

Large, general population-based data on carriage rates of periodontal pathogens hardly exist in the current literature. The objectives of the present study were to examine the salivary detection of Aggregatibacter (formerly Actinobacillus ) actinomycetemcomitans , Campylobacter rectus , Porphyromonas gingivalis , Prevotella intermedia , Tannerella forsythensis , and Treponema denticola in a representative sample of the adult population living in southern Finland and to clarify which determinants are associated with the presence of these pathogens in saliva. 16S rRNA-based PCR methods with species-specific primers were employed to determine the presence of the six target bacteria in stimulated saliva samples, which were available from 1,294 subjects aged ≥30 years. The age group, gender, level of education, marital status, smoking history, number of teeth, and number of teeth with deepened pockets were included in the statistical analysis. In general, the carriage of periodontal pathogens was common, since at least one of the examined pathogens was found in 88.2% of the subjects. In descending order, the total detection rates were 56.9%, 38.2%, 35.4%, 31.3%, 20.0%, and 13.9% for T. forsythensis , T. denticola , P. gingivalis , C. rectus , A. actinomycetemcomitans , and P. intermedia , respectively. Age per se was strongly associated with the carriage of P. gingivalis ( P = 0.000), and the level of education with that of T. denticola ( P = 0.000). There was an association between the number of teeth with deepened pockets and carriage of P. gingivalis ( P = 0.000), P. intermedia ( P = 0.000), T. denticola ( P = 0.000), and A. actinomycetemcomitans ( P = 0.004). The data suggest that distinct species have a different carriage profile, depending on variables such as age, educational level, and periodontal status.

Periodontitis has been associated with an increased risk for atherosclerosis. Prospective data concerning its association with risk of stroke, especially those measuring systemic exposure to periodontal pathogens, are scarce. We analyzed if serum antibody levels to two major periodontopathogens predict stroke. The cases and the controls were nested in a random population-based sample of 8911 subjects aged 30–59 years at baseline, who participated in a cardiovascular disease (CVD) risk factor survey in Eastern Finland in 1977 and were followed for 15 years. CVD-free controls ( n = 516) were matched for sex and 5-year age group with stroke cases ( n = 470). In subjects free from CVD at baseline ( n = 893), systemic exposure to Porphyromonas gingivalis increased the risk of stroke: compared to seronegative subjects, men IgA-seropositive and women IgG-seropositive for P. gingivalis had a multivariate odds ratio (OR) (95% CI) of 1.63 (1.06–2.50) and 2.30 (1.39–3.78) for stroke, respectively. Higher OR was observed in males, who had never smoked: compared to seronegative men, P. gingivalis IgA-seropositive men had a multivariate OR of 3.31 (1.31–8.40, p = 0.012) for stroke. No association between antibody levels to Actinobacillus actinomycetemcomitans and stroke was found. The results suggest that the systemic exposure to P. gingivalis may predispose to incident stroke.