Sex Differences of Oral Anticoagulant Therapy in Atrial Fibrillation

Atrial fibrillation (AF) is a growing epidemic affect- ing mainly older people. Approximately 70 % of individuals with AF are between 65 and 85 years of age. The prevalence of AF is lower in females compared to males. However, the average life expectancy of females is 5.5 years higher compared to males which makes AF a significant problem of older women. After age 75 years, about 60 % of the people with AF are women [1]. The risk of stroke in women is higher in women with AF compared to men. Namely, the Copenhagen City Heart Study has shown that women with AF had a much higher risk of stroke than women without AF (HR 9.1). Men with AF were also at increased risk of stroke compared with men without AF (HR 2.0), but the effect of AF on the risk of stroke was 4 times greater in women than in men (HR 4.5). In addition, the effect of AF on the risk of cardiovascular death was 3 times greater in women than in men (HR 2.9) [2]. Similarly, a US Medicare beneficiaries’ study has shown that the ischemic stroke risk among women with AF was progressively higher with advancing age. Despite lower incidence/prevalence of AF compared with men, ischemic stroke rates are consistently higher in women. A pathobiological rationale for the increased hazard of ischemic stroke in women remains elusive; various explanations including hormonal factors and hemodynamic differences between sexes have been postulated. A supplementary analysis of the Medicare study data identified a significantly higher thromboembolic (CHADS) score for women regardless of age, providing a plausible explanation for higher ischemic stroke rates among women relative to men. Acknowledging all this data AF should probably be treated more rigorously in women. In general studies show that the ischemic stroke rate decreased markedly in all age categories comparing data from 1992 and 2010 which was attributed mainly to the use of anticoagulant therapy. Namely, warfarin use increased from 15 % to 49 %. Using a large population‐based cohort from Quebec, Avgil Tsadok and associates found that although the hazard of stroke was 14 % higher in women than in men, prescription warfarin use was similar for both. This observation led to lack of confidence in the effectiveness of warfarin in reducing stroke among elderly women with AF and to conjecture and debate as to whether newer anticoagulants may be more effective [3]. US Medicare beneficiaries study identified higher warfarin use among men than among women in each age category studied, especially in the most elderly sub- groups [3]. Various clinical factors could contribute to lower warfarin use rates among women, such as higher prevalence of clinical contraindications or higher perceived risk of bleeding complications. This area de- serves further investigation. Nevertheless, women with AF are less likely to receive anticoagulants despite their higher risk of stroke compared with men. A meta-analysis of randomized clinical trials that reported on major bleeding and stroke with DOACs in women and men with AF included more than 66 000 patients and only 37,8 % were women. Women treated with DOACs were at higher risk of stroke and systemic embolism compared with men (RR = 1.19) but there was a significantly lower risk of major bleed- ing in women compared with men (RR = 0.86) [4]. According to the conclusions of the meta-analysis DOAC use should probably be sex specific and encouraged even more in women with AF than in men

Moyamoya sindrom s arteriovenskom fistulom dure nakon ozljede glave

Moyamoya vascular pattern and dural arteriovenous fistula (dAVF) are rare vascular abnormalities and both can be secondary to head trauma. The role of dural angiogenesis in the pathophysiology of vascular malformation is rather unclear. We report a unique case of moyamoya vasculopathy simultaneously associated with dAVF after heavy head trauma. It seems that both moyamoya syndrome and dAVFs are associated with dural angiogenesis induced by head trauma. The interrelationship between vascular abnormalities is complex and unclear.Vaskularna struktura moyamoya i arteriovenska fistula dure (dAVF) su rijetke krvožilne nepravilnosti koje mogu nastati kao posljedica ozljede glave. Uloga duralne angiogeneze u patofiziologiji vaskularne malformacije prilično je nejasna. Opisujemo jedinstven slučaj moyamoya vaskulopatije istodobno udružene s dAVF nakon teške traume glave. Čini se da su i sindrom moyamoya i dAVF udruženi s duralnom angiogenezom izazvanom ozljedom glave. Međuodnos vaskularnih nepravilnosti je složen i nejasan

Associations between cerebral and systemic endothelial function in migraine patients: a post-hoc study

<p>Abstract</p> <p>Background</p> <p>There is a growing interest in the role of the endothelium in migraine. Recently, our group showed differences in endothelial function between the anterior and posterior cerebral circulation in healthy subjects, reduced vasodilatatory capacity of the posterior cerebral circulation and unimpaired systemic endothelial function in migraine patients without comorbidities. However, the relationship between cerebral and systemic endothelial function and the anterior and posterior cerebral endothelial function in migraine patients is still not clear.</p> <p>Methods</p> <p>We compared cerebral and systemic endothelial function through post-hoc linear regression analysis of cerebrovascular reactivity (CVR) to L-arginine between the middle cerebral artery (MCA) and flow-mediated vasodilatation (FMD) of the right brachial artery and the posterior cerebral artery (PCA) and FMD in migraine patients without comorbidities and in healthy subjects. The anterior and posterior cerebral endothelial function was also compared using post-hoc linear regression analysis between CVR to L-arginine in the MCA and the PCA.</p> <p>Results</p> <p>No significant correlation was found between CVR to L-arginine in the MCA and FMD and in the PCA and FMD in migraine patients with aura (p = 0.880 vs. p = 0.682), without aura (p = 0.153 vs. p = 0.179) and in healthy subjects (p = 0.869 vs. p = 0.662). On the other hand, we found a significant correlation between CVR to L-arginine in the MCA and PCA in migraine patients with aura (p = 0.004), without aura (p = 0.001) and in healthy subjects (p = 0.002). Detailed analysis of the linear regression between all migraine patients and healthy subjects did not show any difference in the regression coefficient (slope) (p = 0.382). However, a significant difference in curve elevation (intercept) was found (p = 0.002).</p> <p>Conclusions</p> <p>Our study suggests that the endothelial function in the cerebral and systemic circulation might be different in migraine patients without comorbidities, while that of the anterior and posterior cerebral circulation might be coupled. These results could improve understanding of endothelial function in migraine patients without comorbidities.</p

Cerebral Endothelial Function Determined by Cerebrovascular Reactivity to L-Arginine

Endothelium forms the inner cellular lining of blood vessels and plays an important role in many physiological functions including the control of vasomotor tone. Cerebral endothelium is probably one of the most specific types but until recently it was impossible to determine its function. In this review, the role of cerebrovascular reactivity to L-arginine (CVR-L-Arg) for assessment of cerebral endothelial function is discussed. L-Arginine induces vasodilatation through enhanced production of nitric oxide (NO) in the cerebral endothelium. Transcranial Doppler sonography is used for evaluation of cerebral blood flow changes. The method is noninvasive, inexpensive, and enables reproducible measurements. CVR-L-Arg has been compared to flow-mediated dilatation as a gold standard for systemic endothelial function and intima-media thickness as a marker for morphological changes. However, it seems to show specific cerebral endothelial function. So far CVR-L-Arg has been used to study cerebral endothelial function in many pathological conditions such as stroke, migraine, etc. In addition CVR-L-Arg has also proven its usefulness in order to show potential improvement after pharmacological interventions. In conclusion CVR-L-Arg is a promising noninvasive research method that could provide means for evaluation of cerebral endothelial function in physiological and pathological conditions

Mechanical recanalization for acute bilateral cerebral artery occlusion – literature overview with a case

Acute bilateral internal carotid artery (ICA) and/or middle cerebral artery (MCA) occlusion is extremely rare and associated with poor clinical outcomes. There are only a few reports in the literature about mechanical thrombectomy being performed for acute bilateral occlusions. The treatment strategies and prognoses (clinical outcomes) are therefore unclear

Are impaired endothelial function in the posterior cerebral circulation and intact endothelial function in the anterior cerebral and systemic circulation associated with migraine: A post hoc study

SummaryIt seems that migraine patients might suffer from localized and not systemic endothelial dysfunction. However, the probability whether impaired endothelial function in the posterior cerebral circulation, and intact endothelial function elsewhere is associated with migraine is not known. This is a post hoc study based on two of our previous published studies that evaluated cerebral and systemic endothelial function in 40 migraine patients (20 with (MwA) and 20 without aura (MwoA)) without comorbidities, and 20 healthy subjects. Cerebrovascular reactivity (CVR) to l-arginine in the middle (MCA) and posterior (PCA) cerebral artery as well as flow mediated vasodilatation (FMD) were used for this purpose. The logistic regression analysis was used to evaluate the association between CVR to l-arginine, FMD and migraine. We found a significant association between CVR to l-arginine in the PCA and migraine (OR: 0.38; CI 95%: 0.19–0.79; p=0.01), but not between CVR to l-arginine in the MCA and migraine (OR: 0.74; CI 95%: 0.34–1.59; p=0.44). Similar results were obtained in MwA and MwoA. We did not find any significant association between FMD and migraine (OR: 0.99; CI 95%: 0.83–1.19; p=0.96). The same conclusion was reached in both migraine groups (MwA OR: 1.0; CI 95%: 0.83–1.19; p=0.99, MwoA OR: 0.99; CI 95%: 0.81–1.21; p=0.99). We could conclude that impaired endothelial function in the posterior cerebral circulation is associated with migraine, both MwA and MwoA, while intact endothelial function in the anterior cerebral and systemic circulation is not associated only with migraine

Neuropathological criteria of anti-IgLON5-related tauopathy

We recently reported a novel neurological syndrome characterized by a unique NREM and REM parasomnia with sleep apnea and stridor, accompanied by bulbar dysfunction and specific association with antibodies against the neuronal cell-adhesion protein IgLON5. All patients had the HLA-DRB1*1001 and HLA-DQB1*0501 alleles. Neuropathological findings in two patients revealed a novel tauopathy restricted to neurons and predominantly involving the hypothalamus and tegmentum of the brainstem. The aim of the current study is to describe the neuropathological features of the anti-IgLON5 syndrome and to provide diagnostic levels of certainty based on the presence of associated clinical and immunological data. The brains of six patients were examined and the features required for the neuropathological diagnosis were established by consensus. Additional clinical and immunological criteria were used to define "definite", "probable" and "possible" diagnostic categories. The brains of all patients showed remarkably similar features consistent with a neurodegenerative disease with neuronal loss and gliosis and absence of inflammatory infiltrates. The most relevant finding was the neuronal accumulation of hyperphosphorylated tau composed of both three-repeat (3R) and four-repeat (4R) tau isoforms, preferentially involving the hypothalamus, and more severely the tegmental nuclei of the brainstem with a cranio-caudal gradient of severity until the upper cervical cord. A "definite" diagnosis of anti-IgLON5-related tauopathy is established when these neuropathological features are present along with the detection of serum or CSF IgLON5 antibodies. When the antibody status is unknown, a "probable" diagnosis requires neuropathological findings along with a compatible clinical history or confirmation of possession of HLA-DRB1*1001 and HLA-DQB1*0501 alleles. A "possible" diagnosis should be considered in cases with compatible neuropathology but without information about a relevant clinical presentation and immunological status. These criteria should help to identify undiagnosed cases among archival tissue, and will assist future clinicopathological studies of this novel disorder