Established Stroke Risk Factors Research Articles

ETA Receptor Blockade and Vascular Function in Patients with Sickle Cell Disease

Endothelin-1 (ET1) is a potent vasoconstrictor, mitogen, proinflammatory mediator, and a mediator of nociception, whose synthesis is increased by hypoxia, ischemia, shear stress, oxidative stress and reduced nitric oxide (NO) bioavailability, all of which are well documented mechanisms in the pathophysiology of sickle cell disease (SCD). We earlier reported on our studies on the role of ET-1 in SCD, and in transgenic mouse models showed that ETA receptor blockade with ambrisentan provides renal protection by preventing the development of glomerular hyperfiltration and proteinuria (Kasztan et al, 2017, Taylor et al, 2019, Kasztan and Pollock, 2019). ETA receptor blockade was also shown to decrease pulmonary inflammation in response to hypoxia/reoxygenation and LPS (Meiler et al.). Additionally, Lutz et al (2018) showed that pharmacologic inhibition or neuron specific knockdown of ETA receptor in primary sensory neurons of dorsal root ganglia in Berk mice alleviated basal and post-hypoxia evoked pain sensitivity. More recently (Kutlar et al, Blood 2019, 617,130036) we reported the preliminary results of a placebo controlled, double-blind phase I trial of ambrisentan in 26 subjects with SCD (SS and S-ß0 thalassemia) and microalbuminuria, and showed that the drug was well tolerated without any dose limiting toxicities and patients on ambrisentan had a reduction in microalbuminuria, especially in the subgroup who had been on concomitant ACEi/ARB therapy at a stable dose for at least six months (n=6, 286.1 mg/g Cr at baseline to 197.7 mg/g on day 85, p=0.06). FMD measurements showed increased arterial diameter, and improved microvascular function. We analyzed data collected on secondary end points during the phase I study, including Tricuspid regurgitant jet velocity (TRV), Transcranial Doppler (TCD) velocities in distal internal carotid (dICA) and middle cerebral (MCA) arteries, and eGFR (calculated with CKD-Epi formula). Fig. 1a shows eGFRs in ambrisentan and placebo groups; Fig. 1b and Fig. 1c show a breakdown of ambrisentan and placebo groups based on concomitant ACEi/ARB usage. There is a reduction in glomerular hyperfiltration in the ambrisentan group compared to placebo, more pronounced in the subgroup who have not been on ACEi/ARBs. Fig. 1d depicts the change in flow velocity in MCA (TAMMV, Time Averaged Mean Maximal Velocity, cm/sec) between the ambrisentan and placebo groups; similarly, Fig. 1e and 1f show the breakdown of baseline and Day 85 TAMMVs in MCA according to ACEi/ARB usage. A similar trend is also observed in dICA flow (fig. 1g-1i), and suggests a synergistic effect of ETA receptor blockade with ACEi/ARBs in preventing an increase in blood flow velocities. TRV was available on 7 subjects, 6 of which were in the ambrisentan group. Fig. 1j shows the change in TRV in the ambrisentan group, and again is suggestive of a synergistic effect of ambrisentan and ACEi/ARBs in decreasing TRV. These data are clearly very preliminary, and are obtained on a small number of subjects, and as such, do not warrant any conclusions and or speculations. Nevertheless, an interesting observation is the apparent interaction of ETA receptor blockade and ACEi/ARBs in altering vascular flow/function in SCD patients. Decrease in microalbuminuria has been reported with ACEi and ARBs in SCD (Yee et al, 2018), without any effect on GFR. A reduction in hyperfiltration would likely have a significant renoprotective effect, at an earlier stage in the development of sickle nephropathy. ETA receptor antagonists are approved for the treatment of pulmonary arterial hypertension; thus, a decrease in TRV would have a beneficial effect. Increase in blood flow velocity in major intracranial vessels is a well established risk factor for ischemic stroke in children with SCD; however, much less is known in adults. In summary, the effect of ETA receptor blockade with or without ACEi/ARB, may have a significant effect on vascular function/blood flow in different organ systems, and should be explored in a large, multi-center phase II trial, with and without concomitant and or serial ACEi/ARBs, for a longer period of time, with a dose escalation, to further clarify the pleiotropic effects on multiple aspects of SCD pathology. Figure 1 Disclosures Kutlar: NIH/NHLBI (SCDIC): Research Funding; Global Blood Therapeutics: Research Funding, Speakers Bureau; Micelle Biopharma: Consultancy; Novartis Pharmaceuticals: Consultancy, Research Funding; Novo Nordisk: Research Funding; Forma Therapeutics: Research Funding; REACH: Other: DSMB Member; NOHARM: Other: DSMB Member; Bluebird Bio: Other: DSMB Member.

Gastrointestinal Disorders and Risk of First-Ever Ischemic Stroke.

Recent studies suggest that alteration of the normal gut microbiome contributes to atherosclerotic burden and cardiovascular disease. While many gastrointestinal diseases are known to cause disruption of the normal gut microbiome in humans, the clinical impact of gastrointestinal diseases on subsequent cerebrovascular disease remains unknown. We conducted an exploratory analysis evaluating the relationship between gastrointestinal diseases and ischemic stroke. We performed a retrospective cohort study using claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included only beneficiaries ≥66 years of age. We used previously validated diagnosis codes to ascertain our primary outcome of ischemic stroke. In an exploratory manner, we categorized gastrointestinal disorders by anatomic location, disease chronicity, and disease mechanism. We used Cox proportional hazards models to examine associations of gastrointestinal disorder categories and ischemic stroke with adjustment for demographics and established vascular risk factors. Among a mean of 1 725 246 beneficiaries in each analysis, several categories of gastrointestinal disorders were associated with an increased risk of ischemic stroke after adjustment for established stroke risk factors. The most notable positive associations included disorders of the stomach (hazard ratio, 1.17 [95% CI, 1.15-1.19]) and functional (1.16 [95% CI, 1.15-1.17]), inflammatory (1.13 [95% CI, 1.12-1.15]), and infectious gastrointestinal disorders (1.13 [95% CI, 1.12-1.15]). In contrast, we found no associations with stroke for diseases of the anus and rectum (0.97 [95% CI, 0.94-1.00]) or neoplastic gastrointestinal disorders (0.97 [95% CI, 0.94-1.00]). In exploratory analyses, several categories of gastrointestinal disorders were associated with an increased risk of future ischemic stroke after adjustment for demographics and established stroke risk factors.

COVID-19 and Stroke: Incidence and Etiological Description in a High-Volume Center

BackgroundAn increased rate of thrombotic events has been associated to Coronavirus Disease 19 (COVID-19) with a variable rate of acute stroke. Our aim is to uncover the rate of acute stroke in COVID-19 patients and identify those cases in which a possible causative relationship could exist. MethodsWe performed a single-center analysis of a prospective mandatory database. We studied all patients with confirmed COVID-19 and stroke diagnoses from March 2nd to April 30th. Demographic, clinical, and imaging data were prospectively collected. Final diagnosis was determined after full diagnostic work-up unless impossible due to death. ResultsOf 2050 patients with confirmed SARS-CoV-2 infection, 21 (1.02%) presented an acute ischemic stroke 21 and 4 (0.2%) suffered an intracranial hemorrhage. After the diagnostic work-up, in 60.0% ischemic and all hemorrhagic strokes patients an etiology non-related with COVID-19 was identified. Only in 6 patients the stroke cause was considered possibly related to COVID-19, all of them required mechanical ventilation before stroke onset. Ten patients underwent endovascular treatment; compared with patients who underwent EVT in the same period, COVID-19 was an independent predictor of in-hospital mortality (50% versus 15%; Odds Ratio, 6.67; 95% CI, 1.1-40.4; p 0.04). ConclusionsThe presence of acute stroke in patients with COVID-19 was below 2% and most of them previously presented established stroke risk factors. Without other potential cause, stroke was an uncommon complication and exclusive of patients with a severe pulmonary injury. The presence of COVID-19 in patients who underwent EVT was an independent predictor of in-hospital mortality.

Interpretive Complications Underlying Cerebrovascular Response To Hypercapnia; Significance Of The Central Respiratory Chemoreflex Transient

Cerebral blood flow (CBF) is sensitive to changes in the arterial partial pressure of carbon dioxide (CO2) with cerebrovascular reactivity an established risk factor for stroke and neurodegenerative disease. However, its interpretation can be complicated given subtle differences in cerebrovascular and central respiratory chemoreflex response transients. PURPOSE: To examine to what extent exposure time to CO2 influences CBF response. METHOD: We measured CBF response to hypercapnia (FICO2 = 5%) in five healthy participants for 10 min in the supine position. End-tidal partial pressures of CO2 (PETCO2), minute ventilation (VE), and middle cerebral artery blood velocity (MCAv) were assessed during both the early (3~4 min) and late phases (9~10 min) of exposure. RESULT: We observed elevated VE larger during the late compared to the early phase of exposure (from 11 ± 2 to 29 ± 8 vs. 23 ± 4 L/min, P = 0.047) despite no differences in PETCO2 (P = 0.304). The corresponding increase in MCAv during the late phase was suppressed compared to the early phase (from 48 ± 11 to 58 ± 14 vs. 63 ± 13 cm/sec, P = 0.029). Thus, the response of CBF to change in PETCO2 at late phase was lower than that of early phase (1.1 ± 1 %/mmHg vs. 1.7 ± 1 %/mmHg, P=0.07). CONCLUSION: These findings highlight the importance of considering the central respiratory chemoreflex transient during the clinical assessment of cerebrovascular reactivity.

Current Status of Dyslipidemia Treatment for Stroke Prevention.

Elevated cholesterol is an established risk factor for ischemic stroke. The value of statins for stroke prevention has been clear for more than a decade. However, the use of new medication combinations such as ezetimibe or proprotein convertase subtilisin-kexin type 9 inhibitors plus statins is increasing and the value for reducing stroke has been shown for these combination therapies. Recent data also support the strategy of lowering triglycerides for stroke prevention. A modern approach to dyslipidemia treatment and its relation to stroke prevention is summarized in this paper.

Siesta and Risk for Ischemic Stroke: Results from a Case-Control Study.

Background and objectives: Siesta, which is a short afternoon nap, is a habit that is commonly practiced in the Mediterranean and tropical areas. Data on the association between siesta and coronary artery disease has been conflicting. A protective effect has been demonstrated in the countries that commonly practice siesta, but a harmful effect has been observed in the countries that infrequently practice the siesta habit. Information on the association between siesta and ischemic stroke has been, however, lacking. Hence, the purpose of our study was to determine the effect of siesta on ischemic stroke. Materials and Methods: This was a case-control study, conducted on the patients with acute ischemic stroke who came for their first follow-up visit to the neurology clinic. Controls were randomly selected from the patients visiting the neurology clinic on the same day as the patients with ischemic stroke. In addition to basic demographics and the occurrence of established stroke risk factors, information about siesta practice was also collected from both groups. A multivariate logistic regression analysis was utilized to determine the relationship between siesta practice and ischemic stroke. Results: A total of 206 patients were recruited from the neurology clinic of King Khalid university hospital; of which only 194 subjects were included in the analysis (98 ischemic stroke cases and 96 controls). The mean age of the participants was 59.68 ± 13.75 years and 98 (50.52%) were male. Interestingly, 43% of the whole study cohort practiced regular siesta. However, when compared to the stroke population, the control group practiced siesta more frequently (30% vs. 56%). In a multivariate logistic regression analysis, hypertension, diabetes mellitus, excess body weight (body mass index > 25 kg/m2) and dyslipidemia were found to increase the risk of ischemic stroke (OR 2.12, 95% CI: 1.02–4.66, p = 0.005; OR 2.72, 95% CI: 1.94–4.88, p = 0.014; OR 2.94, 95% CI: 1.5164–5.7121 p = 0.0014; OR 3.27, 95% CI: 2.42–5.199, p ≤ 0.001, respectively). On the contrary, the practice of regular siesta lowered the risk of ischemic stroke (OR 0.58, 95% CI: 0.3551–0.9526, p = 0.031). Conclusions: Siesta was associated with a reduced risk for the occurrence of ischemic stroke. Large prospective longitudinal studies should be conducted to verify the protective effect of siesta on stroke.

Obesity paradox and stroke: a narrative review

Despite obesity is an established risk factor for stroke, several studies reported a better outcome after stroke in obese and overweight patients. This counterintuitive finding, which was described in the whole spectrum of cardiovascular diseases, is known as obesity paradox. This is a narrative overview on the obesity paradox and stroke. We used as sources MEDLINE/PubMed, CINAHL, EMBASE, and Cochrane Library from inception to 2019, and selected papers that discussed the association of obesity with outcome and mortality after stroke. The majority of studies reported lower mortality rates and better functional outcome after stroke in obese and overweight patients compared with normal weight and underweight patients, suggesting the existence of an obesity paradox in stroke. However, available studies are limited by several major methodological concerns including absence of randomized trials, retrospective nature of most studies, assessment of obesity with body mass index (BMI), non-linear relationship between BMI and outcome, short follow-up period, and differences in co-morbid conditions and stroke characteristics. The existence of an obesity paradox in stroke is still controversial and further higher quality evidence is needed to clarify the relationship between obesity and stroke outcome. Level V, narrative review.

Impact of carotid atherosclerosis in CHA2DS2-VASc-based risk score on predicting ischemic stroke in patients with atrial fibrillation.

Background/AimsVascular disease is an established risk factor for stroke in patients with atrial fibrillation (AF), which is included in CHA2DS2-VASc score. However, the role of carotid atherosclerosis remains to be determined.MethodsThree hundred-ten patients with AF who underwent carotid sonography were enrolled.ResultsDuring a median follow-up of 31 months, 18 events (5.8%) of stroke were identified. Patients with stroke had higher carotid intima-media thickness (CIMT) (1.16 ± 0.33 mm vs. 0.98 ± 0.25 mm, p = 0.017). CIMT was significantly increased according to the CHA2DS2-VASc score (p < 0.001) and it was correlated with left ventricular mass index and early diastolic mitral annular velocity (e’), a ratio of early transmitral flow velocity to e’ (E/e’) and pulmonary artery systolic pressure (all p < 0.05). Cox regression using multivariate models showed that carotid plaque was associated with the risk of stroke (hazard ratio, 3.748; 95% confidence interval [CI], 1.107 to 12.688; p = 0.034). C-statistics increased from 0.648 (95% CI, 0.538 to 0.757) to 0.716 (95% CI, 0.628 to 0.804) in the CHA2DS2-VASc score model after the addition of CIMT and carotid plaque as a vascular component (p = 0.013).ConclusionsIncreased CIMT and presence of carotid plaque are associated with a high risk of ischemic stroke, and CIMT is related to myocardial remodeling and diastolic dysfunction, suggesting that carotid atherosclerosis can improve risk prediction of stroke in patients with AF, when included under vascular disease in the CHA2DS2-VASc scoring system.

Abstract WP25: The Impact of Body Mass Index on Outcomes of Mechanical Thrombectomy for Acute Ischemic Stroke

Background: Obesity is an established risk factor for acute ischemic stroke (AIS), but its impact on clinical outcomes and mortality after AIS remains controversial. In this study, we evaluate the association of body mass index (BMI) on outcomes after mechanical thrombectomy (MT) for large vessel occlusion acute ischemic stroke (LVOS). Methods: We reviewed our prospective MT database for LVOS between 2015 and 2018. BMI was analyzed as a continuous and categorical variable with underweight BMI &lt;18.5, normal BMI 18.5-24.9, overweight BMI 25-29.9, and obese BMI&gt;30. Multivariate analysis was used to determine predictors of outcome. Results: 335 patients underwent MT with 7 (2.1%) patients classified as underweight, 107 (31.9%) normal, 141 (42.1%) overweight, and 80 (23.9%) obese. Compared to normal weight (reference), obese patients had higher rates of hypertension and hyperlipidemia, while underweight patients had higher rates of previous stroke and presentation NIHSS. The time from symptom onset to puncture, procedural techniques, and reperfusion success (&gt;TICI 2b) was not significantly different between BMI categories. There was a significant inverse linear correlation between BMI and symptomatic hemorrhagic. In patients with successful reperfusion (&gt;TICI 2b), there was also a significant bell-shaped relationship between BMI and functional independence (mRS &lt; 3) with both low and high BMIs associated with worse outcomes. In patients without post-procedural symptomatic hemorrhage, there was a significant linear correlation between BMI and inpatient mortality. Conclusion: In LVOS patients treated with MT, BMI is inversely related with post-procedural symptomatic hemorrhage. Yet in those whom reperfusion is achieved, both lower and higher than normal BMI were associated with worse functional outcomes. Thus, the obesity paradox does not appear to pertain to mechanical thrombectomy, although larger prospective studies are necessary.

Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke

Recent genome-wide association studies in stroke have enabled the generation of genomic risk scores (GRS) but their predictive power has been modest compared to established stroke risk factors. Here, using a meta-scoring approach, we develop a metaGRS for ischaemic stroke (IS) and analyse this score in the UK Biobank (n = 395,393; 3075 IS events by age 75). The metaGRS hazard ratio for IS (1.26, 95% CI 1.22–1.31 per metaGRS standard deviation) doubles that of a previous GRS, identifying a subset of individuals at monogenic levels of risk: the top 0.25% of metaGRS have three-fold risk of IS. The metaGRS is similarly or more predictive compared to several risk factors, such as family history, blood pressure, body mass index, and smoking. We estimate the reductions needed in modifiable risk factors for individuals with different levels of genomic risk and suggest that, for individuals with high metaGRS, achieving risk factor levels recommended by current guidelines may be insufficient to mitigate risk.

Study of Serum Homocysteine Level in Young Patients with Myocardial Infarction and Cerebrovascular Stroke

Background: Nowadays, vascular disease is the leading cause of death and disability. India too is facing epidemic of cardiovascular and cerebrovascular disease. The established risk factors for heart disease and stroke account for one half to three fourth of cases. The remainders are the result of other factors that promote atherosclerosis. Elevated blood levels of homocysteine have been linked to increased risk of premature coronary artery disease, stroke and thromboembolism, even among people who have normal cholesterol levels. Hence screen for homocysteine is recommended in patients with premature atherosclerotic disease and unexplained venous thrombosis. Methods: The present study was performed to correlate the levels of serum homocysteine levels in young patients (</=40 yrs) with myocardial infarction and ischemic cerebrovascular stroke. Thirty cases were studied along with assessment of their risk factor. Result: It was observed that serum homocysteine levels were significantly raised in coronary artery disease and ischemic stroke patients. Conclusion: Increase levels of homocysteine is an important factor that assesses risk independently for coronary artery disease and ishchemic stroke.

Atrial fibrillation-related stroke in women: Evidence and inequalities in epidemiology, mechanisms, clinical presentation, and management.

BackgroundAtrial fibrillation (AF) is the most common clinical arrhythmia and one of the major causes of stroke, heart failure, sudden death, and cardiovascular morbidity. Despite substantial advances in (interventional) rhythm control treatment during the last decade, anticoagulation for stroke prevention remains a major component of AF treatment.HypothesisThere are important sex‐specific differences in AF‐related stroke, resulting from sex‐specific mechanisms and therapeutic differences.MethodsThis review summarizes available data on sex differences in risk assessment and prevention of stroke and highlights current knowledge gaps in AF‐related stroke mechanisms, prevention and management that warrant further research.ResultsIncreased thrombotic risk in women is multifactorial, involving hormonal changes after menopause, structural, endocrine and lifestyle/social factors and their interactions. It is clear from randomized studies that women benefit from anticoagulant treatment and that their bleeding risk is similar to men. Women should therefore receive equivalent treatment to men, based on the validated criteria for anticoagulation therapy. However, women are not represented equally in the large randomized studies and sex‐related information in many fields is lacking.ConclusionsFemale sex is an established risk factor for stroke in AF patients. The evidence for sex‐specific differences in stroke risk assessment and stroke prevention is accumulating. However, the underlying biological mechanisms remain incompletely understood and further studies are required in order to decrease AF‐related morbidity and mortality.

Endothelial SIRT6 blunts stroke size and neurological deficit by preserving blood-brain barrier integrity: a translational study.

Aging is an established risk factor for stroke; genes regulating longevity are implicated in the pathogenesis of ischaemic stroke where to date, therapeutic options remain limited. The blood-brain barrier (BBB) is crucially involved in ischaemia/reperfusion (I/R) brain injury thus representing an attractive target for developing novel therapeutic agents. Given the role of endothelial cells in the BBB, we hypothesized that the endothelial-specific expression of the recently described longevity gene SIRT6 may exhibit protective properties in stroke. SIRT6 endothelial expression was reduced following stroke. Endothelial-specific Sirt6 knockout (eSirt6-/-) mice, as well as animals in which Sirt6 overexpression was post-ischaemically induced, underwent transient middle cerebral artery occlusion (tMCAO). eSirt6-/- animals displayed increased infarct volumes, mortality, and neurological deficit after tMCAO, as compared to control littermates. Conversely, post-ischaemic Sirt6 overexpression decreased infarct size and neurological deficit. Analysis of ischaemic brain sections revealed increased BBB damage and endothelial expression of cleaved caspase-3 in eSIRT6-/- mice as compared to controls. In primary human brain microvascular endothelial cells (HBMVECs), hypoxia/reoxygenation (H/R) reduced SIRT6 expression and SIRT6 silencing impaired the barrier function (transendothelial resistance) similar to what was observed in mice exposed to I/R. Further, SIRT6-silenced HBMVECs exposed to H/R showed reduced viability, increased cleaved caspase-3 expression and reduced activation of the survival pathway Akt. In ischaemic stroke patients, SIRT6 expression was higher in those with short-term neurological improvement as assessed by NIHSS scale and correlated with stroke outcome. Endothelial SIRT6 exerts a protective role in ischaemic stroke by blunting I/R-mediated BBB damage and thus, it may represent an interesting novel therapeutic target to be explored in future clinical investigation.

Midlife Hypertension and Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Hypertension is an established risk factor for stroke and vascular dementia but recent meta-analyses examining the association between Alzheimer's disease (AD) and hypertension have found no significant association. These meta-analyses included short term studies starting in late life which may have obscured the real effect of midlife hypertension. To examine the association of AD with midlife hypertension, by including only studies with a sufficiently long follow up duration. Relevant studies were found by searches of MEDLINE, EMBASE, and PubMed. Study outcomes were grouped by measures of blood pressure and definition of hypertension (e.g., systolic hypertension > 140 mmHg or > 160 mmHg). We assessed pooled effect estimates using random effects models and heterogeneity of pooled estimates through the I2 statistic. Literature search found 3,426 publications of which 7 were eligible studies. There was a significant association between systolic hypertension (>160 mm Hg) and AD (HR 1.25, 95CI 1.06 - 1.47, p = 0.0065). Similarly, for systolic hypertension > 140 mm Hg, there was a smaller but still significant association (HR 1.18, 95CI 1.02 - 1.35, p = 0.021). For diastolic hypertension, all four studies found no significant associations between diastolic hypertension and AD, and these data could not be pooled due to heterogeneity in reporting. Our study found that midlife stage 1 and stage 2 systolic hypertension is associated with increased risk of AD by 18 and 25%, respectively, although no association was found for diastolic hypertension. It is likely that assertive control of systolic hypertension starting in midlife is important to preventing AD.

Obesity Paradox in Intracerebral Hemorrhage.

Background and Purpose- Although obesity is an established risk factor for cardiovascular disease and stroke, studies have shown evidence of an obesity paradox-a protective effect of obesity in patients who already have these disease states. Data on the obesity paradox in intracerebral hemorrhage is limited. Methods- Clinical data for adult intracerebral hemorrhage patients were extracted from the National Inpatient Sample between 2007 and 2014. Multivariable logistic regression analyzed the association of body habitus with in-hospital mortality, discharge disposition, length of stay, tracheostomy or gastrostomy placement, and ventriculoperitoneal shunt placement. Results- There were 99 212 patients who were eligible. Patients with both obesity (OR=0.69; 95% CI=0.62-0.76; P<0.001) and morbid obesity (OR=0.85; 95% CI=0.74-0.97; P=0.02) were associated with decreased odds of in-hospital mortality. Morbid obesity was significantly associated with increased odds of a tracheostomy or gastrostomy placement (OR=1.42; 1.20-1.69; P<0.001) and decreased odds of a routine discharge disposition (OR=0.84; 0.74-0.97; P=0.014). Conclusions- Obesity and morbid obesity appear to protect against mortality in intracerebral hemorrhage.

Abstract WP265: Racial Differences in Left Atrial Size Among Patients With Ischemic Stroke

Introduction: Blacks in the U.S. face twice the risk of ischemic stroke as whites, and this disparity is not fully explained by established stroke risk factors. Although atrial fibrillation (AF) is a major risk factor for stroke, blacks are less often diagnosed with AF than whites. It is unclear whether this paradox exists because AF is less thoroughly ascertained in blacks compared to whites or because blacks have less predisposing substrate and thus a truly lower risk of AF. Hypothesis: Based on our prior work, we hypothesized that black patients with ischemic stroke less often have left atrial enlargement, a major predisposing factor for AF. Methods: We compared left atrial size in black versus white patients in the Greater Cincinnati/Northern Kentucky Stroke Study, a study of racial disparities in stroke incidence in a nationally representative population of 1.3 million. We obtained reports of echocardiograms performed for stroke evaluation among patients in the 2010 and 2015 study periods. Patients with known AF or atrial flutter were excluded. Investigators blinded to patients’ characteristics abstracted left atrial diameter from echocardiogram reports. Linear regression was used to examine the association between race and left atrial diameter after adjustment for demographics, body mass index, and comorbidities. Results: Among 2,980 cases of ischemic stroke without AF, the median age was 66 years, 52% were female, and 30% were black. The overall mean left atrial diameter was 3.65 (±0.69) cm. Despite a higher burden of vascular risk factors and comorbidities, blacks had significantly smaller left atrial diameters (mean difference, -0.10 cm; 95% CI, -0.04 to -0.17 cm). This difference persisted after adjustment for demographics, comorbidities, and body mass index (adjusted mean difference, -0.15 cm; 95% CI, -0.09 to -0.21 cm). Conclusions: In a population-based sample, we found that black patients with ischemic stroke had smaller left atrial size than white patients. Our results suggest that the paradox of greater stroke risk but lower AF risk in blacks compared with whites at least partly stems from a lesser degree of AF substrate in blacks.

Abstract TMP51: Pre-existing Atherosclerotic Risk Factors Increase Short-Term Ischemic Stroke Risk After Traumatic Head or Neck Injury

Introduction: Trauma is an established risk factor for ischemic stroke in the young. We speculated that atherosclerotic disease, increasingly prevalent at younger ages, could predispose to dissection or artery-to-artery embolism after trauma. In a cohort of young patients with head or neck trauma, we aimed to measure the association of atherosclerotic risk factors with short-term ischemic stroke risk. Methods: Nested case-control study of patients (birth to 50 years old) with head or neck trauma while enrolled in a population-based Northern California integrated healthcare delivery system, 1997-2011. Within the trauma cohort, we identified ischemic stroke ICD-9 codes within 4 weeks of head or neck injury. A panel of neurologists reviewed charts to confirm cases of arterial ischemic stroke and determine whether stroke was attributed to trauma. Three controls per case were randomly identified from the trauma cohort. Atherosclerotic risk factors were abstracted from charts only when documented prior to trauma. We compared cases to controls using logistic regression. Results: The trauma cohort included 120,494 emergency encounters or hospital admissions for head or neck injury over the 15-year study period. We confirmed 45 cases of arterial ischemic stroke attributed to trauma and randomly identified 135 stroke-free controls for comparison. Stroke risk was not associated with sex or race/ethnicity, but was age-related: for each decade older, stroke risk increased 70% (OR 1.7, 95% CI 1.4-2.2). Other pre-existing atherosclerotic risk factors also increased stroke risk. Cases were more likely than controls to have atherosclerotic risk factors documented in the medical record prior to trauma, including hypertension, diabetes mellitus, elevated cholesterol, and history of smoking (Table). Conclusions: Pre-existing atherosclerotic risk factors appear to increase short-term ischemic stroke risk after head or neck injury.

Abstract WP266: Association between Left Ventricular Ejection Fraction, Wall Motion Abnormalities and Embolic Strokes of Undetermined Source

Introduction: Severely reduced left ventricular (LV) ejection fraction (EF) is an established risk factor for ischemic stroke. It is uncertain whether a modest reduction in LVEF (between 35%-50%) or the presence of LV wall motion abnormality may be a potential explanation for some embolic strokes of undetermined source (ESUS). Methods: We performed a retrospective cross-sectional study of patients with acute ischemic stroke enrolled in the Cornell AcutE Stroke Academic Registry (CAESAR) from 2011 through 2016. For this analysis, we restricted the study cohort to patients with ESUS and, as controls, those with small- and large-artery ischemic strokes who received an echocardiogram within 14 days of stroke. A single investigator blinded to stroke subtype recorded LVEF and the presence of LV wall motion abnormalities from reports of echocardiograms performed for routine evaluation of stroke. These variables are uniformly reported in echocardiogram reports at our institution. Multiple logistic regression models adjusted for demographics and stroke risk factors were used to evaluate whether LVEF or LV wall motion abnormality was associated with ESUS. Results: We identified 885 patients with ESUS or small- or large-artery strokes. The mean LVEF was 62.4% (+/- 7.9%). There was no difference in LVEF in patients with ESUS (62.4%; 95% CI, 61.8-63.1%) as compared to patients with small- or large-artery strokes (62.3%; 95% CI, 61.4-63.2%; P =0.8). After adjustment for demographics and stroke risk factors, LVEF was not associated with ESUS (OR per 10% incremental increase in LVEF, 0.9; 95% CI, 0.8-1.0; P = 0.4). LV wall motion abnormality was present in 5.9% of patients, and in multivariable analysis, its presence was not associated with ESUS (OR 0.9; 95% CI, 0.5-1.6; P = 0.7). Conclusions: We found that neither a modest reduction in LVEF nor the presence of LV wall motion abnormality was associated with ESUS.

Television Viewing Time and Stroke Risk: Australian Diabetes Obesity and Lifestyle Study (1999-2012)

Introduction: Having a low level of physical activity is an established risk factor for stroke, but little is known about the importance of common sedentary behavior—television viewing—to stroke risk. Methods: We conducted a retrospective analysis of data that were collected as part of the longitudinal Australian Diabetes, Obesity, and Lifestyle study. Stroke events reported during the study (between baseline assessment in 1999-2000 and April 2011) were confirmed using adjudication based on medical records. Baseline data on minutes per week spent watching television were used as the exposure variable. Other variables were collected in assessments at wave 2 (2004-05) and wave 3 (2011-2012). Univariable and multivariable logistic regression analyses were performed. Results: Among the full Australian Diabetes, Obesity, and Lifestyle study population (n = 11,247), there were 153 participants with confirmed stroke during the study period, and 9207 participants with no stroke in this period. Participants who went on to have their first stroke during the study had significantly higher levels of TV viewing time at baseline than those who did not have a stroke (P = .001). This association was not present (P = .83), however, when age and sex were included in the regression model. Conclusion: In the Australian Diabetes, Obesity, and Lifestyle study dataset, there was no evidence that more TV viewing is independently associated with risk of stroke, although analyses may have been underpowered.

Prevalence of diabetes and its effects on strokeoutcomes: A meta-analysis and literature review.

Aims/IntroductionDiabetes mellitus is an established risk factor for stroke and maybe associated with poorer outcomes after stroke. The aims of the present literature review were to determine: (i) the prevalence of diabetes in acute stroke patients through a meta‐analysis; (ii) the association between diabetes and outcomes after ischemic and hemorrhagic stroke; and (iii) to review the value of glycated hemoglobin and admission glucose‐based tests in predicting stroke outcomes.Materials and MethodsOvid MEDLINE and EMBASE searches were carried out to find studies relating to diabetes and inpatient stroke populations published between January 2004 and April 2017. A meta‐analysis of the prevalence of diabetes from included studies was undertaken. A narrative review on the associations of diabetes and different diagnostic methods on stroke outcomes was carried out.ResultsA total of 66 eligible articles met inclusion criteria. A meta‐analysis of 39 studies (n = 359,783) estimated the prevalence of diabetes to be 28% (95% confidence interval 26–31). The rate was higher in ischemic (33%, 95% confidence interval 28–38) compared with hemorrhagic stroke (26%, 95% confidence interval 19–33) inpatients. Most, but not all, studies found that acute hyperglycemia and diabetes were associated with poorer outcomes after ischemic or hemorrhagic strokes: including higher mortality, poorer neurological and functional outcomes, longer hospital stay, higher readmission rates, and stroke recurrence. Diagnostic methods for establishing diagnosis were heterogeneous between the reviewed studies.ConclusionsApproximately one‐third of all stroke patients have diabetes. Uniform methods to screen for diabetes after stroke are required to identify individuals with diabetes to design interventions aimed at reducing poor outcomes in this high‐risk population.