Sex differences in ischaemic stroke: potential cellular mechanisms

2017 ◽  
Vol 131 (7) ◽  
pp. 533-552 ◽  
Author(s):  
Anjali Chauhan ◽  
Hope Moser ◽  
Louise D. McCullough
Keyword(s):  
Sex Differences ◽  
Ischaemic Stroke ◽  
Recurrent Stroke ◽  
Young Male ◽  
Nursing Home Care ◽  
Cellular Mechanisms ◽  
Ischaemic Injury ◽  
Stroke Incidence ◽  
Incidence And Mortality ◽  
Tissue Plasminogen

Stroke remains a leading cause of mortality and disability worldwide. More women than men have strokes each year, in part because women live longer. Women have poorer functional outcomes, are more likely to need nursing home care and have higher rates of recurrent stroke compared with men. Despite continued advancements in primary prevention, innovative acute therapies and ongoing developments in neurorehabilitation, stroke incidence and mortality continue to increase due to the aging of the U.S. population. Sex chromosomes (XX compared with XY), sex hormones (oestrogen and androgen), epigenetic regulation and environmental factors all contribute to sex differences. Ischaemic sensitivity varies over the lifespan, with females having an “ischaemia resistant” phenotype that wanes after menopause, which has recently been modelled in the laboratory. Pharmacological therapies for acute ischaemic stroke are limited. The only pharmacological treatment for stroke approved by the Food and Drug Administration (FDA) is tissue plasminogen activator (tPA), which must be used within hours of stroke onset and has a number of contraindications. Pre-clinical studies have identified a number of potentially efficacious neuroprotective agents; however, nothing has been effectively translated into therapy in clinical practice. This may be due, in part, to the overwhelming use of young male rodents in pre-clinical research, as well as lack of sex-specific design and analysis in clinical trials. The review will summarize the current clinical evidence for sex differences in ischaemic stroke, and will discuss sex differences in the cellular mechanisms of acute ischaemic injury, highlighting cell death and immune/inflammatory pathways that may contribute to these clinical differences.

Sex differences in stroke metrics among Southeast Asian countries: Results from the Global Burden of Disease Study 2015

2019 ◽  
Vol 14 (8) ◽  
pp. 826-834
Author(s):  
Wen Yea Hwong ◽  
Michiel L Bots ◽  
Sharmini Selvarajah ◽  
Sheamini Sivasampu ◽  
Daniel D Reidpath ◽  
...  
Keyword(s):  
Sex Differences ◽  
Ischemic Stroke ◽  
Southeast Asia ◽  
Burden Of Disease ◽  
Global Burden Of Disease ◽  
Global Burden ◽  
Stroke Mortality ◽  
Stroke Incidence ◽  
Incidence And Mortality ◽  
Disease Study

Background Sex differences in cardiovascular diseases generally disadvantage women, particularly within developing regions. Aims This study aims to examine sex-related differences in stroke metrics across Southeast Asia in 2015. Furthermore, relative changes between sexes are compared from 1990 to 2015. Methods Data were sourced from the Global Burden of Disease Study. Incidence and mortality from ischemic and hemorrhagic strokes were explored with the following statistics derived: (1) women-to-men incidence/mortality ratio and (2) relative percentage change in rate. Results Women had lower incidence and mortality from stroke compared to men. Notable findings include higher ischemic stroke incidence for women at 30–34 years in high-income countries (women-to-men ratio: 1.3, 95% CI: 0.1, 16.2 in Brunei and 1.3, 95% CI: 0.5, 3.2 in Singapore) and the largest difference between sexes for ischemic stroke mortality in Vietnam and Myanmar across most ages. Within the last 25 years, greater reductions for ischemic stroke metrics were observed among women compared to men. Nevertheless, women below 40 years in some countries showed an increase in ischemic stroke incidence between 0.5% and 11.4%, whereas in men, a decline from −4.2% to −44.2%. Indonesia reported the largest difference between sexes for ischemic stroke mortality; a reduction for women whereas an increase in men. For hemorrhagic stroke, findings were similar: higher incidence among young women in high-income countries and greater reductions for stroke metrics in women than men over the last 25 years. Conclusions Distinct sex-specific differences observed across Southeast Asia should be accounted in future stroke preventive guidelines.

scholarly journals EXPRESS: COVID-19 AND STROKE – UNDERSTANDING THE RELATIONSHIP AND ADAPTING SERVICES. A GLOBAL WORLD STROKE ORGANISATION PERSPECTIVE

2021 ◽  
pp. 174749302110064
Author(s):  
Hugh S Markus ◽  
Sheila Cristina Ouriques Martins
Keyword(s):  
Large Scale ◽  
Stroke Care ◽  
Long Term Effects ◽  
Vessel Occlusion ◽  
Stroke Incidence ◽  
Stroke Research ◽  
Incidence And Mortality ◽  
Research Initiatives ◽  
Global World

A year ago the World Stroke Organisation (WSO) highlighted the enormous global impact of the COVID-19 pandemic on stroke care. In this review we consider a year later where we are now, what the future holds, and what the long term effects of the pandemic will be on stroke. Stroke occurs in about 1.4% of patients hospitalised with COVID-19 infection, who show an excess of large vessel occlusion and increased mortality. Despite this association, stroke presentations fell dramatically during the pandemic, although emerging data suggests that total stroke mortality may have risen with increased stroke deaths at home and in care homes. Strategies and guidelines have been developed to adapt stroke services worldwide, and protect healthcare workers. Adaptations include increasing use of telemedicine for all aspects of stroke care. The pandemic is exacerbating already marked global inequalities in stroke incidence and mortality. Lastly the pandemic has had a major impact on stroke research and funding, although it has also emphasised the importnace of large scale collaborative research initiatives.

scholarly journals Efficacy and safety of butylphthalide for patients who had acute ischaemic stroke receiving intravenous thrombolysis or endovascular treatment (BAST trial): study protocol for a randomised placebo-controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e045559
Author(s):  
Xuelei Zhang ◽  
Anxin Wang ◽  
Jing Yu Zhang ◽  
Baixue Jia ◽  
Xiaochuan Huo ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Endovascular Treatment ◽  
Functional Outcome ◽  
Acute Ischaemic Stroke ◽  
Controlled Trial ◽  
Intravenous Thrombolysis ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Ischaemic Injury ◽  
Study Results

IntroductionAs a neuroprotective medication, butylphthalide (NBP) may help protect against cerebral ischaemic injury. However, evidence on whether NBP influences the outcomes of patients who had acute ischaemic stroke who are receiving revascularisation treatment is limited. This study aims to evaluate whether additional NBP therapy can improve the functional outcome of patients who receive intravenous recombinant tissue plasminogen activator and/or endovascular treatment (EVT).Methods and analysisThe study will be a randomised, double-blind, placebo-controlled, multiple-centre, parallel group trial. The sample size is estimated at 1200 patients. Eligible patients will be randomised at a 1:1 ratio to receive either NBP or placebo daily for 90 days, which will include 14 days of injections and 76 days of capsules. The first use of NBP/placebo will be started within 6 hours of onset of ischaemic stroke. The primary outcome is the functional outcome as assessed by the 90-day modified Rankin Scale, adjusted for baseline scores on the National Institutes of Health Stroke Scale. The primary safety outcome is the percentage of serious adverse events during the 90 days of treatment. This trial will determine whether NBP medication benefits patients who had acute ischaemic stroke who receive intravenous thrombolysis or EVT.Ethics and disseminationThe protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board/Ethics Committee of Beijing Tiantan Hospital, Capital Medical University with approval number KY 2018-003-02. Ethics committees of all participating sites have approved the study . Results of the study will be published in peer-reviewed scientific journals and shared in scientific presentations.Trial registration numberNCT03539445.

scholarly journals GRP per capita and hospital characteristics associated with intravenous tissue plasminogen activator adherence rate: evidence from the Chinese Stroke Center Alliance

2021 ◽  
pp. svn-2020-000633
Author(s):  
Suxi Zheng ◽  
Tian Jie Lyu ◽  
Zixiao Li ◽  
Hongqiu Gu ◽  
Xin Yang ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Plasminogen Activator ◽  
Acute Ischaemic Stroke ◽  
Emergency Services ◽  
Influential Factors ◽  
Adherence Rate ◽  
Intravenous Tissue Plasminogen Activator ◽  
Tissue Plasminogen ◽  
Per Capita ◽  
Stroke Center

BackgroundTimely delivery of intravenous tissue plasminogen activator (IV-rt PA) is pivotal to eligible patients who had a stroke while achieving higher rates of IV-rt PA has been problematic. This paper focuses on investigating influential factors associated with the administration of IV-rt PA, primarily per capita gross regional product (GRP) and healthcare system factors.MethodsThe study included 980 hospitals in the Chinese Stroke Center Alliance where 158 003 patients who had an acute ischaemic stroke received IV-rt PA between August 2015 and August 2019. The adherence rate to IV-rt PA within 4.5 hours time window in each hospital was the primary outcome. Influential factors were grouped into two categories: macroeconomic status and hospital characteristics. The outcome was analysed using multivariable linear regression.ResultsGRP per capita (β=2.37, p<0.001), hospital stroke centre certification (β=3.77, p<0.001), number of neurologists (β=0.12, p<0.001), existence of emergency services for neurological treatment (β=7.43, p=0.014), presence of emergency department (β=10.03, p=0.019) and cooperating with emergency centre (β=4.65, p=0.029) were significantly positively associated with the adherence rate to IV-rt PA.ConclusionsHigher GRP per capita, affluent neurological personnel, well-equipped emergency services for neurological treatment and routine cooperation with the emergency centre were important for enhancing the adherence rate to IV-rt PA among patients who had an acute ischaemic stroke in China.

Role of sex hormones in lung cancer

2021 ◽  
pp. 153537022110196
Author(s):  
Nathalie Fuentes ◽  
Miguel Silva Rodriguez ◽  
Patricia Silveyra
Keyword(s):  
Lung Cancer ◽  
Sex Differences ◽  
Sex Hormones ◽  
Hormone Receptors ◽  
Occupational Exposures ◽  
Lung Carcinogenesis ◽  
Male And Female ◽  
Female Sex ◽  
Incidence And Mortality ◽  
Cancer Rates

Lung cancer represents the world’s leading cause of cancer deaths. Sex differences in the incidence and mortality rates for various types of lung cancers have been identified, but the biological and endocrine mechanisms implicated in these disparities have not yet been determined. While some cancers such as lung adenocarcinoma are more commonly found among women than men, others like squamous cell carcinoma display the opposite pattern or show no sex differences. Associations of tobacco product use rates, susceptibility to carcinogens, occupational exposures, and indoor and outdoor air pollution have also been linked to differential rates of lung cancer occurrence and mortality between sexes. While roles for sex hormones in other types of cancers affecting women or men have been identified and described, little is known about the influence of sex hormones in lung cancer. One potential mechanism identified to date is the synergism between estrogen and some tobacco compounds, and oncogene mutations, in inducing the expression of metabolic enzymes, leading to enhanced formation of reactive oxygen species and DNA adducts, and subsequent lung carcinogenesis. In this review, we present the literature available regarding sex differences in cancer rates, associations of male and female sex hormones with lung cancer, the influence of exogenous hormone therapy in women, and potential mechanisms mediated by male and female sex hormone receptors in lung carcinogenesis. The influence of biological sex on lung disease has recently been established, thus new research incorporating this variable will shed light on the mechanisms behind the observed disparities in lung cancer rates, and potentially lead to the development of new therapeutics to treat this devastating disease.

scholarly journals Association between insulin resistance and post-ischaemic stroke outcome in patients without diabetes: protocol for a systematic review and meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e044771
Author(s):  
Jeremiah Hadwen ◽  
Woojin Kim ◽  
Brian Dewar ◽  
Tim Ramsay ◽  
Alexandra Davis ◽  
...  
Keyword(s):  
Systematic Review ◽  
Insulin Resistance ◽  
Ischaemic Stroke ◽  
Functional Outcome ◽  
Recurrent Stroke ◽  
Meta Analysis ◽  
Secondary Outcome ◽  
Stroke Outcome ◽  
Post Stroke ◽  
Meta Analyses

IntroductionInsulin resistance is an independent risk factor for atherosclerosis, coronary artery disease and ischaemic stroke. Currently, insulin resistance is not usually included in post-stroke risk stratification. This systematic review and meta-analysis intends to determine if available scientific knowledge supports an association between insulin resistance and post-stroke outcomes in patients without diabetes.Methods and analysisThe authors will conduct a literature search in Medline, Embase, Web of Science and Cochrane Central. The review will include studies that assess the association between elevated insulin homeostasis model of insulin resistance (HOMA-IR) and post-stroke outcome (functional outcome and recurrent stroke). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines will be used. The primary outcome will be post-stroke functional outcome (Modified Rankin Scale), and the secondary outcome will be recurrent ischaemic stroke. Comparison of outcome will be made between highest and lowest HOMA-IR range (as defined in each article included in this systematic review). Risk of bias will be assessed qualitatively. Meta-analysis will be performed if sufficient homogeneity exists between studies. Heterogeneity of outcomes will be assessed by I².Ethics and disseminationNo human or animal subjects or samples were/will be used. The results will be published in a peer-reviewed journal, and will be disseminated at local and international neurology conferences.PROSPERO registration numberCRD42020173608.

scholarly journals Secondary prevention medication persistence and prognosis of acute ischaemic stroke or transient ischaemic attack

2021 ◽  
pp. svn-2020-000471
Author(s):  
Lei Zhang ◽  
Junfeng Shi ◽  
Yuesong Pan ◽  
Zixiao Li ◽  
Hongyi Yan ◽  
...  
Keyword(s):  
Secondary Prevention ◽  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Transient Ischaemic Attack ◽  
Recurrent Stroke ◽  
Medication Persistence ◽  
Level Ii ◽  
Composite Events ◽  
Ischaemic Attack ◽  
Level I

IntroductionThe risk of disability and mortality is high among recurrent stroke, which highlights the importance of secondary prevention measures. We aim to evaluate medication persistence for secondary prevention and the prognosis of acute ischaemic stroke or transient ischaemic attack (TIA) in China.MethodsPatients with acute ischaemic stroke or TIA from the China National Stroke Registry II were divided into 3 groups based on the percentage of persistence in secondary prevention medication classes from discharge to 3 months after onset (level I: persistence=0%, level II: 0%<persistence<100%, level III: persistence=100%). The primary outcome was recurrent stroke. The secondary outcomes included composite events (stroke, myocardial infarction or death from cardiovascular cause), all-cause death and disability (modified Rankin Scale score=3–5) from 3 months to 1 year after onset. Recurrent stroke, composite events and all-cause death were performed using Cox regression model, and disability was identified through logistic regression model using the generalised estimating equation method.Results18 344 patients with acute ischaemic stroke or TIA were included, 315 (1.7%) of whom experienced recurrent strokes. Compared with level I, the adjusted HR of recurrent stroke for level II was 0.41 (95% CI 0.31 to 0.54) and level III 0.37 (0.28 to 0.48); composite events for level II 0.41 (0.32 to 0.53) and level III 0.38 (0.30 to 0.49); all-cause death for level II 0.28 (0.23 to 0.35) and level III 0.20 (0.16–0.24). Compared with level I, the adjusted OR of disability for level II was 0.89 (0.77 to 1.03) and level III 0.82 (0.72 to 0.93).ConclusionsPersistence in secondary prevention medications, especially in all classes of medications prescribed by the physician, was associated with lower hazard of recurrent stroke, composite events, all-cause death and lower odds of disability in patients with acute ischaemic stroke or TIA.

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