Association of Traditional and Nontraditional Risk Factors in the Development of Strokes Among Young Adults by Sex and Age Group: A Retrospective Case-Control Study.

BACKGROUND: Despite women having fewer traditional risk factors (eg, hypertension, diabetes), strokes are more common in women than men aged ≤45 years. This study examined the contributions of traditional and nontraditional risk factors (eg, migraine, thrombophilia) in the development of strokes among young adults. METHODS: This retrospective case-control study used Colorado's All Payer Claims Database (2012-2019). We identified index stroke events in young adults (aged 18-55 years), matched 1:3 to stroke-free controls, by (1) sex, (2) age±2 years, (3) insurance type, and (4) prestroke period. All traditional and nontraditional risk factors were identified from enrollment until a stroke or proxy-stroke date (defined as the prestroke period). Conditional logistic regression models stratified by sex and age group first assessed the association of stroke with counts of risk factors by type and then computed their individual and aggregated population attributable risks. RESULTS: We included 2618 cases (52% women; 73.3% ischemic strokes) and 7827 controls. Each additional traditional and nontraditional risk factors were associated with an increased risk of stroke in all sex and age groups. In adults aged 18 to 34 years, more strokes were associated with nontraditional (population attributable risk: 31.4% men and 42.7% women) than traditional risk factors (25.3% men and 33.3% women). The contribution of nontraditional risk factors declined with age (19.4% men and 27.9% women aged 45-55 years). The contribution of traditional risk factors peaked among patients aged 35 to 44 years (32.8% men and 39.7% women). Hypertension was the most important traditional risk factor and increased in contribution with age (population attributable risk: 27.8% men and 26.7% women aged 45 to 55 years). Migraine was the most important nontraditional risk factor and decreased in contribution with age (population attributable risk: 20.1% men and 34.5% women aged 18-35 years). CONCLUSIONS: Nontraditional risk factors were as important as traditional risk factors in the development of strokes for both young men and women and have a stronger association with the development of strokes in adults younger than 35 years of age.

Diversity, equity, and inclusion (DEI) in medical education: DEI at the bedside.

BACKGROUND: The ability to recognize and address bias is an important communication skill not typically addressed during training. We describe the design of an educational curriculum that aims to identify and change behavior related to diversity, equity, and inclusion (DEI). "DEI at the Bedside" uses the existing infrastructure of bedside teaching and provides a tool to normalize DEI discussions and develop skills to address bias during a neurology inpatient rotation. METHODS: As part of traditional clinical rounds, team members on an inpatient service shared experiences with DEI topics, including bias. The team developed potential responses should they encounter a similar situation in the future. We report the results of our needs assessment and curriculum development to evaluate the feasibility of incorporating a DEI educational curriculum in the neurology inpatient setting. RESULTS: Forty-two DEI experiences were recorded. Medical students were the most frequent discussants (44%). Direction of bias occurred between healthcare team members (33%), against patients (31%), and patients against healthcare team members (28%). Experiences ranged from microaggressions to explicit comments of racism, sexism, and homophobia. CONCLUSIONS: Based on needs assessment data, we developed a DEI educational curriculum for the inpatient neurology setting aimed to improve knowledge and skills related to DEI topics as well as to normalize conversation of DEI in the clinical setting. Additional study will demonstrate whether this initiative translates into measurable and sustained improvement in knowledge of how bias and disparity show up in the clinical setting and behavioral intent to discuss and address them.

Evidence and Mechanisms for Embolic Stroke in Contralateral Hemispheres From Carotid Artery Sources.

BACKGROUND: Disambiguation of embolus pathogenesis in embolic strokes is often a clinical challenge. One common source of embolic stroke is the carotid arteries, with emboli originating due to plaque buildup or perioperatively during revascularization procedures. Although it is commonly thought that thromboemboli from carotid sources travel to cerebral arteries ipsilaterally, there are existing reports of contralateral embolic events that complicate embolus source destination relationship for carotid sources. Here, we hypothesize that emboli from carotid sources can travel to contralateral hemispheres and that embolus interactions with collateral hemodynamics in the circle of Willis influence this process. METHODS AND RESULTS: We use a patient-specific computational embolus-hemodynamics interaction model developed in prior works to conduct an in silico experiment spanning 4 patient vascular models, 6 circle of Willis anastomosis variants, and 3 different thromboembolus sizes released from left and right carotid artery sites. This led to a total of 144 different experiments, estimating trajectories and distribution of approximately 1.728 million embolus samples. Across all cases considered, emboli from left and right carotid sources showed nonzero contralateral transport (P value <-0.05). Contralateral movement revealed a size dependence, with smaller emboli traveling more contralaterally. Detailed analysis of embolus dynamics revealed that collateral flow routes in the circle of Willis played a role in routing emboli, and transhemispheric movement occurred through the anterior and posterior communicating arteries in the circle of Willis. CONCLUSIONS: We generated quantitative data demonstrating the complex dynamics of finite size thromboembolus particles as they interact with pulsatile arterial hemodynamics and traverse the vascular network of the circle of Willis. This leads to a nonintuitive source-destination relationship for emboli originating from carotid artery sites, and emboli from carotid sources can potentially travel to cerebral arteries on contralateral hemispheres.

Evidence And Mechanisms For Embolic Stroke In Contralateral Hemispheres From Carotid Artery Sources.

Disambiguation of embolus etiology in embolic strokes is often a clinical challenge. One common source of embolic stroke is the carotid arteries, with emboli originating due to plaque build up, or perioperatively during revascularization procedures. While it is commonly thought that thromboemboli from carotid sources travel to cerebral arteries ipsilaterally, there are existing reports of contralateral embolic events which complicate embolus source destination relationship for carotid sources. Here, we hypothesize that emboli from carotid sources can travel to contralateral hemispheres, and that embolus interactions with collateral hemodynamics in the Circle of Willis influences this process. We use a patient-specific computational embolus-hemodynamics interaction model developed in prior works to conduct an in silico experiment spanning 4 patient vascular models, 6 Circle of Willis anastomosis variants, and 3 different thromboembolus sizes released from left and right carotid artery sites. This led to a total of 144 different experiments, estimating trajectories and distribution of approximately 1.728 million embolus samples. Across all cases considered, emboli from left and right carotid sources showed non-zero contralateral transport (p value < 0.05). Contralateral movement revealed a size-dependence, with smaller emboli traveling more contralaterally. Detailed analysis of embolus dynamics revealed that collateral flow routes in Circle of Willis played a role in routing emboli, and transhemispheric movement occurred through the anterior and posterior communicating arteries in the Circle of Willis. We generated quantitative data demonstrating the complex dynamics of finite size thromboembolus particles as they interact with pulsatile arterial hemodynamics, and traverse the vascular network of the Circle of Willis. This leads to a non-intuitive source-destination relationship for emboli originating from carotid artery sites, and emboli from carotid sources can potentially travel to cerebral arteries on contralateral hemispheres.

Thalamic Volume Loss Is Greater in Children Than in Adults Following Middle Cerebral Artery Territory Arterial Ischemic Stroke.

Background: Younger stroke patients may suffer worse outcomes than older patients; however, the extent to which age at stroke impacts remote areas of the brain remains unclear. The objective of this study was to determine thalamic volume changes ipsilateral to middle cerebral artery territory strokes based on age at acute ischemic stroke onset. Methods: Acute ischemic stroke patients <9 years, 9-18 years, and >18 years old were retrospectively recruited from a large quaternary care system. Each subject underwent an acute (<72 hours from AIS) and chronic (>90 days) magnetic resonance imaging (MRI) scan. Manual thalamic segmentation was performed. Results: Younger and older children had significantly greater stroke-side thalamic volume loss compared to adults (48.2%, P = .022; 40.7%, P = .044, respectively). Conclusions: Stroke-side thalamic volumes decreased across the age spectrum but to a greater degree in pediatric patients. This observation can affect functional and cognitive outcomes post stroke and warrants further research.

Sex Differences in Physical Activity and Incident Stroke: A Systematic Review.

PURPOSE: Physical inactivity, a modifiable risk factor for cardiovascular disease, is independently associated with stroke. Though some prior data have suggested sex differences in levels of physical activity, whether there are sex differences in the role of physical activity in primary stroke prevention is largely unknown. This systematic review identifies and describes recent findings on sex differences in the association between physical activity and incident (first-ever) stroke. This review also describes the current evidence on the strength of the association between physical activity and a reduced stroke risk in women in particular. METHODS: Using a prespecified strategy, PubMed/MEDLINE and Cochrane Central were searched to identify observational studies or trials published from 2000 to 2020 and reporting sex differences in physical activity and incident stroke. To be included, among other criteria, studies had to include sex-specific effect estimates from women, men, or both. Titles, abstracts, and full-text articles were screened to identify studies meeting the inclusion criteria, and adjusted sex-specific estimates of the association between physical activity and incident stroke for total stroke (ischemic plus hemorrhagic) or ischemic stroke were abstracted. FINDINGS: Thirty-seven studies met the inclusion criteria. Of 17 studies that included data on total incident stroke (ischemic and hemorrhagic combined) in both women and men, 7 (41%) showed similar associations between physical activity and incident stroke between women and men, 6 (35%) suggested a significant effect in women but not in men, and 3 (18%) showed a significant effect in men but not in women. Of 10 studies that included data on ischemic stroke in women and men, 5 (50%) suggested similar effects in women and men, 4 (40%) suggested a significant effect in women but not in men, and 1 (10%) showed an effect in men but not women. In women specifically, the majority of included studies demonstrated a reduced risk for incident stroke with physical activity, with relative risk reductions ranging from 11% to 72%, though most estimates fell between 20% and 40%. IMPLICATIONS: The majority of studies indicated a clear association between physical activity and a reduction in stroke risk. Studies were split as to the potential for sex differences in this association. Future prospective investigations should identify strategies for the use of increased physical activity for primary stroke prevention, with sex-specific considerations as warranted. The data on sex-specific dose-response relationship between physical activity and stroke risk are inconclusive and warrant more research.

Systematic Review of Sex Differences in Ischemic Strokes Among Young Adults: Are Young Women Disproportionately at Risk?

BACKGROUND AND PURPOSE: Recent evidence suggests that young women (18-45 years) may be at higher risk of ischemic strokes than men of the same age. The goal of this systematic review is to reconcile and synthesize existing evidence of sex differences among young adults with ischemic strokes. METHODS: We searched PubMed from January 2008 to July 2021 for relevant articles and reviews and consulted their references. We included original studies that (1) were population based and (2) reported stroke incidence by sex or sex-specific incidence rate ratios of young adults ≤45 years. We excluded studies that (1) omitted measurements of error for incidence rates or incidence rate ratios, (2) omitted age adjustment, and (3) were not in English. Statistical synthesis was performed to estimate sex difference by age group (≤35, 35-45, and ≤45) and stroke type. RESULTS: We found 19 studies that reported on sex-specific stroke incidence among young adults, including 3 that reported on overlapping data. Nine studies did not find a statistically significant sex difference among young adults ≤45 years. Three studies found higher rates of ischemic stroke among men among young adults ≥30 to 35 years. Four studies found more women with ischemic strokes among young adults ≤35 years. Overall, in young adults ≤35 years, the estimated effect size favored more ischemic strokes in women (incidence rate ratio, 1.44 [1.18-1.76], I2=82%) and a nonsignificant sex difference in young adults 35 to 45 years (incidence rate ratio, 1.08 [0.85-1.38], I2=95%). CONCLUSIONS: Overall, there were 44% more women ≤35 years with ischemic strokes than men. This gap narrows in young adults, 35 to 45 years, and there is conflicting evidence whether more men or women have ischemic strokes in the 35 to 45 age group.

Large Vessel Occlusion Prediction in the Emergency Department with National Institutes of Health Stroke Scale Components: A Machine Learning Approach.

OBJECTIVE: To determine the feasibility of using a machine learning algorithm to screen for large vessel occlusions (LVO) in the Emergency Department (ED). MATERIALS AND METHODS: A retrospective cohort of consecutive ED stroke alerts at a large comprehensive stroke center was analyzed. The primary outcome was diagnosis of LVO at discharge. Components of the National Institutes of Health Stroke Scale (NIHSS) were used in various clinical methods and machine learning algorithms to predict LVO, and the results were compared with the baseline method (aggregate NIHSS score with threshold of 6). The Area-Under-Curve (AUC) was used to measure the overall performance of the models. Bootstrapping (n = 1000) was applied for the statistical analysis. RESULTS: Of 1133 total patients, 67 were diagnosed with LVO. A Gaussian Process (GP) algorithm significantly outperformed other methods including the baseline methods. AUC score for the GP algorithm was 0.874 ± 0.025, compared with the simple aggregate NIHSS score, which had an AUC score of 0.819 ± 0.024. A dual-stage GP algorithm is proposed, which offers flexible threshold settings for different patient populations, and achieved an overall sensitivity of 0.903 and specificity of 0.626, in which sensitivity of 0.99 was achieved for high-risk patients (defined as initial NIHSS score > 6). CONCLUSION: Machine learning using a Gaussian Process algorithm outperformed a clinical cutoff using the aggregate NIHSS score for LVO diagnosis. Future studies would be beneficial in exploring prospective interventions developed using machine learning in screening for LVOs in the emergent setting.

Young Women Had More Strokes Than Young Men in a Large, United States Claims Sample.

BACKGROUND AND PURPOSE: Cardiovascular risk factors, which are overall more prevalent in men, are considered the major risk factors for strokes among young adults. However, recent European data found the incidence of strokes to be higher in young women. Using a large US claims sample, we examined sex differences in the index stroke rate of young adults. METHODS: We performed a retrospective cohort study of enrollees in a 10% random sample of PharMetrics, a nationally representative claims database of insured Americans from 2001 to 2014. Outcomes were index ischemic stroke events, based on inpatient admissions using International Classification of Diseases-Ninth Revision codes. The index stroke rate was estimated from Poisson rate models with time varying covariates for 2-year periods, stratified by sex and age groups. RESULTS: We identified 20 554 index strokes (50.4% women; mean age 63) including 5198 in young adults ages 15 to 54. There was no difference by sex in the index stroke rate in the extremes of age groups 15 to 24 and ≥75 years old. However, in the 25 to 34 and 35 to 44 year age groups, more women had strokes than men (incidence rate ratio: men:women, 0.70 [95% CI, 0.57-0.86]; 0.87 [95% CI, 0.78-0.98], respectively). In contrast, in the 45 to 54, 55 to 64, and 65 to 74 year age groups, more men had strokes (incidence rate ratio, 1.25 [95% CI, 1.16-1.33]; 1.41 [95% CI, 1.18-1.34]; 1.18 [95% CI, 1.12-125], respectively). CONCLUSIONS: More young women than men have strokes, suggesting possible importance of sex-mediated etiologies of stroke. Understanding these drivers is critical to stroke treatment and prevention efforts in young adults.

Temporal Trends in Stroke Incidence Over Time by Sex and Age in the GCNKSS.

Background and Purpose- Sex differences in stroke incidence over time were previously reported from the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study). We aimed to determine whether these differences continued through 2015 and whether they were driven by particular age groups. Methods- Within the GCNKSS population of 1.3 million, incident (first ever) strokes among residents ≥20 years of age were ascertained at all local hospitals during 5 periods: July 1993 to June 1994 and calendar years 1999, 2005, 2010, and 2015. Out-of-hospital cases were sampled. Sex-specific incidence rates per 100 000 were adjusted for age and race and standardized to the 2010 US Census. Trends over time by sex were compared (overall and age stratified). Sex-specific case fatality rates were also reported. Bonferroni corrections were applied for multiple comparisons. Results- Over the 5 study periods, there were 9733 incident strokes (56.3% women). For women, there were 229 (95% CI, 215-242) per 100 000 incident strokes in 1993/1994 and 174 (95% CI, 163-185) in 2015 (P<0.05), compared with 282 (95% CI, 263-301) in 1993/1994 to 211 (95% CI, 198-225) in 2015 (P<0.05) in men. Incidence rates decreased between the first and last study periods in both sexes for IS but not for intracerebral hemorrhage or subarachnoid hemorrhage. Significant decreases in stroke incidence occurred between the first and last study periods for both sexes in the 65- to 84-year age group and men only in the ≥85-year age group; stroke incidence increased for men only in the 20- to 44-year age group. Conclusions- Overall stroke incidence decreased from the early 1990s to 2015 for both sexes. Future studies should continue close surveillance of sex differences in the 20- to 44-year and ≥85-year age groups, and future stroke prevention strategies should target strokes in the young- and middle-age groups, as well as intracerebral hemorrhage.

Relationship between early follow-up and readmission within 30 and 90 days after ischemic stroke.

OBJECTIVE: To examine whether early follow-up with primary care or neurology is associated with lower all-cause readmissions within 30 and 90 days after acute ischemic stroke admission. METHODS: We performed a retrospective cohort study of patients who were discharged home after acute ischemic stroke, identified by ICD-9 and ICD-10 codes, using PharMetrics, a nationally representative claims database of insured Americans from 2009 to 2015. The primary predictor was outpatient primary care or neurology follow-up within 30 and 90 days of discharge, and the primary outcome was all-cause 30- and 90-day readmissions. Multivariable Cox models were used with primary care and neurology visits specified as time-dependent covariates, with adjustment for patient demographics, comorbid conditions, and stroke severity measures. RESULTS: The cohort included 14,630 patients. Readmissions within 30 days occurred in 7.3% of patients, and readmissions within 90 days occurred in 13.7% of patients. By 30 days, 59.3% had a primary care visit, and 24.4% had a neurology visit. Primary care follow-up was associated with reduced 30-day readmissions (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.72-0.98). Primary care follow-up before 90 days did not reach significance (HR 0.92, 95% CI 0.83-1.03). Neurology follow-up was not associated with reduced readmissions within 30 or 90 days (HR 1.05, 95% CI; HR 1.00, 95% CI, respectively). CONCLUSION: Early outpatient follow-up with primary care is associated with a reduction in 30-day hospital readmissions. Early outpatient follow-up may represent an important opportunity for intervention after acute stroke admissions.

Is Prevalence of Atherosclerotic Risk Factors Increasing Among Young Adults? It Depends on How You Ask.

Background Incidence of cardiovascular disease in young adults is unabated. Increased prevalence of self-reported atherosclerotic risk factors may be driving this trend. The goal of this study was to examine whether the prevalence of atherosclerotic risk factors in young adults is increasing over time using both self-report and standard clinical criteria. Methods and Results Data from young adults, aged 20 to 45 years, in the National Health and Nutrition Examination Survey from 1999/2000 to 2013/2014 were analyzed. Risk factor prevalence of hypertension, diabetes mellitus, and hyperlipidemia was measured using clinical criteria and self-report. Smoking was based on self-report only, and obesity was based clinically on body mass index and waist to height ratio. Prevalence by survey was adjusted for age, sex, and race/ethnicity. By clinical criteria, adjusted prevalence of any 3 risk factors (hypertension, diabetes mellitus, and hyperlipidemia) declined slightly from 21.8% to 18.9% ( P for trend=0.05). However, by self-report, the adjusted prevalence of any 3 risk factors increased from 17.8% to 26.5% ( P<0.01). Hypertension was unchanged by clinical criteria ( P=0.32) but increased by self-report ( P<0.08). Diabetes mellitus, by clinical diagnosis and self-report, remained unchanged ( P=0.35 and P=0.29, respectively). Hyperlipidemia, by clinical criteria, declined over time ( P<0.01), but increased by self-report ( P<0.01). Smoking declined ( P<0.01), and obesity increased by both body mass index ( P<0.01) and waist/height ratio ( P<0.01). Conclusions The perception that young adult risk factors are increasing is consistent with increasing self-reported risk factors. However, evidence does not suggest that clinical risk factor prevalence overall has increased in young adults.

A Clinical Paradigm for Classifying Neurologic Symptoms to Screen for Emergent Large Vessel Occlusions.

BACKGROUND: With newly-extended treatment windows for endovascular therapy in emergent large vessel occlusions, it is increasingly important to identify thrombectomy-eligible patients without overwhelming resources dedicated to acute stroke care. We devised a simple paradigm to classify patient's presenting neurologic symptoms to screen for large vessel occlusions. METHODS: We reviewed the presenting symptoms, imaging findings, and final diagnoses of consecutive emergency department stroke alert cases. Patients were classified based on their neurologic exams as focal objective, focal subjective, or nonfocal. Outcomes of final diagnoses of acute ischemic stroke and large vessel occlusions were compared across groups. Comparisons were made to other large vessel occlusion prediction scales. RESULTS: Of 521 patients, 342 (65.6%) were categorized as focal objective, 142 (27.2%) as focal subjective, and 37 (7.1%) as nonfocal. Ischemic stroke and large vessel occlusions were diagnosed in 114 (21.9%) and 27 (5.2%) of patients, respectively. Classification as focal objective significantly predicted stroke (odds ratio 3.77; 95% confidence interval 2.17-6.55) and captured all large vessel occlusions (P = .0001). The focal objective categorization was the only tool which achieved 100% sensitivity for large vessel occlusions (with a specificity of 36%) compared to other large vessel occlusion prediction tools. CONCLUSIONS: Patients who presented as stroke alerts without focal neurologic symptoms were unlikely to have large vessel occlusions. With high sensitivity, classifying patients' neurologic exams into focal objective versus subjective or nonfocal categories may serve as a useful tool to screen for large vessel occlusions and prevent unnecessary emergent workup in patients unlikely to be endovascular candidates.