Prevalence of potential drug-drug interactions with disease-specific treatments in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension: A registry study.

Polypharmacy increases the risk of drug-drug interactions that may disturb treatment effects. The aim of this study was to investigate the frequency of codispensing of potentially interacting or contraindicated drugs related to PH-specific treatment in the Swedish pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) population. All prescribed drugs, on an individual level, dispensed 2016-2017 at pharmacies to patients with PAH or CTEPH were obtained from The National Board of Health and Welfare's pharmaceutical registry. Potential drug-drug interactions were investigated using the Drug Interaction tool in the IBM Micromedex® database. There were 4785 different dispensed drugs from 572 patients (mean age 61 ± 16 years, 61% female, mean number of drugs per patient 8.4 ± 4.2) resulting in 1842 different drug combinations involving a PH-specific treatment. Of these drug combinations, 67 (3.5%) had a potential drug-drug interaction considered clinically relevant and it affected 232 patients (41%). The PH-specific drugs with the highest number of potential drug-drug interactions was bosentan (n = 23, affected patients = 171) while the most commonly codispensed, potentially interacting drug combination was sildenafil/furosemide (119 patients affected). Other common codispensed and potentially interacting drugs were anticoagulants (n = 11, affected patients = 100) and antibiotic treatment (n = 12, affected patients = 26). In conclusion, codispensing of PH-specific therapy and potentially interacting drugs was common, but codispensing of potentially contraindicated drugs was rare.

Long-term prognosis after a first myocardial infarction: eight years follow up of the case-control study PAROKRANK.

Objective. To explore long-term cardiovascular outcomes and mortality in patients after a first myocardial infarction (MI) compared with matched controls in a contemporary setting. Methods. During 2010-2014 the Swedish study PAROKRANK recruited 805 patients <75 years with a first MI and 805 age-, gender-, and area-matched controls. All study participants were followed until 31 December 2018, through linkage with the National Patient Registry and the Cause of Death Registry. The primary endpoint was the first of a composite of all-cause death, non-fatal MI, non-fatal stroke, and heart failure hospitalization. Event rates in cases and controls were calculated using a Cox regression model, subsequently adjusted for baseline smoking, education level, and marital status. Kaplan-Meier curves were computed and compared by log-rank test. Results. A total of 804 patients and 800 controls (mean age 62 years; women 19%) were followed for a mean of 6.2 (0.2-8.5) years. The total number of primary events was 211. Patients had a higher event rate than controls (log-rank test p < .0001). Adjusted hazard ratio (HR) for the primary outcome was 2.04 (95% CI 1.52-2.73). Mortality did not differ between patients (n = 38; 4.7%) and controls (n = 35; 4.4%). A total of 82.5% patients and 91.3% controls were event-free during the follow up. Conclusions. In this long-term follow up of a contemporary, case-control study, the risk for cardiovascular events was higher in patients with a previous first MI compared with their matched controls, while mortality did not differ. The access to high quality of care and cardiac rehabilitation might partly explain the low rates of adverse outcomes.

Five year risk assessment and treatment patterns in patients with chronic thromboembolic pulmonary hypertension.

AIMS: Repeated risk assessments and treatment patterns over long time are sparsely studied in chronic thromboembolic pulmonary hypertension (CTEPH); thus, we aimed to investigate changes in risk status and treatment patterns in incident patients with CTEPH over a 5 year period. METHODS AND RESULTS: Descriptive and explorative study including 311 patients diagnosed with CTEPH 2008-2019 from the Swedish pulmonary hypertension registry, stratified by pulmonary endarterectomy surgery (PEA). Risk and PH-specific treatment were assessed in surgically treated (PEA) and medically treated (non-PEA) patients at diagnosis and up to 5 years follow-up. Data are presented as median (Q1-Q3), count or per cent. Prior to surgery, 63% in the PEA-group [n = 98, age 64 (51-71) years, 37% female] used PH-specific treatment and 20, 69, and 10% were assessed as low, intermediate or high risk, respectively. After 1 year post-surgery, 34% had no PH-specific treatment or follow-up visit registered despite being alive at 5 years. Of patients with a 5 year visit (n = 23), 46% were at low and 54% at intermediate risk, while 91% used PH-specific treatment. In the non-PEA group [n = 213, age 72 (65-77) years, 56% female], 28% were assessed as low, 61% as intermediate and 11% as high risk. All patients at high risk versus 50% at low risk used PH-specific treatment. The 1 year mortality was 6%, while the risk was unchanged in 57% of the patients; 14% improved from intermediate to low risk, and 1% from high to low risk. At 5 years, 27% had a registered visit and 28% had died. Of patients with a 5 year visit (n = 58), 38% were at low, 59% at intermediate and 1% at high risk, and 86% used PH-specific treatment. CONCLUSIONS: Risk status assessed pre-surgery did not foresee long-term post-PEA risk and pre-surgery PH-specific treatment did not foresee long-term post-PEA treatment. Medically treated CTEPH patients tend to remain at the same risk over time, suggesting a need for improved treatment strategies in this group.

Periodontitis, assessed using periodontal treatment as a surrogate marker, has no association with a first myocardial infarction in a Swedish population.

BACKGROUND: Periodontitis is suggested to be associated with a risk of cardiovascular events. Using periodontal treatment recorded in Swedish national registries as a surrogate marker, we aimed to investigate whether periodontitis was associated with a first myocardial infarction. METHODS: This nationwide case-control study, with data from national registries, involved 51,880 individuals with a first myocardial infarction in 2011 to 2013 (index date) and 246,978 controls matched 5:1 for age, gender, and geographic area. Periodontal treatment in the 3 years preceding the index date was classified as (1) no dental treatment, (2) no periodontal treatment, (3) one or more supragingival curettages, or (4) one or more treatments with scaling/root planing and/or periodontal surgery. Annual frequencies of treatment with scaling/root planing and/or periodontal surgery were also calculated. In all analyses, conditional logistic regression analyses estimated ORs for myocardial infarction with 95% CIs, adjusted for matched variables, income, education, and diabetes. RESULTS: Although fewer cases than controls received treatment with scaling/root planing and/or periodontal surgery (19.2% versus 19.8%, P < 0.001), annual frequencies for cases were higher. We found no association of scaling/root planing and/or periodontal surgery with a first myocardial infarction (OR = 1.02; 95% CI: 1.00, 1.05). We did observe a non-significant trend, however, between risk of a first myocardial infarction and a high frequency of scaling/root planing and/or periodontal surgery (OR 1.14; 95% CI: 1.00, 1.29). CONCLUSION: In the contemporary Swedish nationwide setting, no association between a first myocardial infarction and periodontitis, assessed as periodontal treatment, was found.

Antiphospholipid antibodies in patients with dysglycaemia: A neglected cardiovascular risk factor?

BACKGROUND: Cardiovascular disease is a serious complication in patients with dysglycaemia, defined as either type 2 diabetes or impaired glucose tolerance. Research focusing on the identification of potential markers for atherothrombotic disease in these subjects is warranted. The antiphospholipid syndrome is a common acquired prothrombotic condition, defined by a combination of thrombotic events and/or obstetric morbidity and positivity of specific antiphospholipid antibodies. Available information on antiphospholipid antibodies in dysglycaemia is scarce. OBJECTIVE: This study investigates the association between antiphospholipid antibodies and dysglycaemia. PATIENTS/METHODS: The PAROKRANK (periodontitis and its relation to coronary artery disease) study included 805 patients, investigated 6-10 weeks after a first myocardial infarction, and 805 matched controls. Participants without known diabetes (91%) underwent an oral glucose tolerance test. Associations between antiphospholipid antibodies (anti-cardiolipin and anti-ß2 glycoprotein-I IgG, IgM and IgA) and dysglycaemia were analysed. RESULTS: In total, 137 (9%) subjects had previously known type 2 diabetes and 371 (23%) newly diagnosed dysglycaemia. Compared with the normoglycaemic participants, those with dysglycaemia had a higher proportion with first myocardial infarction (61% vs 45%, p < 0.0001) and were more often antiphospholipid antibody IgG positive (8% vs 5%; p = 0.013). HbA1c, fasting glucose and 2-h glucose were significantly associated to antiphospholipid antibody IgG. Odds ratios (ORs) were 1.04 (95% confidence interval [CI] 1.02-1.06), 1.14 (95% CI 1.00 - 1.27) and 1.12 (95% CI 1.04 - 1.21), respectively, after adjustments for age, gender and smoking. CONCLUSIONS: This study reports an association between antiphospholipid antibody IgG positivity and dysglycaemia. Further studies are needed to verify these findings and to investigate if antithrombotic therapy reduces vascular complications in antiphospholipid antibody positive subjects with dysglycaemia.

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

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

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

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

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

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

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

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

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

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

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

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