scholarly journals Coagulation factor XII, XI, and VIII activity levels and secondary events after first ischemic stroke

Author(s):  
Jessica L. Rohmann ◽  
Shufan Huo ◽  
Pia S. Sperber ◽  
Sophie K. Piper ◽  
Frits R. Rosendaal ◽  
...  

AbstractBackground and PurposeThough risk for recurrent vascular events is high following ischemic stroke, little is known about risk factors for secondary events post-stroke. The coagulation factors XII, XI, and VII (FXII, FXI, and FVIII) have already been implicated in first thrombotic events, and our aim was to estimate their effects on vascular outcomes within 3 years after first stroke.MethodsIn the PROSpective Cohort with Incident Stroke Berlin (PROSCIS-B) study, we followed participants aged 18 and older for three years after first mild to moderate ischemic stroke event or until occurrence of recurrent stroke, myocardial infarction or all-cause mortality (combined endpoint). High coagulation factor activity levels were compared to normal and low levels, and activities were also analyzed as continuous variables. We used Cox proportional hazards models adjusted for age, sex, and cardiovascular risk factors to estimate hazard ratios (HRs) for the combined endpoint.ResultsIn total, 92 events occurred in 570 included participants, resulting in an absolute rate of 6.6 events per 100 person-years. After confounding adjustment, high FVIII activity showed the strongest relationship with the combined endpoint (HR=2.05, 95%CI 1.28-3.29). High FXI activity was also associated with an increased risk (HR=1.80, 95%CI 1.09-2.98). Contrarily, high FXII activity was not associated with the combined endpoint (HR=0.86, 95%CI 0.49-1.51). Continuous analyses per standard deviation of each biomarker yielded similar results.ConclusionsIn our study of mild to moderate ischemic stroke patients, high activity levels of FXI and FVIII but not FXII were associated with worse vascular outcomes in the three-year period after first ischemic stroke. This is of special interest in light of the ongoing trials of antithrombotic treatments targeting FXI.

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Matthew A Mercuri ◽  
Alexander E Merkler ◽  
Neal S Parikh ◽  
Michael E Reznik ◽  
Hooman Kamel

Background: Vascular brain injury can result in epilepsy. It is posited that seizures in elderly patients might reflect subclinical vascular disease and thus herald future clinical vascular events. Hypothesis: Seizures in elderly patients are associated with an increased risk of ischemic stroke or myocardial infarction (MI). Methods: We obtained inpatient and outpatient claims data from 2008-2014 on a 5% sample of Medicare beneficiaries ≥66 years of age. The predictor variable was epilepsy, defined as two or more inpatient or outpatient claims with a diagnosis of seizure. The primary outcome was a composite of ischemic stroke or acute MI. The predictors and outcomes were all ascertained with previously validated ICD-9-CM code algorithms. Survival statistics and Cox proportional hazards models were used to assess the relationship between epilepsy and incident ischemic stroke or MI while adjusting for demographic characteristics and vascular risk factors. Patients were censored at the first occurrence of a stroke or MI, at the time of death, or on December 31, 2014. Results: Among 1,548,556 beneficiaries with a mean follow-up of 4.4 (±1.8) years, 15,055 (1.0%) developed epilepsy and 121,866 (7.9%) experienced an ischemic stroke or acute MI. Patients with seizures were older (76.1 versus 73.7 years) and had a significantly higher burden of vascular comorbidities than the remainder of the cohort. The annual incidence of stroke or acute MI was 3.28% (95% confidence interval [CI], 3.10-3.47%) in those with seizures versus 1.79% (95% CI, 1.78-1.80%) in those without (unadjusted hazard ratio [HR], 1.89; 95% CI, 1.78-2.00). After adjustment for demographics and risk factors, epilepsy had a weak association with the composite outcome (adjusted HR, 1.36; 95% CI, 1.29-1.44), a stronger association with ischemic stroke (adjusted HR, 1.77; 95% CI, 1.65-1.90), and no association with acute MI (adjusted HR, 0.95; 95% CI, 0.86-1.04). Conclusions: We found an association between epilepsy in elderly patients and future ischemic stroke but not acute MI. Therefore, seizures might signify occult cerebrovascular disease but not necessarily occult disease in other vascular beds.


2017 ◽  
Vol 13 (6) ◽  
pp. 576-584 ◽  
Author(s):  
Peter Jin ◽  
Ivan Matos Diaz ◽  
Laura Stein ◽  
Alison Thaler ◽  
Stanley Tuhrim ◽  
...  

Background In older adults with stroke, there is an increased risk of cardiovascular events in the intermediate period, up to one year after stroke. The risk of cardiovascular events in this period in young adults after stroke has not been studied. We hypothesized that in the intermediate risk period, young adults with ischemic stroke have an increased risk of recurrent stroke and a smaller increase of cardiac events. Methods Using the National Readmissions Database during the year 2013, we identified ischemic stroke admissions among those aged 18–45 years using International Classification of Disease, Ninth Revision, Clinical Modification codes to identify index vascular events and risk factors. Primary outcomes were readmission for cardiac events and stroke. Multivariable Cox proportional hazard models and Kaplan–Meier analysis were used to estimate risk of primary outcomes. Results We identified 12,392 young adults with index stroke. The readmission rate due to recurrent stroke was higher than for cardiac events (2913.3.1 vs. 1132.4 per 100,000 index hospitalizations at 90 days). There was a higher cumulative risk of both cardiac events and recurrent stroke in the presence of baseline diabetes and hypercholesterolemia. Conclusion In a large, nationally representative database, the intermediate risk of recurrent stroke after index stroke in young adults was higher than the risk of cardiac events. The presence of vascular risk factors augmented this risk but did not entirely account for it. The aggressive control of hypercholesterolemia and diabetes may play an important role in secondary prevention in young adults with stroke.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Joon-tae Kim ◽  
Hee-Joon Bae ◽  

Introduction: Atrial fibrillation (AF) and large artery diseases (LAD) share several risk factors and often coexist in the same patient. Optimal treatments for acute ischemic stroke (AIS) patients with concomitant AF and LAD have not been extensively studied so far. Objective: This study aimed to compare the effectiveness of the addition of antiplatelet (AP) to oral anticoagulant (OAC) with that of OAC alone in AIS with AF according to the LAD. Methods: Using a multicenter stroke registry, acute (within 48h of onset) and mild-to-moderate (NIHSS score ≤15) stroke patients with AF were identified. Propensity scores using IPTW were used to adjust baseline imbalances between the OAC+AP group and the OAC alone group in all patients and in each subgroup by LAD. The primary outcome was major vascular events, defined as the composite of recurrent stroke, MI, and all-cause mortality at up to 3 months after index stroke. Results: Among the 5469 patients (age, 72±10yrs; male, 54.9%; initial NIHSS score, 4 [2-9]), 79.0% (n=4323) received OAC alone, and 21.0% (n=1146) received OAC+AP. By weighted Cox proportional hazards analysis, a tendency of increasing the risk of 3-months primary composite events in the OAC+AP group vs the OAC alone (HR 1.36 [0.99-1.87], p=0.06), with significant interaction with treatments and LAD (Pint=0.048). Briefly, among patients with moderate-to-severe large artery stenosis, tendency of decrease in 3-months primary composite events of the OAC+AP group, compared with OAC alone group, was observed (HR 0.54 [0.17-1.70]), whereas among patients with complete occlusion, the OAC+AP group markedly increased the risk of 3-months composite events (HR 2.00 [1.27-3.15]), compared with the OAC alone group. No interaction between direct oral anticoagulant and warfarin on outcome was observed (Pint=0.35). Conclusion: In conclusion, treatment with addition of AP to OAC had a tendency to increase the risk of 3-months vascular events, compared with OAC alone in AIS with AF. However, the effects of antithrombotic treatment could be modified according to the LAD, with substantial benefits of OAC alone in subgroup of large artery occlusion. Our results address the need for the further study to tailor the optimal treatment in AIS with concomitant AF and LAD.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Cesare Russo ◽  
Zhezhen Jin ◽  
Ralph L Sacco ◽  
Shunichi Homma ◽  
Tatjana Rundek ◽  
...  

BACKGROUND: Aortic arch plaques (AAP) are a risk factor for cardiovascular embolic events. However, the risk of vascular events associated with AAP in the general population is unclear. AIM: To assess whether AAP detected by transesophageal echocardiography (TEE) are associated with an increased risk of vascular events in a stroke-free cohort. METHODS: The study cohort consisted of stroke-free subjects over age 50 from the Aortic Plaques and Risk of Ischemic Stroke (APRIS) study. AAP were assessed by multiplane TEE, and considered large if ≥ 4 mm in thickness. Vascular events including myocardial infarction, ischemic stroke and vascular death were recorded during the follow-up. The association between AAP and outcomes was assessed by univariate and multivariate Cox proportional hazards models. RESULTS: A group of 209 subjects was studied (mean age 67±9 years; 45% women; 14% whites, 30% blacks, 56% Hispanics). AAP of any size were present in 130 subjects (62%); large AAP in 50 (24%). Subjects with AAP were older (69±8 vs. 63±7 years), had higher systolic BP (146±21 vs.139±20 mmHg), were more often white (19% vs. 8%), smokers (20% vs. 9%) and more frequently had a history of coronary artery disease (26% vs. 14%) than those without AAP (all p<0.05). Lipid parameters, prevalence of atrial fibrillation and diabetes mellitus were not significantly different between the two groups. During the follow up (94±29 months) 30 events occurred (13 myocardial infarctions, 11 ischemic strokes, 6 vascular deaths). After adjustment for other risk factors, AAP of any size were not associated with an increased risk of combined vascular events (HR 1.07, 95% CI 0.44 to 2.56). The same result was observed for large AAP (HR 0.94, CI 0.34 to 2.64). Age (HR 1.05, CI 1.01 to 1.10), body mass index (HR 1.08, CI 1.01 to 1.15) and atrial fibrillation (HR 3.52, CI 1.07 to 11.61) showed independent association with vascular events. In a sub-analysis with ischemic stroke as outcome, neither AAP of any size nor large AAP were associated with an increased risk. CONCLUSIONS: In this cohort without prior stroke, the incidental detection of AAP was not associated with an increased risk of future vascular events. Associated co-factors may affect the AAP-related risk of vascular events reported in previous studies.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Joon-Tae Kim ◽  
Beom Joon Kim ◽  
Jong-Moo Park ◽  
Soo Joo Lee ◽  
Jae-Kwan Cha ◽  
...  

Abstract Uncertainty regarding an optimal antiplatelet regimen still exists in patients with breakthrough acute ischemic stroke (AIS) while on aspirin. This study provides an analysis of a prospective multicenter registry between April 2008 and April 2014. Eligible patients were on aspirin at the time of AIS and treated with antiplatelet regimens (aspirin, clopidogrel, or clopidogrel-aspirin). Potential factors associated with the choice of each antiplatelet regimen were explored and included a predictive risk score for future vascular events, the Essen Stroke Risk Score (ESRS). A total of 2348 patients (age, 69 ± 11 years; male, 57.7%) were analyzed, and 55.3%, 25.3% and 19.4% were treated with clopidogrel-aspirin, aspirin and clopidogrel, respectively. While the likelihood of choosing clopidogrel-aspirin increased as the ESRS increased, the likelihood of choosing aspirin decreased as the ESRS increased (Ptrend < 0.001). The ESRS category (0–1/2–3/ ≥ 4) modified the effect of antiplatelet regimens for 1-year vascular events (Pinteraction < 0.01). Among patients with ESRS ≥ 4, clopidogrel-aspirin (HR 0.47 [0.30–0.74]) and clopidogrel (HR 0.30 [0.15–0.60]) significantly reduced the risk of outcome events. Our study showed that more than half of the patients with aspirin failure were treated with clopidogrel-aspirin. In particular, a higher ESRS, which indicates an increased risk of recurrent stroke, was associated with the choice of clopidogrel-aspirin rather than aspirin.


2020 ◽  
Author(s):  
Yanting Ping Ping ◽  
Qianqian Yang Yang ◽  
Yuwen Huang Huang ◽  
Huimin Xu Xu ◽  
Haibin Dai

Abstract Background: Identifying risk factors of cardiovascular events is crucial for stroke prevention and they can be used as predictive factors of stroke outcomes.In this study, it is to evaluate the risk factors that predict outcomes of acute non-cardioembolic ischemic stroke in patients stratified by Essen Stroke Risk Score (ESRS). Methods: A retrospective study was carried out in acute non-cardioembolic ischemic stroke patients in a Chinese tertiary-care teaching hospital. ESRS stratification and factors that might influence the outcomes of stroke, as indicated by fatal or non-fatal combined vascular events of recurrent stroke, myocardial infarction, or primary intracranial hemorrhage, were documented. Univariate analysis and multivariable regression analysis was used to identify independent predictors of stroke outcomes. Results: A total of 878 patients with acute non-cardioembolic ischemic stroke who completed a mean follow-up of 5.2 years were enrolled, and 163 patients experienced at least one component of the combined vascular event. In patients with an ESRS ≤ 3, age ≥ 65 years (OR , 2.935; 95% CI 1.625-5.301, P < 0.001) and clopidogrel treatment (OR , 1.685 ; 95% CI , 1.026-2.768; P = 0.041) were significantly associated with stroke outcomes. In patients with an ESRS > 3, age ≥ 65 years (OR , 2.107, 95% CI , 1.208-3.673 ; P = 0.008) and history of diabetes (OR , 1.465 ; 95% CI , 1.041–2.062 ; P = 0.027) were risk factors for stroke outcomes , whereas clopidogrel treatment (OR , 0.542; 95% CI , 0.356–0.824; P = 0.003) was a protective factor for stroke outcomes. Conclusions: According to this study, clopidogrel treatment, blood pressure control, and glycemic control are protective factors for stroke outcomes in high-risk patients (ESRS>3).


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Neal S Parikh ◽  
Babak B Navi ◽  
Yecheskel Schneider ◽  
Hooman Kamel

Introduction: Liver cirrhosis is characterized by a coagulopathy associated with both hemorrhagic and thrombotic complications. However, the risk of stroke - hemorrhagic and ischemic - in patients with cirrhosis has not been rigorously assessed. Methods: We performed a retrospective cohort study of Medicare beneficiaries ≥66 years of age using a 5% sample of inpatient and outpatient claims from 2008-2014. Our predictor was liver cirrhosis, defined by presence of at least two ICD-9-CM inpatient or outpatient claims for liver cirrhosis or its complications, a validated algorithm previously used to study cirrhosis in Medicare beneficiaries. The primary outcome was stroke, and the secondary outcomes were ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Outcomes were defined by validated ICD-9-CM algorithms. Patients were censored at the time of an outcome, death, or on December 31, 2014. We used survival analysis to compare stroke incidence in patients with and without liver cirrhosis. Cox proportional hazards analysis was used to evaluate the association between cirrhosis and stroke while adjusting for demographics and established stroke risk factors. Results: Among the 1,564,277 beneficiaries in our sample, we identified 10,512 (0.7%) patients with liver cirrhosis. The mean age of patients with cirrhosis was 74.1 (±6.5) years. Over a median follow-up of 5 years, 76,195 patients were hospitalized with a stroke. The incidence of stroke was 1.9% (95% confidence interval [CI], 1.7-2.1%) per year in patients with cirrhosis and 1.1% (95% CI, 1.1-1.1%) per year in patients without cirrhosis. After adjusting for demographics and vascular risk factors, patients with cirrhosis experienced a higher risk of stroke (hazard ratio [HR], 1.4; 95% CI, 1.2-1.5); however, associations appeared more robust for intracerebral hemorrhage (HR, 2.2; 95% CI, 1.7-2.8) and subarachnoid hemorrhage (HR, 2.0; 95% CI, 1.2-3.1) than for ischemic stroke (HR, 1.3; 95% CI, 1.1-1.4). Conclusions: We found that liver cirrhosis was associated with an increased risk of stroke, particularly hemorrhagic stroke. Our results build on recent work investigating the hemorrhagic and thrombotic complications of liver cirrhosis outside of the portal circulation.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Silvia Koton ◽  
James R Pike ◽  
Michelle C Johansen ◽  
David Knopman ◽  
Kamakshi Lakshminarayan ◽  
...  

Background: Ischemic Stroke (IS) is associated with an increased risk of dementia, but the relative contribution of IS severity or recurrence to cognition is not known. We aimed to determine the risk of dementia after incident IS and how it varies by stroke severity and recurrence in the Atherosclerosis Risk in Communities (ARIC) study. Methods: 15,405 ARIC participants free of stroke and dementia at baseline (1987-9) were followed for IS and dementia through 2019. Incident and recurrent IS were classified by expert review of hospital records, with stroke severity by the National Institutes of Health Stroke Scale (NIHSS) classified as NIHSS≤5, 6-10, 11-15, ≥16. Dementia cases were adjudicated through expert review of in-person evaluations, informant interviews, phone assessments, hospitalization code or death certificates. Poisson regression models with robust error variance were used to estimate dementia incidence in participants with and without IS, and associations between time-dependent IS incidence (excluding dementia in the first year after stroke), frequency and severity, and dementia were studied with Cox proportional hazards models, adjusting for demographics, APOE ε4 and vascular risk factors . Results: 1151 IS (970 incident) and 2807 dementia cases were identified. NIHSS was available for 877 IS (76%). Adjusted incidence rates (95% CI) of dementia per 100 person-years were 0.45 (0.42-0.49) in participants without IS vs. 1.33 (1.15-1.55) in those with IS. Compared to no IS, risk of dementia (adjusted HR, 95% CI) increased with IS number and severity from 1.71 (1.47-1.99) for participants with one IS to 6.68 (3.58-12.46) for those with ≥3 events, and from 1.64 (1.36-1.98) for NIHSS≤5 to 4.43 (1.84-10.68) for NIHSS≥16 ( Table ). Conclusion: Risk of dementia is significantly increased after stroke, independent of vascular risk factors. These data suggest a dose-response relationship between number of stroke events and stroke severity, and risk of dementia.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Jaclyn E Burch ◽  
Neal S Parikh ◽  
Hooman Kamel ◽  
Lisa M DeAngelis ◽  
Babak B Navi

Introduction: Patients with systemic cancer often develop acute ischemic stroke from unique mechanisms, including cancer-mediated hypercoagulability, and their risk of recurrence is high. Conversely, stroke mechanisms in patients with primary brain tumors are incompletely understood, and the risk of recurrent thromboembolism in these patients is uncertain. Methods: We performed a retrospective cohort study of adult patients treated for a primary brain tumor at Memorial Sloan Kettering Cancer Center who were diagnosed with MRI-confirmed acute ischemic stroke from 2005 to 2015. Study neurologists used all available electronic records to collect data on patients’ cancer history, stroke risk factors, treatments, and outcomes. Stroke mechanisms, including the TOAST stroke subtype classification, were adjudicated by consensus. The primary outcome was recurrent thromboembolism (arterial or venous) and the secondary outcome was recurrent ischemic stroke. Kaplan-Meier survival statistics were used to calculate cumulative outcome rates, and multivariate Cox proportional hazards analysis was used to evaluate the association between several prespecified potential risk factors and outcomes. Results: We identified 83 patients with primary brain tumors and acute ischemic stroke. Median age was 60 years (IQR 51-67) and 53% were women. Tumors were mostly gliomas (72%) and meningiomas (13%). Prior head and neck radiotherapy was common (71%). Most strokes were from unconventional mechanisms, particularly radiation vasculopathy (36%) and surgical manipulation (19%). Small- or large-vessel disease or cardioembolism caused 13% of strokes, while 28% were cryptogenic. Median survival from index stroke was 2.2 years. Cumulative rates of recurrent thromboembolism were 11% at 30 days, 17% at 180 days, and 27% at 360 days; while cumulative rates of recurrent stroke were 5% at 30 days, 8% at 180 days, and 13% at 360 days. We found no significant predictors of outcomes, although radiation vasculopathy was nonsignificantly associated with recurrent stroke (HR 2.4, 95% CI 0.7-7.8). Conclusions: Patients with primary brain tumors generally develop strokes from unique mechanisms and their risk of recurrence is high.


2021 ◽  
pp. 1-9
Author(s):  
Anxin Wang ◽  
Shuang Cao ◽  
Xue Tian ◽  
Yingting Zuo ◽  
Xia Meng ◽  
...  

<b><i>Introduction:</i></b> Serum potassium abnormality is a risk factor of incident stroke, but whether it is associated with recurrent stroke in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) remains unknown. This study aimed to investigate the association of serum potassium with the risk of recurrent stroke in patients with AIS or TIA. <b><i>Methods:</i></b> We included 12,425 patients from the China National Stroke Registry III. Patients were classified into 3 groups according to tertiles of potassium. The outcomes were recurrence of stroke and combined vascular events at 1 year. Cox proportional hazards regression was adopted to explore the associations by calculating hazard ratios (HRs) and their 95% confidence intervals (CIs). <b><i>Results:</i></b> Among 12,425 enrolled patients, the median (interquartile range) of potassium was 3.92 (3.68–4.19) mmol/L. Compared with the highest tertile, after adjusted for confounding factors, the lowest tertile potassium was associated with increased risk of recurrent stroke at 1 year. The adjusted HR with 95% CI was 1.21 (1.04–1.41). There was an independent, linear association between serum potassium and stroke recurrence. Per 1 mmol/L decrease of potassium was associated with 19% higher risk of recurrent stroke (HR, 1.19; 95% CI, 1.04–1.37). Similar trends were found in ischemic stroke and combined vascular events. <b><i>Conclusions:</i></b> Lower serum potassium level was independently associated with elevated risk of recurrent stroke in patients with AIS or TIA. The finding suggested that monitoring serum potassium may help physicians to identify patients at high risk of recurrent stroke and to stratify risk for optimal management.


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