Mi Ji Lee

Presence of baseline prehypertension and risk of incident stroke: A meta-analysis

Objective: To qualitatively and quantitatively assess the association of prehypertension with incident stroke through a meta-analysis of prospective cohort studies. Methods: We searched Medline, Embase, the Cochrane Library, and bibliographies of retrieved articles. Prospective cohort studies were included if they reported multivariate-adjusted relative risks (RRs) and corresponding 95%confidence intervals (CI) of stroke with respect to baseline prehypertension. Results: Twelve studies with 518,520 participants were included. Prehypertension was associated with risk of stroke (RR 1.55, 95% CI 1.35–1.79; p < 0.001). Seven studies further distinguished a low prehypertensive population (systolic blood pressure [SBP] 120–129 mm Hg or diastolic blood pressure [DBP] 80–84 mm Hg) and a high prehypertensive population (SBP 130–139 mm Hg or DBP 85–89 mm Hg). Among persons with lower-range prehypertension, stroke risk was not significantly increased (RR 1.22, 0.95–1.57). However, for persons with higher values within the prehypertensive range, stroke risk was substantially increased (RR 1.79, 95% CI 1.49–2.16). Conclusions: Prehypertension is associated with a higher risk of incident stroke. This risk is largely driven by higher values within the prehypertensive range and is especially relevant in nonelderly persons. Randomized trials to evaluate the efficacy of blood pressure reduction in persons with this designation are warranted.

Differential Vascular Pathophysiologic Types of Intracranial Atherosclerotic Stroke A High-Resolution Wall Magnetic Resonance Imaging Study

Background and Purpose— Intracranial atherosclerotic stroke (ICAS) has various stroke mechanisms, including branch occlusive disease (BOD), subcortical infarcts caused by parent arterial disease occluding the perforator’s orifice, and non-BOD, infarcts beyond the subcortical area caused by artery-to-artery embolism. To test whether these 2 types of ICAS had different vascular pathophysiologies, we compared the high-resolution magnetic resonance imaging characteristics between BOD and non-BOD ICAS. Methods— Eighty patients with acute infarcts caused by ICAS of proximal middle cerebral artery or basilar artery without carotid/cardiac embolic sources or nonatherosclerotic causes were enrolled (36 BOD and 44 non-BOD patients). The steno-occlusive intracranial artery at the maximal stenosis was analyzed for vascular remodeling and wall enhancement. Results— BOD had distinct radiological features in terms of vascular morphology and enhancement. BOD showed a milder stenosis than non-BOD (P<0.001). Positive remodeling was more frequently observed in non-BOD than in BOD (P=0.005). Wall area index was also lower in BOD. Plaque enhancement was observed in all but one non-BOD patient and in one fourth of BOD patients (P=0.003). Although both types showed an eccentric enhancement, this enhancement was more frequently distributed in the BOD group on the side where the perforators arose. As the number of asymptomatic intracranial stenosis increased, the degree of stenosis (rho=0.513, P=0.003) increased in the BOD group, whereas enhanced plaque area (rho=0.343, P=0.030) increased in the non-BOD group. Conclusions— Our data indicate that BOD is a common and unique form of ICAS, distinct from non-BOD. These 2 types of ICAS have different vascular pathophysiologies in terms of vascular remodeling and plaque characteristics.

A Polymorphism in RNF213 Is a Susceptibility Gene for Intracranial Atherosclerosis

Background Both intracranial atherosclerotic stenosis (ICAS) and moyamoya disease (MMD) are prevalent in Asians. We hypothesized that the Ring Finger protein 213 gene polymorphism (RNF213), a susceptibility locus for MMD in East Asians, is also a susceptibility gene for ICAS in patients whose diagnosis had been confirmed by conventional angiography (absence of basal collaterals) and high-resolution MRI (HR-MRI, presence of plaque). Methods We analyzed 532 consecutive patients with ischemic events in the middle cerebral artery (MCA) distribution and relevant stenotic lesion on the distal internal carotid artery or proximal MCA, but no demonstrable carotid or cardiac embolism sources. Additional angiography was performed on 370 (69.5%) patients and HR-MRI on 283 (53.2%) patients. Results Based on angiographic and HR-MRI findings, 234 patients were diagnosed with ICAS and 288 with MMD. The RNF213 variant was observed in 50 (21.4%) ICAS patients and in 119 (69.1%) MMD patients. The variant was observed in 25.2% of patients with HR-MRI-confirmed ICAS. Similarly, 15.8% of ICAS patients in whom MMD was excluded by angiography had this variant. Among the ICAS patients, RNF213 variant carriers were younger and more likely to have a family history of MMD than non-carriers were. Multivariate testing showed that only the age of ICAS onset was independently associated with the RNF213 variant (odds ratio, 0.97; 95% CI, 0.944–0.99). Conclusions RNF213 is a susceptibility gene not only for MMD but also for ICAS in East Asians. Further studies are needed on RNF213 variants in ICAS patients outside East Asian populations.

Patent Foramen Ovale and Stroke-Current Status.

Patent foramen ovale (PFO) is growing in clinical interest because of a renewed focus on embolic stroke of undetermined source (ESUS), the PFO attributable fraction (the 10-point Risk of Paradoxical Embolism score), technical advances in PFO diagnosis, and the emergence of endovascular device closure as a treatment option. However, recent randomized controlled trials of the management of patients with ESUS and PFO failed to demonstrate the superiority of closure over medical treatment. The mechanisms of stroke other than paradoxical embolism may be important in patients with ESUS and PFO. This paper reviews the current understanding of the pathophysiology of stroke and therapeutic options in patients with PFO and ESUS.

Hypercoagulability and Mortality of Patients with Stroke and Active Cancer: The OASIS-CANCER Study

Background and Purpose Patients with active cancer are at an increased risk for stroke. Hypercoagulability plays an important role in cancer-related stroke. We aimed to test whether 1) hypercoagulability is a predictor of survival, and 2) correction of the hypercoagulable state leads to better survival in patients with stroke and active cancer. Methods We recruited consecutive patients with acute ischemic stroke and active systemic cancer between January 2006 and July 2015. Hypercoagulability was assessed using plasma D-dimer levels before and after 7 days of anticoagulation treatment. The study outcomes included overall and 1-year survival. Plasma D-dimer levels before and after treatment were tested in univariate and multivariate Cox regression models. We controlled for systemic metastasis, stroke mechanism, age, stroke severity, primary cancer type, histology, and atrial fibrillation using the forward stepwise method. Results A total of 268 patients were included in the analysis. Patients with high (3rd–4th quartiles) pre-treatment plasma D-dimer levels showed decreased overall and 1-year survival (adjusted HR, 2.19 [95% CI, 1.46–3.31] and 2.70 [1.68–4.35], respectively). After anticoagulation treatment, post-treatment D-dimer level was significantly reduced and independently associated with poor 1-year survival (adjusted HR, 1.03 [95% CI, 1.01–1.05] per 1 μg/mL increase, P=0.015). The successful correction of hypercoagulability was a protective factor for 1-year survival (adjusted HR 0.26 [CI 0.10–0.68], P=0.006). Conclusions Hypercoagulability is associated with poor survival after stroke in patients with active cancer. Effective correction of hypercoagulability may play a protective role for survival in these patients.

Predicting Collateral Status With Magnetic Resonance Perfusion Parameters: Probabilistic Approach With a Tmax-Derived Prediction Model.

Background and Purpose— Good collateral flow is an important predictor for favorable responses to recanalization therapy and successful outcomes after acute ischemic stroke. Magnetic resonance perfusion–weighted imaging (MRP) is widely used in patients with stroke. However, it is unclear whether the perfusion parameters and thresholds would predict collateral status. The present study evaluated the relationship between hypoperfusion severity and collateral status to develop a predictive model for good collaterals using MRP parameters. Methods— Patients who were eligible for recanalization therapy that underwent both serial diffusion-weighted imaging and serial MRP were enrolled into the study. A collateral flow map derived from MRP source data was generated through automatic postprocessing. Hypoperfusion severity, presented as proportions of every 2-s Tmax strata to the entire hypoperfusion volume (Tmax≥2 s), was compared between patients with good and poor collaterals. Prediction models for good collaterals were developed with each Tmax strata proportion and cerebral blood volumes. Results— Among 66 patients, 53 showed good collaterals based on MRP-based collateral grading. Although no difference was noted in delays within 16 s, more severe Tmax delays (Tmax16–18 s, Tmax18–22 s, Tmax22–24 s, and Tmax>24 s) were associated with poor collaterals. The probability equation model using Tmax strata proportion demonstrated high predictive power in a receiver operating characteristic analysis (area under the curve=0.9303; 95% confidence interval, 0.8682–0.9924). The probability score was negatively correlated with the volume of infarct growth (P=0.030). Conclusions— Collateral status is associated with more severe Tmax delays than previously defined. The present Tmax severity–weighted model can determine good collaterals and subsequent infarct growth.

Role of Statin in Atrial Fibrillation-Related Stroke: An Angiographic Study for Collateral Flow

Background: Currently, intensive lipid lowering is recommended in patients with atherosclerotic ischemic stroke or transient ischemic attack. However, the role of statin in cardioembolic stroke is unclear. We investigated the association of statin with pretreatment collateral status in cardioembolic stroke. Methods: A collaborative study from two stroke centers in distinct geographic regions included consecutive patients with acute middle cerebral artery (MCA) infarction due to atrial fibrillation (AF) who underwent cerebral angiography. The relationship between pretreatment collateral grade and the use/dose of statin at stroke onset was assessed. The angiographic collateral grade was evaluated according to the ASITN/SIR Collateral Flow Grading System. Results: Ninety-eight patients (76 statin-naïve, 22 statin users) were included. Compared with statin-naïve patients, statin users were older and more frequently had hypertension, hyperlipidemia and coronary heart disease. Excellent collaterals (grade 3-4) were more frequently observed in statin users (11 patients, 50%) than in statin-naïve patients (21 patients, 27.6%; p = 0.049). The use of atorvastatin 10 mg equivalent or higher doses of statin was associated with excellent collaterals (p for trend = 0.025). In multiple regression analysis, prestroke statin use was independently associated with excellent collaterals (odds ratio, 7.841; 95% confidence interval, CI, 1.96-31.363; p = 0.004). Conclusions: Premorbid use of statin in AF patients is associated with excellent collateral flow. Although most statin trials excluded patients with cardioembolic stroke, our data suggests the possibility that statin may be beneficial in AF-related stroke.

Volume and morphology of left atrial appendage as determinants of stroke subtype in patients with atrial fibrillation

BACKGROUND Atrial fibrillation (AF) is a leading cause of stroke, but not all cases of stroke in patients with AF are due to AF. OBJECTIVE The purpose of this study was to determine whether morphometric or volumetric parameters of left atrial appendage (LAA) would be related to the development of cardioembolism in subjects with AF. METHODS A total of 433 consecutive patients with acute ischemic stroke underwent multidetector cardiac computed tomography (MDCT). Of these patients, 88 with AF were divided into cardioembolic stroke (CES; n = 57) and non-CES (n = 31) groups, and 95 age- and sex-matched patients with non-CES without AF served as controls. Clinical factors, echocardiographic findings, and MDCT parameters were evaluated. RESULTS Brain infarct volume, LAA orifice diameter, and LAA volume were larger in patients with CES with AF than in those with non-CES with AF (P<.05 in all cases), but no difference was observed between patients with non-CES with AF and those with non-CES without AF. MDCT and echocardiographic parameters of left atrial (LA) dysfunction were different depending on the presence of AF but not between patients with CES with AF vs non-CES with AF. After adjusting for covariates, LAA orifice diameter (odds ratio 1.19, 95% confidence interval 1.06-1.33, P = .004) and LAA volume (odds ratio 12.20, 95% confidence interval 2.58-57.79, P = .002) were independently associated with CES with AF, as was infarct volume. CONCLUSION In patients with AF, LAA orifice diameter and LAA volume, but not left atrial dysfunction, were determinants of CES and were useful for stratifying noncardioembolic risk in patients with AF.

Blood–brain barrier breakdown in reversible cerebral vasoconstriction syndrome: Implications for pathophysiology and diagnosis

Diagnosis of reversible cerebral vasoconstriction syndrome (RCVS) is currently based on luminographic findings of vasoconstriction. In addition to vasoconstriction, the blood–brain barrier (BBB) breakdown has been postulated as a central mechanism of RCVS. Our aim was to document BBB breakdown in patients with RCVS and its role for the pathophysiology‐based diagnosis of RCVS.

Previous Statin Use and High-Resolution Magnetic Resonance Imaging Characteristics of Intracranial Atherosclerotic Plaque: The Intensive Statin Treatment in Acute Ischemic Stroke Patients With Intracranial Atherosclerosis Study

Background and Purpose— Although statin use has been linked to the stabilization of systemic atherosclerosis, its effect on symptomatic intracranial atherosclerotic plaques has yet to be explored. We hypothesized that premorbid statin use is associated with plaque instability in intracranial arteries and may lead to differential patterns (size and distribution) of ischemic lesions in patients with acute intracranial atherosclerotic stroke. Methods— One hundred and thirty-six patients with acute infarcts caused by intracranial atherosclerotic stroke underwent high-resolution magnetic resonance imaging. Patients were categorized into 3 groups based on their premorbid statin use: nonuser, low-dose user, and high-dose user, according to the 2013 American College of Cardiology/American Heart Association guidelines on blood cholesterol. Symptomatic lesions in intracranial arteries were analyzed using high-resolution magnetic resonance imaging for vascular morphology (degree of stenosis, remodeling index, and wall index) and plaque activation (pattern and volume of enhancement). The cortical distribution and volume of ischemic brain lesions were measured using diffusion-weighted imaging. Results— Among the enrolled patients, 38 (27.94%) were taking statins before the index stroke (22 low-dose statins and 16 high-dose statins). The degree of stenosis, remodeling index, and wall index did not differ between the 3 groups. However, the volume of plaque enhancement was significantly lower in statin users (nonuser, 33.26±40.72; low-dose user, 13.15±17.53; high-dose user, 3.13±5.26; P=0.002). Premorbid statin use was associated with a higher prevalence of nonembolic stroke and a decrease in large cortical infarcts (P=0.012). Conclusions— Premorbid statin usage is independently associated with reduced plaque enhancement and a decrease in large cortical lesions in patients with intracranial atherosclerotic stroke.