BACKGROUND AND AIMS:Antiplatelet treatment is recommended to start 24 h after intravenous thrombolysis due to concerns about haemorrhagic transformation. This study aimed to investigate the potential benefit of early antiplatelet after intravenous thrombolysis in minor stroke. METHODS:A multicentre, double-blind, randomized trial was conducted in China between 7 August 2022 and 1 August 2024, to evaluate the efficacy and safety of early antiplatelet in acute ischaemic stroke patients presenting with mild neurological deficits, as indicated by a National Institutes of Health Stroke Scale (NIHSS) score of 0-5, who received intravenous thrombolysis. Patients were randomly assigned to receive either clopidogrel and aspirin or placebo within 6 h after intravenous thrombolysis. The primary endpoint was an excellent functional outcome at 90 days, indicated by a modified Rankin Scale (mRS) score of 0-1. Statistical analysis was based on a modified intention-to-treat population. Symptomatic intracranial haemorrhage, any intracranial haemorrhage, and major systemic bleeding were safety endpoints. RESULTS:The primary endpoint was not met in this study. Of the randomly assigned 1022 patients, 995 patients were included in the modified intention-to-treat analysis (503 with early antiplatelet treatment and 492 with placebo). The primary endpoint occurred in 89.7% (451/503) of patients receiving early antiplatelet vs 89.6% (441/492) of those receiving placebo with no significant difference (odds ratio 1.00, 95% confidence interval .67-1.51, P = .99). Similar safety profiles were found between the two groups. CONCLUSIONS:Among Chinese patients with acute minor ischaemic stroke who received intravenous thrombolysis, early antiplatelet treatment with clopidogrel plus aspirin was safe but did not improve already excellent functional outcome (mRS 0-1) at 90 days.

The genetic and immunological mechanisms underlying post-acute ischemic stroke (IS) remain incompletely understood, particularly those involving neutrophil-mediated inflammation. This study aimed to identify genes associated with IS using a multi-omics Mendelian randomization framework. Summary-data-based Mendelian Randomization (SMR) was used to identify upstream genetic regulators of neutrophil-driven pathogenesis. We systematically screened 949 neutrophil-related genes using SMR analyses across multi-omics quantitative trait loci (QTL) datasets (methylation, expression, and protein). We then validated temporal expression patterns in independent IS cohorts and constructed a diagnostic nomogram to assess clinical discrimination. Multi-omics SMR analysis identified CCR1, DEFA4, SH2B3 and CDKN1A as potential genes associated with IS risk. In independent clinical validation cohorts, CCR1 and DEFA4 were consistently upregulated in the peripheral blood of IS patients. Notably, CCR1 emerged as a central hub gene; its expression exhibited a potential association with neutrophil abundance (R = 0.31) and functional hyperactivation pathways, including chemotaxis and cytotoxicity. Furthermore, a diagnostic nomogram integrating CCR1 and DEFA4 demonstrated high discriminatory power (AUC = 0.875), underscoring their potential as precision biomarkers. Identified as a potential neutrophil-related genetic factor, CCR1 is associated with ischemic injury and may contribute to neutrophil chemotaxis and functional hyperactivation. Consequently, targeting CCR1 offers a precision therapeutic strategy to attenuate neuroinflammation.

Paraquat (PQ), a widely used bipyridyl herbicide, exerts neurotoxic effects on dopaminergic neurons and can lead to Parkinson’s disease (PD)-like syndrome. Although immune dysfunction has been implicated in PD progression, the role of neuroimmune interactions in PQ-induced neurotoxicity remains poorly understood. This study aimed to investigate the mechanism by which microglia, the innate immune cells of the central nervous system, regulate the neurotoxic effects of PQ exposure. Network toxicology analysis revealed a link between microglia-mediated neuroinflammation and PQ-induced neurodegeneration, as well as astrocyte differentiation. Single-cell RNA sequencing (scRNA-seq) analysis identified the PI3K/AKT pathway as a potential regulatory mechanism underlying astrocyte phenotypic transformation. Our experimental evidence showed that PQ exposure induced neuroinflammation, dopaminergic neuron degeneration, and a pro-inflammatory astrocytes phenotype, all of which were reversed by microglial depletion. In vitro experiments using primary astrocytes cultured in conditioned medium from PQ-activated microglia demonstrated that activated microglia promoted a pro-inflammatory astrocyte phenotype, which was associated with inhibition of the PI3K/AKT pathway. This effect was alleviated by pretreatment with a PI3K activator. Taken together, our results suggest that PQ exposure disrupts microglia-astrocytes homeostasis, leading to aberrant neuroimmune crosstalk and inflammatory cascades that may underlie dopaminergic neurodegeneration. Therefore, this work provides crucial insights into the neuroimmune mechanisms of PQ-induced pathology, thereby informing both future research and environmental health policy.

Restoring blood flow through intravenous thrombolysis (IVT) or endovascular treatment (EVT) is the most effective therapy for acute ischemic stroke (AIS). However, reocclusion remains a common complication in patients who achieve successful revascularization. Currently, there is no recommendation for the treatment of reocclusion in the guidelines for stroke. Antiplatelet and anticoagulant drugs, repeated IVT (rIVT) and repeated EVT (rEVT) can be considered. We present a case of an AIS patient who underwent three IVTs and two EVTs. A 59-year-old man with AIS manifesting as recurrent reocclusion of the left internal carotid artery received three IVTs and two EVTs within 103 h and eventually achieved a good outcome. During the treatment, tirofiban and heparin were administrated for antithrombotic therapy. rIVT and rEVT may be viable for patients with early recurrent reocclusion after a full evaluation. This case report highlights the potential efficacy and safety of multiple revascularization therapy in a short period.

Intracranial atherosclerotic stenosis (ICAS) is an important cause of ischemic stroke and transient ischemic attack (TIA), which is also associated with increased risks of cognitive impairment and dementia. The prevalence of both asymptomatic and symptomatic ICAS (asICAS and sICAS) is significantly higher in Asian populations than in Western populations. In recent years, substantial new evidence has emerged regarding the epidemiology, diagnosis, assessment, prognosis, and treatment of asICAS and sICAS. The China ICAS Research Group has developed this guideline based on published research and relevant domestic and international guidelines or expert consensus, to further clarify the definition, epidemiology, and prognosis of ICAS and the profiles of high-risk ICAS patients and provide evidence-based recommendations on screening, diagnosis, assessment, and treatment strategies of asICAS and sICAS. For imaging exams, noninvasive and contrast-independent modalities are generally suitable for screening and assessment of ICAS in stroke-free individuals with multiple risk factors as well as for routine exams of stroke patients, while contrast-dependent or invasive imaging methods may be employed for further assessment or guiding treatment decision-making in sICAS patients. In addition, vessel wall imaging is valuable for distinguishing the etiology of intracranial stenosis, particularly in young stroke patients. Multiple imaging modalities or methods are available for the assessment of cerebral perfusion, hemodynamics, and collateral circulation that may meet different needs. Regarding interventions, lifestyle modifications (healthy diet, safe exercise, smoking cessation) are recommended for both asICAS and sICAS patients. For stroke-free individuals with asICAS, controlling vascular risk factor is the primary strategy, while routine aspirin or endovascular treatment for primary stroke prevention is not recommended. For sICAS patients, the cornerstone is intensive medical management, including short-term dual antiplatelet therapy in high-risk patients (such as those with severe luminal stenosis, minor stroke, or high-risk TIA) followed by lifelong monotherapy, aggressive lipid control (targeting low-density lipoprotein cholesterol < 1.8 mmol/L), blood pressure control (<140/90 mmHg), and glycemic control (targeting HbA1c < 7.0%), with structured follow-up to enhance treatment adherence. Endovascular treatment is not recommended for sICAS with mild to moderate luminal stenosis (<70%) but may be considered for carefully selected patients with severe (70-99%), medically refractory sICAS, particularly those with hypoperfusion, with a preference to delay the intervention for more than 21 days after stroke to enhance safety.

ABSTRACT Intravenous thrombolysis (IVT) is the treatment with the highest level of evidence for acute ischemic stroke, but about half of patients fail to achieve a favorable prognosis. This study (NCT05598658) proposed a treatment strategy of adjunctive two sessions of remote ischemic conditioning (RIC) within 24 h after IVT, and evaluated the effects through cerebral autoregulation (CA) and brain‐injury biomarkers. Patients were randomized (1:1) to the RIC or sham‐RIC groups, which received 200 and 60 mmHg RIC, respectively, at 6 and 18–24 h after IVT. CA was assessed at 2 and 7 days after IVT and serum brain‐injury biomarkers were evaluated at 24 h after IVT. The primary outcome was CA at 2 days after IVT. A total of 100 patients were randomized to the RIC or sham‐RIC group. Ipsilateral CA was significantly higher in the RIC group than in the sham‐RIC group at 2 days (β: 14.970 [95% confidence interval, 7.741–22.199; p < 0.001]) and 7 days after IVT. Simultaneously, neuron‐specific enolase level at 24 h after IVT was significantly lower in the RIC than the sham‐RIC group. These results suggest that adjunctive two sessions of RIC within 24 h after IVT can effectively exert neuroprotective effects in patients with IVT.

OBJECTIVE:To assess the efficacy and safety of edaravone dexborneol, a multitarget brain cytoprotectant composed of antioxidant and anti-inflammatory ingredients, in improving functional outcomes among patients with acute ischaemic stroke undergoing endovascular thrombectomy. DESIGN:Multicentre, double blind, randomised, placebo controlled trial. SETTING:106 hospitals in China between March 2022 and May 2023. PARTICIPANTS:1362 patients with clinically diagnosed acute ischaemic stroke within 24 hours of symptom onset, aged 18-80 years, with a National Institutes of Health Stroke Scale (NIHSS) score of 6-25 and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 6-10, confirmed large vessel occlusion in the anterior circulation, and planned endovascular thrombectomy. INTERVENTIONS:Patients were randomly allocated in a 1:1 ratio to receive edaravone dexborneol 37.5 mg (edaravone, 30 mg; (+)-dexborneol, 7.5 mg; 690 patients) or placebo (672 patients) before endovascular thrombectomy and continued the regimen twice daily for a consecutive period of 10-14 days. MAIN OUTCOME MEASURES:Functional independence at 90 days, defined as a modified Rankin Scale score (range 0 (no symptoms) to 6 (death)) of 0-2, and serious adverse events. RESULTS:One patient from each group was lost to follow-up at 90 days. Of the 1360 patients included in the intention-to-treat analysis, 379 (55.0%) of 689 patients in the edaravone dexborneol group and 333 (49.6%) of 671 patients in the placebo group achieved functional independence on day 90 (risk ratio 1.11, 95% confidence interval (CI) 1.00 to 1.23; P=0.05; risk difference 5.4%, 95% CI 0.1% to 10.7%). Patients with mismatch at admission (defined as NIHSS score ≥10 and ASPECTS ≥9 or NIHSS score ≥20 and ≥7) were more likely to achieve functional independence in the subgroup analysis (55.5% (178/321) versus 42.9% (134/312); risk ratio 1.29, 1.10 to 1.52; risk difference 13.0%, 5.6% to 20.3%; P for interaction=0.003). The rates of serious adverse events were similar in the two groups (27.2% (188/690) versus 25.7% (173/672); risk ratio 1.06, 0.89 to 1.26; risk difference 1.5%, -3.2% to 6.2%: P=0.53). CONCLUSIONS:Among patients with acute ischaemic stroke within 24 hours of symptom onset who underwent endovascular thrombectomy, those treated with edaravone dexborneol, compared with placebo, were more likely to achieve functional independence at 90 days without increased safety concerns. This effect seemed to be primarily driven by the subgroup with mismatch present at admission, suggesting that dedicated trials in this population may be warranted. TRIAL REGISTRATION:ClinicalTrials.gov NCT05249920.

BACKGROUND AND AIMS:Even after endovascular thrombectomy, more than half of patients with acute large vessel occlusion stroke do not achieve favourable outcomes. This study aimed to assess the efficacy and safety of remote ischaemic conditioning (RIC), a promising neuroprotective treatment, in patients with acute ischaemic stroke who received endovascular thrombectomy. METHODS:This participant-blinded, randomized controlled clinical trial was conducted at 25 hospitals. Patients were randomized 1:1 to either the RIC (cuff pressure, 200 mmHg; twice daily for 7 days) or sham RIC (60 mmHg; same procedure) groups. The primary outcome was the proportion of patients with a modified Rankin Scale score of 0-2 on Day 90. The primary safety outcome was the proportion of patients with haemorrhagic transformation within 7 days. RESULTS:In total, 498 participants were recruited. Ten patients (2.0%) were excluded because they did not receive any intervention. Thus, 488 participants (244 in the RIC group and 244 in the sham RIC group) were included in the modified intention-to-treat analysis. At 90 days, 61.1% of the patients in the RIC group and 48.9% in the sham RIC group achieved a modified Rankin Scale score of 0-2 (unadjusted risk ratio 1.25, 95% confidence interval 1.06-1.47; P = .009). The proportion of patients with haemorrhagic transformation was 37.7% and 35.2% in the RIC and sham RIC groups, respectively. CONCLUSIONS:Among patients with acute ischaemic stroke who underwent endovascular thrombectomy, intervention with RIC for 7 days, compared with sham RIC, resulted in an improved functional outcome at 90 days.

Metal-free hydrogen-bonded organic frameworks (HOFs) are porous materials formed via hydrogen bonding of organic building blocks, offering excellent biocompatibility and enzyme compatibility for biomedical applications. However, leveraging HOFs to create multienzyme cascade antioxidant nanozymes for cerebral ischemia-reperfusion injury (CIRI) therapy remains challenging. Here, selenium-containing nano-HOFs (SeHOFs) were synthesized as glutathione peroxidase mimics, encapsulating superoxide dismutase (SOD) and catalase (CAT) enzymes in situ to form a hybrid cascade antioxidant system (SeHOF@CAT@SOD). SeHOFs exhibited enhanced catalytic activity, preserved enzyme functionality, and provided protection against temperature, proteolysis, and denaturation. The metal-free nanozyme demonstrated excellent biocompatibility and cascade catalytic efficacy, scavenging reactive oxygen species and mitigating apoptosis and ferroptosis in vitro. Peptide modifications enhanced infarct site accumulation, effectively reducing infarct volume, oxidative stress, neuronal apoptosis, ferroptosis, and inflammation in CIRI models. This study underscores the potential of nano-HOFs as scaffolds for advanced therapeutic nanozyme development in ischemic stroke treatment.

OBJECTIVE:To compare the clinical outcomes among various infarct patterns and to investigate the associations between the morphological parameters of contralateral middle cerebral artery (cMCA) M1 segment and infarct patterns in ischemic stroke attributed to large vessel occlusion (LVO) in M1 segment caused by intracranial atherosclerotic disease (ICAD). METHODS:Patients with stroke attributed to M1-ICAD-LVO were enrolled. The infarct patterns were categorized into artery-to-artery embolism (AAE), large infarct, borderzone infarct (BZI), and perforating artery infarction (PAI). The morphological parameters of cMCA-M1 segment included proximal and distal diameter, arc, and chord length. The tortuosity index of cMCA-M1 segment was calculated by (arc length/chord length - 1) × 100%. RESULTS:A total of 171 participants were enrolled. Compared to AAE, the risk of poor outcome increased in BZI (odds ratio [OR] = 5.51, 95% confidence interval [CI] = 1.71-17.78, p = 0.004) and large infarct (OR = 10.92, 95% CI = 2.01-59.27, p = 0.006) and was comparable in PAI. The tortuosity index (OR = 2.85, 95% CI = 1.13-7.18, p = 0.026) and arc length (OR = 2.47, 95% CI = 1.02-5.97, p = 0.045) significantly increased in BZI than other three patterns. Participants other than BZI were categorized into large infarct (n = 32) and non-large-infarct (n = 46) groups, and the proximal diameter (OR = 0.22, 95% CI = 0.07-0.72, p = 0.012), arc length (OR = 0.88, 95% CI = 0.78-0.98, p = 0.018), and chord length (OR = 0.87, 95% CI = 0.77-0.995, p = 0.042) were associated with large infarct. CONCLUSION:For patients with M1-ICAD-LVO, large infarct and BZI had poorer outcomes than PAI and AAE. The cMCA-M1 segment with elevated tortuosity and arc length was associated with BZI, whereas a thin and short M1 segment was correlated with large infarct in patients with a less tortuous cMCA trunk.

AIM:To investigate whether the tortuosity of the culprit middle cerebral artery (MCA) is correlated with the recurrence of ipsilateral ischemic events in patients with ischemic stroke caused by intracranial atherosclerotic disease (ICAD) on M1 segment of MCA. METHODS:A total of 279 patients with first-ever M1-ICAD-related stroke were enrolled. The morphology of the culprit M1 segment was measured using MR or CT angiography, including the arc and chord length. The tortuosity index was calculated as (arc length / chord length - 1) × 100%. During the follow-up, the primary endpoints included recurrent transient ischemic attack and ischemic stroke attributable to culprit M1-ICAD. The participants were stratified into subgroups according to the tertiles of the tortuosity index: Q1 (＜9.98%), Q2 (9.98%-19.17%), and Q3 (＞19.17%). Multivariate Cox regression was performed to identify the factors associated with recurrence and the recurrence rates of subgroups was analyzed by log-rank test. RESULTS:The recurrence rates (group Q1, 20.4%, group Q2, 10.6%, group Q3, 4.3%, p = 0.003) are statically different. The tortuosity index (HR[hazard ratios] = 0.96, 95% CI[confidence intervals] = 0.92-0.997, p = 0.037) is inversely associated with the recurrence. The Q1 group exhibits a higher risk of recurrence (HR = 5.39, 95% CI: 1.66-17.48, p = 0.005) than the Q3 group, with the rate difference of 16.1% (95% CI: 6.9%-25.3%, p = 0.002). CONCLUSION:In patients with M1-ICAD-related stroke, lower tortuosity index of culprit MCA is associated with a higher risk of recurrent ipsilateral ischemic events.

BACKGROUND:Current hypertension prevention strategies predominantly focus on identifying and treating individuals with established hypertension. Whether a coordinated community- and family-based intervention can shift the population distribution of systolic blood pressure (SBP) remains uncertain. OBJECTIVES:The purpose of this study was to evaluate whether a coordinated, community- and family-centered intervention could shift the distribution of SBP at the population level in rural China. METHODS:In this cluster-randomized trial conducted in rural China, village clusters comprising adults aged 40 to 80 years, irrespective of blood pressure (BP) level or hypertension status, were randomly assigned (1:1) to a multifaceted intervention or usual care. The intervention included community instructor support, potassium-enriched low-sodium salt substitute, home BP and weight monitoring, physical activity promotion, and facilitation of antihypertensive treatment during an initial 6-month active intervention phase, followed by continued digital BP monitoring support through 12 months. Office BP was measured at baseline and at 6 and 12 months by trained staff independent of the intervention team. The primary outcome was the between-group difference in change in SBP from baseline to 6 months. Analyses followed the intention-to-treat principle using linear mixed-effects regression models. RESULTS:A total of 80 village clusters, comprising 8,001 participants, underwent randomization. Baseline mean SBP was 133.1 mm Hg in the intervention group and 131.4 mm Hg in the control group. At 6 months, mean SBP fell by 6.0 mm Hg in the intervention group and increased by 5.1 mm Hg in the control group, resulting in an adjusted between-group difference of -10.7 mm Hg (95% CI: -11.8 to -9.6 mm Hg). BP <130/80 mm Hg was achieved in 46.2% of participants in the intervention group vs 23.6% in the control group (adjusted OR: 5.3; 95% CI: 4.3-6.6). At 12 months, the adjusted between-group difference in SBP was -3.7 mm Hg (95% CI: -4.9 to -2.6 mm Hg). Serious adverse events occurred in 2.8% of participants in the intervention group and 2.3% in the control group. CONCLUSIONS:In rural China, a coordinated community- and family-based intervention significantly shifted the population distribution of SBP toward lower levels over 6 months. Attenuation of the treatment effect over time suggests that sustained population BP reduction may require ongoing implementation infrastructure and continued community support. (Effect of Healthy Family Program on Population Blood Pressure; NCT06427096).

Following a stroke, a local inflammatory cascade is triggered, resulting in the systemic diminishment of immune function, known as stroke-induced immunosuppression. The association of stroke-induced immunosuppression with brain injury and stroke prognosis after intravenous thrombolysis remains unclear. In this cohort study, we prospectively enrolled 1023 patients across 16 centers. Lymphocyte counts and the neutrophil-to-lymphocyte ratio were used as indicators of the severity of stroke-induced immunosuppression. The primary outcomes were the 90-day functional outcome, assessed using the modified Rankin Scale, and the severity of brain injury, evaluated by serum biomarkers (glial fibrillary acidic protein, S100β, ubiquitin c-terminal hydrolase L1, and neuron-specific enolase). Key secondary outcomes included infarct volume, 24 h and 7-day National Institutes of Health Stroke Scale, early neurological deterioration, hemorrhagic transformation, and 3-month mortality. Our results demonstrated that stroke-induced immunosuppression was independently associated with functional outcomes at 3 months and the severity of brain injury. In addition, patients with severe stroke-induced immunosuppression had increased infarct volume, higher National Institutes of Health Stroke Scale scores, increased risk of hemorrhagic transformation, and higher 3-month mortality. These results suggest that stroke-induced immunosuppression is independently associated with brain injury and poor outcomes in patients with acute ischemic stroke undergoing intravenous thrombolysis.

Acute ischemic stroke (AIS) is a major contributor to long-term disability despite current therapies. Although remote ischemic conditioning (RIC) has potential benefits in patients with AIS, its underlying mechanisms remain poorly understood. We aimed to explore the effects of RIC on the regulation of cerebral blood flow (CBF) among patients with AIS. This was a randomized controlled trial with participant-and-blinded endpoints that included 120 patients with AIS from June 2023 to May 2024. RIC/sham RIC treatment was performed at a pressure of 200 mmHg or 60 mmHg twice a day for seven consecutive days. The primary efficacy outcome was the difference in CBF regulation 7 days after randomization between the two groups. Patients were followed up for 90 days after randomization to assess modified Rankin Scale (mRS) scores. One hundred and twenty (120) patients with AIS were included in the intention-to-treat population (60 in each group). The results showed that the phase difference, which is a key parameter of CBF regulation, in the RIC group was significantly higher than that in the sham RIC group [affected side: RIC group: 36.84° (interquartile range [IQR], 21.49° to 51.36°), sham RIC group: 28.57° (17.17°, 38.52°), adjusted β coefficient = 11.336, 95

Age-related breakdown of the blood-brain barrier (BBB) is associated with cerebrovascular and neurodegenerative diseases, yet its underlying mechanisms remain unclear. Here, we find that BBB leakage begins in midlife and is driven primarily by increased endothelial caveolar transcytosis rather than tight junction disruption. AAV-mediated knockdown of caveolin-1 or restoration of Mfsd2a expression reduces endothelial vesicle formation and BBB leakage in aged mice. Transforming growth factor (TGF)-β1, originating from both brain and systemic circulation, increases with aging and directly suppresses Mfsd2a transcription via the Tgfbr2-Smad2/4 signaling in brain microvascular endothelial cells, thereby promoting caveolar transcytosis and BBB leakage. Endothelial-specific Tgfbr2 knockout or pharmacological inhibition of TGF-β signaling reduces endothelial caveolar transcytosis and BBB leakage and attenuates neurological dysfunction in aged mice. These findings identify TGF-β1-induced endothelial transcytosis as a central mechanism underlying age-related BBB breakdown and offer potential therapeutic targets for preserving brain health in age-related neurovascular disorders.

Adult obstructive sleep apnoea (OSA) is an established cardiovascular risk factor, but paediatric OSA has been framed mainly around neurocognition and growth. We reviewed PubMed, Ovid-Embase and Web of Science (2000-2026), prioritising eligible paediatric studies with quantifiable outcomes (ambulatory/office blood pressure (BP), autonomic indices/heart-rate variability, endothelial function/arterial stiffness, carotid intima-media thickness (cIMT) and echocardiographic structure/function) and key interventional data. Across cohorts, 24-h ambulatory blood pressure monitoring (ABPM) most consistently demonstrates higher nocturnal BP and reduced dipping; emerging exposure metrics such as hypoxic burden (the integrated depth and duration of oxygen desaturation across sleep) may capture physiological stress better than the apnoea-hypopnoea index alone. Autonomic imbalance, including sympathetic predominance, altered sleep-stage autonomic modulation and reduced baroreflex gain, provides a plausible bridge between respiratory events and early vascular/cardiac remodelling, and often improves after adenotonsillectomy. Vascular data suggest early functional abnormalities (endothelial reactivity, wave reflection/central haemodynamics) with smaller and inconsistent differences in structural markers, such as cIMT, strongly modified by obesity and development. Cardiac studies most reproducibly show increased left-ventricular mass/geometry and impaired diastolic relaxation, while right-heart and pulmonary vascular signals appear most relevant in selected higher-risk groups. Treatment effects appear more readily detectable in autonomic/endothelial measures than in office BP over short follow-up, reinforcing ABPM as a preferred research and selected high-risk clinical end-point. Paediatric OSA should therefore be approached through an early-risk framework, including identifying higher-risk phenotypes, quantifying nocturnal haemodynamic burden when feasible and integrating OSA therapy with weight and guideline-directed BP management.