Background: Vasoregulatory autoantibodies including autoantibodies targeting G-protein-coupled receptors might play a functional role in vascular diseases. We investigated the impact of... Show moreBackground: Vasoregulatory autoantibodies including autoantibodies targeting G-protein-coupled receptors might play a functional role in vascular diseases. We investigated the impact of vasoregulatory autoantibodies on clinical outcome after ischemic stroke.Methods and results: Data were used from the PROSCIS-B (Prospective Cohort With Incident Stroke-Berlin). Autoantibody-targeting receptors such as angiotensin II type 1 receptor (AT1R), endothelin-1 type A receptor, complement factor-3 and -5 receptors, vascular endothelial growth factor receptor-1 and -2, vascular endothelial growth factor A and factor B were measured. We explored associations of high antibody levels with (1) poor functional outcome defined as modified Rankin Scale >2 or Barthel Index <60 at 1 year after stroke, (2) Barthel Index scores over time using general estimating equations, and (3) secondary vascular events (recurrent stroke, myocardial infarction) or death up to 3 years using Cox proportional hazard models. We included 491 patients with ischemic stroke with data on autoantibody levels and outcome. In models adjusted for demographics and vascular risk factors, high autoantibody concentrations (quartile 4) targeting complement factor C3a receptor, vascular endothelial growth factor receptor-2, and vascular endothelial growth factor B were associated with poor functional outcome at 1 year: (odds ratio, 2.0 [95% CI, 1.1-3.6]; odds ratio, 1.8 [95% CI, 1.1-3.2]; and odds ratio, 2.1 [95% CI, 1.2-3.6], respectively) and with lower Barthel Index scores over 3 years (complement factor C3a receptor: adjusted beta=-3.3 [95% CI, -5.7 to -0.5]; VEGF-B: adjusted beta=-2.4 [95% CI, -4.8 to -0.06]). Patients with high autoantibody levels were not at higher risk for secondary vascular events or death.Conclusions: High levels of autoantibodies against vascular endothelial growth factor receptor-2, vascular endothelial growth factor B, and complement factor C3a receptor measured are associated with poor functional outcome after stroke but not with recurrent vascular events or death. Show less
Background and importanceChest pain is one of the most common presentations to the emergency department (ED). The HEART-score is used to assess the 30-day risk of developing a major adverse cardiac... Show moreBackground and importanceChest pain is one of the most common presentations to the emergency department (ED). The HEART-score is used to assess the 30-day risk of developing a major adverse cardiac event (MACE). The HEART-score enables clinicians to classify patients in low, intermediate, or high-risk groups though little is known as to whether this can be done reliably and reproducibly in a prehospital setting.ObjectiveThe aim of this study was to compare the interobserver agreement of the HEART-score between ambulance nurses and ED physicians.Design, settings, and participantsPatients >= 18 years, with chest pain of suspected cardiac origin presented by ambulance to the EDs of four regional hospitals, were prospectively enrolled between October 2018 and April 2019.Outcomes measure and analysisThe primary endpoint was interobserver agreement of the HEART-scores calculated by ambulance nurses compared to those calculated by ED physicians. Agreement was measured using Cohen's Kappa (K) both for overall HEART-score and dichotomized HEART categories. A secondary endpoint was the occurrence of a MACE at 30 days after inclusion.Main resultsA total of 307 patients were enrolled of which 166 patients were male (54%). The mean age was 64.8 years. In 23% (95% confidence interval, 18-27), patients were scored in the low-risk category by both ambulance nurses and ED physicians. The K for the overall HEART-score compared between ambulance nurses and ED physicians was 0.514. The K for the low-risk category versus intermediate and high-risk category was 0.591. Both are defined as 'moderate'. MACE within 30 days occurred in 64 patients (21%). In the low-risk group as defined by the ambulance nurses, there was a 7% risk of MACE compared to an average 5% MACE risk in the ED physician group.ConclusionsThe moderate interobserver agreement of the HEART-score does not currently support the use of the HEART-score by ambulance nurses in a prehospital setting. Training for prehospital nurses is vital to ensure that they are able to calculate the HEART-score accurately. Show less
Background: In premenopausal women, treatment with direct oral factor Xa inhibitors is associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists (VKA).... Show moreBackground: In premenopausal women, treatment with direct oral factor Xa inhibitors is associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists (VKA). Treatment with the direct oral thrombin inhibitor dabigatran appears to be associated with a reduced risk of HMB compared with VKA. These findings come from small observational studies or post hoc analyses of trials in which HMB was not a primary outcome. Use of tranexamic acid during the menstrual period may be effective in patients with HMB, but prospective data regarding efficacy and safety in patients on anticoagulant treatment are lacking.Rationale and Design: A direct comparison of a factor Xa inhibitor and a thrombin inhibitor with HMB as primary outcome, as well as an evaluation of the effects of adding tranexamic acid in women with anticoagulant-associated HMB is highly relevant for clinical practice. The MEDEA study is a randomized, open-label, pragmatic clinical trial to evaluate management strategies in premenopausal women with HMB associated with factor Xa inhibitor therapy.Outcomes: Women using factor Xa inhibitors with proven HMB, as assessed by a pictorial blood loss assessment chart (PBAC) score of >150, will be randomized to one of three study arms: (i) switch to dabigatran; (ii) continue factor Xa inhibitor with addition of tranexamic acid during the menstrual period; or (iii) continue factor Xa inhibitor without intervention. The primary outcome is the difference in PBAC score before and after randomization. Here, we present the rationale and highlight several unique features in the design of the study. Show less
Background Family history of myocardial infarction (FHMI) is known to increase the risk of venous thromboembolism (VTE). Objectives To investigate the effect of prothrombotic genotypes on the... Show moreBackground Family history of myocardial infarction (FHMI) is known to increase the risk of venous thromboembolism (VTE). Objectives To investigate the effect of prothrombotic genotypes on the association between FHMI and VTE in a case-cohort recruited from a general population. Methods Cases with a first VTE (n = 1493) and a subcohort (n = 13 072) were sampled from the Tromso study (1994-2012) and the Nord-Trondelag health (HUNT) study (1995-2008). The DNA samples were genotyped for rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11). Participants with missing information on risk alleles (n = 175), FHMI (n = 2769), and BMI (n = 52) were excluded. Cox regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for VTE. To explore the role of prothrombotic genotypes for the association between FHMI and VTE, we (a) included the genotypes in the multivariable-adjusted models and (b) assessed the joint effects between FHMI and genotypes on VTE risk. Results The FHMI was associated with a 1.3-fold increased risk of VTE (HR 1.32, 95% CI 1.16-1.50) and 1.5-fold increased risk of unprovoked VTE (HR 1.47, 95% CI 1.22-1.78). The risk of VTE by FHMI did not alter after adjustment for the five genotypes. The combination of FHMI and the different prothrombotic genotypes did not result in an excess VTE risk (i.e. no biological interaction). Conclusions Our findings suggest that the risk of VTE by FHMI is not explained by rs8176719 (ABO), rs6025 (F5), rs1799963 (F2), rs2066865 (FGG), and rs2036914 (F11). The combination of FHMI with prothrombotic genotypes had an additive effect on VTE risk. Show less
Serial measurements of coronary plaque volume have been used to evaluate drug efficacy in atherosclerotic progression. However, the usefulness of computed tomography for this purpose is unknown. We... Show moreSerial measurements of coronary plaque volume have been used to evaluate drug efficacy in atherosclerotic progression. However, the usefulness of computed tomography for this purpose is unknown. We investigated whether the change in total plaque volume on coronary computed tomographic angiography is associated with the change in segment plaque volume on intravascular ultrasound.We prospectively enrolled 11 consecutive patients (mean age, 56.3 +/- 5 yr; 6 men) who were to undergo serial invasive coronary angiographic examinations with use of grayscale intravascular ultrasound and coronary computed tomography, performed <180 days apart at baseline and from 1 to 2 years later. Subjects underwent 186 serial measurements of total plaque volume on coronary computed tomography and 22 of segmental plaque volume on intravascular ultrasound. We used semiautomated software to examine percentage relationships and changes between total plaque and segmental plaque volumes.No significant correlations were found between percentages of total coronary and segment coronary plaque volume, nor between normalized coronary plaque volume. However, in the per-patient analysis, there were strong correlations between the imaging methods for changes in total coronary and segment coronary plaque volume (r=0.62; P=0.04), as well as normalized plaque volume (r=0.82; P=0.002).Per-patient change in plaque volume on coronary computed tomography is significantly associated with that on intravascular ultrasound. Computed tomographic angiography may be safer and more widely available than intravascular ultrasound for evaluating atherosclerotic progression in coronary arteries. Larger studies are warranted. Show less
