Gut microbiota and their metabolites in cardiovascular disease.

The gut microbiome affects the development and progress of various types of disease such as obesity, diabetes, atherosclerosis and arterial thrombosis. Gut microbiome derived metabolites have been established to be predictive of arterial thrombosis in epidemiological studies. In these studies atherosclerosis and prothrombotic effect cannot be distinguished but preclinical studies show gut derived metabolites can induce platelet hyperreactivity and increase thrombotic potential. Gut commensals can also influence platelets through serotonin synthesis and may enhance Von Willebrand factor production. The effects on secondary haemostasis are less studied. In antiphospholipid syndrome, a thrombotic auto-immune disorder, autoreactive T cells and antibodies cross-react with auto-antigen mimicking peptides from gut commensals which appears to contribute to the pathophysiology. This review focusses on the prothrombotic effect of the gut microbiome and aims to provide insight into its influence on thromboembolic disease and the haemostatic system.

Self-reported oral health and quality of life in patients with type 2 diabetes mellitus in primary care: a multi-center cross-sectional study.

Background: Guidelines for primary diabetes care recommend to pay attention to oral health in patients with diabetes mellitus type 2 (T2DM). However, research about dental care utilization and the extent of problems regarding oral health in these patients is limited. Purpose: To assess self-reported oral health, general health-related quality of life (QoL) and oral health-related QoL in patients with T2DM who regularly attend a family physician office. Methods: Family physician offices were recruited in the area of Amsterdam, the Netherlands, as part of a cluster-randomized controlled trial. At these offices, patients with T2DM were included by family physicians and/or nurse practitioners. Patient data on general characteristics, self-reported oral health (including periodontitis), general health-related QoL (SF-36) and oral health-related QoL (OHIP-NL14) were collected. Results: Twenty-four family physician offices participated, who enrolled 764 patients with T2DM (mean age: 65.9±10.7 years, 56% male, 16% smoker). Almost 11% of the patients were metabolically poorly controlled (HbA1c >63 mmol/mol), 39% were obese (body mass index≥30 kg/m2), 37% had hypertension (systolic blood pressure ≥140 mmHg) and 44% had dyslipidemia (LDL-cholesterol >2.5 mmol/L). About a quarter (24%) reported not to visit a dentist regularly and 30% did not have dental insurance coverage. Furthermore, 16% of the patients were edentulous and having full dental prostheses, while 29% had a partial dental prosthesis. Pain in the mouth, dry mouth and bad breath were reported by 15%, 37% and 12% of the patients, respectively. Almost 70% suffered from periodontitis. Oral health-related QoL was impaired in 19% of the patients, and those subjects also had worse general health-related QoL. Conclusion: Almost a quarter of patients with T2DM at Dutch family physician offices does not visit the dentist regularly. The estimated prevalence of periodontitis is particularly high, but other oral health complaints and impaired oral health-related QoL are also relatively common.

Influenza infection and risk of acute pulmonary embolism.

BACKGROUND: Influenza infections have been associated with procoagulant changes. Whether influenza infections lead to an increased risk of pulmonary embolism remains to be established. METHODS: We conducted a nested case control study in a large cohort of patients with a clinical suspicion of having pulmonary embolism. Blood samples were collected to investigate the presence of influenza A and B by complement fixation assay (CFA). We compared case patients, in whom pulmonary embolism was proven (n = 102), to controls, in whom pulmonary embolism was excluded (n = 395). Furthermore, we compared symptoms of influenza-like illness in both patient groups 2 weeks prior to inclusion in the study, using the influenza-like illness (ILI) score, which is based on a questionnaire. We calculated the risk of pulmonary embolism associated with influenza infection. RESULTS: The percentage of patients with influenza A was higher in the control group compared to the case group (4.3% versus 1.0%, respectively, odds ratio 0.22; 95% CI: 0.03-1.72). Influenza B was not detectable in any of the cases and was found in 3 of the 395 controls (0.8%). The ILI score was positive in 24% of the cases and 25% in the control persons (odds ratio 1.16, 95% CI: 0.67-2.01). We did not observe an association between the ILI score and proven influenza infection. CONCLUSION: In this clinical study, influenza infection was not associated with an increased risk of acute pulmonary embolism. The ILI score is non-specific in this clinical setting.

Recurrent deep venous thrombosis during optimal anticoagulation and overt hyperthyroidism: a case report.

Recurrent deep venous thrombosis despite well conducted anticoagulant treatment is an uncommon, but possible, event. It has been hypothesized that overt hyperthyroidism may increase thromboembolic risk. We present the case of an elderly man with a recurrent episode of deep venous thrombosis during optimal oral vitamin K antagonist treatment, associated with a new diagnosis of overt hyperthyroidism, with no evidence of occult cancer and normal levels of antiphosholipid antibodies.

The Hypercoagulable state in Hyperthyroidism is mediated via the Thyroid Hormone ß Receptor pathway.

OBJECTIVE: Hyperthyroidism is associated with a hypercoagulable state, but the underlying mechanism is unknown. Patients with resistance to thyroid hormone (RTH) due to defective thyroid hormone receptor ß (TRß) exhibit elevated circulating thyroid hormones (TH) with refractoriness to TH action in TRß-expressing tissues. We tested the hypothesis that the hypercoagulable state in hyperthyroidism is mediated via the TRß. DESIGN: We conducted a cross-sectional study from November 2013 to January 2015 in 3 hospitals in the Netherlands and the United Kingdom. METHODS: Patients with RTH due to defective TRß (n=18), patients with hyperthyroidism (n=16) and euthyroid subjects (n=18) were included. TH concentrations and markers of coagulation and fibrinolysis were measured. Data are expressed as median [interquartile range]. RESULTS: Free thyroxine (FT4) levels were slightly higher in hyperthyroid patients than in RTH patients (53.9 [30.5-70.0] and 34.9 [28.4-42.2]pmol/l, respectively, P=0.042). Both groups had raised FT4 levels compared to euthyroid subjects (14.0 [13.0-15.8] pmol/l, P≤0.001). Levels of von Willebrand factor (VWF), factor (F) VIII, fibrinogen, and D-dimer were significantly higher in hyperthyroid patients than in RTH patients (VWF 231 [195-296] vs. 111 [82-140]%, FVIII 215 [192-228] vs. 145 [97-158]%, fibrinogen 3.6 [3.0-4.4] vs. 2.8 [2.5-3.2]g/L, D-dimer 0.41 [0.31-0.88] vs. 0.20 [0.17-0.26]mg/L, respectively, P≤0.001), while there were no differences between RTH patients and euthyroid controls. CONCLUSIONS: Parameters of coagulation and fibrinolysis were elevated in hyperthyroid patients compared to patients with RTH due to defective TRß, whereas these parameters were not different between euthyroid controls and RTH patients, despite elevated FT4 concentrations in RTH patients. This indicates that the procoagulant effects observed in hyperthyroidism are mediated via the TRß.