Atherothrombotic Infarction Research Articles

Functional recoveries of patients with branch atheromatous disease after rehabilitation: Comparison with other types of cerebral infarction and importance of stratification by clinical categories.

Functional recoveries after rehabilitation of patients with branch atheromatous disease (BAD) have not been well investigated, however, clinical category of cerebral infarction including BAD itself could be a potential predictive factor for functional outcome. To describe characteristics of functional recoveries of patients with BAD through comparison with other types of cerebral infarction. We retrospectively compared outcomes of patients with BAD (N = 222), cardioembolic cerebral infarction (CE: N = 177) and atherothrombotic cerebral infarction (AT: N = 219) by using functional independence measure (FIM) and FIM effectiveness (the proportion of potential for improvement achieved). Univariate analysis showed that FIM on discharge was comparable among three types of cerebral infarction, but that FIM effectiveness in patients with BAD was significantly higher than those with CE or AT. Stratified analysis revealed higher FIM effectiveness in patients with BAD compared to patients with CE or AT, if they were male, younger (≤72 years) or had supratentorial brain lesions. Multiple regression analysis demonstrated that location of the brain lesion (supratentorial vs infratentorial) and gender (male vs female) were significantly associated with FIM on discharge, and that cognitive function on admission as well as gender were significantly associated with FIM effectiveness in patients with BAD, but not in patients with CE or AT. Outcomes after rehabilitation of patients with BAD may be characterized by better functional improvement, especially if patients are male, relatively younger or with supratentorial lesions. The impact and the type of factors related to functional recoveries of patients with BAD may be different from other types of stroke. The present study suggested that clinical category of stroke should be taken into consideration in prediction of outcomes and planning of rehabilitation management.

Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker

BackgroundSpontaneous Coronary Artery Dissection (SCAD) is an important cause of acute coronary syndromes, particularly in young to middle-aged women. Differentiating acute SCAD from coronary atherothrombosis remains a major clinical challenge. MethodsA case-control study was used to explore the usefulness of circulating miRNAs to discriminate both clinical entities. The profile of miRNAs was evaluated using an unbiased human RT-PCR platform and confirmed using individual primers. miRNAs were evaluated in plasma samples from acute SCAD and atherothrombotic acute myocardial infarction (AT-AMI) from two independent cohorts; discovery cohort (SCAD n = 15, AT-AMI n = 15), and validation cohort (SCAD n = 11, AT-AMI n = 41) with 9 healthy control subjects. Plasma levels of IL-8, TGFB1, TGBR1, Endothelin-1 and MMP2 were analysed by ELISA assays. FindingsFrom 15 differentially expressed miRNAs detected in cohort 1, we confirmed in cohort 2 the differential expression of 4 miRNAs: miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p, whose expression was higher in SCAD compared to AT-AMI. The combined expression of these 4 miRNAs showed the best predictive value to distinguish between both entities (AUC: 0.879, 95% CI 0.72–1.0) compared to individual miRNAs. Functional profiling of target genes identified an association with blood vessel biology, TGF-beta pathway and cytoskeletal traction force. ELISA assays showed high plasma levels of IL-8, TGFB1, TGFBR1, Endothelin-1 and MMP2 in SCAD patients compared to AT-AMI. InterpretationWe present a novel signature of plasma miRNAs in patients with SCAD. miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p discriminate SCAD from AT-AMI patients and also shed light on the pathological mechanisms underlying this condition. FundingSpanish Ministry of Economy and Competitiveness (MINECO): Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV). Fundación BBVA a equipos de Investigación Científica 2018 and from Caixa Banking Foundation under the project code HR17-00016 to F.S.M. Instituto de Salud Carlos III (AES 2019): PI19/00565 to F.R, PI19/00545 to P.M. CAM (S2017/BMD-3671-INFLAMUNE-CM) from Comunidad de Madrid to FSM and PM. The UK SCAD study was supported by BeatSCAD, the British Heart Foundation (BHF) PG/13/96/30608 the NIHR rare disease translational collaboration and the Leicester NIHR Biomedical Research Centre PI17/01865, Instituto de Salud Carlos III and FEDER (European Regional Development Fund).

Cardioembolic Stroke: Risk Factors, Clinical Features, and Early Outcome in 956 Consecutive Patients

There is little information about the early clinical features of cardioembolic stroke before complementary examinations. The aim of this study was to identify risk factors, clinical features, and early outcomes of cardioembolic stroke. Retrospective study based on prospectively collected data available from a university medical center hospitalbased stroke registry. Consecutive patients diagnosed with cardioembolic infarction were selected and compared to those diagnosed with an atherothrombotic stroke. Predictors of cardioembolic infarction were assessed by multivariate analysis. From a cohort of 4597 consecutive patients, we studied 956 patients diagnosed with cardioembolic infarction (80 years [standard deviation (SD) 9.14]; 63% women) and 945 with atherothrombotic infarction (77.01 years [SD 9.75]; 49.8% women). The univariate comparative analysis reported that advanced age (≥ 85 years), female gender, atrial fibrillation (AF), ischemic heart disease, and congestive heart failure were significantly more frequent in the cardioembolic group, whereas hypertension, diabetes, peripheral vascular disease, heavy smoking, hyperlipidemia, and previous transient ischemic attack were significant in the atherothrombotic group. In the logistic regression model, AF (odds ratio [OR] 15.75, 95% confidence interval [CI]: 12.14-20.42), ischemic heart disease (OR 3.12, 95% CI: 2.16-4.5), female gender (OR 1.56, 95% CI: 1.22-2.00), and sudden-onset (OR 1.97, 95% CI: 1.54-2.51), were independent significant predictors of cardioembolic stroke. Potential cardioembolic stroke requires a comprehensive evaluation, since early classification and identification through predictors would improve effective management.

Development and Validation of a Risk Prediction Model for Atherosclerotic Cardiovascular Disease in Japanese Adults: The Hisayama Study.

Aim: To develop and validate a new risk prediction model for predicting the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in Japanese adults. Methods: A total of 2,454 participants aged 40–84 years without a history of cardiovascular disease (CVD) were prospectively followed up for 24 years. An incident ASCVD event was defined as the first occurrence of coronary heart disease or atherothrombotic brain infarction. A Cox proportional hazards regression model was used to construct the prediction model. In addition, a simplified scoring system was translated from the developed prediction model. The model performance was evaluated using Harrell’s C statistics, a calibration plot with the Greenwood-Nam-D’Agostino test, and a bootstrap validation procedure. Results: During a median of a 24-year follow-up, 270 participants experienced the first ASCVD event. The predictors of the ASCVD events in the multivariable Cox model included age, sex, systolic blood pressure, diabetes, serum high-density lipoprotein cholesterol, serum low-density lipoprotein cholesterol, proteinuria, smoking habits, and regular exercise. The developed models exhibited good discrimination with negligible evidence of overfitting (Harrell’s C statistics: 0.786 for the multivariable model and 0.789 for the simplified score) and good calibrations (the Greenwood-Nam-D’Agostino test: P =0.29 for the multivariable model, 0.52 for the simplified score). Conclusion: We constructed a risk prediction model for the development of ASCVD in Japanese adults. This prediction model exhibits great potential as a tool for predicting the risk of ASCVD in clinical practice by enabling the identification of specific risk factors for ASCVD in individual patients.

Pre-Therapeutic Factors Predicting for the Necessity of Rescue Treatments in Mechanical Thrombectomy.

Mechanical thrombectomy for acute large vessel occlusion (LVO) is currently widely performed. However, rescue treatment (RT), such as percutaneous transluminal angioplasty (PTA) and stenting, is occasionally required, particularly in the case of atherothrombotic brain infarction (ATBI) or dissection. As RT requires higher levels of therapeutic skills and additional devices, early prediction of its performance and preparation are important. We retrospectively investigated the pre-therapeutic factors for predicting the necessity of RT. We reviewed 149 consecutive patients who underwent mechanical thrombectomy for acute LVO between April 2014 and December 2019. Eight patients were excluded because of missing clinical data. RT was performed when severe stenosis was observed in occluded vessels or proximal to them during mechanical thrombectomy. We investigated pre-therapeutic neurological, laboratory, and radiological findings in the 141 remaining patients, and compared them between RT and non-RT groups. RT was performed on 23 of the 141 patients. We found four pre-therapeutic factors with significantly different rates between RT/non-RT as follows: (1) Atrial fibrillation 8.7%/71.1% (p <0.001), (2) diabetes mellitus 39.1%/19.5% (p = 0.04), (3) susceptibility vessel sign (SVS) by T2-weighted imaging 17.4%/66.1% (p <0.001), and (4) tapered occlusion by magnetic resonance angiography (MRA) 47.8%/11.9% (p <0.001). The plasma level of brain natriuretic peptide (BNP) was also significantly different between the two groups. When the BNP level was less than 70 pg/mL, the sensitivity for being in the RT group was 86.9% and the specificity was 83.5%. Pre-therapeutic findings, such as diabetes mellitus, tapered occlusion, absence of atrial fibrillation, negative SVS, and BNP level less than 70 pg/mL, are predictors of RT in mechanical thrombectomy.

Acceleration of opportunistic atrial fibrillation screening for elderly patients in routine primary care.

Cardio-embolic ischemic stroke caused by atrial fibrillation is more severe compared with other types of stroke, such as lacunar infarction and atherothrombotic infarction in patients without atrial fibrillation. Therefore, it is important to prevent cardio-embolic ischemic stroke by detecting atrial fibrillation early in at-risk patients and administering appropriate anticoagulation therapy. This prospective observational study aimed to evaluate the effectiveness of opportunistic atrial fibrillation screening at 12 primary clinics in Japan. The study included a 12-month pre-campaign period and a 12-month campaign period. During the campaign period, an awareness campaign was conducted to encourage physicians to be mindful of screening patients aged ≥65 years for atrial fibrillation by checking their pulses and performing subsequent electrocardiography when an irregular pulse was detected. The primary outcome was the proportion of patients with newly diagnosed atrial fibrillation. A sub-analysis focusing on first-time outpatients was performed. There were 9921 and 10,282 patients with no history of atrial fibrillation in the pre-campaign and campaign periods, respectively. In the whole population, the proportion of patients with newly diagnosed atrial fibrillation was 0.9% throughout the pre-campaign and campaign periods. In the sub-analysis limited to first-time outpatients, the detection proportion increased from 1.6% to 1.9% during the campaign period. In terms of age stratification, a large increase in detection was observed, especially among patients aged 65–74 years (detection increased from 0.9% to 1.5%) and ≥85 years (detection increased from 2.9% to 3.3%) during the campaign period. Our findings suggest the feasibility of opportunistic atrial fibrillation screening in routine primary care practice in Japan. Of note, our findings suggest that opportunistic atrial fibrillation screening targeting first-time outpatients may be of clinical value.

Initial Results of Percutaneous Transluminal Angioplasty/Stenting for Vertebrobasilar Occlusion due to Atherothrombotic Disease during Acute Phase.

The efficacy and safety of acute percutaneous transluminal angioplasty or stenting (PTA/PTAS) for vertebrobasilar artery occlusion with atherothrombotic brain infarction (ATBI) have not been confirmed despite the resistance to medical therapy alone. There are few reports about this disease and its treatment. Therefore, the treatment outcomes at our hospital were summarized to evaluate the efficacy and safety. This was a retrospective study of acute PTA/PTAS for vertebrobasilar artery occlusion due to atherosclerotic change in 19 consecutive patients with a modified Rankin Scale (mRS) score of 0-2 before stroke between March 2010 and December 2018. The factors related to prognosis were investigated. Outcomes were assessed at 90 days of follow-up. Of 19 patients with acute vertebrobasilar artery occlusion treated by PTA/PTAS, 8 had good outcomes (mRS 0-2) and 11 had poor outcomes (mRS 3-6). There were no differences in the clinical or patient background except for the National Institutes of Health Stroke Scale (NIHSS) score between groups. The good outcome group had a lower NIHSS score than the poor outcome group (median: 9.5 vs 35, p <0.001). The Thrombolysis in Cerebral Ischemia (TICI) 2b-3 group had a slightly more favorable outcome than the TICI0-2a group (p = 0.10). There were no differences in outcome between PTA and PTAS groups (p = 0.65). Reperfusion of the posterior circulation by PTA/PTAS may be necessary for a good outcome. Although acute stenting must be performed under careful observation, a stent can be placed when recurrence in the early phase is estimated with high probability.

Effect of Statin Administration After Onset of Acute Ischemic Stroke With Large Vessel Occlusion: Insights From RESCUE-Japan Registry 2.

BackgroundStatins have been associated with reduced recurrence and better functional outcomes in patients with acute ischemic stroke. However, the effect of statins in patients with acute large vessel occlusion (LVO) is not well scrutinized.Methods and ResultsRESCUE (Recovery by Endovascular Salvage for Cerebral Ultra‐Acute Embolism)‐Japan Registry 2, a physician‐initiated registry, enrolled 2420 consecutive patients with acute LVO who were admitted to 46 centers across Japan within 24 hours of onset. We compared patients with and without statin use after acute LVO onset (statin group and nonstatin group, respectively) in terms of the modified Rankin scale at 90 days. We estimated that the odds ratios for the primary outcome was modified Rankin scale and we estimated the odds ratios for a 1‐scale lower modified Rankin scale adjusting for confounders. After excluding 12 patients without LVO and 9 patients without follow‐up, the mean age of 2399 patients was 75.9 years; men accounted for 55% of patients. Statins were administered to 447 (19%) patients after acute LVO onset. Patients in the statin group had more atherothrombotic cerebral infarctions (34.2% versus 12.1%, P<0.0001), younger age (73.4 years versus 76.5 years, P<0.0001), and lower median National Institutes of Health Stroke Scale on admission (14 versus 17, P<0.0001) than the nonstatin group. The adjusted common OR of the statin group for lower modified Rankin scale was 1.29 (95% CI, 1.04–1.37; P=0.02). The mortality at 90 days was lower in the statin group (4.7%) than the nonstatin group (12.5%; P<0.0001). The adjusted OR of the statin group relative to the nonstatin group for mortality was 0.36 (95% CI, 0.21–0.62; P=0.02).ConclusionsStatin administration after acute LVO onset is significantly associated with better functional outcome and mortality at 90 days.

Vascular events from carotid artery atherosclerosis after radiation therapy for laryngeal and hypopharyngeal cancer: the incidence and risk factors.

ABSTRACTIn this retrospective cohort study, we evaluated the incidence of vascular events from carotid artery atherosclerosis after radiotherapy indication for laryngeal and hypopharyngeal cancer. From January 2007 to December 2016, we investigated 111 laryngeal/hypopharyngeal cancer patients who underwent curative radiotherapy and were followed up for ≥1 year (median follow-up duration, 60 months). We evaluated the incidence of vascular events from carotid artery atherosclerosis, defined as a transient ischemic attack or an atherothrombotic cerebral infarction, or from undergoing treatment such as carotid artery stenting for carotid artery stenosis. The median radiation dose was 66 Gy (range, 60–74); 48 patients (43.2%) received concurrent chemotherapy. The 5-year overall survival was 86.2%. Six patients required treatment for carotid artery disease. Carotid stenting was performed in three patients with carotid artery stenosis; three patients developed atherosclerotic cerebral infarction and received medical treatment, with a median of 51.7 months (range, 0.3–78.3) after radiotherapy initiation. The vascular event occurrence rate was 5.4% within 5 years and 10.7% within 8 years. In the univariate analysis, dyslipidemia, diabetes mellitus, and carotid calcification were significant factors for event occurrence. Because three out of six cases occurred out of the irradiated field, no carotid artery or carotid bulb dosimetric parameters showed significant correlation. As laryngeal/hypopharyngeal cancer patients, particularly with complications including dyslipidemia and diabetes mellitus, are at a high risk of carotid artery stenosis after radiotherapy, long-term carotid artery evaluation is necessary. Early intervention by stroke specialists can reduce the risk of fatal cerebral infarction.

Increased serum alkaline phosphatase and early neurological deterioration in patients with atherothrombotic brain infarction attributable to intracranial atherosclerosis.

ObjectiveThe purpose of this study was to determine whether increased alkaline phosphatase (ALP) was associated with early neurological deterioration (END) in patients with atherothrombotic brain infarction (ATBI) attributable to intracranial atherosclerosis (ICAS) or not.MethodsWe analyzed data derived from 70 patients (47 men; mean age, 72.4 ± 12.8 years) with symptomatic ICAS who were admitted within 3 days of ATBI onset between April 2013 and December 2018. We defined END as an increase of ≥2 in the National Institutes of Health Stroke Scale scores during the first 72 h of hospitalization.ResultsEleven (15.7%) patients had END. Serum ALP levels on admission were significantly higher among patients with, than without END (median [interquartile range], 296 [233–338] vs. 216 [187–262] U/L, p = .0081).ConclusionIncreased serum ALP levels on admission may be able to predict developing END in patients with symptomatic ICAS.

Transient atrial mechanical dysfunction assessed in acute phase of embolic stroke of undetermined source

Background and Purpose: Paroxysmal atrial fibrillation (PAF) has been suggested as a major cause of embolic stroke of undetermined source (ESUS). Transient atrial mechanical dysfunction (stunning) frequently occurs after conversion of atrial fibrillation to sinus rhythm. The study aim was to determine if reversible atrial mechanical dysfunction in ESUS could help elucidate the mechanism of stroke. Methods: Eighty-five consecutive patients with acute ischemic stroke were enrolled according to the following inclusion criteria: [1] ≥55 years old; [2] normal sinus rhythm upon admission; [3] no apparent embolic source; and [4] transthoracic echocardiographic evaluation had been performed in both the early phase (<72 h) and late phase (>7 days) after stroke onset. There were 27 patients in the lacunar or atherothrombotic infarction group (controls), 22 in the PAF group, and 36 in the ESUS group. To determine atrial stunning, transmitral flow velocity profiles (Doppler peak E- [early diastolic] and A- [atrial systolic] waves) were obtained. Results: In the early phase, an E/A velocity ratio ≥ 1.0 was less common in the control group (1 patient, 3.7%) than in the PAF group (19 patients, 86.4%; p < 0.001) and ESUS group (10 patients, 27.8%; p < 0.05). In the late phase, the E/A ratio decreased to less than 1.0 in six patients (31.6%) who had PAF and in eight patients (80.0%) who had ESUS. Conclusion: Transient atrial mechanical dysfunction could be a helpful finding for elucidating the stroke mechanism in patients with ESUS, and early echocardiographic assessment could improve its detection.

Abstract TP88: Usefulness of High and Standard B-value DWI for Analysis of Pathophysiology in Acute Stage Cerebral Infarction

Introduction: Standard b-value DWI (sDWI) and high b-value DWI (hDWI) and ADC calculation from each DWI have been widely used for diagnosis of (acute ischemic stroke) AIS. However, diagnosis of AIS subtypes by using hDWI and ADC have not been well investigated. Hypothesis: AIS has several pathophysiological subtypes such as lacunar infarction, cardio-embolism(CE), and atherothrombotic brain infarction (ATBI), and so on, and condtion of collateral circulations differ among those subtypes. Several studies have shown that hDWI is relatively dominant in intracellular diffusion, conversely, sDWI is comparatively dominant in extracellular diffusion. Therefore, our hypothesis is that calculation of ADC from sDWI and hDWI could give valuable information for differentiation among AIS subtypes. Methods: We evaluated 130 AIS patients from medical records. Pathophysiological diagnoses were made by experienced neurologists. We acquired sDWI and hDWI at 3T MRI in all patients. 321 ADC values were obtained by calculating 200 ischemic lesions sequentially. We used relative ADC (rADC) value to adjust the difference caused by location and age. The rADC values were measured by manually placing regions of interest on the ADC maps at the ischemic lesion defined by DWI high and divided by the ADC values on the contralateral normal brain. For assessment of the AIS (within 30hrs from the onset) relationship between ATBI and CE, we subtract high b-value rADC (hrADC) from standard b-value rADC (srADC) to focus on the extracellular diffusion. To analyze the subacute phase stroke relationship between ATBI and CE, we evaluated the each rADC. And at both phase we conducted Mann-Whitney U test. Results: In superacute phase, hDWI more clearly showed hyper-intense signal than sDWI. From the onset, rADC of CE was lower than that of ATBI (median srADC-hrADC: ATBI/CE =0.0699/0.0244) (P=0.0445), this might imply the poor collateral status in CE. Contrary, for subacute phase, CE rapidly underwent necrosis in the ischemic core, rADC was higher than ATBI rADC (median ATBI/CE:0.5939/0.6480) (P=0.0011). Conclusions: We found that quantitative assessment of hrADC and srADC could give valuable information for differential diagnoses of AIS subtypes.

Abstract WP166: The Effectiveness of Statin Therapy After Onset of Acute Ischemic Stroke With Large Vessel Occlusion

Background: Statin therapy was reported to be associated with lower risk of recurrence of stroke and better functional outcomes in patients with acute ischemic stroke. However, the effect of statin therapy in patients with acute large vessel occlusion (LVO) was not well scrutinized. Thus, we evaluated the effect of statin administration after the onset of stroke on functional outcome based on the large registry study of acute LVO. Methods: RESCUE-Japan Registry-2 was a physician initiated registry study enrolled consecutive patients with acute LVO who were admitted within 24 hours of onset. We compared those with and without statin after onset in terms of modified Rankin Scale (mRS) at 90 days. We estimated the common odds ratio (OR) for a shift towards better mRS adjusting for confounders. Result: Among 2420patients registered, 2399 patients were eligible. Mean age was 75.9 years and men accounted for 55%. Statin were administered in 447 patients(19%) after admission. There are more atherothrombotic cerebral infarction (statin group: 34.2% vs non-statin group: 12.1%, p &lt;0.0001), younger age (73.4 vs 76.5, p &lt;0.0001), and lower NIHSS on admission (14 vs 17, p &lt;0.0001) in the statin group. The adjusted common OR of the statin group was 1.22 (95% confidence interval [CI], 1.04 - 1.37; p =0.02) compared with the non-statin group. The safety profile was similar between groups. The mortality at 90 days was 4.7 % in the statin group lower than 12.5 % in the non-statin group (p &lt;0.0001). The adjusted OR of statin group for mortality was 0.36 (95%CI 0.21 to 0.62, p = 0.022). Conclusions: Statin administration after onset of acute LVO was significantly associated with better functional outcome and mortality within 90 days. Our findings should be attested by randomized clinical trials in patients with acute LVO in future

Suitable methods of measuring acceleration time in the diagnosis of internal carotid artery stenosis

PurposeTo enhance the utility of acceleration time (AcT) in the diagnosis of internal carotid artery (ICA) stenosis, we assessed the value of AcT measurements with different waveform patterns.MethodsNinety-three patients with acute atherothrombotic cerebral infarction were enrolled, and they underwent both carotid ultrasonography and digital subtraction angiography (DSA). AcT was determined by a conventional procedure (using the first peak point or the bending point) and the peak systolic velocity (PSV) procedure. The AcT ratio was calculated as (AcT of ICA)/(AcT of the ipsilateral common carotid artery). We evaluated the correlation of stenosis rate as assessed by the North American Symptomatic Carotid Endarterectomy Trial method using DSA (DSA-NASCET) with the AcT of ICA (ICA-AcT), the AcT ratio measured by the conventional procedure (conventional AcT ratio), and the AcT ratio measured by the PSV procedure (PSV AcT ratio). The area under receiver operating characteristic curves (AUC) for DSA-NASCET was calculated based on the ICA-AcT and AcT ratio.ResultsForty-five vessels had 50% or greater ICA stenosis. DSA-NASCET was positively correlated with the conventional AcT ratio (r = 0.723), conventional ICA-AcT (r = 0.638), and PSV AcT ratio (r = 0.245). The corresponding AUCs for ICA stenosis ≥ 50% were 0.971, 0.886, and 0.572, respectively.ConclusionWe demonstrated the usefulness of the conventional procedure for diagnosing stenosis of ICA origin using AcT and showed that the AcT ratio was a more beneficial parameter than AcT.

Change in matrix metalloproteinase 2, 3, and 9 levels at the time of and after acute atherothrombotic myocardial infarction.

Elevated measures of matrix metalloproteinases (MMPs) are associated with acute myocardial infarction (MI), but it is not known how long these changes persist post-MI or if these measures differ between atherothrombotic versus non-atherothrombotic MI. MMPs-2, 3, and 9 were measured in 80 subjects with acute MI (atherothrombotic and non-atherothrombotic MI) or stable coronary artery disease (CAD). Measurements were made at, the time of acute MI, and > 3-month following acute MI (quiescent phase). Outcome measures were compared between groups and between time of acute MI and quiescent post-MI follow-up using Wilcoxon's and repeated measures analysis of variance. Forty-nine subjects met the criteria for acute MI with clearly defined atherothrombotic (n = 22) and non-atherothrombotic (n = 12) subsets. Fifteen subjects met criteria for stable CAD. MMP-3 was higher in acute MI versus stable CAD subjects at the time of acute MI: (453 vs. 217pg/mL, p = 0.010) but not at quiescent phase follow-up (p > 0.05). MMP-9 was higher in acute MI versus stable CAD subjects at the time of acute MI: (412 vs. 168pg/mL, p = 0.002) but not at the quiescent phase follow-up (p > 0.05). MMP-9 was higher at the time of acute MI versus quiescent phase follow-up in acute MI (412 vs. 213pg/mL, p = 0.001) and atherothrombotic MI specifically (458 vs. 212pg/mL, p = 0.001). No difference in MMP-2, 3, or 9 was observed between atherothrombotic versus non-atherothrombotic MI subgroups. MMPs-3 and 9 are significantly elevated in acute MI verses stable CAD subjects at time of acute MI but not different at quiescent phase follow-up. MMP-9 is elevated at the time of acute MI and specifically in acute atherothrombotic MI at time of MI versus quiescent phase follow-up.

Association of serum apolipoprotein A1 levels with atherothrombotic infarction and plaque properties of carotid artery

The aim of this study is to investigate the association of serum apolipoprotein A1 (ApoA1) levels with ischemic stroke subtypes and plaque properties. We enrolled a total of 113 patients with ischemic stroke and age matched controls (CONT, n=21). The stroke patients were divided into 3 subtypes: cardioembolic (CE, n=15), atherothrombotic (ATBI, n=52), lacunar infarction (LI, n=25). Carotid plaques were into 3 types: low, intermediate, high intensity, and were into 2 types: simple and mixed. Serum lipids (TC, LDL-C, HDL-C, TG), ApoA1, and ApoB were analyzed using commercially available kits. There was no difference in TC, LDL-C, HDL-C, and ApoB levels among 4 groups. Serum ApoA1 levels in the ATBI group were significantly lower compared with CONT groups. Among ATBI group, serum ApoA1 levels in the low intensity plaque type were significantly lower compared with intermediate or hard intensity type. Furthermore, serum ApoA1 levels in the mixed plaque type were significantly lower compared with simple type. These findings suggest that serum ApoA1 levels might be associated with the development of ATBI and plaque properties of carotid artery.

Association of Ultrasonography and MRI Findings with Stroke Recurrence: Differences Between Patients with Past Histories of Atherothrombotic Versus Lacunar Infarctions

Objective: This study investigated the association of MRI and ultrasonography findings with stroke recurrence in patients with past histories of atherothrombotic infarctions (ATIs) or lacunar infarctions (LIs). Methods: We prospectively analyzed the incidence of stroke recurrence. Deep and lobar cerebral microbleeds (MBs), asymptomatic lacunae, asymptomatic intracerebral hemorrhages (ICHs), severe white matter lesions (WML), and intima-media thickness (IMT) were investigated on enrollment. Stroke recurrence rates were compared by using the log-rank test. The odds ratios for recurrent strokes were derived using multivariate logistic regression models, adjusted for risk factors. Results: We evaluated the stroke recurrence rate in 362 ATI patients and 309 LI patients. The log-rank test and multivariate analyses revealed that the incidence of recurrent stroke was significantly higher in ATI patients with mean IMT greater than or equal to 1.1 mm, asymptomatic ICHs, or lobar MBs than in those without. The incidence was significantly higher in LI patients with asymptomatic ICHs, asymptomatic LIs, and severe WMLs than in those without. In ATI patients, those with strictly lobar MBs or mixed MBs (deep and lobar MBs) had significantly higher recurrence rates than those without MB. In LI patients, those with strictly deep MBs or mixed MBs had higher recurrence rates than those without MB, and the incidences of those with mixed MBs was larger than those with strictly deep MBs. Conclusions: There were differences between ATI and LI patients in terms of the association of MRI and ultrasonography findings, in particularly strictly lobar or deep MBs, with the incidence of stroke recurrence.

Baseline Carotid Intima-Media Thickness and Stroke Recurrence During Secondary Prevention With Pravastatin.

Background and Purpose- As a prespecified post hoc analysis of the J-STARS (Japan Statin Treatment Against Recurrent Stroke) Echo Study, the 5-year stroke recurrence rate according to the baseline mean carotid intima-media thickness (IMT) with and without pravastatin treatment was investigated. Methods- Patients were randomly assigned to receive pravastatin 10 mg/day (pravastatin group) or control group (nonstatin treatment; 1:1) for 5 years. Baseline mean IMT of the common carotid artery was measured by ultrasonography. Cox proportional hazards models were used to investigate whether the stroke (any ischemic stroke, atherothrombotic brain infarction, or lacunar infarction) recurrence rate was different according to tertiles of baseline mean IMT. Results- A total of 793 patients, including 388 in the pravastatin group and 405 in the control group, were investigated. In the control group, Cox proportional hazards models showed that participants in the highest tertile IMT group (≥0.931 mm) had a higher rate of atherothrombotic brain infarction than those in the lowest tertile IMT group (<0.812 mm; [hazard ratio, 9.08; 95% CI, 1.15-71.43]). Patients in the pravastatin group had a lower risk of atherothrombotic brain infarction than those in the control group only in the highest tertile IMT group by the log-rank test ( P value=0.045). Conclusions- Long-term pravastatin administration may prevent the occurrence of atherothrombotic brain infarction in noncardioembolic infarction patients with the highest tertile IMT. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00361530.

Statins in Ischemic Stroke Prevention: What Have We Learned in the Post-SPARCL (The Stroke Prevention by Aggressive Reduction in Cholesterol Levels) Decade?

We describe the current status of lipid-lowering therapies for ischemic stroke prevention. The SPARCL trial published in 2006 has been a landmark study in vascular neurology. The trial demonstrated that high-dose atorvastatin prevents recurrent stroke, and led the AHA/ASA to recommend statin therapy for patients with stroke or TIA of atherosclerotic origin. Recently, the J-STARS study demonstrated that therapy with low-dose pravastatin reduced atherothrombotic infarction incidence among patients with prior ischemic stroke. Besides, several trials have shown improved stroke outcomes with non-statin lipid-lowering medications: IMPROVE-IT with ezetimibe on top of simvastatin and PCSK9 inhibitors-FOURIER with evocolumab and ODYSSEY-OUTCOMES with alirocumab-on top of statin therapy. LDL-cholesterol remains the primary lipid treatment target for reduction of stroke risk. Randomized trials have shown that each reduction of 40mg/dL in the level of LDL-cholesterol reduces the stroke risk by approximately one quarter, and further, reductions in LDL-cholesterol levels have shown to produce additional reductions in stroke risk. Currently, we have evidence of benefit for adding non-statin lipid-modifying therapies to statins to reduce stroke risk. Surely, these novel strategies to reduce residual lipidic risk will provide future benefits on stroke prevention.

Vasospasm as a major complication after acute mechanical thrombectomy with stent retrievers

ObjectiveMechanical thrombectomy using a stent retriever for acute large vessel occlusion is indispensable in stroke treatment, however, vasospasm may occur. The objective of this retrospective study was to investigate which cases are more likely to experience vasospasm after thrombectomy with stent retrievers. MethodsWe included 29 patients diagnosed with acute cardiogenic cerebral embolism who were treated with stent retrievers at our facility from December 2014 to December 2017. Atherothrombotic brain infarction cases were excluded because it was difficult to evaluate for vasospasms. Vasospasm was defined as reversible arterial narrowing of <80% of the normal vessel diameter after usage of the stent retriever. The age, sex, type of stent retriever, occlusion site, number of procedures, thrombolysis in cerebral infarction (TICI) grade, degree of vasospasm, intracranial hemorrhage by the procedure, and neurological outcomes were analyzed. ResultsAmong the 29 cases, 12 (41.4%) resulted in vasospasm; nine cases were mild (20–50% stenosis) and 3 cases were severe (≥50% stenosis). Vasospasm frequently occurred in the distal part of the anterior circulation when compared to the proximal part. In addition, the frequency of vasospasm increased as the number of procedures increased. Pooled analysis showed significant difference in the intravenous tissue-type plasminogen activator group (P = 0.029). There was no significant difference in the other groups. ConclusionStent retrievers appear to cause vasospasm more than expected when including mild cases. Vasospasm tends to occur especially in cases with IV-tPA; prognosis is generally good, and it rarely requires any treatment.