Periodontitis and coronary artery disease : Studies on the association between periodontitis and coronary artery disease

Periodontitis and coronary artery disease (CAD) are highly prevalent in Sweden’s population; both diseases have complicated pathogeneses and clinical manifestations due to immune-system triggered inflammation. Research in recent years reported that inflammation is a significant active participant in many chronic diseases. The literature described a CAD-periodontitis association, but underlying mechanisms are not fully understood. It is important to acquire knowledge about how periodontitis might influence CAD, which is one of the major causes of illness and death in western countries. Because periodontitis can be treated, this knowledge, when complemented with more knowledge about the CAD-periodontitis association, could lead to CAD prevention. The overall aim of studies reported in this thesis were to investigate the CAD-periodontitis association, and specifically, to: (i) compare periodontal conditions in patients with CAD and subjects without a history of CAD; (ii) study whether or not periodontal status influences outcomes in known CAD over an 8-year period; (iii) study whether or not concentrations and biological activity of hepatocyte growth factor (HGF) in serum from patients with severe CAD are different – depending on whether or not the subjects had periodontitis; and (iv) study concentrations and biological activity of hepatocyte growth factor in serum, saliva, and gingival crevicular fluid in healthy subjects with or without periodontitis. Here is a brief summary: In study I, 161 patients with CAD and 162 controls were compared regarding periodontal disease prevalence and severity. CAD patients had significant coronary stenosis and underwent percutaneous coronary intervention (PCI) or coronary artery by-pass grafts (CABG). Healthy controls were recruited from Sweden’s population database. Twenty-five per cent of the CAD patients had severe periodontitis, compared to 8% of the controls. In a multiple logistic regression analysis (controlled for age and smoking), severe periodontitis indicated an odds ratio of 5.74 (2.07–15.90) for CAD. Study II: Periodontal status was re-examined in 126 CAD patients and 121 controls from the initial sample after 8 years. Periodontal status at baseline was analysed and related to CAD endpoints (i.e., myocardial infarction, new PCI or CABG or death due to CAD) recorded from patients’ medical records and from the death index maintained by the National Board of Health and Welfare. The difference in periodontitis prevalence and severity between the two groups remained unchanged during the 8-year follow up. No significant differences were found regarding CAD endpoints during follow-up in relation to baseline periodontal status in the CAD-patient group. In study III, higher HGF serum concentrations (p&lt;0.001) were found in CAD patients, compared to healthy blood donors, which reflects chronic inflammation. In CAD patients without periodontitis, HGF concentrations increased significantly 24 hours after PCI – in parallel with increased HGF biological activity. In CAD patients with periodontitis, only small fluctuations were seen in HGF values, i.e., concentration and biological activity. HGF biological activity was temporarily elevated after PCI but only in patients without periodontitis. Thus chronic inflammation related to periodontitis might reduce HGF biological activity. In study IV, HGF concentration and biological activity in saliva, in gingival crevicular fluid (GCF), and serum were compared between 30 generally healthy subjects with severe untreated periodontitis and 30 healthy subjects without periodontitis. Compared to periodontally healthy controls, periodontal patients showed higher HGF concentrations in saliva p&lt;0.001, gingival crevicular fluid p&lt;0.0001, and in serum p&lt;0.001. HGF biological activity (measured as the binding affinity to its HSPG and c-MET receptors) was significantly reduced in saliva (p&lt;0.0001) and GCF samples (p&lt;0.0001 for HSPG and p&lt;0.01 for c-MET) from periodontitis patients. The only significant difference in serum samples was an increases in c-MET binding three minutes after subgingival debridement in periodontitis patients (p&lt;0.05), which might reflect that patients had active bursts of periodontitis. In conclusion, CAD patients more often showed severe periodontitis but there were no differences in CAD endpoints during the eight-year follow-up in relation to baseline periodontal status. Periodontitis seems to influence HGF concentration and biological activity in CAD patients, but studies on factors that cause lower HGF biological activity are necessary – to find out if periodontal treatment influences HGF biological activity. Healthy periodontitis patients had higher HGF concentrations locally and systemically, but biological activity was reduced. This might indicate that periodontitis can influence wound healing and tissue repair in other body parts.The ISBN 987‐91‐7519‐748‐7 is incorrect. Correct ISBN is 978‐91‐7519‐748‐7.</p

Periodontitis and coronary artery disease : Studies on the association between periodontitis and coronary artery disease

Periodontitis and coronary artery disease (CAD) are highly prevalent in Sweden’s population; both diseases have complicated pathogeneses and clinical manifestations due to immune-system triggered inflammation. Research in recent years reported that inflammation is a significant active participant in many chronic diseases. The literature described a CAD-periodontitis association, but underlying mechanisms are not fully understood. It is important to acquire knowledge about how periodontitis might influence CAD, which is one of the major causes of illness and death in western countries. Because periodontitis can be treated, this knowledge, when complemented with more knowledge about the CAD-periodontitis association, could lead to CAD prevention. The overall aim of studies reported in this thesis were to investigate the CAD-periodontitis association, and specifically, to: (i) compare periodontal conditions in patients with CAD and subjects without a history of CAD; (ii) study whether or not periodontal status influences outcomes in known CAD over an 8-year period; (iii) study whether or not concentrations and biological activity of hepatocyte growth factor (HGF) in serum from patients with severe CAD are different – depending on whether or not the subjects had periodontitis; and (iv) study concentrations and biological activity of hepatocyte growth factor in serum, saliva, and gingival crevicular fluid in healthy subjects with or without periodontitis. Here is a brief summary: In study I, 161 patients with CAD and 162 controls were compared regarding periodontal disease prevalence and severity. CAD patients had significant coronary stenosis and underwent percutaneous coronary intervention (PCI) or coronary artery by-pass grafts (CABG). Healthy controls were recruited from Sweden’s population database. Twenty-five per cent of the CAD patients had severe periodontitis, compared to 8% of the controls. In a multiple logistic regression analysis (controlled for age and smoking), severe periodontitis indicated an odds ratio of 5.74 (2.07–15.90) for CAD. Study II: Periodontal status was re-examined in 126 CAD patients and 121 controls from the initial sample after 8 years. Periodontal status at baseline was analysed and related to CAD endpoints (i.e., myocardial infarction, new PCI or CABG or death due to CAD) recorded from patients’ medical records and from the death index maintained by the National Board of Health and Welfare. The difference in periodontitis prevalence and severity between the two groups remained unchanged during the 8-year follow up. No significant differences were found regarding CAD endpoints during follow-up in relation to baseline periodontal status in the CAD-patient group. In study III, higher HGF serum concentrations (p&lt;0.001) were found in CAD patients, compared to healthy blood donors, which reflects chronic inflammation. In CAD patients without periodontitis, HGF concentrations increased significantly 24 hours after PCI – in parallel with increased HGF biological activity. In CAD patients with periodontitis, only small fluctuations were seen in HGF values, i.e., concentration and biological activity. HGF biological activity was temporarily elevated after PCI but only in patients without periodontitis. Thus chronic inflammation related to periodontitis might reduce HGF biological activity. In study IV, HGF concentration and biological activity in saliva, in gingival crevicular fluid (GCF), and serum were compared between 30 generally healthy subjects with severe untreated periodontitis and 30 healthy subjects without periodontitis. Compared to periodontally healthy controls, periodontal patients showed higher HGF concentrations in saliva p&lt;0.001, gingival crevicular fluid p&lt;0.0001, and in serum p&lt;0.001. HGF biological activity (measured as the binding affinity to its HSPG and c-MET receptors) was significantly reduced in saliva (p&lt;0.0001) and GCF samples (p&lt;0.0001 for HSPG and p&lt;0.01 for c-MET) from periodontitis patients. The only significant difference in serum samples was an increases in c-MET binding three minutes after subgingival debridement in periodontitis patients (p&lt;0.05), which might reflect that patients had active bursts of periodontitis. In conclusion, CAD patients more often showed severe periodontitis but there were no differences in CAD endpoints during the eight-year follow-up in relation to baseline periodontal status. Periodontitis seems to influence HGF concentration and biological activity in CAD patients, but studies on factors that cause lower HGF biological activity are necessary – to find out if periodontal treatment influences HGF biological activity. Healthy periodontitis patients had higher HGF concentrations locally and systemically, but biological activity was reduced. This might indicate that periodontitis can influence wound healing and tissue repair in other body parts.The ISBN 987‐91‐7519‐748‐7 is incorrect. Correct ISBN is 978‐91‐7519‐748‐7.</p

Unstimulated Parotid Saliva Sampling in Juvenile Idiopathic Arthritis and Healthy Controls : A Proof-of-Concept Study on Biomarkers

The aims of this proof-of-concept study were to develop a collecting method for unstimulated parotid saliva in juvenile idiopathic arthritis (JIA) patients and healthy children and to investigate if inflammatory biomarkers could be detected in these samples. Forty-five children with JIA (median age of 12 years and 25th-75th percentile of 10-15 years; 33 girls and 12 boys) and 16 healthy children as controls (median age of 13 years and 25-75th percentile of 10-13 years; 11 girls and 5 boys) were enrolled in this study. Unstimulated parotid saliva was collected with a modified Carlson-Crittenden collector. The salivary flow rate and salivary concentrations of total protein and inflammatory mediators were assessed. The Meso Scale Discovery electrochemiluminescence immunoassay was used for analyzing protein concentrations and the inflammatory biomarkers. Sufficient parotid saliva volumes to be analyzed could be collected with the collection device. JIA patients had a lower sampling saliva volume (p = 0.008) and saliva flow rate (p = 0.039) than controls. The total protein concentrations and inflammatory biomarkers were measured in the last six healthy subjects. The median protein concentration was 1312 mu g/mL (25th percentile: 844 mu g/mL and 75th percentile: 2062 mu g/mL; n = 6) and quantifiable concentrations of 39 inflammatory proteins could be assessed in these samples. In conclusion, this study indicates that the saliva sampling method, as used in the present study, is able to collect sufficient sample volumes in children, and that it is possible to analyze various inflammatory biomarkers in the collected saliva

Orofacial pain in juvenile idiopathic arthritis is associated with stress as well as psychosocial and functional limitations

Background The aim of this study was to investigate relations between psychosocial factors, signs and symptoms of orofacial pain and jaw dysfunction in patients with juvenile idiopathic arthritis (JIA). Methods Forty-five patients with JIA (median age 12 years) and 16 healthy matched controls (median age 13 years) were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The subjects answered the DC/TMD questionnaires regarding psychosocial factors (pain intensity, pain–related disability, depression, stress, catastrophizing, pain locations and jaw function). Results JIA patients with orofacial pain had higher degree of stress, depression, catastrophizing and jaw dysfunction compared to subjects without. In turn, these factors were associated with orofacial pain intensity. Also, patients with orofacial pain had higher systemic inflammatory activity. Conclusions Orofacial pain in patients with JIA is associated with stress, psychological distress, jaw dysfunction and loss of daily living activities. Pain intensity seems to be the major pain aspect related to these factors. In addition, systemic inflammatory activity appears to be an important factor contributing to orofacial pain in JIA.Funding Agencies|Research Council in Southeast Sweden; Public dental health Scientific Funds in Ostergotland; County (Ostergotland County Council) Sweden; Swedish Dental-Societys Scientific Funds; American Dental Society of Sweden; Malmo University</p

Le anfore di Apani (Brindisi)

Palazzo Paola. Le anfore di Apani (Brindisi). In: Amphores romaines et histoire économique. Dix ans de recherche. Actes du colloque de Sienne (22-24 mai 1986) Rome : École Française de Rome, 1989. pp. 548-553. (Publications de l'École française de Rome, 114

Modified lipoproteins in periodontitis : a link to cardiovascular disease?

There is a strong association between periodontal disease and atherosclerotic cardiovascular disorders. A key event in the development of atherosclerosis is accumulation of modified lipoproteins within the arterial wall. We hypothesise that patients with periodontitis have an altered lipoprotein profile towards an atherogenic form. Therefore, the present study aims at identifying modifications of plasma lipoproteins in periodontitis. Lipoproteins from ten female patients with periodontitis and gender- and age-matched healthy controls were isolated by density-gradient ultracentrifugation. Proteins were separated by 2D gel-electrophoresis and identified by map-matching or by nano-LC followed by MS. Apolipoprotein (Apo) A-I (ApoA-I) methionine oxidation, Oxyblot, total antioxidant capacity and a multiplex of 71 inflammation-related plasma proteins were assessed. Reduced levels of apoJ, phospholipid transfer protein, apoF, complement C3, paraoxonase 3 and increased levels of alpha-1-antichymotrypsin, apoA-II, apoC-III were found in high-density lipoprotein (HDL) from the patients. In low-density lipoprotein (LDL)/very LDL (VLDL), the levels of apoL-1 and platelet-activating factor acetylhydrolase (PAF-AH) as well as apo-B fragments were increased. Methionine oxidation of apoA-I was increased in HDL and showed a relationship with periodontal parameters. alpha-1 antitrypsin and alpha-2-HS glycoprotein were oxidised in LDL/VLDL and antioxidant capacity was increased in the patient group. A total of 17 inflammation-related proteins were important for group separation with the highest discriminating proteins identified as IL-21, Fractalkine, IL-17F, IL-7, IL-1RA and IL-2. Patients with periodontitis have an altered plasma lipoprotein profile, defined by altered protein levels as well as post-translational and other structural modifications towards an atherogenic form, which supports a role of modified plasma lipoproteins as central in the link between periodontal and cardiovascular disease (CVD).Funding Agencies|Swedish Knowledge Foundation [Dnr20150037]; Foundation Langmanska Kulturfonden; Magnus Bergwalls Foundation</p

Hepatocyte growth factor in patients with coronary artery disease and its relation to periodontal condition

Hepatocyte growth factor (HGF) is an angiogenic, cardioprotective factor important for tissue and vascular repair. High levels of HGF are associated with chronic inflammatory diseases, such as coronary artery disease (CAD) and periodontitis, and are suggested as a marker of the ongoing atherosclerotic event in patients with CAD. Periodontal disease is more prevalent among patients with CAD than among healthy people. Recent studies indicate a reduced biological activity of HGF in different chronic inflammatory conditions. Biologically active HGF has high affinity to heparan sulfate proteoglycan (HSPG) on cell-membrane and extracellular matrix. The aim of the study was to investigate the serum concentration and the biological activity of HGF with ELISA and surface plasmon resonance (SPR), respectively, before and at various time points after percutaneous coronary intervention (PCI) in patients with CAD, and to examine the relationship with periodontal condition. The periodontal status of the CAD patients was examined, and the presence of P. gingivalis in periodontal pockets was analyzed with PCR. The HGF concentration was significantly higher, at all time-points, in patients with CAD compared to the age-matched controls (P&lt; 0.001), but was independent of periodontal status. The HGF concentration and the affinity to HSPG adversely fluctuated over time, and the biological activity increased one month after intervention in patients without periodontitis. We conclude that elevated concentration of HGF but with reduced biological activity might indicate a chronic inflammatory profile in patients with CAD and periodontitis