NCMP-06. THE RISK AND BURDEN OF THROMBOEMBOLIC AND HEMORRHAGIC EVENTS IN PATIENTS WITH MALIGNANT GLIOMA RECEIVING BEVACIZUMAB

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi148-vi148
Author(s):  
Alexander Ou ◽  
Heather Lin ◽  
Ying Yuan ◽  
Charles Bornstein ◽  
Kristin Alfaro-Munoz ◽  
...  

Abstract BACKGROUND Patients with high-grade gliomas (HGG) often receive anti-angiogenic therapy with bevacizumab to slow disease progression and/or palliate neurological symptoms. Bevacizumab has been associated with an increased risk of two major vascular complications: venous thromboembolism (VTE) and intracranial hemorrhage (ICH). We sought to identify clinical, pathologic, and radiographic variables correlated with risk of either event occurring in patients with HGG receiving bevacizumab. METHODS We retrospectively identified 94 patients with HGG who received bevacizumab at our center from 2015-2021. Variables included demographics, performance status, IDH, MGMT, vascular risk factors, baseline anti-coagulant/anti-platelet use, concurrent chemotherapy, and presence of macrobleeds on MRI (>1 cm3 susceptibility) at the time of bevacizumab initiation. We conducted competing risk analysis using subdistribution hazard models with death as competing risk for ICH or VTE. The effects of covariates on the incidence of hemorrhage or VTE were evaluated in univariate and multivariate settings. RESULTS Of 94 patients, 36 (38.3%) and 27 (28.7%) developed VTE and ICH, respectively. 31 (33%) did not develop either. ICH and VTE events occurred after a mean of 4.46 and 5.94 cycles of bevacizumab, respectively. 20 had baseline anti-platelet/anticoagulant use, and 16 had prior VTEs. Patients with macrobleeds on MRI had a larger HR of developing acute hemorrhage [HR=2.368 (1.112, 5.043), p=0.0254]. Patients older than 50 trended toward larger HR of developing VTE in univariate analysis that approached significance [HR=1.799 (0.889, 3.637), p=0.1023]. Sex, performance status, IDH, MGMT, vascular risk factors, baseline anticoagulant/anti-platelet use and concurrent chemotherapy were not significantly associated with occurrence of VTE. CONCLUSIONS The presence of macrobleeds on MRI is associated with increased risk of developing acute ICH while on bevacizumab. Older age at diagnosis of HGG may be associated with an increased risk of VTE in patients receiving bevacizumab. Larger studies are needed to confirm these findings.

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Elizabeth R Mayeda ◽  
Mary N Haan ◽  
John Neuhaus

Background: Stroke is a leading cause of death in the United States and has been linked to an increased risk of dementia and cognitive impairment. The prevalence of stroke and vascular risk factors are higher among Mexican Americans than non-Hispanic whites, but the literature on stroke and dementia and cognitive impairment among this growing ethnic group remains largely unexplored. Objective: We evaluated the association between non-fatal stroke and incidence of dementia/cognitive impairment without dementia (CIND) in a cohort of older Mexican Americans, accounting for the competing risk of mortality. Methods: The present study included 1,617 participants from the Sacramento Area Latino Study on Aging (SALSA), a population-based study of Mexican Americans aged 60-98 years, who were free of dementia/CIND at baseline in 1998-1999 and followed through 2007. At annual study visits, stroke events were identified by self-report of a physician diagnosis or hospitalization and dementia and CIND cases were identified with a three-phase clinical assessment protocol. We evaluated the association between baseline and time dependent stroke and incidence of dementia/CIND with Fine and Gray competing risk regression models to account for the competing risk of mortality. Results: There were 221 participants with a history of stroke at baseline or who experienced a non-fatal stroke during the study. Over a mean follow-up of 6.5 years, there were 159 incident dementia/CIND cases and 298 deaths (n=61 deaths due to stroke). After accounting for the competing risk of mortality and adjusting for sex, education, waist circumference, diabetes, and systolic blood pressure, individuals with a stroke event had a three-fold increased risk of dementia/CIND compared to those with no stroke event (hazard ratio=2.97, 95% CI: 2.05-4.30). Conclusions: These results suggest that among older Mexican Americans, stroke is strongly associated with incidence of dementia/CIND, even after accounting for traditional vascular risk factors and the competing risk of mortality.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Ava L Liberman ◽  
Alexander E Merkler ◽  
Gino Gialdini ◽  
Michael P Lerario ◽  
Steven R Messe ◽  
...  

Introduction: Cerebral vein thrombosis (CVT) is associated with an increased risk of subsequent venous thromboembolism. It is unknown whether the risk of pulmonary embolism (PE) after CVT is similar to that of PE after deep venous thrombosis (DVT). Methods: We performed a retrospective cohort study using administrative claims data from all emergency department visits and hospitalizations in California from 2005-2011, New York from 2006-2013, and Florida from 2005-2013. We identified patients with CVT or DVT as well as the primary outcome of PE using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD-9-CM ) codes. In order to minimize misclassification error, patients with both CVT and DVT during the same index hospitalization were excluded and patients with CVT were censored at the time of development of DVT and vice versa. Kaplan-Meier survival statistics and Cox proportional hazards models were used to compare the risk of PE after CVT versus after DVT while adjusting for demographics, vascular risk factors, and the Elixhauser comorbidity index. Results: We identified 4,450 patients with CVT and 217,589 patients with DVT. During a mean follow-up of 2.0 (±1.7) years, 124 patients with DVT developed a PE and 18,698 patients with DVT developed a PE. Patients with CVT were younger (mean age 45 vs 63), more often female (71% vs 52%), more often pregnant, and had fewer vascular risk factors than patients with DVT. During the index hospitalization, the rate of PE was 1.5% (95% confidence interval [CI], 1.1-1.8%) in patients with CVT and 6.2% (95% CI, 6.1-6.3%, p<0.001) in patients with DVT. By 5 years, the cumulative rate of PE after CVT was 3.7% (95% CI, 3.0-4.4%) compared to 10.5% (95% CI, 10.3-10.6%, p<0.001) after DVT. After adjustment for demographics and comorbidities, CVT was associated with a significantly lower hazard of PE when compared to DVT (hazard ratio, 0.31; 95% CI, 0.26-0.38). Conclusion: In a large, heterogeneous population, we found that the risk of PE after CVT was significantly lower than that of PE after DVT. Among patients with CVT, the greatest risk for PE was apparent during the index hospitalization.


2020 ◽  
Vol 22 (11) ◽  
Author(s):  
Adrian Scutelnic ◽  
Mirjam R. Heldner

Abstract Purpose of review To elucidate the intertwining of vascular events, vascular disease and vascular risk factors and COVID-19. Recent findings Strokes are a leading cause of disability and death worldwide. Vascular risk factors are important drivers of strokes. There are unmodifiable vascular risk factors such as age and ethnicity and modifiable vascular risk factors. According to the INTERSTROKE study, the 10 most frequent modifiable vascular risk factors are arterial hypertension, physical inactivity, overweight, dyslipidaemia, smoking, unhealthy diet, cardiac pathologies, diabetes mellitus, stress/depression and overconsumption of alcohol. Also, infection and inflammation have been shown to increase the risk of stroke. There is high-quality evidence for the clinical benefits of optimal primary and secondary stroke prevention. The COVID-19 pandemic brought a new perspective to this field. Vascular events, vascular disease and vascular risk factors—and COVID-19—are strongly intertwined. An increased risk of vascular events—by multifactorial mechanisms—has been observed in COVID-19 patients. Also, a higher rate of infection with COVID-19, severe COVID-19 and bad outcome has been demonstrated in patients with pre-existing vascular disease and vascular risk factors. Summary At present, we suggest that regular interactions between healthcare professionals and patients should include education on COVID-19 and on primary and secondary vascular prevention in order to reduce the burden of disease in our ageing populations.


2008 ◽  
Vol 22 (3) ◽  
pp. 153-163 ◽  
Author(s):  
Alicia J. Jenkins ◽  
Michelle Rothen ◽  
Richard L. Klein ◽  
Karina Moller ◽  
Leslie Eldridge ◽  
...  

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Stefania Nannoni ◽  
Vanessa Palumbo ◽  
Alessandra Del Bene ◽  
Giovanni Pracucci ◽  
Domenico Inzitari

Background. Lacunar stroke (LS) accounts for a quarter of all ischemic strokes and is considered to have a benign prognosis. However, 20-30% of patients experience worsening of neurological deficit in hours or days after stroke onset. Mechanisms of progression are not known and no reliable clinical predictor has been identified. Aim of this study was to explore vascular risk factors and baseline clinical or laboratory features potentially associated with progression in LS. Methods. We performed a retrospective analysis of consecutive patients with LS admitted to the Stroke Unit of Careggi University Hospital (Florence, Italy) between January 2002 and December 2010. Patients were included in the study if they presented with a lacunar syndrome according to OCSP classification and/or small vessel disease according to TOAST classification and/or a lacunar infarct on neuroimaging consistent with the clinical deficit. Patients were divided into “progressive” and “non progressive”. Progression was defined as an increase of at least one point on one of the motor items of the NIHSS during the first 72 hours after stroke onset. Factors associated with progression after univariate analysis were entered into a multiple logistic regression model in order to select independent determinants of progression. Results. Out of 1502 patients with ischemic stroke admitted during the study period, 156 met the inclusion criteria. Thirty-nine (25%) patients showed neurological worsening. Latency of progression was 25.7 hours. Patients who progressed were younger than those who did not (mean age: 67.9±10.7 vs 70.6±13.0). There were no significant differences for single vascular risk factors distribution, laboratory parameters and baseline stroke severity comparing the two groups. When considering the presence of one versus more than one factor among hypertension, diabetes, smoking and hypercholesterolemia, the risk of progression increased with increasing number of risk factors: neurological worsening was observed in 0% (0/17) of patients with no risk factor, 24% (15/62) of those with one risk factor and 31% (24/77) of those with more than one risk factor (p=0.025). After adjustment for univariate predictors (age, sex, diastolic hypertension and lesion location in pons or internal capsule), the presence of multiple vascular risk factors maintained an independent effect on progression: risk of progression increased with an OR=1.7 (95%IC=1.1-2.8) for any additional risk factor. Conclusion. Our results suggest that a high risk factors profile is associated with an increased risk of progression. Translating this observation into a hypothetical pathological setting, it could support the hypothesis of mural atheroma involving the parent artery and proximal portion of the perforating arteries, eventually leading to the progressive enlargement of the ischemic area as a putative mechanism of progressive LS.


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.


Cephalalgia ◽  
2014 ◽  
Vol 35 (2) ◽  
pp. 146-164 ◽  
Author(s):  
Simona Sacco ◽  
Francesca Pistoia ◽  
Diana Degan ◽  
Antonio Carolei

Introduction Migraine, in particular migraine with aura, has been found to be associated with cardiovascular disease. However, the role of conventional vascular risk factors in the association is still debated. The aim of the present review is to address the association between migraine and conventional cardiovascular risk factors as well as to address their possible role in the association between migraine and cardiovascular disease. Methods Data for this review were obtained through searches in multiple sources up to May 2014 using the terms “migraine” OR “headache” in combination with all the vascular risk factors of interest. Results Data about the possible association between migraine and high blood pressure values are heterogeneous, hindering any final conclusion. Data addressing the possible association between migraine and diabetes mellitus indicate the lack of any association or in some cases a negative association between the two conditions. The body of evidence on the role of dyslipidemia in migraineurs is relatively homogeneous and, with few exceptions, reports an association between migraine and an unfavorable lipid profile; however, the difference in lipid levels between migraineurs and non-migraineurs is small and its clinical implication unclear. Regarding obesity, a trend has been observed of increased risk of migraine with increasing obesity, especially in young patients, albeit in the midst of conflicting data. Evidence about the association between cigarette smoking and migraine mostly indicates that migraineurs are more commonly smokers than non-migraineurs. On the other hand, the majority of the available studies report less alcohol use in migraineurs than in non-migraineurs. Finally, many of the available studies suggest a more frequent family history of cardiovascular disease in migraineurs as compared to non-migraineurs. Since most of the studies that supported the association between migraine and cardiovascular disease adjusted the analyses for the presence of several vascular risk factors, they cannot entirely explain this association. Conclusions Based on the available reported data, it seems unlikely that the higher risk of cardiovascular disease in migraineurs is mediated by any single vascular risk factor. For this reason the role of specific interactions among risk factors with the contribution of genetic, environmental, personality and psychological factors should be appropriately investigated.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Rebecca F Gottesman ◽  
Marilyn Albert ◽  
Laura Coker ◽  
Josef Coresh ◽  
Sonia M Davis ◽  
...  

Background: Vascular risk factors have been associated with risk of cognitive decline, with increasing evidence that midlife exposure to these risk factors may be most important in conferring late-life risk of cognitive impairment. We explored associations between vascular risk factors measured in midlife and the development of dementia over 25 years in the biracial Atherosclerosis Risk in Communities (ARIC) cohort. Methods: Participants in the ARIC study were recruited from four U.S. communities in 1987-1989, at ages 45-64, with four additional in-person visits, surveillance for hospitalizations, annual phone calls, and repeated cognitive evaluations over a 25-year period. In 2011-2013, ARIC participants were seen for the ARIC Neurocognitive Study (ARIC-NCS), and underwent a detailed neurocognitive battery and informant interviews. Through adjudicated review, dementia cases were defined. Additional dementia cases were identified through the telephone interview for cognitive status (TICS) or informant interview for those participants not attending ARIC-NCS; or by a prior dementia ICD-9 code during a hospitalization. Results: Of 15,744 participants in the cohort, 1516 cases of dementia were identified, of whom over one third were among black participants. Risk of dementia was highest in individuals of black race, with less than a high school education, older age, APOE ε4 carriage, and who, at ARIC baseline, had hypertension, diabetes, or were current smokers (table). APOE ε4 and smoking were each stronger risk factors for dementia in whites than in blacks. Discussion: Vascular risk factors measured in midlife are associated with increased risk of dementia in this biracial cohort, in black and white participants. The risk associated with diabetes nears the increased risk associated with having an APOE ε4 allele. Further studies are needed to evaluate the mechanism of and opportunities for prevention of the cognitive sequelae of these risk factors in midlife.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Jens Witsch ◽  
Saad Mir ◽  
Neal S Parikh ◽  
Santosh Murthy ◽  
Hooman Kamel ◽  
...  

Background: Cervical artery dissection (CAD) often affects young, otherwise healthy people. Few data exist on whether patients with CAD face an increased vulnerability to aortic dissection. Herein we tested the hypothesis that CAD is associated with an increased risk of aortic dissection. Methods: We performed a retrospective cohort study using statewide administrative claims data from all Emergency Department visits and admissions at nonfederal hospitals in Florida from 2005 to 2015 and New York from 2006 to 2015. We used previously validated International Classification of Disease, Ninth Revision, Clinical Modification codes (ICD-9-CM) to identify patients with CAD and aortic dissection. Patients with prevalent aortic dissection were excluded. Our exposure variable was CAD and the outcome was incident aortic dissection after discharge from CAD hospitalization. Survival statistics were used to calculate incidence rates and Cox proportional hazards analysis was used to determine the association between CAD and aortic dissection while adjusting for demographics and vascular risk factors. In a secondary analysis, we excluded patients who had a traumatic CAD, defined as having concomitant ICD-9-CM codes for head or neck trauma at the time of CAD. Results: Among 19,715,114 patients, 4,537 (0.02%) had a CAD. The mean age of patients with CAD was 52.3±16.4 years. During 4.2±3.1 years of follow up, 16,571 patients were diagnosed with an aortic dissection (0.08%). The incidence of aortic dissection was 2.5 (95% CI, 1.7-3.7) per 1,000 patients per year in those with CAD versus 0.2 (95% CI, 0.2-0.2) per 1,000 patients per year in those without CAD. After adjustment for demographics and vascular risk factors, we found that CAD was associated with subsequent aortic dissection (HR 3.0, 95% CI, 2.1-4.5). Our results were similar in a secondary analysis excluding patients with traumatic CAD (HR 3.3, 95% CI, 2.2-4.8). Conclusions: In a large population-based cohort, we found that CAD was associated with a 3-fold increased risk of aortic dissection. Future studies should evaluate the utility of performing screening aortic imaging in patients with CAD.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Marie-Luise Mono ◽  
Timo Kahles ◽  
David E. Thaler ◽  
Patrik Michel ◽  
Christian Weimar ◽  
...  

Background and purpose: Recurrent ischemic stroke in patients with CS and PFO has been proposed as a marker of increased risk for paradoxical embolism. It is unclear, whether the excess risk is driven by specific features of the PFO (right-to-left shunt (RLS) size, RLS at rest, associated atrial septum aneurysm (ASA)) or the presence of vascular risk factors (vRF). We compare the prevalence of vRF, TEE features, and baseline medications in PFO patients with first-ever versus multiple CS. Methods: From September 2008 to March 2013, the International PFO Consortium enrolled 993 patients with ischemic stroke or transient ischemic attack (TIA) and newly diagnosed PFO. In this analysis of baseline data, we included 386 patients with first-ever CS and no radiological evidence of prior cerebral ischemia (first-ever CS group, mean age, 52y) as well as 71 patients with recurrent CS and multiple ischemic lesions on CT and/or MRI (multiple CS group, mean age, 59y). Patients with TIA as index event, those with first-ever CS but additional “silent” ischemic lesions on imaging as well as those with recurrent CS without radiological findings of prior cerebral ischemia were excluded. We used nonparametric tests for independent samples and the Bonferroni correction for multiple comparisons. Results: Age > 55y (63% vs. 44%, P=0.001), hypertension (52% vs. 30%, P=0.001), hyperlipidemia (64% vs. 44%, P=0.003), and coronary artery disease (15% vs. 3%, P=0.001) were significantly more frequent in the multiple CS than in the first-ever CS group. The frequencies of male gender, current smoking, diabetes, migraine with or without aura, associated ASA, RLS size, and RLS at rest did not differ between groups. At baseline, patients with multiple CS were more likely to be on antiplatelets (50% vs. 18%), antihypertensive (51% vs. 22%) or lipid lowering drugs (44% vs. 10%, P=0.001 for each comparison) than patients with first-ever CS. The frequency of anticoagulant treatment did not differ between groups. Conclusions: In patients with CS, vRF but not specific PFO features were associated with recurrent cerebral ischemic events. The ongoing prospective part of the International PFO Consortium will likely shed light upon the role of vRF control for secondary stroke prevention in patients with PFO.


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