Statin treatment in stroke patient with low-density lipoprotein cholesterol levels below 70 mg/dL.

BACKGROUND AND PURPOSE: The effectiveness of hyperlipidemia treatment in strokes secondary prevention has been established. However, whether pretreatment with statins could confer protective effects when a patient's baseline low-density lipoprotein cholesterol (LDL-C) level is <70 mg/dL remains uncertain. Additionally, the ability of statin treatment to reduce poststroke complications, mortality, and recurrence in this patient group is unclear. METHODS AND RESULTS: In this retrospective observational study, we enrolled patients who had experienced an ischemic stroke with LDL-C levels <70 mg/dL. We analyzed the association of statin use with baseline characteristics, stroke severity, in-hospital complications, mortality rates, stroke recurrence rate, and mortality rate. Patients who used and patients who did not use statins were similar in terms of age and sex. Patients using statins had higher rates of diabetes mellitus, hypertension, prior stroke, and coronary artery disease but a lower incidence of atrial fibrillation. Stroke severity was less pronounced in those using statins. We also evaluated the relationship between in-hospital statin use and complications. We noted that in-hospital statin use was associated with lower rates of infection, hemorrhagic transformation, gastrointestinal hemorrhage, and mortality, as well as higher rates of positive functional outcomes. The 1-year recurrence rate was similar in both groups. CONCLUSIONS: Statin use is associated with milder strokes and improved poststroke outcomes, even in patients with well-controlled LDL levels. Neurologists may consider prescribing statins for patients with ischemic stroke who do not overt hyperlipidemia. Further research into potential underlying mechanisms is warranted.

Effects of cancer on stroke recurrence and mortality: A single-center retrospective cohort study.

Background: Whether patients with stroke and cancer have specific characteristics remains controversial. In addition, research regarding the effects of individual cancer types on stroke outcomes remains scarce. This study investigated the mortality and stroke recurrence rates in patients with stroke and concomitant cancer and evaluated outcome predictors. Methods: This study retrospectively enrolled 2610 patients in the Taipei Veterans General Hospital Stroke Registry registered from January 2019 to December 2020. A total of 1868 patients were included after excluding those without acute ischemic stroke or hospitalization. The patients were then categorized into the following diagnostic groups: cancer-associated stroke (CAS), stroke and inactive cancer, and stroke without cancer. The discharge mortality rate, 1-year mortality rate, and 1-year stroke recurrence rate were compared. Multiple clinical characteristics and comorbidities-age, sex, stroke severity, coagulopathy, common vascular risk factors, and acute stroke treatment-were also assessed. Results: A total of 302 (16.2%) patients had concomitant cancer; 39 (2.1%) patients were classified as having CAS and 263 (14.1%) as having stroke with inactive cancer. The baseline characteristics, stroke severity, and type of acute reperfusion therapy were similar among the three groups. However, the stroke recurrence and mortality rates were much higher in the patients with CAS in both short-term and long-term follow-up. The 30-day and 1-year mortality rates for the CAS, inactive cancer, and no cancer groups were 17.9%, 12.5%, and 4.7%, (p < 0.001) and 51.3%, 33.8%, and 12.4%, (p < 0.001) respectively. Conclusion: Patients with stroke and active cancer had similar stroke severity. However, the 1-year mortality and stroke recurrence rates were higher in these patients than in patients with inactive cancer or the control group.

Monogenic Causes in Familial Stroke Across Intracerebral Hemorrhage and Ischemic Stroke Subtypes Identified by Whole-Exome Sequencing.

Whole exome sequencing (WES) has been used to detect rare causative variants in neurological diseases. However, the efficacy of WES in genetic diagnosis of clinically heterogeneous familial stroke remains inconclusive. We prospectively searched for disease-causing variants in unrelated probands with defined familial stroke by candidate gene/hotspot screening and/or WES, depending on stroke subtypes and neuroimaging features at a referral center. The clinical significance of each variant was determined according to the American College of Medical Genetics guidelines. Among 161 probands (mean age at onset 53.2 ± 13.7 years; male 63.4%), 33 participants (20.5%) had been identified with 19 pathogenic/likely pathogenic variants (PVs; WES applied 152/161 = 94.4%). Across subtypes, the highest hit rate (HR) was intracerebral hemorrhage (ICH, 7/18 = 38.9%), particularly with the etiological subtype of structural vasculopathy (4/4 = 100%, PVs in ENG, KRIT1, PKD1, RNF213); followed by ischemic small vessel disease (SVD, 15/48 = 31.3%; PVs in NOTCH3, HTRA1, HBB). In contrast, large artery atherosclerosis (LAA, 4/44 = 9.1%) and cardioembolism (0/11 = 0%) had the lowest HR. NOTCH3 was the most common causative gene (16/161 = 9.9%), presenting with multiple subtypes of SVD (n = 13), ICH (n = 2), or LAA (n = 1). Importantly, we disclosed two previously unreported PVs, KRIT1 p.E379* in a familial cerebral cavernous malformation, and F2 p.F382L in a familial cerebral venous sinus thrombosis. The contribution of monogenic etiologies was particularly high in familial ICH and SVD subtypes in our Taiwanese cohort. Utilizing subtype-guided hotspot screening and/or subsequent WES, we unraveled monogenic causes in 20.5% familial stroke probands, including 1.2% novel PVs. Genetic diagnosis may enable early diagnosis, management and lifestyle modification. Among 161 familial stroke probands, 33 (20.5%) had been identified pathogenic or likely pathogenic monogenic variants related to stroke. The positive hit rate among all subtypes was high in intracerebral hemorrhage (ICH) and ischemic small vessel disease (SVD). Notably, two previously unreported variants, KRIT1 p.E379* in a familial cerebral cavernous malformation and F2 p.F382L in familial cerebral venous sinus thrombosis, were disclosed. CVT cerebral venous thrombosis; HTN Hypertensive subtype; LAA large artery atherosclerosis; SV structural vasculopathy; U Undetermined.

Etiology and risk factors of intracranial hemorrhage and ischemic stroke in young adults.

BACKGROUND: Young stroke incidence has increased worldwide with lifestyle changes. Etiology and risk factors for both ischemic and hemorrhagic stroke in young Asians remain underexplored. METHODS: We retrospectively reviewed consecutive acute stroke patients aged 16-45 years admitted to the Taipei Veterans General Hospital between 2009 and 2019 to analyze etiologic subtypes, risk factors, and serial modified Rankin Scale scores for 1 year and compare the age groups of 16-30 and 31-45 years. RESULTS: Among 670 young Taiwanese patients (mean age at onset 37.5 ± 7.0 years; male 65.1%), there were 366 nontraumatic spontaneous hemorrhagic stroke (including 259 intracerebral hemorrhage [ICH] and 107 subarachnoid hemorrhage, SAH), 292 ischemic stroke and 12 cerebral venous thromboses. Notably, ICH was more prevalent in patients aged 16-30 than in those aged 31-45 (54.8% vs 36.8%). Specifically, structural vasculopathy (e.g., arteriovenous malformation, cavernoma) was the most common etiologic subtype in patients aged 16-30 (p < 0.001), whereas hypertensive ICH was the most common subtype in patients aged 31-45 (p < 0.001). On the other hand, the top ischemic subtype for both age groups was other determined diseases (e.g., arterial dissection, autoimmune diseases, moyamoya disease, etc.) rather than large artery atherosclerosis. Hyperlipidemia, diabetes, and cigarette smoking were more common risk factors for infarction than ICH. Familial stroke patients whose first- or second-degree relatives had a stroke by age 80 (n = 104, 15.5%) had more infarctions than those without a familial stroke history. In multivariate analyses, initial stroke severity, and infarction type were important predictors of favorable outcomes after 3 months. At the 1-year follow-up, patients with ICH and SAH had worse functional outcomes and survival rates than those with infarction. CONCLUSION: An aggressive approach to elucidate the etiology of stroke is indicated because structural vasculopathy-induced ICH and other determined infarction are distinctively prevalent in young adults, particularly those aged 16-30.

Total and differential leukocyte counts in ischemic stroke caused by vertebrobasilar artery dissection.

INTRODUCTION: Vertebrobasilar artery dissection(VBD) is a common etiology of posterior circulation stroke(PCS). However, the etiology of VBD itself remains unclear. The present study aimed to test whether inflammation is involved in the mechanism of VBD by evaluating its relationship with total and differential leukocyte counts. METHODS: Patients with PCS caused by VBD or by large artery atherosclerosis(LAA) were recruited between January 1, 2012 and December 31, 2014 from the Taipei Veterans General Hospital. Age- and sex-matched non-stroke(NS) volunteers were also included. Univariate and multivariate analyses were performed to compare total/differential leukocyte counts among VBD, LAA, and NS groups. RESULTS: One-hundred-one patients with VBD [average age: 64.8(15.1) years; 77(76.2%) males], 70 with LAA [average age: 73.9(10.6) years; 44(62.9%) males], and 202 NS [average age: 64.8(15.1) years; 77(76.2%) males] patients were included in the present study. Compared with the NS and LAA groups, respectively, the VBD group had significantly higher total leukocyte and neutrophil counts and frequency of high leukocyte (>10,000 × 106/L) and high neutrophil (>8000 × 106/L) counts. Multivariate analyses, adjusted for age, sex, and vascular risk factors, showed that the VBD group, compared with the other groups, had an odds-ratio of 5.04 (95% confidence interval:2.43-10.43) and 5.90 (2.70-12.92) with respect to the prevalence of high leukocyte and high neutrophil counts. CONCLUSION: VBD was associated with high leukocyte and neutrophil counts. Our results support that inflammation and neutrophil-related pathophysiology might be involved in the mechanism of VBD; however, the causal relationship would need further investigations.

Investigating CYP2C19 loss-of-function allele statuses and their association with stroke of different etiologies in a Taiwanese population.

BACKGROUND: CYP2C19 loss-of-function single-nucleotide polymorphisms (SNPs) are associated with poor responses of clopidogrel in secondary prevention of ischemic stroke (IS). It is still unclear whether these SNPs, which may result in poor cytochrome P450 2C19 (CYP2C19) enzymatic activity, affect the occurrence of IS and its subtypes. The present study evaluated the relationship between the CYP2C19 loss-of-function alleles and IS. METHODS: Eight hundred sixty-eight patients with IS and 557 nonstroke (NS) control individuals were prospectively recruited. Stroke etiologies, including large-artery atherosclerosis (LAA), cardioembolism (CE), and small-vessel occlusion (SVO), were determined. The two most common CYP2C19 loss-of-function alleles worldwide, CYP2C19*2 and CYP2C19*3, were investigated by genotyping. Patients with two loss-of-function alleles of the CYP2C19 genes were classified as poor metabolizers. RESULTS: Our population has a high frequency of CYP2C19 loss-of-function alleles, mostly contributed by CYP2C19*2, being present in 51.3% to 57.5% of patients with IS of different etiologies and 53.1% of NS individuals. The proportions of CYP2C19 poor metabolizers within NS group and each IS group with disparate etiology are similar (NS 73 [13.1%]; LAA 44 [14.2%], p = 0.623; CE 26 [14.0%], p = 0.541; SVO 38 [13.3%], p = 0.443). Nevertheless, the frequencies of CYP2C19*3 allele were different among the NS and different IS subgroups. Multivariate analyses adjusting for age, sex, and vascular risk factors revealed that CYP2C19*3 allele was a protective factor for SVO (odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.3 to 0.9, p = 0.015 [vs NS], OR = 0.5, 95% CI = 0.3 to 0.8, p = 0.010 [vs LAA and CE]). CONCLUSION: The CYP2C19 poor metabolizer is not associated with IS and its subtypes. Furthermore, CYP2C19*3 may be a protective factor for SVO and its mechanism warrants further investigation.

Functional recovery of stroke patients with postacute care: a retrospective study in a northern medical center.

BACKGROUND: Taiwan's NHI Administration proposed a nationwide postacute care-cerebral vascular disease (PAC-CVD) program, which transfers stroke patients at postacute phase in medical centers to community hospitals. Its aim is mainly to prevent a prolonged stay in medical centers, which usually results in higher medical costs. The present study evaluated the 3-months functional outcomes of stroke patients receiving PAC-CVD. METHODS: We retrogradely retrieved patients' data from Stroke Registry of a Northern medical center. Patients admitted between January 2014 and March 2018 were screened. We included patients receiving PAC-CVD and age/sex/stroke severity/functional status-matched acute stroke patients (regular rehabilitation group). Baseline clinical characteristics and 3-months functional outcomes were analyzed. We defined 3-months mRS 0 to 2 as better, 3 to 4 as same, and 5 to 6 as worse functional recovery. RESULTS: One-hundred-and-seventy-three patients receiving PAC-CVD and 173 matched controls (68.2 ± 14.0-years-old, 68.5% ± 11.22% men) were recruited. All patients were with mRS 3 to 4 at discharge from our medical center. The distributions of 3-months functional recovery in two groups were as follows: better/same/worse 3-months functional outcomes, PAC-CVD = 40.4%/57.8%/1.8%; controls (regular rehabilitation) = 33.9%/50.3%/5.8%. Multivariate analyses adjusted for age, sex, NIHSS, and cardiovascular risk factors were performed to evaluate whether PAC-CVD predicted better or poor functional outcomes. The results showed that compared with controls, PAC-CVD group had similar frequency of better functional recovery (odds ratio [OR] = 0.97, 95% CI = 0.54-1.74, p = 0.924) but less frequency of worse functional outcomes (OR = 0.08, 95% CI = 0.008-0.84, p = 0.035). CONCLUSION: About one-third of patients with mRS 3 to 4 recovered well in 3-months after stroke in both PAC-CVD and regular rehabilitation groups. Our results showed that PAC-CVD program can significantly decrease functional decline after acute stroke.

Characteristics and Outcomes of Vertebrobasilar Artery Dissection with Accompanied Atherosclerosis.

BACKGROUND: With the popularity of MRI use, vertebrobasilar artery dissection (VBD) has been found more frequently in patients with posterior circulation ischemic stroke (PCS). The relationship between VBD and atherosclerosis is unknown. The present study aimed to prove the hypothesis that PCS with pure VBD (p-VBD) and with VBD and accompanied cervical or cerebral artery atherosclerosis (a-VBD) have distinct manifestations. METHODS: Patients with VBD-related PCS who were prospectively enrolled in the Taipei Veterans General Hospital Stroke Registry between January 1, 2010 and August 31, 2014 were recruited for the present study. Patients who had (1) atherosclerotic plaques with or without stenotic flow in cervical arteries on Duplex ultrasonography or (2) focal >30% stenosis in cerebral arteries other than the dissecting region (usually in arterial bifurcations which are prone to atheroma formation) on brain MRA were defined as a-VBD. RESULTS: There were 91 patients (67 [73.6%] males, mean age 65.5 years [SD = 15.2, range, 21-91]) with VBD-related PCS recruited for the present study; 31 were a-VBD and 60 were p-VBD. The results showed that there were significant differences in onset age, frequency of cigarette smoking, dissecting vascular involvement, and infarct locations between the 2 groups. In addition, compared with p-VBD, the a-VBD group had poorer functional recovery at 3 months and 1 year, respectively, which was independent of age, sex, vascular risk factors, stroke severity at admission, and treatment options. CONCLUSION: VBD-related PCS with and without accompanied atherosclerosis had different manifestations and should be regarded as distinct arterial diseases.

Greater periventricular white matter hyperintensity severity in basilar artery branch atheromatous disease.

BACKGROUND: Basilar artery branch atheromatous disease (BABAD), in which basilar artery atheroma occludes penetrating arteries at their origin, is a common etiology of posterior circulation stroke (PCS). It is currently unknown whether white matter hyperintensity(WMH), a marker of small vessel disease(SVD), is associated with BABAD. METHODS: The present study analyzed data from patients with PCS who were enrolled in the Taipei Veterans General Hospital Stroke Registry between January 1, 2010 and February 28, 2014. WMH severity was rated using the Scheltens scale. We used multivariate analyses to: (1) compare the severity of WMH between patients with BABAD, patients with large-artery > 50% atherosclerotic stenosis-related PCS(LAA), and non-stroke subjects(NS); and (2) evaluate the relationship between WMH severity and the 3-month prognosis of patients with BABAD. RESULTS: The study pool included 151 BABAD, 97 LAA, and 78 non-stroke patients. Multivariate analyses adjusting for age, sex, and vascular risk factors showed that compared to patients with LAA [Odds ratio(OR) = 0.51, p = 0.037] and NS (OR = 0.40, p = 0.004), patients with BABAD (OR = 1) had greater WMH severity (score ≥ 50th percentile) in periventricular, but not subcortical, regions. Moreover, greater periventricular WMH severity predicted poor 3-month functional outcomes (modified Rankin Scale > 3) with an OR of 3.21 (p = 0.028) in BABAD patients. CONCLUSIONS: We are the first to show a significant association between WMH and BABAD that is independent of vascular risk factors and atherosclerotic large-artery disease. Our results suggest that small vessel abnormalities other than lipohyalinosis may be involved in BABAD pathophysiology. A future management strategy should include both large and small vessel protection.

Impacts of Cigarette Smoking and Basilar Artery Flow on 1-year Recovery in 3-Month survivors of Intracranial Vertebrobasilar Artery Dissection-related Ischemic Stroke.

OBJECTIVE: Intracranial vertebrobasilar artery dissection (iVBD) is an important etiology for posterior circulation ischemic stroke (PCS); however, its long-term functional outcome has been seldom reported. The present study aimed to elucidate the functional outcomes and the predictors of poor functional recovery at 1-year after iVBD-caused PCS. METHODS: Patients with iVBD-caused PCS who had been recruited in the Stroke Registry of Taipei Veterans General Hospital between January 1, 2012 to February 28, 2014 were included. Multivariate analysis was used to detect predictors for poor 1-year functional recovery [modified Rankin Scale (mRS) ≥ 4]. RESULTS: Sixty patients [age: 66.3±15.1 years; 45(75%) men] were included. At 1-year after stroke, 61.7% of patients had good functional status (mRS 0-1); however, 21.6% of patients were disabled (mRS≥4). Multivariate analyses showed that older age, cigarette-smoking history and low basilar-artery (BA) flow velocity were significantly associated with poor functional recovery independent of stroke severity at admission. The results also revealed a synergistic effect of cigarette-smoking and low BA flow on poor 1-year functional recovery: patients with both, a history of cigarette-smoking and low BA flow (≤24cm/s) had an odds ratio of 276.1 (p=0.007) leading to poor 1-year functional recovery, versus patients with neither cigarette-smoking history nor low BA flow. CONCLUSIONS: Our results suggest that adequate blood flow may be key to functional recovery after iVBDcaused PCS. Methods to improve blood flow and tissue perfusion after iVBD-caused PCS should be considered in the future clinical studies with the purpose to improve functional recovery in these patients.

Posterior Circulation Ischemic Stroke Caused by Arterial Dissection: Characteristics and Predictors of Poor Outcomes.

BACKGROUND: Posterior circulation ischemic stroke (PCS) caused by arterial dissection (AD-PCS) was rarely discussed. The present study aimed to evaluate the clinical characteristics and predictors of poor outcomes in AD-PCS patients. METHODS: A total of 286 PCS patients were recruited from Taipei Veterans General Hospital Stroke Registry (between January 1, 2012 and February 28, 2014). Clinical/image data of recruited PCS patients were reviewed by stroke specialists who reached a consensus on the stroke etiologies. Data of AD-PCS patients were analyzed. RESULTS: Seventy-four patients (65.8 ± 15.6 years, 56 (75.7%) men) were determined as AD-PCS. Headache and neck pain at admission were only presented in 18.9 and 6.8% of patients, respectively. The location of AD was initiated in the vertebral artery (66.2%), basilar artery (27.0%), posterior inferior cerebellar artery (5.4%) and posterior cerebral artery (1.4%). The involvement of intracranial arteries was present in the majority of patients (97.3%). Of the patients, 9.5% died, and 29.7% had poor functional outcomes (modified Rankin Scale ≥4) at 3-month. Conscious change independently predicted mortality at 3 months. Quadriparesis, National Institutes of Health Stroke Scale (NIHSS) score >8 and infarct lesions involving >1 category were independent predictors for poor functional outcomes at 3 months. CONCLUSION: AD is an important etiology of PCS. Physicians should be more vigilant in recognizing AD-PCS. Intracranial arteries are more important in AD-PCS; very few patients of AD-PCS had dissection solely in extracranial arteries. Short-term outcomes of AD-PCS were not favorable. Conscious change, quadriparesis, NIHSS score >8 and infarct lesions involving >1 category were independent predictors for poor outcomes. Patients presenting these factors should be monitored closely.

Stroke etiology is associated with outcome in posterior circulation stroke.

OBJECTIVE: Stroke research and clinical trials have focused mainly on anterior circulation stroke (ACS). Since clinical characteristics, mechanisms, and outcomes of posterior circulation stroke (PCS) have been reported different from ACS, more PCS studies are required, particularly researching the etiologies, to help establish an optimal management strategy. METHODS: The present study analyzed patients of PCS who were consecutively admitted and registered in Taipei Veterans General Hospital Stroke Registry between 1 January 2012 to 28 February 2014. We demonstrated the distribution of etiologies, compared the clinical characteristics/outcomes among different etiology groups, and used univariate/multivariate analyses to identify the predictors for poor functional outcome (modified Rankin Scale ≥5) at discharge and 3 month. RESULTS: About 286 patients of PCS were included for analyses. Basilar artery atheromatous branch occlusive disease (BABO, 28.0%) and large artery dissection (25.9%) were the two most common etiologies, followed by large artery atherosclerotic stenosis/occlusion (LAA, 20.6%), cardioembolism (CE, 18.5%) and small vessel disease (7.0%). Age, vascular risk factors, infarct locations and patterns, and outcomes were different among these five etiology groups. Multivariate analyses showed that age >70 y/o (discharge/3 month, OR, 95% CI: 3.05, 1.23-7.56/8.39, 2.32-30.33), admission NIH Stroke Scale >9 (19.50, 8.69-43.75/13.45, 5.59-32.39), and etiology (LAA versus BABO: 5.00, 1.58-15.83/4.00, 1.19-13.4; CE versus BABO: 3.36, 1.02-11.09/4.66, 1.40-15.46) were independently associated with poor functional outcome. INTERPRETATION: The etiologies of PCS are heterogeneous and shown to be associated with functional outcomes. Our results have shed lights on future pathophysiological research and designs of clinical trials for PCS.