Cerebrovascular Diseases最新文献

Background: Intracranial aneurysm (IA), known as pathological dilation of cerebral arteries, commonly occurring at bifurcating arteries, carries a high risk of severe morbidity and mortality if left untreated. Although the treatment and early diagnosis have significantly improved, the complex pathophysiological process of IA formation presents significant challenges in the development of targeted therapies. Efficient disease-modifying therapies for IA are not yet available. This study aimed to utilize the Mendelian randomization (MR) approach to identify potential pharmaceutical targets for preventing and treating IA.

Methods: We systematically identified genetic variants associated with 1,577 druggable genes utilizing gene expression, DNA methylation, and protein expression quantitative trait loci. Genome-wide association study (GWAS) summary statistics were derived from a meta-analysis concentrating on IA, encompassing 10,754 cases and 306,882 controls. Subsequently, we conducted MR analysis integrating the identified druggable genes to estimate the causal effects on IAs. The robustness of the MR results was additionally validated through sensitivity analyses employing diverse techniques, such as the HEIDI test and Bayesian colocalization.

Results: Our study reveals that increased expression of SLC22A5 and SLC22A4 in the blood is associated with higher risk of IA and subarachnoid hemorrhage (SAH), while higher expression of NT5C2 is linked to a reduced risk of IA and SAH. Methylation of SLC22A5 is positively correlated with IA prevalence, while NT5C2 methylation shows an inverse correlation. We also found that higher methylation of CHRNA3 is associated with increased IA prevalence. Additionally, increased blood protein expression of HTRA1 is associated with elevated risks of both IA and SAH; the Bayesian colocalization analysis further supports the involvement of HTRA1 in both IA and SAH.

Conclusion: This large-scale MR analysis pinpointed four druggable target genes associated with IA and SAH, also highlighting HTRA1 as a potential prior druggable protein for medical intervention of IA.

Introduction: Stroke is a major cause of death in China. The epigenetic factors, especially the methylation of ABCA1/G1 genes implicated in cholesterol regulation, are being examined to comprehend their association with stroke.

Methods: In this nested case-control study, we examined data from the Northwest China Cohort (CNC-NX) initial phase. During follow-up, 63 incident stroke cases were identified, of which 10 were excluded due to predefined criteria (e.g., cancer, severe infections, or missing baseline/follow-up blood samples). After 1:1 matching by age, sex, ethnicity, and residence, 53 case-control pairs were initially enrolled. However, due to DNA degradation in long-term stored samples, only 35 matched pairs were ultimately included for analysis. All participants were adults aged ≥18 years. We used conditional logistic regression models to determine the odds ratio (OR) and 95% confidence interval (95% CI) for stroke occurrence.

Results: CpG_10.11.12.13 methylation levels in ABCA1 were associated with stroke risk (OR 0.93, 95% CI: 0.87-0.99), and dynamic changes in CpG_19.20 methylation levels in ABCG1 were associated with stroke risk (OR 1.62, 95% CI: 1.11-2.37). In dynamic methylation, high methylation levels of CpG_19.20 in ABCG1 were associated with a 5.10 times higher risk of stroke compared to low methylation levels (OR 5.10, 95% CI: 1.60-16.30).

Conclusions: In a rural population in northwest China, the hypomethylation status of ABCA1 and ABCG1 genes was strongly associated with the incidence of stroke. Significant correlations between CpG_19.20 methylation levels change in ABCG1 and stroke risk.

Introduction: Elevated blood pressure (BP) is a key modifiable risk factor for cardiovascular (CV) complications in patients with atrial fibrillation (AF). While current guidelines recommend modest BP targets, the optimal target in AF patients remains uncertain. The Cardiovascular Risk Reduction in Atrial Fibrillation Trial (CRAFT) is a multicenter, prospective, randomized, open-label, blinded endpoint trial that evaluates whether intensive home systolic BP control (<120 mm Hg) is superior to standard BP control (<135 mm Hg) in reducing major CV events. The primary outcome is a hierarchical composite of time to CV death, stroke, myocardial infarction, and heart failure hospitalization. A total sample of 1,675 participants provides 80% power to detect a win ratio of 1.50 between groups after a mean of 3 years of follow-up.

Methods: This statistical analysis plan (SAP) was developed by the trial statistician and principal investigators, in collaboration with the Steering Committee and international experts. The SAP specifies the planned analyses of baseline characteristics, patients' intervention, primary and secondary outcomes, subgroup effects, and safety outcomes. Analyses will be conducted on an intention-to-treat analysis using the win ratio method for the primary endpoint and Cox proportional hazards and Poisson regression for secondary analyses. Sensitivity analyses and strategies for handling missing data are also described.

Conclusion: A predefined SAP was established for the CRAFT trial to ensure a transparent and verifiable analysis. The SAP was finalized prospectively, independent of treatment assignment, with the goal of preserving internal validity and minimizing analytical bias.

Introduction: As digital health and artificial intelligence (AI) become integral to medicine, there is a growing need for physicians to develop computational thinking skills. In vascular neurology, a specialty reliant on algorithmic decision-making and complex data interpretation, programming logic (PL) offers a powerful cognitive framework. This review argues that PL can enhance diagnostic precision, clinical efficiency, and data-driven reasoning.. By aligning core programming structures-such as conditional statements, loops, and data abstraction-with clinical workflows, neurologists can improve protocol adherence, patient monitoring, and anatomical localization.

Methods: This narrative review aims to examine how programming logic concepts can enhance clinical reasoning, workflow organization, and data handling in vascular neurology. A non-systematic selection of relevant literature and expert insights was used to support the theoretical discussion.

Review: Programming logic parallels medical reasoning through multiple mechanisms. Concepts such as conditional statements mirror diagnostic algorithms, guiding step-by-step decision-making in acute stroke management. Loop structures reflect the iterative nature of patient monitoring, where repeated neurological assessments are performed based on evolving clinical conditions. Data structuring principles help neurologists organize complex information, improving the analysis of patient registries and clinical trial datasets. Furthermore, debugging methods encourage physicians to systematically re-evaluate diagnoses when patients deviate from expected recovery pathways, refining clinical hypotheses based on new evidence. The modularity principle aligns with stroke care strategies, allowing neurologists to divide complex treatment plans into manageable components spanning acute intervention, secondary prevention, rehabilitation, and long-term outpatient follow-up.. Pattern recognition skills developed through coding are directly applicable to identifying clinical syndromes, neuroimaging findings, and complications. Furthermore, familiarity with programming languages like Python or R enhances a neurologist's ability to manage and analyze clinical data, critically appraise AI-driven evidence, and contribute to the design of error-reducing digital workflows.

Conclusion: While not a substitute for clinical intuition, programming literacy is a complementary skill set that strengthens methodical thinking, innovation, and adaptability. Fostering these skills can improve patient care across the continuum of stroke management, optimize system-level outcomes, and empower neurologists to critically evaluate and co-create the next generation of digital health tools.

Background: The health disparities faced by transgender and gender-diverse (TGD) individuals in accessing healthcare, particularly in the context of non-communicable diseases (NCDs) and cerebrovascular diseases, are a significant public health concern.

Summary: This article highlights the importance of the early identification of NCDs and cerebrovascular diseases in TGD populations, emphasizing the need for culturally competent care and comprehensive healthcare strategies. Gender-affirming hormone therapy plays a crucial role in the health of transgender individuals. Yet, it is associated with increased cardiovascular risk, particularly among transgender females undergoing estrogen therapy. Studies show a higher prevalence of hypertension, hypercholesterolemia, prediabetes, and smoking in the TGD population, reinforcing the need for regular cardiovascular monitoring and targeted preventive strategies. Early identification of NCDs and cerebrovascular disease signs and symptoms is essential in mitigating long-term health complications and improving patient outcomes. Proactive screening and timely interventions can enhance quality of life, reduce healthcare disparities, and contribute to more cost-effective care strategies. Strengthening the integration of diagnostic tools and promoting inclusive healthcare policies will foster greater trust and engagement between transgender individuals and healthcare providers.

Key messages: Overall, this article underscores the need for inclusive healthcare policies and practices that address the unique healthcare needs of TGD individuals, improve health outcomes, and reduce disparities within this vulnerable population.

Introduction: The impact of antihypertensive drugs on functional outcome in patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT) remains controversial and may vary with collateral status (CS). We aimed to investigate the joint effect of CS and antihypertensive drugs on functional outcome in patients with AIS.

Methods: We retrospectively analyzed anterior circulation large-vessel occlusion AIS patients who underwent EVT in our hospital between January 2018 and December 2022. The patients were dichotomized to good CS, reflected by hypoperfusion index ratio (HIR) ≤0.4, and poor CS, reflected by HIR >0.4. Functional outcome was assessed using modified Rankin Scale (90d mRS). The primary outcome was defined as the 90d mRS > 2. The association between antihypertensive drugs within 48 h after EVT and functional outcome was evaluated. Furthermore, the interaction between HIR and antihypertensive drugs was measured.

Results: A total of 372 patients were included. The proportion of patients receiving antihypertensive drugs was comparable between the good CS and poor CS group (51% vs. 56%, p = 0.285). Antihypertensive drugs were significantly associated with higher odds ratio (OR) of unfavorable outcome {OR 3.83 (95% confidence interval [CI], 2.12-6.90); p < 0.001} in poor CS group. No correlation was found in good CS group (p = 0.159). The interaction between antihypertensive drugs and baseline CS was statistically significant (P_interaction = 0.040, adjusted P_interaction = 0.029).

Conclusion: The association between antihypertensive drugs and functional outcome varied based on the CS. These findings suggest that antihypertensive drugs should be used with caution in AIS patients with poor CS after EVT.

Introduction: The influence of multiple long-term conditions on the outcomes from acute ischaemic stroke (AIS) is not well defined. This study aimed to determine the association of multiple long-term conditions in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).

Methods: ENCHANTED was an international, multicentre, 2 × 2 quasi-factorial, open, randomized controlled, blinded endpoint assessed trial that assessed the effectiveness and safety of intensive blood pressure lowering and low-dose thrombolysis against standard of care in adults with AIS. Multiple long-term condition was defined as two or more coexisting chronic conditions according to medical history. The primary outcome was function recovery (distribution of scores on the modified Rankin scale) and mortality at 90 days post-randomization. Associations were estimated in multivariate logistic regression models, and an assessment of heterogeneity was undertaken in subgroups including age, sex, baseline systolic blood pressure, and clinical features.

Results: In 4,566 AIS participants (mean age 66.7 years, 37.8% female), those with multiple long-term conditions were older, more often female, and had more severe neurological impairment. Multiple long-term conditions increased the odds of poor functional outcome (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI]: 1.03-1.30; p = 0.020) and mortality (aOR 1.35, 95% CI: 1.04-1.76; p = 0.024). The association between multiple long-term conditions and mortality/functional outcome was consistent across all subgroups.

Conclusion: Individuals with multiple long-term conditions have higher odds of poor functional outcome and death after thrombolytic treatment for AIS.

Introduction: Moderate blood pressure (BP) reduction reduces hematoma growth, but this has not been shown to translate into improved functional recovery after intracerebral hemorrhage (ICH). This study aimed to define patient profiles according to hematoma growth and functional recovery patterns, and explore the prognostic factors of the patterns.

Methods: Analysis of the Blood Pressure in Acute Stroke Collaboration (BASC) dataset involved randomized controlled trials of early BP lowering in acute ICH. Latent class analysis was used to identify patient profiles by hematoma volume change from baseline to 24 h on outcome trajectories. Clinical outcomes include functional outcomes measured according to modified Rankin Scale (mRS) and serious adverse events at follow-up (usually 90 days). Generalized linear mixed models were used with adjustment of source trial as a random effect for clustering to identify the prognostic factors.

Results: Among 6,221 participants from BASC, 2,450 patients (mean age 64.1 + 13.1 years, female 36.7%) were included. Baseline hematoma volumes (mL) were 6.8, 13.2, 27.1, and 59.2, respectively, for each class identified by patient profiles: no growth with favorable outcome (52.1%, median growth 0.2 [IQR -0.4 to 1.1] mL, median mRS 2 [IQR 1 to 2]), mild growth with disability (32.6%, 0.8 [-0.8 to 4.6] mL, mRS 4 [4 to 5]), moderate growth with death or disability (13.2%, 11.2 [4.9 to 27.0] mL, mRS 4 [3 to 6]), and large growth with death (2.1%, 35.2 [12.8 to 81.2] mL, mRS 6 [6 to 6]). Patients with moderate growth were younger and more likely to undergo neurosurgery than those in the mild or large growth groups. Baseline hematoma volume was the only significant factor associated with all the hematoma pattern groups.

Conclusions: Patients with moderate growth were younger and more likely to receive neurosurgery than those in the mild or large growth groups. Baseline hematoma volume is the most important factor for hematoma growth and clinical outcome.

Introduction: Serum gamma-glutamyl transferase (GGT) was associated with cardiovascular disease. However, limited research has explored the relationship between GGT and polyvascular atherosclerosis.

Methods: This study is based on the baseline cross-sectional survey of the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study, a population-based cohort study. Serum GGT levels were categorized into quartiles. Atherosclerotic plaques and stenosis were evaluated using magnetic resonance imaging and computed tomography angiography. The extent of atherosclerotic plaques and stenosis was assessed based on the number of these 8 vascular sites (e.g., intracranial, extracranial, coronary, subclavian, aortic, renal, iliofemoral, and peripheral arteries) and was classified as affected vascular sites as zero, one, two-three, or four-eight extensive atherosclerotic sites. The correlation of GGT with the presence and extent of plaques and stenosis was assessed by binary logistic and ordinal logistic regression models.

Results: A total of 3,046 participants were included with a mean age of 61.2 ± 6.7 years. GGT levels were associated with the presence (Q4 vs. Q1, odds ratio [OR] 2.14; 95% confidence interval [CI] 1.35-3.39) and the extent (common odds ratio [cOR], 2.08; 95% CI, 1.68-2.57) of atherosclerotic plaques and the presence (OR, 1.57; 95% CI, 1.24-2.00) and extent (cOR, 1.64; 95% CI, 1.30-2.06) of atherosclerotic stenosis after adjusting for age, sex, smoking, and alcohol consumption. However, associations were not significant after further adjusting for body mass index, low-density lipoprotein cholesterol, hypertension, diabetes mellitus, dyslipidemia, and medication history.

Conclusion: GGT levels were associated with the presence and burden of atherosclerotic plaques and stenosis but not after adjusting some metabolism-related factors.