Sex Differences in Hemostatic Factors in Patients With Ischemic Stroke and the Relation With Migraine—A Systematic Review

Background: Women are more affected by stroke than men. This might, in part, be explained by sex differences in stroke pathophysiology. The hemostasis system is influenced by sex hormones and associated with female risk factors for stroke, such as migraine.Aim: To systematically review possible sex differences in hemostatic related factors in patients with ischemic stroke in general, and the influence of migraine on these factors in women with ischemic stroke.Results: We included 24 studies with data on sex differences of hemostatic factors in 7247 patients with ischemic stroke (mean age 57–72 years, 27–57% women) and 25 hemostatic related factors. Levels of several factors were higher in women compared with men; FVII:C (116% ± 30% vs. 104% ± 30%), FXI (0.14 UI/mL higher in women), PAI-1 (125.35 ± 49.37 vs. 96.67 ± 38.90 ng/mL), D-dimer (1.25 ± 0.31 vs. 0.95 ± 0.24 μg/mL), and aPS (18.7% vs. 12.0% positive). In contrast, protein-S (86.2% ± 23.0% vs. 104.7% ± 19.8% antigen) and P-selectin (48.9 ± 14.4 vs. 79.1 ± 66.7 pg/mL) were higher in men. Most factors were investigated in single studies, at different time points after stroke, and in different stroke subtypes. Only one small study reported data on migraine and hemostatic factors in women with ischemic stroke. No differences in fibrinogen, D-dimer, t-PA, and PAI-1 levels were found between women with and without migraine.Conclusion: Our systematic review suggests that sex differences exist in the activation of the hemostatic system in ischemic stroke. Women seem to lean more toward increased levels of procoagulant factors whereas men exhibit increased levels of coagulation inhibitors. To obtain better insight in sex-related differences in hemostatic factors, additional studies are needed to confirm these findings with special attention for different stroke phases, stroke subtypes, and not in the least women specific risk factors, such as migraine.

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Abstract P663: Polygenic Risk Scores for Plasma Levels of Fibrin D-Dimer and Tissue Plasminogen Activator Are Associated With Non-Lacunar Stroke

Stroke ◽

10.1161/str.52.suppl_1.p663 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Yonit A Addissie ◽

Brady Gaynor ◽

Thomas Jaworek ◽

Huichun Xu ◽

Colin O Stine ◽

...

Keyword(s):

Ischemic Stroke ◽

Plasma Levels ◽

Early Onset ◽

Late Onset ◽

Plasma Concentrations ◽

Risk Scores ◽

Lacunar Stroke ◽

Related Factors ◽

Pai 1 ◽

D Dimer

Introduction: Plasma concentrations of prothrombotic factors such as fibrinogen have previously been associated with ischemic stroke risk. To extend this observation, we examined the association of polygenic risk scores (PRS) for increased plasma levels of thrombosis-related factors with ischemic stroke. Our hypotheses were that these PRS would be more associated with early than late onset stroke and with non-lacunar than lacunar stroke. Methods: We identified 9053 late onset (≥ 60 years) stroke cases from the NINDS International Stroke Genetics Consortium (SiGN) with 24804 controls and 6594 early onset (< 60 years) stroke cases from the Genetics of Early Onset Ischemic Stroke Consortium with 30561 controls. We identified previously known loci associated with plasma levels of four thrombosis-related factors: fibrinogen, fibrin D-dimer, tPA and PAI-1 from prior GWAS studies and developed genome-wide PRS for plasma concentrations of these factors. We then used logistic regression to test the association of these scores with risk of stroke and stroke subtype. Results: PRS for fibrin D dimer levels were associated with increased risk for all stroke and specifically for older (p = 0.019), but not younger (p = 0.22) onset stroke. PRS for tPA levels were also marginally associated with older (p = 0.06), but not younger (p = 0.24) onset stroke. Genetic risk scores for both D dimer and tPA were associated with non-lacunar stroke (Table 1). Further analyses stratified by age revealed PRS for D dimer to be significantly associated with non-lacunar stroke (but not lacunar stroke) in both late and early onset cohorts. PRS for fibrinogen and PAI-1 were not associated with stroke. Conclusion: Genomic risk scores for thrombosis-related factors including D dimer and tPA levels were associated with risk for ischemic stroke, and specifically, non-lacunar stroke.

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Sex Differences in Stroke Subtypes, Severity, Risk Factors, and Outcomes among Elderly Patients with Acute Ischemic Stroke

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2015.00174 ◽

2015 ◽

Vol 7 ◽

Cited By ~ 24

Author(s):

Changshen Yu ◽

Zhongping An ◽

Wenjuan Zhao ◽

Wanjun Wang ◽

Chunlin Gao ◽

...

Keyword(s):

Risk Factors ◽

Sex Differences ◽

Ischemic Stroke ◽

Elderly Patients ◽

Acute Ischemic Stroke ◽

Stroke Subtypes

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Sex differences in the association between major risk factors and the risk of stroke in the UK Biobank cohort study

Neurology ◽

10.1212/wnl.0000000000010982 ◽

2020 ◽

Vol 95 (20) ◽

pp. e2715-e2726 ◽

Cited By ~ 1

Author(s):

Sanne A.E. Peters ◽

Cheryl Carcel ◽

Elizabeth R.C. Millett ◽

Mark Woodward

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Sex Differences ◽

Ischemic Stroke ◽

Low Socioeconomic Status ◽

Hemorrhagic Stroke ◽

Uk Biobank ◽

Cox Models ◽

Stroke Subtypes ◽

The Uk

ObjectiveTo determine whether there are sex differences in the association between risk factors and incident stroke, including stroke subtypes.MethodsA total of 471,971 (56% women) UK Biobank participants without a history of cardiovascular disease were included. During 9 years of follow-up, 4,662 (44% women) cases of stroke were recorded. Cox models yielded adjusted hazard ratios (HRs) and women-to-men ratios of HRs (RHRs) for stroke associated with 7 risk factors.ResultsThe incidence rate per 10,000 person-years was 8.66 (8.29–9.04) in women and 13.96 (13.44–14.50) in men for any stroke, 6.06 (5.75–6.38) in women and 11.35 (10.88; 11.84) in men for ischemic stroke, and 1.56 (1.41–1.73) in women and 2.23 (2.02–2.45) in men for hemorrhagic stroke. The association between increases in blood pressure, body anthropometry, and lipids, diabetes, and atrial fibrillation and any stroke was similar between men and women. Hypertension, smoking, and a low socioeconomic status were associated with a greater HR of any stroke in women than men; the RHRs were 1.36 (1.26–1.47), 1.18 (1.02–1.36), and 1.17 (1.03–1.33), respectively. Diabetes was associated with a higher HR of ischemic stroke in women than men (RHR 1.25 [1.00–1.56]). Atrial fibrillation was associated with a higher HR of hemorrhagic stroke in women than men (RHR 2.80 [1.07–7.36]).ConclusionSeveral risk factors are more strongly associated with the risk of any stroke or stroke subtypes in women compared with men. Despite this, the incidence of stroke remains higher among men than women.

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Lack of Associations Between PAI-1 and FXIII Polymorphisms and Arterial Ischemic Stroke in Children: A Systematic Review and Meta-Analysis

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029619869500 ◽

2019 ◽

Vol 25 ◽

pp. 107602961986950 ◽

Cited By ~ 1

Author(s):

Beata Sarecka-Hujar ◽

Ilona Kopyta ◽

Michał Skrzypek

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Ischemic Stroke ◽

Plasminogen Activator ◽

Meta Analysis ◽

Plasminogen Activator Inhibitor ◽

Arterial Ischemic Stroke ◽

Meta Analyses ◽

Activator Inhibitor ◽

Pai 1

The role of genetic risk factors for ischemic stroke seems to be in particular significance in pediatric patients. Numerous polymorphic variants of genes encoding proteins, that is, plasminogen activator inhibitor as well as coagulation factors, involved in the coagulation cascade may be related to arterial ischemic stroke (AIS) both in adults and children. We performed systematic review and 2 meta-analyses to assess possible correlations between common plasminogen activator inhibitor ( PAI-1) and FXIII polymorphisms and ischemic stroke in children. We searched PubMed to identify available data published before October 2018 using appropriate keywords and inclusion criteria. Finally, 12 case–control studies were included: 8 analyzing PAI-1 polymorphism (600 children with stroke and 2152 controls) and 4— FXIII polymorphism (358 children with stroke and 451 controls). R and Comprehensive Meta-Analysis software were used to analyze the impact of the particular polymorphism in the following models: dominant, recessive, additive, and allelic. No publication bias was observed in both meta-analyses. In case of PAI-1 polymorphism, we observed no relation between 4G4G genotype of 4G allele and ischemic stroke in children. We also demonstrated lack of association between FXIII polymorphism and childhood ischemic stroke. In children with AIS, the PAI-1 and FXIII polymorphisms are not risk factors for the disease.

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The physiopathology of spontaneous hemorrhagic stroke: a systematic review

Reviews in the Neurosciences ◽

10.1515/revneuro-2020-0131 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Alcivan Batista de Morais Filho ◽

Thiago Luis de Holanda Rego ◽

Letícia de Lima Mendonça ◽

Sulyanne Saraiva de Almeida ◽

Mariana Lima da Nóbrega ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Ischemic Stroke ◽

Subarachnoid Hemorrhage ◽

Natural History ◽

Hemorrhagic Stroke ◽

Recent Literature ◽

Clinical Manifestations ◽

The Road ◽

History Of

Abstract Hemorrhagic stroke (HS) is a major cause of death and disability worldwide, despite being less common, it presents more aggressively and leads to more severe sequelae than ischemic stroke. There are two types of HS: Intracerebral Hemorrhage (ICH) and Subarachnoid Hemorrhage (SAH), differing not only in the site of bleeding, but also in the mechanisms responsible for acute and subacute symptoms. This is a systematic review of databases in search of works of the last five years relating to the comprehension of both kinds of HS. Sixty two articles composed the direct findings of the recent literature and were further characterized to construct the pathophysiology in the order of events. The road to the understanding of the spontaneous HS pathophysiology is far from complete. Our findings show specific and individual results relating to the natural history of the disease of ICH and SAH, presenting common and different risk factors, distinct and similar clinical manifestations at onset or later days to weeks, and possible complications for both.

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Differing risk factors and outcomes in ischemic stroke subtypes: focus on lacunar stroke

Future Neurology ◽

10.2217/fnl.11.1 ◽

2011 ◽

Vol 6 (2) ◽

pp. 201-221 ◽

Cited By ~ 5

Author(s):

Joanna M Wardlaw

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Lacunar Stroke ◽

Stroke Subtypes

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Patient Demographics, Characteristics, and Intrahospital Mortality of Different Ischemic Stroke Subtypes in a Tertiary Hospital during Five-Year Period

Medical Sciences Forum ◽

10.3390/iecmd2021-10315 ◽

2021 ◽

Vol 6 (1) ◽

pp. 6

Author(s):

Sintija Strautmane ◽

Kristaps Jurjāns ◽

Estere Zeltiņa ◽

Evija Miglāne ◽

Andrejs Millers

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Reperfusion Therapy ◽

Cardioembolic Stroke ◽

Study Group ◽

Large Artery ◽

Patient Demographics ◽

Stroke Subtypes ◽

Female Predominance ◽

Study Population

Background and Objectives. Ischemic stroke (IS) is one of the leading causes of disability, morbidity, and mortality worldwide. The goal of the study was to evaluate patient demographics, characteristics, and intrahospital mortality among different ischemic stroke subtypes. Materials and Methods. A retrospective observational non-randomized study was conducted, including only ischemic stroke patients, admitted to Pauls Stradins Clinical university hospital, Riga, Latvia, from January of 2016 until December 2020. Ischemic stroke subtypes were determined according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria as a stroke due to (1) large-artery atherosclerosis (atherothrombotic stroke (AS)), (2) cardioembolism (cardioembolic stroke (CS)), (3) small-vessel occlusion (lacunar stroke (LS)), (4) stroke of other determined etiology (other specified stroke (OSS)), and (5) stroke of undetermined etiology (undetermined stroke (US)). The data between different stroke subtypes were compared. Results. There was a slight female predominance among our study population, as 2673 (56.2%) patients were females. In our study group, the most common IS subtypes were cardioembolic stroke (CS), 2252 (47.4%), and atherothrombotic stroke (AS), 1304 (27.4%). CS patients were significantly more severely disabled on admission, 1828 (81.4%), and on discharge, 378 (16.8%), p < 0.05. Moreover, patients with CS demonstrated the highest rate of comorbidities and risk factors. This was also statistically significant, p < 0.05. Differences between the total patient count with no atrial fibrillation (AF), paroxysmal AF, permanent AF, and different IS subtypes among our study population demonstrated not only statistical significance but also a strong association, Cramer’s V = 0.53. The majority of patients in our study group were treated conservatively, 3389 (71.3%). Reperfusion therapy was significantly more often performed among CS patients, 770 (34.2%), p < 0.05. The overall intrahospital mortality among our study population was 570 (12.0%), with the highest intrahospital mortality rate noted among CS patients, 378 (66.3%), p < 0.05. No statistically significant difference was observed between acute myocardial infarction and adiposity, p > 0.05. Conclusions. In our study, CS and AS were the most common IS subtypes. CS patients were significantly older with slight female predominance. CS patients demonstrated the greatest disability, risk factors, comorbidities, reperfusion therapy, and intrahospital mortality.

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Abstract T P153: Women and Men with Ischemic Stroke in SiGN Have Different Subtype Distributions and Risk Factors

Stroke ◽

10.1161/str.45.suppl_1.tp153 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Kathryn M Rexrode ◽

Braxton D Mitchell ◽

Kathleen A Ryan ◽

Steven J Kittner ◽

Hakan Ay ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Stroke Risk ◽

Cardioembolic Stroke ◽

Relative Distribution ◽

Large Artery ◽

Stroke Risk Factors ◽

Stroke Subtypes ◽

Small Artery Occlusion ◽

Ischemic Stroke Risk

Introduction: The relative distribution of stroke risk factors, as well as ischemic stroke subtypes, in women compared with men is not well described. Hypothesis: We hypothesized that the distribution of ischemic stroke risk factors and subtypes would differ by sex, with a later onset in women and greater proportion of comorbidities. Methods: The NINDS Stroke Genetics Network (SiGN) consortium was established to evaluate genetic risk factors for ischemic stroke. A total of 23 separate studies performed Causative Classification of Stroke (CCS) typing using standardized criteria on ischemic stroke cases and contributed data on risk factors. We compared the distribution of ischemic stroke risk factors and CCS phenotypes between men and women with ischemic stroke. Results: Of the 16,228 ischemic strokes in SiGN, 8005 (49.3%) occurred in women. Median age at stroke was older in female than male stroke cases (73 vs. 66 years) (p=<0.0001). Among stroke cases, women were more likely than men cases to have hypertension or atrial fibrillation and less likely to have diabetes or coronary artery disease, or to smoke (p <0.003 for all). The distribution of stroke subtypes also differed by sex, with women less likely than men to have large artery infarction and small artery occlusion, and more likely to have cardioembolic stroke and undetermined stroke due to incomplete work-up (p values all <0.0001; see Table). Results were similar when the distribution of stroke subtypes was examined for those <70 years and ≥70 years, except for cardioembolic stroke remaining more common only among women ≥70. Conclusions: In this large group of carefully phenotyped ischemic strokes, the distribution of ischemic stroke subtypes and risk factor profiles differ significantly by sex. Evaluation of the causes of these differences may highlight areas for improved prevention and risk reduction in both genders.

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