International Journal of Stroke最新文献

Background: Lithium, a naturally occurring element in drinking water, has demonstrated beneficial effects for stroke in prior research, yet its relationship with stroke risk in the general population remains uncertain.

Aims: To evaluate the association between environmental lithium exposure and stroke risk.

Methods: We assessed environmental lithium exposure across the US using monitoring data of 4,700 wells for drinking groundwater from the US Geological Survey. Ecological and individual-level analyses were conducted. Ecological associations between county level lithium concentration and stroke mortality (2015-2019) were evaluated in 3108 counties using multivariable linear regression adjusted for county-level socioeconomic factors. Individual level associations were examined in 303153 adults (≥35 years old) from the All of Us Research Program with electronic health records followed up through October 1, 2023 using stratified Cox models adjusted for individual-level sociodemographic, behavioral, and clinical factors. Lithium was analyzed per interquartile range (IQR) increase and by quartiles.

Results: In ecological analysis, each IQR increase in lithium exposure corresponded to 8.2 fewer stroke deaths per 100,000 population (95% CI: -9.8, -6.5). Compared with the lowest quartile (≤6.6 µg/L), the highest quartile (>23.3 µg/L) showed 22.6 fewer deaths per 100,000 (95% CI: -27.4, -17.8); middle quartiles were not associated. In All of Us, each IQR increase was associated with a 23% lower incident stroke risk (HR=0.77, 95% CI: 0.66, 0.90). The highest exposure quartile (>17.7 µg/L) had a 52% lower risk (HR=0.48, 95% CI: 0.34, 0.67) versus the lowest; second (HR=1.23, 95% CI: 0.73, 2.09) and third (HR=0.92, 95% CI: 0.50, 1.69) quartile showed non significant associations. Results were robust to alternate exposure windows and residential stability restrictions.

Conclusion: Higher naturally occurring lithium concentrations in US groundwater are associated with reduced stroke mortality and incidence, whereas low to moderate levels confer no benefit.

Background: Vertebral artery origin stenosis (VAOS) is a common cause of posterior circulation ischemic events, and endovascular treatment serves as an alternative treatment. However, conventional endovascular treatment methods are related to high risk of restenosis. It is unclear whether the drug-coated balloon (DCB) can reduce restenosis risk of VAOS.

Methods: This was a prospective, multicenter, randomized trial conducted from 6 January 2020 to 1 October 2023 in China. Symptomatic patients with severe VAOS were randomly allocated in a 1:1 ratio to undergo either DCB or bare-metal stent (BMS) and followed up for 12 months. The primary safety endpoint was the incidence of transient ischemic attack, stroke, or death related to target vessel within 30 days post-procedure. The primary efficacy endpoint was the rate of 12-month restenosis.

Results: A total of 179 patients were enrolled with 91 in the DCB group and 88 in the BMS group. No significant difference was observed in the rates of transient ischemic attack, stroke, or death related to target vessel within 30 days between the DCB and BMS groups (0 (0.0%) vs. 1 (1.1%); P = 0.49). The 12-month restenosis rate was significantly lower in the DCB group compared to the BMS group (10/76 (13.2%) vs. 27/76 (35.5%); risk ratio = 0.37; 95% confidence interval = 0.19 to 0.71; P = 0.001).

Conclusion: This trial demonstrated that DCB may reduce restenosis risk in symptomatic patients with severe VAOS compared to BMS.

Registration: URL: https://clinicaltrials.gov (unique identifier: NCT03910166).

Background: High-density lipoprotein cholesterol (HDL-C) is traditionally considered protective in cardiovascular disease, but its role in acute ischemic stroke (AIS) remains unclear, particularly in patients undergoing mechanical thrombectomy (MT). This study aimed to assess the association between HDL-C levels and clinical outcomes in AIS patients treated with MT for anterior circulation large vessel occlusion (LVO).

Methods: We conducted a multicentre, observational, post hoc analysis of AIS patients treated with MT between January 2016 and March 2023 across three stroke centers. HDL-C levels at admission were categorized, and outcomes included 90-day functional dependence (mRS: 3-6), symptomatic intracranial hemorrhage (sICH), hemorrhagic transformation, and 90-day mortality. We used logistic regression with restricted cubic splines to define an HDL-C threshold associated with increased risk and applied inverse probability weighting (IPW) to adjust for confounding.

Results: Among 2166 patients (median age: 71 years; 52.3% female), HDL-C levels > 1.33 mmol/L were independently associated with a higher risk of poor functional outcome at 90 days (risk ratio (RR): 1.72, 95% confidence interval (CI): 1.55-1.90), increased odds of sICH (RR: 2.3, 95% CI: 1.64-3.12), and higher mRS shift (OR: 2.10, 95% CI: 1.79-2.46). Subgroup analyses revealed significant sex-specific differences, with women at greater risk of adverse outcomes at higher HDL-C levels.

Conclusion: Elevated HDL-C levels (>1.33 mmol/L) are associated with worse functional outcomes and increased hemorrhagic complications following MT for anterior circulation AIS.

This World Stroke Organization Scientific Statement highlights how sex and gender differences shape stroke risk, treatment, care, and research. Estrogen confers a relative protection before menopause, with risk increasing thereafter. Beyond shared cardiovascular determinants (hypertension, atrial fibrillation, and diabetes), women face sex-specific risks-hypertensive disorders of pregnancy, menopause, and hormone therapy, with clear implications for stroke prevention and management. Despite comparable efficacy of acute and secondary stroke therapies in women and men, women are less likely to receive timely acute treatment and often experience delays in recognition and access. The statement recommends gender-responsive prevention and care pathways; systematic consideration of pregnancy-related and menopausal factors; and public and professional education to improve stroke symptom recognition and purposeful inclusion of women across the research continuum. By integrating evidence from epidemiology, acute care, and secondary prevention, this statement provides clear and timely guidance for reducing inequities and shaping future research and policy to achieve equitable stroke care globally.

Background and aims: FLAIR vessel hyperintensities (FVH)-Alberta Stroke Program Early CT Score (ASPECTS) is an imaging marker but its clinical implications remain unclear. We estimated the correlation between FVH-ASPECTS and clinical outcomes in patients with wake-up stroke or unknown time of stroke onset.

Methods: The THrombolysis for Acute Wake-up and Unclear-onset Strokes with Alteplase at 0.6 mg/kg (THAWS) trial was a multicenter, randomized controlled trial conducted at 40 sites in Japan between 2014 and 2018. Patients with unknown stroke onset and diffusion-weighted imaging (DWI)-FLAIR mismatch were randomly assigned to receive either intravenous alteplase (0.6 mg/kg) or standard medical treatment. FVH-ASPECTS, a semiquantitative scoring system assessing FVH prominence in the seven cortical ASPECTS regions, was evaluated for its association with favorable outcomes (modified Rankin Scale 0-2 at 90 days). The optimal FVH-ASPECTS threshold was determined using receiver operating characteristic (ROC) analysis and its correlation with favorable outcomes was assessed.

Results: Among 131 patients (mean age, 76 ± 13 years; 42% women), 71 received alteplase and 60 did not. Median NIHSS score was 7 (interquartile range [IQR] 4-13), and median FVH-ASPECTS was 4 (IQR 2-4). ROC analysis identified FVH-ASPECTS 3 or more as predictive of favorable outcomes (sensitivity 80%, specificity 51%, area under the ROC curve [AUC] 0.717). A significant correlation was observed between FVH-ASPECTS 3 or more and favorable outcomes (adjusted odds ratio [OR] 4.50, 95% confidence interval [CI] 1.89-10.75; p < 0.001).

Conclusion: FVH-ASPECTS could offer an indicator for achieving favorable clinical outcomes among stroke patients with unknown time of onset, with a threshold of 3 or more.

Background and aims: Clopidogrel may be a less effective antiplatelet agent for secondary prevention after cardiovascular events in carriers of the CYP2C19 Loss of Function (LoF) allele. Randomized controlled trials (RCTs) of clopidogrel in patients with known CYP2C19 carrier status have provided inconsistent results. This meta-analysis aims to pool evidence on the effect of different antiplatelet strategies on outcomes according to CYP2C19 LoF status.

Methods: We conducted a systematic review and meta-analysis of RCTs to evaluate the interaction of CYP2C19 LoF allele on clopidogrel versus placebo or other antiplatelet agents in patients with cardiovascular disease or transient ischemic attack (TIA) or ischemic stroke. Primary outcomes were major adverse cardiovascular events (MACEs) including ischemic stroke, with major bleeding events assessed as a safety outcome. Random effects analysis estimated pooled odds ratios for LoF carriers and non-carriers.

Results: Fifteen RCTs with 35,189 participants in total were included. When all interaction effects are pooled, the occurrence of MACE was 1.29 times higher in LoF variant carriers compared to non-carriers for clopidogrel treatment (p-interaction = 0.01). Risk of MACE was 1.20 times higher in LoF carriers compared to non-carriers when clopidogrel was compared to placebo (p-interaction = 0.13). In TIA or minor stroke patients, the interaction effect was 1.63 times larger (p-interaction = 0.02). Clopidogrel was less effective than prasugrel for MACE occurrence (1.57 times higher, p-interaction = 0.02) and ticagrelor (1.21 times higher, p-interaction = 0.19) in CYP2C19 LoF variant carriers. Bleeding outcomes were similar across groups.

Conclusion: Clopidogrel is less effective in patients with CYP2C19 LoF genotype and cardiovascular disease, minor stroke, or TIA. The size and direction of the interaction warrant further research into the role of LoF genotypes and the cost-effectiveness of genetic testing. Prasugrel may be a more effective alternative for CYP2C19 LoF carriers.Registration-URL:https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021242993.

Background: Rheumatoid arthritis (RA) has been associated with an increased stroke risk, but associations by serostatus (seropositive RA (SPRA) vs seronegative RA (SNRA)) and with subtypes of stroke (ischemic stroke (IS) or hemorrhagic stroke (HS)) are not well established. In addition, it is not well-known whether the use of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) are associated with altered stroke risk.

Methods: This nationwide cohort study used the Korean National Health Insurance Service database and included participants who were first diagnosed with RA in the period 2010-2017 with no previous history of stroke, and who had a health checkup within 2 years before the index date (45,175 RA patients). They were compared (1:3 ratio) with non-RA controls matched by age and sex (135,525 non-RA controls).

Results: Patients with RA had a significantly higher risk of both IS (adjusted hazard ratio (aHR) = 1.47, 95% confidence interval (CI) = 1.36-1.58) and HS (aHR = 1.31, 95% CI = 1.15-1.50) compared to controls. SPRA patients showed higher risk for both IS (aHR = 1.56, 95% CI = 1.43-1.69 SPRA vs aHR = 1.23, 1.08-1.41 SNRA) and HS (aHR = 1.40, 95% CI = 1.21-1.62 SPRA vs aHR = 1.09, 95% CI = 0.86-1.38 SNRA). No difference in stroke risk was observed between bDMARDs users and non-users (aHR = 1.66 for users, aHR = 1.41 for non-users). However, potential differences were noted with tsDMARDs use (aHR = 0.81 for users vs aHR = 1.43 for non-users), although not statistically significant.

Conclusion: Patients with RA are at significantly greater risk for both IS and HS compared to those without RA, and SPRA patients showed higher risk than SNRA patients. Further studies are required to determine the potential of tsDMARDs in the prevention of stroke in RA.

Background: Intracranial arterial calcification (ICAC) is common, but data on its impact on future stroke risk and outcomes remain limited. We conducted a systematic review and meta-analysis to investigate the association of ICAC with stroke risk and outcomes.

Methods: We searched three multidisciplinary databases from inception to July 2025. We selected studies that investigated incidence of stroke and its outcomes in patients with ICAC. We assessed the studies' risk of bias using the Newcastle Ottawa Quality Assessment Scale. Statistical analysis was conducted using Cochrane Review Manager (RevMan 5.4).

Results: After reviewing 660 citations, we selected 94 studies for full-text screening. We extracted data from a total of 20 studies, reporting outcomes on 14,599 patients. Overall, the risk of bias was low. The included studies were heterogeneous, with varying outcomes assessed and differing measures of associations reported. ICAC was associated with an increased risk of ischaemic stroke, with a pooled odds ratio (OR) of 2.28 (95% confidence interval (CI): 1.39-3.73), and one study reported a hazard ratio (HR) of 1.49 (95% CI: 1.24-1.78). ICAC also showed a trend toward increased mortality, with a pooled OR 1.40 (95% CI: 0.96-2.05) and high heterogenicity across the studies (I² = 65%). The pooled HR per 1-standard deviation (1-SD) increase in ICAC was 1.25 (95% CI: 1.10-1.42), with low heterogenicity (I² = 1%) between 2 studies reporting the HR.

Conclusions: ICAC is significantly associated with an increased risk of stroke as well as a trend toward increased mortality (PROSPERO ID: CRD42023414813).

Background: Patients with acute ischemic stroke secondary to distal and medium vessel occlusion (AIS-DMVO) and minor strokes present a challenge in determining the most appropriate emergent treatment. Factors leading to early neurological deterioration (END) in this patient population are understudied, but END is known to result in poor functional outcomes. Therefore, we aimed to investigate the factors contributing to END in minor AIS-DMVO cases.

Methods: We included patients with AIS-DMVO and minor strokes from 37 sites across North America, Asia, and Europe. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score of ⩽5. The primary outcome measure, END, was defined as a shift of ⩾4 points in the NIHSS score at day one after treatment compared to baseline. Univariable and multivariable logistic regression analyses were performed to identify factors associated with END.

Results: Among 559 consecutive patients with DMVO and minor strokes, END was reported in 68 patients. In multivariable analysis, mechanical thrombectomy (MT) was independently associated with higher odds of END (adjusted odds ratio [aOR] 2.37, 95% CI 1.12-5.02, p = 0.02), while intravenous thrombolysis (IVT) was associated with lower odds of END (aOR 0.46, 95% CI 0.26-0.81, p = 0.008). However, the association between MT and END was no longer statistically significant in the IPTW-adjusted analysis (OR 1.65, 95% CI 0.69-3.98, p = 0.26). Hypertension and antiplatelet use at baseline were also independently associated with END. Among MT-treated patients, successful and excellent recanalization and first-pass effect were protective against END.

Conclusion: MT was associated with END in patients with minor AIS-DMVO, although this association was not significant after IPTW adjustment. IVT was independently associated with reduced risk of END. These findings support careful patient selection and further study in randomized trials.