Search Results (245)

Background/Objectives: The apelin/APJ system has demonstrated neuroprotective effects in experimental studies by regulating key pathogenic mechanisms of ischemic stroke, including oxidative stress, apoptosis, cerebral edema, and inflammation. This study aimed to investigate the role of serum apelin levels measured within the first 24 h in predicting 28-day and long-term mortality in patients with ischemic cerebrovascular disease. Methods: This prospective cohort study included 44 patients hospitalized with a diagnosis of acute ischemic stroke due to large artery atherosclerosis. Serum apelin levels were measured using the ELISA method from blood samples obtained within the first 24 h after symptom onset. Patients were prospectively followed for 28-day and long-term mortality. Results: During the follow-up period, 32.6% of the patients died. The median serum apelin level was significantly higher in the deceased group compared to the survivors [105.0 pg/mL vs. 55.8 pg/mL]. In ROC analysis, the area under the curve (AUC) for apelin in predicting mortality was 0.727 (95% CI: 0.550–0.903). The optimal cut-off value was determined as ≥70.47 pg/mL (sensitivity: 85.71%, specificity: 62.07%). In Kaplan–Meier analysis, the 28-day mortality rate was 52.2% in the high-apelin group (≥70.47 pg/mL), whereas it was 10.0% in the low-apelin group (<70.47 pg/mL) (p = 0.004). In multivariate Cox regression analysis, an apelin level <70.47 pg/mL was identified as an independent prognostic factor (HR: 0.16; 95% CI: 0.03–0.94). The cumulative survival rates at days 28, 56, and 180 were 56.1%, 46.7%, and 11.7%, respectively, in the high-apelin group, while these rates were 100%, 100%, and 81.8%, respectively, in the low-apelin group. The mean NIHSS score was significantly higher in the high-apelin group, and a strong, positive, and highly significant correlation was found between serum apelin level and NIHSS score (r = 0.703, p < 0.001). Conclusions: High serum apelin levels measured within the first 24 h in acute ischemic stroke are associated with increased 28-day and long-term mortality. The association of high endogenous apelin levels with poor prognosis in the clinical setting suggests that apelin is mobilized as a stress response during ischemia, and that elevated circulating levels may actually reflect the severity of the ischemic insult. Full article

Background: Assessment of cerebrovascular reserve capacity (CVRC) is central to treatment planning in adult Moyamoya disease. [¹⁵O]-water-PET with acetazolamide challenge (PET-ACZ) serves as the reference standard but is resource-intensive and not universally available, whereas breathhold BOLD MRI (bh-fMRI) may offer a practical noninvasive alternative for screening and triage. Methods: This retrospective diagnostic accuracy study compared bh-fMRI and PET-ACZ in 67 adult MMD patients (1072 ROIs across 402 supratentorial vascular territories) to determine correlation and clinically useful MRI thresholds for impaired cerebrovascular reserve. Data were analyzed using Pearson’s correlation and ROC curves (STARD-compliant). Cerebellum-normalized percent signal change (CN-PSC) was referenced against PET-ACZ < 66% for pathological CVRC. Results: Supratentorial territories showed strong correlation (r = 0.71, 95%CI 0.62–0.80). Optimal diagnostic threshold was <28.2% CN-PSC on bh-fMRI (Youden index; sensitivity 83.8%, specificity 80.9%, AUROC = 0.87); screening threshold < 60% CN-PSC yielded sensitivity 94.6% and NPV 91.1%. No patient factors (age, Suzuki stage, etc.) influenced agreement (univariate/multivariate analyses). Conclusions: Bh-fMRI supplements PET-ACZ as a screening and diagnostic tool for cerebrovascular reserve impairment in adult MMD. PET remains the reference standard for confirmation, especially in intermediate or discordant cases, and the proposed thresholds (<30% CN-PSC: impaired CVRC; 30–60%: confirm with PET-ACZ; >60%: monitor) require prospective validation before routine decision-making use. Full article

Background: Candida auris (C. auris) has emerged as a multidrug-resistant fungal pathogen causing healthcare-associated outbreaks worldwide, particularly in intensive care units (ICUs). Its environmental persistence, multidrug resistance, and high mortality make it a major challenge for infection prevention and clinical management. This study aimed to investigate the clinical characteristics, clinical exposures, treatment outcomes, and mortality of adult ICU patients with C. auris candidemia during the first 30 months after the opening of a tertiary care hospital. Methods: This retrospective observational study included all adult patients (≥18 years) admitted to five ICUs between 1 July 2020 and 31 December 2022 who developed culture-confirmed C. auris candidemia. Isolates were identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) with the Microflex LT/SH Smart MS system (Bruker Daltonics, Bremen, Germany) according to routine microbiological laboratory procedures. Demographic characteristics, underlying diseases, invasive procedures, clinical exposures, microbiological findings, treatment, APACHE II scores, and clinical outcomes were retrospectively analyzed. Results: During the 30-month study period, 3716 adult patients were admitted to the ICUs, and candidemia developed in 432 (11.6%). Of these episodes, 22 (5.1%) were caused by C. auris. The first C. auris candidemia case occurred 184 days after hospital opening. The mean age was 55 ± 17 years, and overall ICU mortality was 77.3%. Sepsis (36.4%), malignancy (22.7%), and cerebrovascular disease (18.2%) were the most common reasons for ICU admission. All patients had received broad-spectrum antibiotics, whereas central venous catheterization and invasive mechanical ventilation were present in 77.3% of cases. The mean interval from ICU admission to candidemia was 49 ± 15 days. Caspofungin was used as first-line antifungal therapy in all patients. Non-survivors had significantly higher APACHE II scores (32.8 ± 4.9 vs. 26.4 ± 6.6, p = 0.029) and predicted mortality rates (80.1% vs. 53.3%, p = 0.012). Antifungal treatment duration was significantly shorter among non-survivors (p < 0.001), whereas no significant differences were observed in age, ICU length of stay, or time to blood culture clearance. Conclusions: C. auris candidemia was observed in critically ill patients with prolonged ICU stays and frequent invasive interventions and was associated with high all-cause ICU mortality. Higher APACHE II scores were associated with mortality in this cohort, reflecting greater baseline severity of illness. Given the small sample size and descriptive, exploratory nature of the study, these findings should be interpreted with caution. The effectiveness of specific infection-control, diagnostic, or therapeutic interventions was not evaluated. Larger multicenter prospective studies are needed to better characterize the epidemiology, clinical outcomes, and factors associated with mortality in C. auris candidemia. Full article

The tree shrew (Tupaia belangeri) is increasingly recognized as an important experimental model for studying human diseases due to its close phylogenetic relationship with humans. Because the basilar artery’s response to endogenous vasoactive mediators varies among species, we investigated the effects of vasoactive substances on isolated tupaia basilar arteries to determine whether this species is suitable as a human model. 5-Hydroxytryptamine (5-HT) and histamine (His) induced contraction, while bradykinin (BK) and acetylcholine (ACh) produced concentration-dependent relaxation. Pharmacological analysis revealed that contractions triggered by 5-HT were regulated through 5-H₁ and 5-HT₂ receptors, while His-induced responses were mediated by H₁ receptors. BK-induced relaxation was inhibited by the B₂ antagonist HOE140 and N^ω-nitro-L-arginine (L-NA), but not by B₁ antagonists or indomethacin, suggesting a B₂ receptor-mediated nitric oxide (NO) pathway. ACh-induced relaxation was markedly reduced in the presence of L-NA and the M₃ antagonist pFHHSiD, indicating M₃ receptor-mediated NO release. At basal tone, L-NA evoked a contractile response, while indomethacin led to relaxation, suggesting basal regulation by NO and prostanoids. These findings demonstrate that 5-HT₁/5-HT₂ and H₁ receptors mediate contraction, while B₂ and M₃ receptors mediate relaxation in the tupaia basilar artery. This study highlights species-specific cerebrovascular regulation and supports the tupaia as a relevant model for investigating human cerebrovascular physiology and pathophysiology. Full article

Background/Objectives: Italy is among the countries with the highest life expectancy and extreme longevity worldwide, yet marked regional disparities persist. This nationwide ecological study examined temporal trends in population aging and extreme longevity across the 20 Italian regions (1982–2025) and explored regional correlates non-communicable disease (NCD) mortality and contemporary behavioral/nutritional indicators, with attention to emerging southern hotspots such as Cilento. Methods: Longevity indicators (Aging Tendency, Longevity Index [LI%], Centenarity Index [CI%], 85+ and 90+ ratios) were derived from ISTAT demographic data. Age-standardized mortality rates for five major NCDs (1990–2023) were obtained from WHO HFA-DB. Behavioral and nutritional indicators for adults aged ≥65 years (2024) were extracted from HFA-Italy. Regional associations were assessed using Spearman correlations within an ecological, hypothesis-generating framework. Results: All longevity indicators increased steadily from 1982 to 2025, with northern and central regions showing the highest values. Lower long-term mortality from diabetes mellitus and cerebrovascular diseases showed the strongest regional correlations with higher LI% and CI%. Nutritional profiles were generally more favorable in northern regions. The Cilento area emerged as a notable southern hotspot, displaying longevity indicators comparable to Sardinia and above the regional average. Conclusions: Regional patterns of extreme longevity in Italy reflect the interplay of demographic dynamics, NCD mortality burden, and contemporary lifestyle profiles. While northern regions maintain a clear advantage, specific southern areas such as Cilento demonstrate that favorable longevity outcomes can emerge in diverse macro-regional contexts. These findings highlight the value of regionally tailored strategies to promote healthy aging and reduce geographical disparities. Full article

Atherosclerosis (AS) is the primary underlying cause of cardiovascular and cerebrovascular diseases. The occurrence and development of AS are closely related to lipid deposition, chronic inflammation, phenotypic modulation of vascular smooth muscle cells (VSMCs), and extracellular matrix (ECM) remodeling. Numerous studies indicate that low-density lipoprotein receptor-associated protein 1 (LRP1), as a multifunctional receptor, contributes to vascular homeostasis in AS and vascular remodeling by regulating lipid handling, inflammatory responses, transforming growth factor beta (TGFβ) signaling, and platelet-derived growth factor receptor beta (PDGFRβ) trafficking. Rather than treating the LRP1-TGFβ-PDGFRβ relationship as a fully established linear pathway, this review distinguishes demonstrated mechanisms from inferred cross-talk and proposes an integrated, cell- and stage-dependent regulatory model. This article systematically elaborates on the structure and function of LRP1; LRP1-mediated regulation of TGFβ and PDGFRβ in AS and vascular remodeling; the possible relationship among LRP1, TGFβ, and PDGFRβ; and cell-specific effects in VSMCs, macrophages, endothelial cells, and pericytes. Meanwhile, this article summarizes potential translational strategies such as lipid-lowering, anti-inflammatory therapy, PDGFRβ inhibitor repositioning, TGFβ pathway modulation, biomarker-based stratification, and LRP1-targeted delivery. A deeper understanding of the cell-specificity and stage-dependence of the LRP1-TGFβ-PDGFRβ signaling network may help elucidate the progression mechanism of AS and provide new ideas for risk stratification and precise intervention. Full article

Background/Objective: Intracranial arteriovenous malformations (AVMs) are high-flow cerebrovascular lesions associated with a significant risk of intracranial hemorrhage, neurological morbidity, and mortality. Current management strategies, including microsurgical resection, endovascular embolization, stereotactic radiosurgery, and conservative observation, remain limited by procedural risk and uncertain long-term outcomes. Beta-blockers, particularly propranolol, have recently attracted interest as potential adjunctive therapies because of their vasoconstrictive, antiangiogenic, and vascular remodeling properties. This review evaluates the mechanistic rationale and current evidence regarding beta-blocker use in intracranial AVMs. Methods: A comprehensive literature review was conducted using PubMed, Scopus, and Google Scholar databases through January 2026 using combinations of the terms “arteriovenous malformation,” “AVM,” “beta-blocker,” “propranolol,” “angiogenesis,” “hemorrhage,” and “cerebral cavernous malformation.” Eligible studies included experimental investigations, translational studies, observational cohorts, case reports, clinical trials, systematic reviews, and meta-analyses evaluating beta-blocker use in intracranial AVMs or related vascular malformations. Studies unrelated to cerebrovascular lesions, duplicate reports, and non-English publications were excluded. Given the heterogeneity and limited volume of available AVM-specific literature, findings were synthesized narratively rather than through formal systematic review methodology. Discussion: Preclinical studies suggest that beta-blockers modulate molecular pathways implicated in AVM pathophysiology, including VEGF, HIF-1α, SDF1α/CXCR4, MMP-9, and Notch-associated signaling. These mechanisms may reduce abnormal angiogenesis, endothelial instability, and pathological vascular remodeling. Clinical evidence, however, remains limited to retrospective studies, perioperative reports, and indirect evidence from cerebral cavernous malformations. Observational studies have reported associations between beta-blocker exposure and certain favorable AVM characteristics, including lower rates of hemorrhagic presentation and less complex angioarchitecture. However, these findings are highly susceptible to confounding, reverse causation, and selection bias and should not be interpreted as evidence of disease modification. Conclusions: Beta-blockers cannot currently be recommended as definitive therapy for intracranial AVMs. Their established role remains perioperative hemodynamic control, while potential disease-modifying effects require validation through prospective studies and randomized clinical trials. Full article

Alzheimer’s disease (AD), the leading cause of dementia, is characterized by progressive cognitive decline along with hallmark brain pathologies including amyloid-beta accumulation, hyperphosphorylated tau, neuroinflammation and neuronal mitochondrial dysfunction. As current pharmaceutical treatments only provide modest symptomatic improvement, there is an urgent need for effective non-pharmaceutical treatment options for the prevention or slowing down of this disease. This review synthesizes results from randomized controlled trials, observational studies, and animal model research on the ability of exercise to influence cognitive functions, brain structural changes, inflammatory processes, and neuroplasticity-related pathways. Exercise has demonstrated the capacity to enhance neurotrophic signaling, improve the regulation of mitochondria, improve cerebrovascular function and reduce pro-inflammatory cytokine levels in preclinical and mild cognitive impairment (MCI) subjects. Additionally, aerobic and resistance training has been shown to enhance physical performance and functional capacity. Furthermore, mind–body, dual-task and multimodal types of interventions may also provide additional cognitive and psychological benefits. Although the overall cognitive effect of exercise in individuals with established AD is generally small, it has been demonstrated that exercise can contribute to maintaining brain health through multiple interconnected metabolic, vascular and molecular pathways, thereby preserving cognitive reserve and slowing disease progression, particularly when initiated during early to midlife prior to the onset of AD symptoms. Therefore, future research will require establishing stage-specific exercise recommendations based on modality type, intensity and duration to achieve optimal clinical outcomes. Full article

Type 2 diabetes mellitus is a systemic metabolic disorder with an extensive spectrum of complications, which still persist despite improvements in glycemic control. Emerging evidence suggests that gut dysbiosis may be an underpinning factor in the pathogenesis of both microvascular and macrovascular complications associated with diabetes. This narrative review explores the relationship between gut microbiota and the development of diabetes complications, including nephropathy, retinopathy, neuropathy, cardiovascular, cerebrovascular, peripheral vascular, and reproductive system disorders. First, existing evidence regarding the nature of shared and organ-specific microbial patterns is summarized. Next, key mechanistic pathways of inflammation and metabolism underlying tissue damage induced by dysbiosis are illustrated. Lastly, the role of gut microbiota and inflammaging as modifiers of these processes is described. Emerging clinical and translational implications are finally discussed, underscoring the promises of microbiota-based diagnostics as well as therapeutics that could serve as add-on approaches to the management of diabetic complications, alongside the application of artificial intelligence-based approaches to microbiome data analysis which may enhance biomarker discovery and risk stratification. Overall, although most evidence remains associative, increasing data support that gut microbiota dysbiosis may represent a potential disease modifier in the development of various diabetic complications. Further longitudinal and mechanistic studies are needed to clarify causality and to evaluate the clinical utility of microbiome-targeted interventions, including AI-assisted predictive models, in preventing or mitigating diabetic complications. Full article

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening cerebrovascular condition characterized by a dynamic clinical course spanning distinct pathophysiological stages, including aneurysm rupture, early brain injury (EBI), delayed cerebral vasospasm, and long-term neurological outcome. Despite extensive research, no clinically applicable molecular biomarkers exist to predict disease trajectory across these stages. MicroRNAs (miRNAs), small non-coding RNA molecules detectable in blood and cerebrospinal fluid (CSF), have emerged as promising candidates due to their stability and close association with vascular, inflammatory, and neuronal processes. However, existing studies have largely evaluated miRNAs in isolation, without integrating findings into a unified temporal framework. This review provides a structured, translational synthesis of miRNA dynamics in aSAH and proposes a stage-specific conceptual model integrating prospective clinical evidence with the broader literature. Dual-biofluid profiling has identified miR-29a, miR-200a-3p, and miR-451a as robust rupture-associated biomarkers, with distinct compartment-specific expression patterns. CSF-based profiling has demonstrated that miR-221-3p, miR-9-3p, and miR-183-5p predict vasospasm within 24 h of hemorrhage, while miR-24 and miR-21-5p correlate with disease severity and poor outcome. Integrating these findings with the broader literature, we categorize miRNA signatures across four stages: rupture discrimination, early brain injury, vasospasm prediction, and outcome stratification. This stage-specific framework highlights the biological continuum linking endothelial injury, vascular dysfunction, and secondary brain damage. The proposed model provides a foundation for multi-marker biomarker development, prospective validation studies, and future precision medicine strategies in aSAH. Full article

Sodium–glucose cotransporter-2 (SGLT2) inhibitors, initially developed as antidiabetic agents, have recently gained attention for their potential role in modulating processes relevant to Alzheimer’s disease (AD). Preclinical studies suggest that they may influence key mechanisms involved in AD. However, available clinical studies, mainly retrospective and focused on diabetic populations, provide insufficient clarity on whether these effects extend to broader, non-diabetic groups. The heterogeneity of neurodegenerative diseases, which differ in inflammatory and proteotoxic mechanisms, further highlights the need for disease-specific investigations. This review examines mechanistic pathways through which SGLT2 inhibition may influence AD progression and evaluates current clinical evidence, aiming to identify key knowledge gaps and guide future research. This review summarises the latest evidence from the literature, focusing on preclinical experiments, translational studies and early clinical observations. The search focused on pathways related to microglial and astrocytic activation, oxidative stress, metabolic remodeling, neuronal survival, and amyloid and tau dynamics. Accumulating data indicate that SGLT2 inhibitors exert multifaceted actions relevant to AD pathology, including reduced neuroinflammation and oxidative stress, improved mitochondrial and insulin signaling, as well as decreased amyloid deposition and tau hyperphosphorylation. Additionally, SGLT2 inhibition may improve cerebrovascular perfusion and blood–brain barrier stability, potentially supporting cognitive function. Nonetheless, major challenges remain, including variable blood–brain barrier permeability and heterogeneous experimental responses. SGLT2 inhibitors represent a promising pleiotropic class of compounds with potential disease-modifying effects in AD. Their capacity to target metabolic, inflammatory, and proteotoxic pathways makes them attractive candidates for neurodegenerative therapy. Further studies are required to clarify biochemical pathways and validate clinical efficacy. Full article

The cardiovascular risk imposed by chronic kidney disease is significantly enhanced, and carotid atherosclerosis is an early indicator of systemic vascular damage. In this review, we summarize available data relative to primary prevention strategies for carotid atherosclerosis in chronic kidney disease (CKD) with a focus on risk-adapted and stage-specific management. We conducted a narrative review of the literature. A structured literature search was performed in major databases (PubMed, Scopus, Web of Science and Google Scholar), focusing on studies published between 2012 and 2025, including observational studies, randomized controlled trials, and international guideline recommendations. The review focuses on blood pressure management, lipid-lowering therapy, glycemic control, antiplatelet therapy, as well as lifestyle interventions and screening strategies in patients with CKD without a history of cerebrovascular events. CKD-specific processes, such as inflammation, endothelial dysfunction and vascular calcification, may influence the progression of carotid plaques, highlighting the need to improve traditional and non-traditional risk factor management. The focus of prevention continues to emphasize blood pressure (BP) and lipid control as well. At the same time, routine carotid screening and systematically implemented antiplatelet therapy have no known benefit, but the potential for elevated bleeding risk, especially in advanced CKD. Primary prevention should therefore focus on optimal medical treatment, as well as disease-specific strategies according to CKD stage. Additional CKD-specific studies with carotid endpoints are necessary. Full article

Background: Neurological disorders are a leading cause of disability worldwide, placing increasing strain on healthcare systems. In Eastern Europe, and specifically Bulgaria, there is a significant lack of granular data regarding how ambulatory neurology services are utilized and how clinical workloads are distributed across different diagnostic groups. Objective: In this study, we aimed to analyze the clinical workload, demographic patterns, and diagnostic distribution within a single-center ambulatory neurology setting in Bulgaria, while identifying the primary determinants of patient age stratification. Methods: We conducted a retrospective observational study of 518 consecutive clinical encounters recorded over a one-year period in a specialized outpatient neurology clinic. Data on age, gender, visit type (ambulatory vs. dispensary), and ICD-10 diagnostic groups were analyzed. Inferential analyses included a one-way ANOVA for age differences and multivariable linear regression to identify independent predictors of age patterns, with age modeled as a continuous variable. Results: The clinical workload was highly concentrated, with spine-related disorders accounting for over 40% of all visits, and primary consultative examinations were the predominant service type (65.4%). Statistical analysis revealed significant age differences across diagnostic categories (p < 0.001), with neurodegenerative and cerebrovascular diseases associated with the highest mean age, while spine and headache syndromes involved significantly younger populations. Multivariable modeling confirmed that diagnostic category is the sole independent determinant of age distribution (p < 0.001), whereas gender and visit type showed no significant independent associations. Conclusions: Ambulatory neurology utilization in this setting is characterized by a high-turnover primary consultation model and a heavy concentration of musculoskeletal neurological conditions. These findings suggest that outpatient neurology functions as a critical diagnostic filter and pain management hub. The study underscores the need for diagnosis-specific clinical pathways and targeted resource allocation to optimize service efficiency and improve long-term management of chronic neurological morbidity in a public insurance-driven framework. Full article

Cerebrovascular and neurodegenerative diseases are often linked to dysregulated cerebral blood flow, which results in oxidative stress and alterations in energy metabolism. Targeting the underlying initiators and exacerbating factors could offer protective benefits. Among the proposed therapeutic agents, the steroid hormone progesterone (P4) has shown considerable potential. This study evaluates the protective effects of P4 (1.7 mg/kg, administered subcutaneously once daily for a week) in a rat model of chronic cerebral hypoperfusion (CCH), provoked by the permanent bilateral ligation of the common carotid arteries. Redox and metabolic imbalances, specifically lipid and adenine nucleotide metabolism, were examined in serum and striatal crude synaptosomal fractions. Additionally, sensorimotor functions were assessed using non-invasive neurological tests. Biochemical analyses showed that P4 in CCH conditions contributed to the normalization of redox and metabolic homeostasis in both the serum and striatum. In the serum, this was accompanied by increased adenine nucleotide turnover, likely favoring protective adenosine signaling. In parallel, P4 alleviated the striatal oxidative burden while augmenting antioxidant response and promoting nucleotide catabolism. Our findings demonstrate that P4-mediated protection is accomplished through coordinated biochemical serum–striatum responses, linking systemic and synaptic metabolic regulation with improved sensorimotor function and recovery from CCH-induced deficits. Full article

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Epidemiologic evidence increasingly indicates that women with PCOS exhibit elevated risk of ischaemic stroke. Unlike prior reviews that have focused predominantly on general cardiovascular risk in PCOS, this review specifically examines ischaemic stroke risk, its mechanistic links, and the extent to which current stroke and cardiovascular frameworks fail to account for PCOS. We conducted a narrative review examining the association of PCOS on ischaemic stroke and cardiovascular disease (CVD). Large-scale cohort studies and meta-analyses from 2000 to 2025 were identified from Medline, Embase, PubMed, and Google Scholar, with specific emphasis on ischaemic stroke in women with PCOS. Case reports and case series were excluded. There is substantial evidence supporting the relationship between PCOS and increased vascular risk. Large-scale cohort studies and meta-analyses report higher rates of cerebrovascular events among women with PCOS. A recent 2025 meta-analysis pooling 11 studies reported a statistically significantly increased risk of stroke in women with PCOS (OR = 1.89, 95% CI = 1.22–2.55), although heterogeneity was high (I² = 97.7%), indicating important variation in study design, populations, and confounder adjustment. Other meta-analyses report more modest associations, and some studies did not demonstrate significant associations with myocardial infarction or all-cause mortality. Several analyses also showed attenuation of risk following adjustment for body mass index and metabolic factors. The observed association between PCOS and vascular risk should be interpreted with caution, given substantial heterogeneity and potential confounding by cardiometabolic factors. These findings raise the possibility that increased risk may be mediated through established pathways such as obesity, insulin resistance, and dyslipidaemia rather than representing a consistently independent effect. Despite this, PCOS remains inconsistently recognised within clinical frameworks. Current stroke guidelines and widely used risk prediction tools, including QRISK3 and the Essen Stroke Risk Score, do not incorporate PCOS, highlighting a potential gap in sex-specific risk assessment. Evidence demonstrating that inclusion of PCOS improves risk prediction or clinical outcomes remains limited. However, under-recognition of vascular risk in women with PCOS may limit timely risk assessment and intervention. This review highlights a number of implementation gaps globally, including gaps in research and inter-disciplinary communication. Priority next steps include prospective studies to clarify whether PCOS independently contributes to vascular risk, and predictive modelling studies to determine whether including PCOS improves risk stratification. In parallel, multidisciplinary care pathways may support earlier identification and prevention in higher-risk women. Full article