Racial and ethnic differences in restarting antiplatelet therapy in patients with primary intracranial hemorrhage: a systematic review and meta-analysis.

BACKGROUND: There has long been clinical disagreement over the resumption of antiplatelet therapy in patients with primary intracranial hemorrhage (ICH). This meta-analysis aimed to systematically evaluate the efficacy and safety of restarting antiplatelet therapy after ICH among different races and ethnicities. METHODS: All relevant medical studies involving adults with antiplatelet-associated ICH published in PubMed, The Cochrane Library and Chinese National Knowledge Infrastructure from inception to March 2024 were sourced. Outcome measures were thromboembolic events (stroke and myocardial infarction) and recurrence of ICH. After assessing study heterogeneity and publication bias, we performed a meta-analysis using random-effects model to assess the strength of association between resumption of antiplatelet therapy and our outcomes.The review was not registered and the review protocol was not prepared. RESULTS: Thirty-five studies were included, with 9758 ICH patients. Subgroup analysis revealed that restarting antiplatelet therapy was associated with a significantly higher risk of recurrence or aggravation of cerebral hemorrhage in Asians[OR = 1.48, 95% CI (1.13-1.94), P = 0.004]; in Caucasians, on the contrary, reinitiation of antiplatelet therapy was not associated with a significantly higher risk of recurrence or aggravation of cerebral hemorrhage [OR = 0.85, 95% CI (0.67-1.06), P = 0.149]. Reinitiation of antiplatelet therapy was associated with a significantly lower risk of cerebral infarction [OR = 0.61, 95% CI (0.39-0.96), P = 0.033]. Restarting antiplatelet therapy after cerebral hemorrhage was not associated with a higher incidence rate of mortality [OR = 0.79, 95% CI (0.57, 1.08), P = 0.138], myocardial infarction [OR = 2.40, 95%CI (0.53,10.79), P = 0.253], hemiparesis [OR = 0.38, 95%CI (0.03,4.81), P = 0.451], neurological deficit [OR = 0.86,95%CI(0.32,2.33),P = 0.766]. CONCLUSION: Reinstitution of antiplatelet therapy after ICH was associated with a lower risk of thromboembolic complications.Resumption of antiplatelet therapy was not associated with a higher incidence of cerebral hemorrhage in Caucasians, but may be associated with a higher risk of cerebral hemorrhage recurrence in Asian populations.

Disparities between Asian and Non-Asian Thrombolyzed Acute Ischemic Stroke Patients in the Enhanced Control of Hypertension and Thrombolysis Stroke Trial.

BACKGROUND AND PURPOSE: As outcomes for acute ischemic stroke (AIS) vary according to clinical profile and management approaches, we aimed to determine disparities in clinical outcomes between Asian and non-Asian participants of the international, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED). METHODS: ENCHANTED was a multicenter, prospective, partial-factorial, randomized, open trial of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) alteplase, and intensive (target systolic blood pressure [SBP] 130-140 mm Hg) or guideline-recommended (<180 mm Hg) BP management, in thrombolysis-eligible AIS patients. Logistic regression models were used to examine the associations with outcomes of death or disability (modified Rankin scale [mRS] scores 2-6), major disability (mRS 3-5), death, and intracranial hemorrhage (ICH), with adjustment prognostic factors, alteplase dose, and mean SBP over 1-24 h. RESULTS: Among 4,551 thrombolyzed AIS patients (mean age 66.7 years, 37.8% female), there were 65.4% Asians who were younger, fewer female, and with less atrial fibrillation, hypercholesterolemia, premorbid symptoms, and concomitant antihypertensive, antithrombotic and statin treatment, and more prior stroke, compared to non-Asians. Frequencies of hypertension, coronary artery disease, and diabetes mellitus were comparable between groups. Asian patients were less likely to be admitted to an acute stroke unit and receive early mobilization by a therapist or rehabilitation but more likely to receive intensive care. There were no significant differences between Asians and non-Asians in functional outcome (defined by mRS scores 2-6 or 3-5; adjusted odds ratio [OR] 1.00, 95% confidence interval [CI] 0.85-1.19 [p = 0.958] and OR 0.95, 95% CI 0.80-1.13 [p = 0.572], respectively), or death (OR 1.25, 95% CI 0.95-1.65; p = 0.116), despite Asians having greater odds of ICH (OR 1.51, 95% CI 1.23-1.86; p = 0.0001) and neurological deterioration within 24 h (OR 1.58, 95% CI 1.18-2.12; p = 0.002). CONCLUSIONS: Within the context of an international clinical trial of thrombolyzed AIS patients, demography, risk factors, management, and odds of early neurological deterioration and ICH, all differ between Asian and non-Asian participants. However, patterns of functional recovery are similar between these major regional groups.

Non-vitamin K antagonist oral anticoagulants in very elderly east Asians with atrial fibrillation: A nationwide population-based study.

BACKGROUND: The evidence of effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) among elderly East Asians is limited. OBJECTIVES: We aimed to describe the effectiveness and safety outcomes associated with NOACs and warfarin among elderly Koreans aged ≥80 years. METHODS: Using the Korean Health Insurance Review and Assessment service database, patients with atrial fibrillation (AF) who were naïve to index oral anticoagulant between 2015 and 2017 were included in this study (20,573 for NOACs and 4086 for warfarin). Two treatment groups were balanced using the inverse probability of treatment weighting (IPTW) method. The clinical outcomes including ischemic stroke, major bleeding including intracranial hemorrhage (ICH) and gastrointestinal bleeding (GIB), and a composite of these outcomes were evaluated. RESULTS: Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio 0.74 [95% confidence interval 0.62-0.89]), and composite outcome (0.78 [0.69-0.90]). NOACs showed nonsignificant trends towards to lower risks of GIB and major bleeding than warfarin. The risk of ICH of NOAC group was comparable with the warfarin group. Among NOACs, apixaban and edoxaban showed better composite outcomes than warfarin. Among the clinical outcomes, only ischemic stroke and the composite outcome had a significant interaction with age subgroups (80-89 years and ≥90 years, P-for-interaction = .097 and .040, respectively). CONCLUSION: NOACs were associated with lower risks of ischemic stroke and the composite outcome (ischemic stroke and major bleeding) compared to warfarin in elderly East Asians. Physicians should be more confident in prescribing NOACs to elderly East Asians with AF.

Clinical outcomes, edoxaban concentration, and anti-factor Xa activity of Asian patients with atrial fibrillation compared with non-Asians in the ENGAGE AF-TIMI 48 trial.

AIMS: Prior studies suggested that the risks of ischaemic stroke and bleeding in patients of Asian race with atrial fibrillation (AF) may be higher than that of non-Asians. In the analysis of ENGAGE AF-TIMI 48 trial, we compared clinical outcomes, edoxaban concentration, and anti-factor Xa (anti-FXa) activity, between Asian and non-Asian races. METHODS AND RESULTS: There were 2909 patients of Asian race and 18 195 non-Asian race in the ENGAGE AF-TIMI 48 trial. The risks of thromboembolism and bleeding events were compared for Asians and non-Asians treated with warfarin. The trough levels of edoxaban concentration and anti-FXa activity were also compared and correlated with the efficacy and safety of edoxaban vs. warfarin. Compared to non-Asian patients, the Asian population was on average 2 years younger and 20 kg lighter. In the warfarin group, the adjusted risk of ischaemic stroke did not differ significantly for patients of Asian and non-Asian race [adjusted hazard ratio (aHR) = 1.12, P = 0.56). Asians treated with warfarin had a higher-adjusted risk of intracranial haemorrhage (ICH: aHR 1.71, P = 0.03) compared with non-Asians. The trough edoxaban concentration and anti-FXa activity were 20-25% lower for Asians compared with non-Asians. Compared to warfarin, higher dose edoxaban significantly reduced ICH while preserving the efficacy of stroke prevention in both Asians and non-Asians. Two of three net clinical outcomes appeared to be more favourably reduced with edoxaban in Asians compared with non-Asians (Pint = 0.063 for primary, 0.037 for secondary, and 0.032 for third net clinical outcomes, respectively). CONCLUSION: Compared to warfarin, higher dose edoxaban preserved the efficacy for stroke prevention and was associated with a favourable safety profile for Asians, which may be due to the lower trough edoxaban concentration and anti-FXa activity achieved in patients of Asian race.

Predictors and prognoses of new onset post-stroke anxiety at one year in black Africans.

BACKGROUND: There is relatively limited information on the risk factors and outcome of new onset Poststroke Anxiety (PSA) in Low- and Middle-Income Countries. We estimated incidence, cumulative incidence, risk factors and outcome of new onset anxiety in the first year of stroke among African stroke survivors. METHODS: We analyzed the dataset of a completed clinical trial comprising patients enrolled to test an intervention designed to improve one-year blood pressure control among recent (≤ one month) stroke survivors in Nigeria. Anxiety was measured using the Hospital Anxiety and Depression Scale. Outcomes were assessed using the modified Rankin Scale (mRS), Community screening instrument for dementia (CSID) and Health Related Quality of Life in Stroke Patients (HRQOLISP-26). RESULTS: Among 322 stroke survivors who were free of anxiety at baseline, we found a one-year cumulative incidence of 34% (95% CI = 28.6-39.3). Rates were 36.2% (95% CI =29.6-42.7) for men and 29.2% (95% CI =19.9-38.3) for women. In multivariate Cox regression analyses, haemorrhagic stroke type was associated with higher risk of new onset PSA (Hazard Ratio=1.52, 95% CI =1.01-2.29). New onset PSA was independently associated with cognitive [(mean difference (MD) in CSID scores=1.1, 95% C.I=0.2, 1.9)] and motor decline (MD in mRS scores= -0.2, 95% C.I= -0.4, -0.02), as well as poorer quality of life overtime (MD in total HRQOLISP-26 scores=3.6, 95% C.I=1.0, 6.2). CONCLUSION: One in 3 stroke survivors in Nigeria had PSA at one year. Clinicians in SSA should pay special attention to survivors of haemorrhagic stroke as they are at higher risk of incident anxiety and therefore its consequences.

Rates of Intracranial Hemorrhage in Mild Head Trauma Patients Presenting to Emergency Department and Their Management: A Comparison of Direct Oral Anticoagulant Drugs with Vitamin K Antagonists.

Background and objectives: Anticoagulants are thought to increase the risks of traumatic intracranial injury and poor clinical outcomes after blunt head trauma. The safety of using direct oral anticoagulants (DOACs) compared to vitamin K antagonists (VKAs) after intracranial hemorrhage (ICH) is unclear. This study aims to compare the incidence of post-traumatic ICH following mild head injury (MHI) and to assess the need for surgery, mortality rates, emergency department (ED) revisit rates, and the volume of ICH. Materials and Methods: This is a retrospective, single-center observational study on all patients admitted to our emergency department for mild head trauma from 1 January 2016, to 31 December 2018. We enrolled 234 anticoagulated patients, of which 156 were on VKAs and 78 on DOACs. Patients underwent computed tomography (CT) scans on arrival (T0) and after 24 h (T24). The control group consisted of patients not taking anticoagulants, had no clotting disorders, and who reported an MHI in the same period. About 54% in the control group had CTs performed. Results: The anticoagulated groups were comparable in baseline parameters. Patients on VKA developed ICH more frequently than patients on DOACs and the control group at 17%, 5.13%, and 7.5%, respectively. No significant difference between the two groups was noted in terms of surgery, intrahospital mortality rates, ED revisit rates, and the volume of ICH. Conclusions: Patients with mild head trauma on DOAC therapy had a similar prevalence of ICH to that of the control group. Meanwhile, patients on VKA therapy had about twice the ICH prevalence than that on the control group or patients on DOAC, which remained after correcting for age. No significant difference in the need for surgery was determined; however, this result must take into account the very small number of patients needing surgery.

The Risk of Hemorrhagic Transformation After Thrombolysis for Acute Ischemic Stroke in Chinese Versus North Americans: A Comparative Study.

BACKGROUND: There is a widespread belief that Asians are more susceptible to hemorrhagic transformation (HT) after receiving recombinant tissue-type plasminogen activator (rt-PA) for acute ischemic stroke (AIS). However, this has not been examined in clinical practice. This study aims to compare the incidence of symptomatic hemorrhagic transformation (SHT) among thrombolysis-treated AIS patients in China and in the United States. METHODS: We compared 212 consecutive patients receiving thrombolysis within 4.5 hours of onset ± endovascular therapy from an American (n = 86) and a Chinese Stroke Center (n = 126). SHT was defined using various definitions based on the National Institute for Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator (NINDS rt-PA) trials, European-Australian Cooperative Acute Stroke Study 2 (ECASS2), and a modified version of Safe Implementation of Thrombolysis in Stroke-Monitoring Study (mSITS-MOST) study criteria. We used Firth logistic regression to adjust for confounding variables and to identify potential predictors. RESULTS: American patients were older, and had higher prevalence of diabetes, hypertension, cardiac disease, and prestroke use of antithrombotics. They also had higher baseline serum glucose, shorter onset-to-treatment time, and fewer endovascular treatments. The rates of SHT were higher in the American cohort compared to the Chinese cohort: 18.6% versus 14.3% based on NINDS definition of SHT; 15.1% versus 12.7% based on ECASS2; and 11.6% versus 7.2% based on mSITS-MOST. However, none of these differences were significant (unadjusted and adjusted P values > .05). Fatal HT was comparable in Americans versus Chinese (8.1% versus 8.7%). Serum glucose emerged as an independent predictor of SHT (P = .024). CONCLUSIONS: In our cohorts, the rate of SHT after thrombolysis is equivalent between Chinese and North American stroke patients.

Fine Particulate Matter (PM2.5) and the Risk of Stroke in the REGARDS Cohort.

BACKGROUND: Ambient particulate matter has been shown to be associated with declining human health, although the association between fine particulate matter (PM2.5) and stroke is uncertain. METHODS: We utilized satellite-derived measures of PM2.5 to examine the association between exposure and stroke in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. We used a time-stratified case-crossover design, with exposure lags of 1 day, 2 days, and 3 days. We examined all strokes, as well as ischemic and hemorrhagic strokes separately. RESULTS: Among 30,239 participants in the REGARDS study, 746 incident events were observed: 72 hemorrhagic, 617 ischemic, and 57 of unknown type. Participants exposed to higher levels of PM2.5 more often resided in urban areas compared to rural, and in the southeastern United States. After adjustment for temperature and relative humidity, no association was observed between PM2.5 exposure and stroke, regardless of the lag (1-day lag OR = .99, 95% CI: .83-1.19; 2-day lag OR = .95, 95% CI: .80-1.14; 3-day lag OR = .95, 95% CI = .79-1.13). Similar results were observed for the stroke subtypes. CONCLUSIONS: In this large cohort of African-Americans and whites, no association was observed between PM2.5 and stroke. The ability to examine this association with a large number of outcomes and by stroke subtype helps fill a gap in the literature examining the association between PM2.5 and stroke.

Racial differences in the association of insulin resistance with stroke risk: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

BACKGROUND AND PURPOSE: Insulin resistance is associated with increased stroke risk, but the effect has not been adequately examined separately in white and black populations. METHODS: The association of baseline insulin resistance with risk of cerebral infarction (CI) and intracerebral hemorrhage (ICH) was assessed in 12 366 white and 6782 black participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, recruited between 2003 and 2007 and followed for an average of 5.7 years. Insulin resistance was measured with the homeostasis model assessment-insulin resistance. RESULTS: There were 364 incident CI and 41 incident ICH events. The risk for CI increased with the log of insulin resistance in whites (hazards ratio [HR]ln(IR)=1.17; 95% confidence interval [CI], 1.00-1.38) but was largely attenuated by adjustment for stroke risk factors (HRln(IR)=1.05; 95% CI, 0.88-1.26). There was no association in blacks (HRln(IR)=1.01; 95% CI, 0.81-1.25). After adjustment for demographic factors and risk factors, there was a significant difference by race in the association of insulin resistance with risk of ICH (P=0.07), with a decrease in the risk of ICH in whites (HRln(IR)=0.61; 95% CI, 0.35-1.04) but a nonsignificant increase in blacks (HRln(IR)=1.20; 95% CI, 0.60-2.39). CONCLUSIONS: These data support the growing evidence that insulin resistance may play a more important role in stroke risk among white than black individuals and suggest a potentially discordant relationship of insulin resistance on CI and ICH among whites.

Race/Ethnic differences in the risk of hemorrhagic complications among patients with ischemic stroke receiving thrombolytic therapy.

BACKGROUND AND PURPOSE: Race/ethnic-related differences in safety of intravenous thrombolytic therapy have been shown in patients with myocardial infarction, but not studied in ischemic stroke. METHODS: Using data from the Get With The Guidelines (GWTG)-Stroke program (n=54 334), we evaluated differences in risk-adjusted bleeding rates (any, symptomatic intracerebral hemorrhage [sICH], serious life-threatening [excluding sICH], or other) and mortality in white (n=40 411), black (n=8243), Hispanic (n=4257), and Asian (n=1523) patients receiving intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke. RESULTS: Compared with white patients, overall adjusted hemorrhagic complications after tPA were higher in black (odds ratio, 1.14, 95% confidence interval, 1.04-1.28) and Asian (odds ratio, 1.36, 95% confidence interval, 1.14-1.61) patients. Overall adjusted bleeding complications in Hispanics were similar to those of whites. Increased risk of overall bleeding in Asians was related to higher risk of adjusted sICH (odds ratio, 1.47, 95% confidence interval, 1.19-1.82), whereas in blacks, it was related to higher risk of other bleeding. No significant race-related difference was noted in risk of serious or life-threatening bleeding or in overall mortality or death in patients with sICH or any hemorrhagic complications. CONCLUSIONS: In patients with stroke receiving tPA, hemorrhagic complications were slightly higher in blacks and Asians, but not in Hispanics compared with whites. Asians also faced significantly higher risk for sICH relative to other race/ethnic groups. Future studies are needed to evaluate whether reduction in tPA dose similar to that used in many Asian countries could improve the safety of tPA therapy in Asians in the United States with acute ischemic strokes while maintaining efficacy.

A blood-based biomarker panel to detect acute stroke.

BACKGROUND: The aim of this study was to develop an adjunctive, peripheral biomarker test to differentiate ischemic strokes, intracranial hemorrhages (ICHs), and stroke mimics in the acute setting. METHODS: Serum samples were collected from 167 patients who presented with an acute neurologic deficit within 24 hours of symptom onset. Patients were adjudicated to ischemic stroke, ICH, and mimic pathology groups based on clinical and radiographic findings. Samples were tested for levels of 262 potential markers. A multivariate Cox proportional hazards regression model of 5 biomarkers was built by stepwise selection and validated by bootstrapping. Its discriminative capacity was quantified by C index and net reclassification improvement (NRI). RESULTS: The final model consisted of eotaxin, epidermal growth factor receptor, S100A12, metalloproteinase inhibitor-4, and prolactin. It demonstrated a discriminative capacity for ischemic stroke versus mimic (C = .92), ischemic stroke and ICH versus mimic (C = .93), and ischemic stroke versus ICH (C = .82). The inclusion of biomarkers to a model consisting of age, race, and gender resulted in an NRI of 161% when detecting ischemic stroke versus mimic (P < .0001), an improvement of 171% when detecting ischemic strokes plus ICH versus mimic (P < .0001), and an improvement of 56% when detecting ischemic strokes versus ICH (P = .1419). CONCLUSIONS: These results suggest that information obtained from a 5-biomarker panel may add valuable information in the early evaluation and management of patients with stroke-like symptoms.

Net clinical benefit of rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation: a subgroup analysis of J-ROCKET AF.

BACKGROUND: The risk factors that have been identified for bleeding events with rivaroxaban are predominantly the same as those predicting thromboembolic ones in patients with atrial fibrillation (AF). Our aim was to determine the net clinical benefit (NCB) from the results of the J-ROCKET AF trial, in which rivaroxaban was compared with warfarin in Japanese patients with AF. METHODS: Two strategies were adopted to quantify the NCB. First, the NCB was calculated as the number of ischemic strokes avoided with anticoagulation minus the number of excess intracranial hemorrhage (ICH) with a weight of 1.5. Second, the composite end point of major bleeding events and secondary efficacy end points (stroke, noncentral nervous system systemic embolism, myocardial infarction and death) to ascertain the NCB were established. Subgroup analysis by CHADS2 score or creatinine clearance was also performed. RESULTS: The adjusted NCB, which was given a weight of 1.5 for ICH, was nominally significant in favor of rivaroxaban therapy (difference in incidence rate -2.13; 95% confidence interval [CI]: -.26 to -3.99). Furthermore, the event rate of the composite end point tended to be lower in patients treated with rivaroxaban than in those treated with warfarin (rivaroxaban: 4.97% per year, warfarin: 6.11% per year; difference in incidence rate: -1.14; 95% CI: -3.40 to 1.12). The event rate of the composite end point tended to be consistently low in patients treated with rivaroxaban in the subanalysis by CHADS2 score and renal function. CONCLUSION: Analysis of the NCB supports that rivaroxaban therapy provides clinical benefit for Japanese patients with AF.

The iScore predicts clinical response to tissue plasminogen activator in Korean stroke patients.

BACKGROUND: Despite substantial differences in clinical features between Asian and Western stroke patients, there are no published prognostic tools validated in an Asiatic population for thrombolytic therapy. We assessed the ability of the iScore to predict the clinical response after intravenous thrombolysis with tissue plasminogen activator (tPA) in a Korean stroke population. METHODS: We applied the iScore to eligible participants in the nationwide multicenter stroke registry in Korea. Main outcome measures were poor functional outcome defined as having a modified Rankin Scale score 3-6 and death at 3 months. Symptomatic intracranial hemorrhage (sICH) was evaluated as a safety outcome. C statistic was calculated to assess performance of iScore. RESULTS: Among 4760 patients with an acute ischemic stroke, 622 (13.1%) received tPA, 548 patients had complete information for the analysis. C statistics for poor functional outcome and death at 3 months were .813 (95% confidence interval [CI]: .778-.848) and .820 (95% CI: .769-.872), respectively. Overall, there was a high correlation between observed and expected outcome for poor functional outcome (Pearson correlation coefficient, r = .982) and for death at 3 months (r = .950) at the risk score level. An iScore of 180 or more was associated with a more than 2 times risk of poor functional outcome and about 6 times risk of death at 3 months. There was an interaction between the iScore and tPA for a poor functional outcome (P value for the interaction < .001). We found a gradient effect in the incident risk of sICH with the iScore. CONCLUSION: The iScore reliably predicts stroke outcomes after tPA in Asiatic population.

Dietary patterns in stroke patients in Northwest India.

OBJECTIVES: Little is known about the dietary patterns among stroke patients in India. We explored the dietary patterns in stroke patients and attempted to correlate the dietary patterns with stroke characteristics. METHODS: This hospital-based study was carried out in a tertiary referral centre in Northwest India from March 2008 to September 2009. All first ever stroke (ischaemic and hemorrhagic) patients were interviewed by the dietician using an oral diet questionnaire. The demographic information and risk factors were noted and outcome was assessed after 30 days using modified Rankin scale (≤2 = good outcome). RESULTS: A total of 210 stroke patients were enrolled. The mean age was 60 ± 14 years and 126 (60%) patients were men. Hypertension (167 (79.5%)) was the major risk factor. All patients consumed cereals and beverages. Consumption of other food items in the diet were as follows: milk and milk products (203 (96.7%)), saturated fats (butter, butter oil, cream) (133 (63.3%)), bakery items (139 (66.2%)), fried snacks (116 (55.2%)), fruits (96 (45.7%)), and juices (20 (9.5%)). Large proportion of the patients (112 (53.6%)) consumed more food calories than recommended. Use of fried snacks was significant in patients who consumed alcohol (P = 0.03) and patients who had diabetes mellitus were more likely to use saturated fats (P = 0.01). DISCUSSION: Majority of the patients consumed milk and milk products. Fruits and juices were consumed by a small proportion of patients. Our results provide opportunities for stroke prevention by diet modification.

Thrombolysis and outcome of young stroke patients over the last decade: insights from the Nationwide Inpatient Sample.

BACKGROUND: A recent study found a trend toward increasing hospitalizations for acute ischemic stroke (AIS) among young adults, raising concern for this subgroup. In the present study, we evaluated trends of use of thrombolysis and outcome among young adults (19-44 years of age) with AIS using a nationally representative administrative database. METHODS: Discharge data were obtained from Nationwide Inpatient Sample between 2001 and 2009. Hospitalizations with a discharge diagnosis of AIS for patients 19 to 44 years of age were included. Use of thrombolysis was determined within this subset. The Cochran-Armitage test was used for trend analysis. RESULTS: Thrombolysis in young patients with AIS increased from 354 (1.84%) in 2001 to 1,237 (4.97%) in 2009 (P < .0001). The highest increase was noted at urban teaching hospitals. There was a progressive decrease in mortality in young AIS patients, from 6.81% in 2001 to 5.43% in 2009 (trend P = .027) and significant increase in discharges to rehabilitation (3.42% in 2002 to 12.7% in 2009 [trend P < .0001]). Discharge to other facilities decreased significantly (29.1% in 2001 to 17.8% in 2009 [trend P < .0001]). The rate of intracranial hemorrhage (2.70% in 2001; 2.69% in 2009) did not show any significant change despite the increase in the use of thrombolysis (trend P = .39). CONCLUSIONS: The rate of thrombolysis among young patients with AIS increased significantly between 2001 and 2009. A decrease in deaths with increased rehabilitation placements of young patients with AIS was noted over the last decade, suggesting improving outcomes. The lower rate of use of thrombolysis in rural hospitals may be improved with the widespread use of telestroke.

Left ventricular hypertrophy: a comparison among Kurdish patients with first-ever ischemic versus first-ever hemorrhagic stroke.

BACKGROUND AND AIM: Left ventricular hypertrophy (LVH) has been proposed to be associated with an increased risk of stroke. We compared the prevalence of LVH among patients with first-ever ischemic versus first-ever hemorrhagic strokes. MATERIAL AND METHODS: This observational study, which was conducted at the Sulaimaniya general teaching hospital from November 2009 to March 2012, involved 100 consecutive patients with their first-ever stroke. Fifty patients had ischemic stroke while the rest (n = 50) developed hemorrhagic stroke. The presence of LVH was detected using transthoracic echocardiography and a comparison with respect to its prevalence between the 2 aforementioned groups was made. RESULTS: The mean age of patients in the hemorrhagic group was 61.7 +/- SD 11.2 years while in the ischemic group it was 63.9 +/- SD 6.1 years. Out of 100 patients, 66 (66%) patients were males (31 in the hemorrhagic group and 35 in the ischemic group) while the rest (n = 34; 34%) were females (19 in the hemorrhagic group and 15 in the ischemic one). Ninety one (91%) patients were hypertensive (47 in the hemorrhagic group and 34 in the ischemic group). Fifty three (53%) out of 100 patients demonstrated LVH (31 in the hemorrhagic group and 22 in the ischemic group). A head-to-head comparison between the two groups with respect to gender demonstrated no statistically significant difference in terms of the presence of LVH among patients with hemorrhagic versus ischemic strokes; males (P value < 0.26; 95% CI 3.4-39.3); females (P value < 0.43; 95% CI 16.7-43.8). However, a univariate analysis after correction for age and gender revealed a statistically significant difference between these groups (P-value < 0.001; 95% CI 2.7-46.2). CONCLUSION: LVH was more common in Kurdish patients with first-ever hemorrhagic stroke than in those who had sustained their first-ever ischemic stroke. Further analytic studies are required to clarify the prevalence of LVH in patients with ischemic stroke.

Angiopoietin-like 4 (ANGPTL4) gene polymorphisms and risk of brain arteriovenous malformations.

BACKGROUND: Brain arteriovenous malformations (BAVM) are high-flow vascular lesions prone to intracranial hemorrhage (ICH). Abnormal angiogenesis is a key characteristic of BAVM tissue. Angiopoietin-like 4 (ANGPTL4), a secreted glycoprotein, is thought to be involved in angiogenesis and required for proper postnatal blood vessel partitioning. We investigated whether common single nucleotide polymorphisms (SNPs) in ANGPTL4 were associated with risk of BAVM or ICH. METHODS AND RESULTS: We conducted a case-control study of 216 Caucasian BAVM cases and 246 healthy controls, and a secondary case-only analysis, comparing 83 ruptured (ICH) with 133 unruptured BAVM cases at presentation. Four tagSNPs in ANGPTL4 captured variation over a 10-kb region (rs2278236, rs1044250, rs11672433, and rs1808536) and were tested for association with BAVM or ICH. The minor allele (A) of rs11672433 (exon 6, Pro389Pro) was associated with an increased risk of BAVM (p = 0.006), which persisted after adjusting for multiple comparisons (p = 0.03). After adjustments for age and sex, carriers of the minor allele (A) remained at higher risk for BAVM compared to noncarriers (odds ratio, OR = 1.56; 95% confidence interval, CI = 1.01-2.41; p = 0.046) and risk of BAVM was increased with increasing copy of the minor A allele (OR = 1.49, 95% CI = 1.03-2.15; p(trend) = 0.03). Five common haplotypes (frequency >1%) were inferred; overall haplotype distribution differed between BAVM cases and controls (χ(2) = 12.2, d.f. = 4, p = 0.02). Neither SNPs (p > 0.05) nor haplotype distribution (χ(2) = 1.1, d.f. = 4, p = 0.89) were associated with risk of ICH among BAVM cases. CONCLUSION: A synonymous SNP in ANGPTL4 and haplotypes carrying it are associated with risk of BAVM but not with ICH presentation in BAVM cases.

Use of antiplatelets. A survey of secondary prevention of ischemic stroke with intracranial hemorrhage history in Chinese patients.

OBJECTIVE: To explore whether antiplatelet (AP) agent therapy increased intracranial hemorrhage (ICH) incidence and reduced ischemic stroke recurrence. METHODS: A single-center retrospective cohort study involving 256 cases from 336 Chinese in-patients who had ischemic stroke with ICH history in Beijing Chaoyang Hospital, Beijing, China between May 2005 and October 2009 was conducted. Subjects were divided into 2 groups (with AP and without AP), followed by stroke events for 12-38 months. Logistic regression analysis was used to evaluate the effects of AP on cerebral infarction and ICH recurrence. RESULTS: The AP agent did not increase ICH recurrence in the secondary prevention of ischemic stroke with ICH history (odds ratio [OR] 1.431, confidence interval [CI] 0.198-2.467, p=0.577). Hypertension and lobar hemorrhage were risk factors of ICH recurrence. However, there was no statistical difference between recurrence of lobar hemorrhage and AP use (x2=0.516, p=0.468). The AP agent significantly decreased the incidence of cerebral infarction (OR 0.424, CI 0.190-0.950, p=0.037). CONCLUSION: The AP agents may be beneficial to secondary prevention of ischemic stroke with ICH history, with no increased incidence of cerebral hemorrhage. It would be safer to maintain blood pressure in the normal range and to exclude lobar hemorrhage when AP is used.

Low-density lipoprotein cholesterol concentrations and death due to intraparenchymal hemorrhage: the Ibaraki Prefectural Health Study.

BACKGROUND: Few studies have examined the association between low levels of low-density lipoprotein (LDL) cholesterol and risk of intraparenchymal hemorrhage. METHODS AND RESULTS: A total of 30 802 men and 60 417 women, 40 to 79 years of age with no history of stroke or coronary heart disease, completed a baseline risk factor survey in 1993 under the auspices of the Ibaraki Prefectural Health Study. Systematic mortality surveillance was performed through 2003, and 264 intraparenchymal hemorrhage deaths were identified. LDL cholesterol levels were calculated with the Friedewald formula. Persons with LDL cholesterol > or =140 mg/dL had half the sex- and age-adjusted risk of death due to intraparenchymal hemorrhage of those with LDL cholesterol <80 mg/dL. After adjustment for cardiovascular risk factors, the multivariable hazard ratio compared with persons with LDL cholesterol <80 mg/dL was 0.65 (95% CI 0.44 to 0.96) for those with LDL cholesterol 80 to 99 mg/dL, 0.48 (0.32 to 0.71) for 100 to 119 mg/dL, 0.50 (0.33 to 0.75) for 120 to 139 mg/dL, and 0.45 (0.30 to 0.69) for >/=140 mg/dL. These inverse associations were not altered substantially after the exclusion of persons with hypertriglyceridemia, after analysis with a Cox proportional hazard model with time-dependent covariates, or in sensitivity analysis for the potential effect of competing risks. CONCLUSIONS: Low LDL cholesterol levels are associated with elevated risk of death due to intraparenchymal hemorrhage.

Comparison of Clinical Care and In-Hospital Outcomes of Asian American and White Patients With Acute Ischemic Stroke.

Importance: Although overall stroke incidence and mortality in the United States is improving, little is known about the characteristics and clinical outcomes of acute ischemic stroke in Asian American individuals. Objective: To compare the characteristics, care, and outcomes of Asian American and white patients with acute ischemic stroke. Design, Setting, Participants: Retrospective analysis of Asian American and white patients admitted with a primary diagnosis of acute ischemic stroke to hospitals participating in the Get With The Guidelines-Stroke (GWTG-Stroke) program between April 1, 2004, and July 31, 2016. The GWTG-Stroke database is a prospectively collected stroke quality improvement registry sponsored by the American Heart Association/American Stroke Association. Main Outcomes and Measures: Multivariable logistic regression models assessed the association of Asian American race/ethnicity, clinical outcomes, and quality measures. Results: The study population of 1 772 299 patients (mean [SD] age, 72.4 [14.2] years; 51.3% female) consisted of 64 337 Asian American patients (3.6%) and 1 707 962 white patients (96.4%) admitted to 2171 GWTG-Stroke hospitals with acute ischemic stroke. After adjustment for patient and hospital variables, Asian American patients were seen with greater stroke severity compared with white patients (National Institutes of Health Stroke Scale [NIHSS] score ≥16) (odds ratio [OR], 1.35; 95% CI, 1.30-1.40; P < .001), manifested higher in-hospital mortality (OR, 1.14; 95% CI, 1.09-1.19; P < .001), had longer length of stay (OR, 1.17; 95% CI, 1.14-1.20; P < .001), and were less likely to ambulate independently at discharge (OR, 0.84; 95% CI, 0.79-0.90; P < .001). Although Asian American patients had fewer intravenous tissue plasminogen activator (IV tPA) administrations than white patients (OR, 0.95; 95% CI, 0.91-0.98; P = .003), they had more symptomatic hemorrhage after tPA (OR, 1.36; 95% CI, 1.20-1.55; P < .001) and overall post-tPA complications (OR, 1.31; 95% CI, 1.18-1.46; P < .001). Asian American patients had better quality measure adherence overall than white patients, including rehabilitation (OR, 1.27; 95% CI, 1.18-1.36; P < .001), door to tPA within 60 minutes (OR, 1.14; 95% CI, 1.06-1.22; P < .001), and intensive statin therapy (OR, 1.14; 95% CI, 1.10-1.18; P < .001). After adjustment for stroke severity, Asian American patients had lower in-hospital mortality than white patients (OR, 0.95; 95% CI, 0.91-0.99; P = .008). Conclusions and Relevance: Asian American patients manifested more severe ischemic strokes, were less likely to receive IV tPA, and had worse functional outcomes than white patients. These findings warrant additional research toward improving clinical outcomes for Asian American patients with acute ischemic stroke.