Associations of life's essential 8 with extent of multi-territorial atherosclerotic plaques and stenosis: a cross-sectional study.

BACKGROUND: Life's Essential 8 (LE8), the recently updated construct for quantifying cardiovascular health, is related to the risks of cardiovascular events. The present study aimed to evaluate associations of LE8 score with the multi-territorial extent of atherosclerosis in a community-dwelling population. METHODS: Data were derived from the baseline cross-sectional survey of the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in Lishui City. The LE8 included overall, medical and behavior LE8 scores, and were categorized as low (< 60), moderate (60-<80), and high (≥ 80) groups. Vascular magnetic resonance imaging was used to evaluate intracranial and extracranial arteries; thoracoabdominal computed tomography angiography to evaluate coronary, subclavian, aorta, renal, ilio-femoral arteries; and ankle-brachial index to evaluate peripheral arteries. The presence of atherosclerotic plaque or stenosis in any territory was defined as plaque or vascular stenosis with 1 territory affected or more in these arteries. The extent of atherosclerotic plaques or stenosis was assessed according to the number of these 8 vascular sites affected, and graded as four grades (none, single territory, 2-3 territories, 4-8 territories). RESULTS: Of 3065 included participants, the average age was 61.2 ± 6.7 years, and 53.5% were women (n = 1639). The moderate and high overall LE8 groups were associated with lower extent of multi-territorial plaques [common odds ratio (cOR) 0.44, 95% confidence interval (CI), 0.35-0.55; cOR 0.16, 95%CI, 0.12-0.21; respectively] and stenosis (cOR 0.51, 95%CI, 0.42-0.62; cOR 0.16, 95%CI, 0.12-0.21; respectively) after adjustment for potential covariates. Similar results were observed for medical LE8 score with the extent of multi-territorial plaques and stenosis (P < 0.05). We also found the association between behavior LE8 score and the extent of multi-territorial stenosis (P < 0.05). CONCLUSIONS: The higher LE8 scores, indicating healthier lifestyle, were associated with lower presence and extent of atherosclerotic plaque and stenosis in southern Chinese adults. Prospective studies are needed to further validate these findings.

The Influence of Non-High-Density Lipoprotein Cholesterol on the Efficacy of Genotype-Guided Dual Antiplatelet Therapy in Preventing Stroke Recurrence.

BACKGROUND AND PURPOSE: Non-high-density lipoprotein cholesterol (non-HDL-C), which represents the total cholesterol content of all pro-atherogenic lipoproteins, has recently been included as a new target for lipid-lowering therapy in high-risk atherosclerotic patients in multiple guidelines. Herein, we aimed to explore the relationship between non-HDL-C level and the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing stroke recurrence. METHODS: This study comprised a post hoc analysis of the CHANCE-2 (Ticagrelor or Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial, from which 5,901 patients with complete data on non-HDL-C were included and categorized by median non-HDL-C levels, using a cutoff of 3.5 mmol/L. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days. RESULTS: Ticagrelor-aspirin significantly reduced the risk of recurrent stroke in patients with low non-HDL-C (71 [4.8%] vs. 119 [7.7%]; adjusted hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.40-0.74), but not in those with high non-HDL-C (107 [7.3%] vs. 108 [7.6%]; adjusted HR, 0.88; 95% CI, 0.67-1.16), compared with clopidogrel-aspirin (P for interaction=0.010). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin for recurrent stroke decreased as non-HDL-C levels increased. No significant differences in the treatment assignments across the non-HDL-C groups were observed in terms of the rate of severe or moderate bleeding (5 [0.3%] vs. 8 [0.5%] in the low non-HDL-C group; 4 [0.3%] vs. 2 [0.1%] in the high non-HDL-C group; P for interaction=0.425). CONCLUSION: CHANCE-2 participants with low non-HDL-C levels received more clinical benefit from ticagrelor-aspirin versus clopidogrel-aspirin compared to those with high non-HDL-C, following minor ischemic stroke or transient ischemic attack.

Metabolic dysfunction-associated fatty liver disease is associated with the presence of coronary atherosclerotic plaques and plaque burden.

BACKGROUND: Atherosclerosis is closely related with cardiovascular disease risk. The present study aims to evaluate the association between metabolic dysfunction-associated fatty liver disease (MAFLD) and the presence of coronary atherosclerotic plaques and plaques burden as detected by computed tomography angiography (CTA), and further test the screening value of MAFLD on the presence of coronary atherosclerotic plaques and plaques burden. METHODS: We used data from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study, a community-based cohort. Hepatic steatosis was assessed by fatty liver index. Coronary atherosclerotic plaques and burden were detected by CTA. The association of MAFLD with the presence of coronary atherosclerotic plaques and burden was assessed by binary and ordinal logistic regression models, respectively. RESULTS: Among the 3,029 participants (mean age 61.2±6.7 years), 47.9% (1,452) presented with MAFLD. MAFLD was associated with an increased odds of the presence of coronary atherosclerotic plaques (OR, 1.27; 95% CI: 1.03-1.56), segment involvement score [cOR (common odds ratio), 1.25; 95% CI, 1.03-1.51], and segment stenosis score (cOR, 1.29; 95% CI, 1.06-1.57). Participants with severe fibrosis or diagnosed as DM-MAFLD subtypes were with higher odds for the presence of coronary atherosclerotic plaques and plaques burden. In addition, MAFLD demonstrated higher sensitivity for detecting the presence of coronary atherosclerotic plaques and plaques burden (54%-64%) compared to conventional CVD risk factors (like diabetes, obesity, and dyslipidemia). CONCLUSIONS: MAFLD is associated with higher odds of suffering from the presence of coronary atherosclerotic plaques and plaques burden. Moreover, MAFLD may offer better screening potential for coronary atherosclerosis compared to established CVD risk factors.

Dual Antiplatelet Therapy After Embolic Stroke of Undetermined Source: A Subgroup Analysis of the CHANCE-2 Trial.

BACKGROUND: The atherosclerotic sources of embolism are a significant contributor to embolic stroke of undetermined source (ESUS). However, there is limited evidence for the efficacy of intensive dual antiplatelet therapy for ESUS. We conducted an investigation to determine whether gene-directed dual antiplatelet therapy could reduce the risk of recurrent stroke in patients with ESUS. METHODS: CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial that objectively compared ticagrelor plus aspirin and clopidogrel plus aspirin in patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles in China. All study participants were classified into ESUS and non-ESUS groups for the prespecified exploratory analysis. Cox proportional hazards models were used to assess the interaction of the state of ESUS with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin, adjusting for sociodemographic and clinical factors. RESULTS: The subgroup analysis comprised 5796 participants (90.4% of the total 6412 participants) in the CHANCE-2 trial, with a median age of 64.9 years (range, 57.0-71.4 years), of whom 1964 (33.9%) were female. These participants underwent diffusion-weighted imaging as part of the study protocol. After systematic evaluation, 15.2% of patients (881/5796) were deemed to have ESUS. The incidence of stroke recurrence in patients with ESUS was found to be 5.6% in the ticagrelor-aspirin group and 9.2% in the clopidogrel-aspirin group (hazard ratio, 0.57 [95% CI, 0.33-0.99]; P=0.04). In patients without ESUS, the respective incidence rates were 5.6% and 7.5% (hazard ratio, 0.72 [95% CI, 0.58-0.90]; P<0.01). The P value was 0.56 for the treatment × ESUS status interaction effect. CONCLUSIONS: In this prespecified exploratory analysis, ticagrelor with aspirin was superior to clopidogrel with aspirin for preventing stroke at 90 days in patients with acute ischemic stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles and were classified as ESUS. REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT04078737.

Data-Driven Analysis Reveals Cortical Infarction Patterns Correlated With Inflammation and Prognosis: A Retrospective, Multicenter Cohort Study.

BACKGROUND: We aim to identify the distinct lesion patterns and regions associated with functional outcome and inflammation in patients with acute ischemic stroke, and investigate whether the association between lesion patterns and functional outcome was mediated by inflammation. METHODS AND RESULTS: We performed nonnegative matrix factorization to derived low-dimensional lesion patterns (atoms), and Bayesian linear regression models were applied to explore the associations of lesion patterns with inflammatory factors including high-sensitivity C-reactive protein and interleukin-6, as well as functional outcome (defined as modified Rankin Scale score at 3 months). The difference distribution mean and 95% highest probability density interval (HPDI) were calculated. Mediation analysis was used to examine the mediating effects of inflammation on the relationships between lesion patterns and functional outcome. Seven lesion patterns were derived from 5914 patients with acute ischemic stroke. Lesion patterns distributed in the cortical regions were associated with inflammatory response, including atom 1 (interleukin-6: mean, 0.113 [95% HPDI, 0.073-0.162]; high-sensitivity C-reactive protein: mean, 0.082 [95% HPDI, 0.038-0.123]) and atom 4 (interleukin-6: mean, 0.113 [95% HPDI, 0.071-0.167]; high-sensitivity C-reactive protein: mean, 0.108 [95% HPDI, 0.058-0.165]). These lesion patterns were also significantly associated with functional outcome (atom 1: mean, 1.958 [95% HPDI, 1.538-2.383]; atom 4: mean, 2.245 [95% HPDI, 1.773-2.741]). Mediation analysis suggested that interleukin-6 explained 15.34% and 7.47% in the association of atom 1 and atom 4 with functional outcome, respectively. CONCLUSIONS: Certain lesion patterns that are associated with both inflammation and functional outcome of acute ischemic stroke, especially cortical infarction, may play a role in functional outcome through modulating inflammatory reactions.

Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy.

BACKGROUND: Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited. METHODS: In a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment within 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome was the absence of disability, which was defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at day 90. The key safety outcomes were symptomatic intracranial hemorrhage and death. RESULTS: A total of 516 patients were enrolled; 264 were randomly assigned to receive tenecteplase and 252 to receive standard medical treatment. Less than 2% of the patients (4 in the tenecteplase group and 5 in the standard-treatment group) underwent rescue endovascular thrombectomy. Treatment with tenecteplase resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment (33.0% vs. 24.2%; relative rate, 1.37; 95% confidence interval, 1.04 to 1.81; P = 0.03). Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was 3.0% and 0.8%, respectively. CONCLUSIONS: In this trial involving Chinese patients with ischemic stroke due to large-vessel occlusion, most of whom did not undergo endovascular thrombectomy, treatment with tenecteplase administered within 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher. (Funded by the National Natural Science Foundation of China and others; TRACE-III ClinicalTrials.gov number, NCT05141305.).

Reteplase versus Alteplase for Acute Ischemic Stroke.

BACKGROUND: Alteplase is the standard agent used in early reperfusion therapy, but alternative thrombolytic agents are needed. The efficacy and safety of reteplase as compared with alteplase in patients with acute ischemic stroke are unclear. METHODS: We randomly assigned patients with ischemic stroke within 4.5 hours after symptom onset in a 1:1 ratio to receive intravenous reteplase (a bolus of 18 mg followed 30 minutes later by a second bolus of 18 mg) or intravenous alteplase (0.9 mg per kilogram of body weight; maximum dose, 90 mg). The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]) at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after symptom onset. RESULTS: A total of 707 patients were assigned to receive reteplase, and 705 were assigned to receive alteplase. An excellent functional outcome occurred in 79.5% of the patients in the reteplase group and in 70.4% of those in the alteplase group (risk ratio, 1.13; 95% confidence interval [CI], 1.05 to 1.21; P<0.001 for noninferiority and P = 0.002 for superiority). Symptomatic intracranial hemorrhage within 36 hours after disease onset was observed in 17 of 700 patients (2.4%) in the reteplase group and in 14 of 699 (2.0%) of those in the alteplase group (risk ratio, 1.21; 95% CI, 0.54 to 2.75). The incidence of any intracranial hemorrhage at 90 days was higher with reteplase than with alteplase (7.7% vs. 4.9%; risk ratio, 1.59; 95% CI, 1.00 to 2.51), as was the incidence of adverse events (91.6% vs. 82.4%; risk ratio, 1.11; 95% CI, 1.03 to 1.20). CONCLUSIONS: Among patients with ischemic stroke within 4.5 hours after symptom onset, reteplase was more likely to result in an excellent functional outcome than alteplase. (Funded by China Resources Angde Biotech Pharma and others; RAISE ClinicalTrials.gov number, NCT05295173.).

Air pollutants, genetic susceptibility, and incident schizophrenia in later life: A prospective study in the UK Biobank.

OBJECTIVE: Air pollution has been linked to multiple psychiatric disorders, but little is known on its long-term association with schizophrenia. The interaction between air pollution and genetic susceptibility on incident schizophrenia has never been reported. We aimed to explore the associations between long-term air pollution exposure and late-onset schizophrenia and evaluate whether genetic susceptibility could modify the association. METHODS: This population-based prospective cohort study included 437,802 middle-aged and elderly individuals free of schizophrenia at baseline in the UK Biobank. Land use regression models were applied in the estimation of the annual average concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), fine particulate matter (PM2.5), and inhalable particulate matter (PM10) at residence. The associations between air pollutants and schizophrenia were evaluated by using Cox proportional hazard models. A polygenic risk score of schizophrenia was constructed for exploring potential interaction of air pollutants with genetic susceptibility. RESULTS: An interquartile range increase in PM2.5, PM10, NO2, and NOx was associated with the hazard ratios (HR) for incident schizophrenia at 1.19, 1.16, 1.22, and 1.09, respectively. The exposure-response curves for the association of air pollution with incident schizophrenia were approximately linear. There are additive interactions of air pollution score (APS), PM10, NO2, and NOx with genetic risk. Specifically, compared with participants with low genetic susceptibility and low APS, the HR was 3.23 for individuals with high genetic risk and high APS, among which 0.49 excess risk could be attributed to the additive interaction, accounting for 15 % of the schizophrenia risk. CONCLUSION: This large-scale, prospective cohort study conveys the first-hand evidence that long-term air pollution exposure could elevate schizophrenia incidence in later life, especially for individuals with higher genetic risks. The findings highlight the importance of improving air quality for preventing the late-onset schizophrenia in an aging era, especially among those with high genetic risks.

Differential associations of fine and coarse particulate air pollution with cause-specific pneumonia mortality: A nationwide, individual-level, case-crossover study.

BACKGROUND: The connections between fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) and daily mortality of viral pneumonia and bacterial pneumonia were unclear. OBJECTIVES: To distinguish the connections between PM2.5 and PM2.5-10 and daily mortality due to viral pneumonia and bacterial pneumonia. METHODS: Using a comprehensive national death registry encompassing all areas of mainland China, we conducted a case-crossover investigation from 2013 to 2019 at an individual level. Residential daily particle concentrations were evaluated using satellite-based models with a spatial resolution of 1 km. To analyze the data, we employed the conditional logistic regression model in conjunction with polynomial distributed lag models. RESULTS: We included 221,507 pneumonia deaths in China. Every interquartile range (IQR) elevation in concentrations of PM2.5 (lag 0-2 d, 37.6 µg/m3) was associated with higher magnitude of mortality for viral pneumonia (3.03%) than bacterial pneumonia (2.14%), whereas the difference was not significant (p-value for difference = 0.38). An IQR increase in concentrations of PM2.5-10 (lag 0-2 d, 28.4 µg/m3) was also linked to higher magnitude of mortality from viral pneumonia (3.06%) compared to bacterial pneumonia (2.31%), whereas the difference was not significant (p-value for difference = 0.52). After controlling for gaseous pollutants, their effects were all stable; however, with mutual adjustment, the associations of PM2.5 remained, and those of PM2.5-10 were no longer statistically significant. Greater magnitude of associations was noted in individuals aged 75 years and above, as well as during the cold season. CONCLUSION: This nationwide study presents compelling evidence that both PM2.5 and PM2.5-10 exposures could increase pneumonia mortality of viral and bacterial causes, highlighting the more robust effects of PM2.5 and somewhat higher sensitivity of viral pneumonia.

Differentiating the impact of fine and coarse particulate matter on cause-specific cerebrovascular mortality: An individual-level, case-crossover study.

BACKGROUND AND OBJECTIVES: Many studies suggested that short-term exposure to fine particulate matter (PM2.5) and coarse particulate matter (PM2.5-10) was linked to elevated risk of cerebrovascular disease. However, little is known about the potentially differential effects of PM2.5 and PM2.5-10 on various types of cerebrovascular disease. METHODS: We collected individual cerebrovascular death records for all residents in Shanghai, China from 2005 to 2021. Residential daily air pollution data were predicted from a satellite model. The associations between particulate matters (PM) and cerebrovascular mortality were investigated by an individual-level, time-stratified, case-crossover design. The data was analyzed by the conditional logistic regression combined with the distributed lag model with a maximum lag of 7 days. Furthermore, we explored the effect modifications by sex, age and season. RESULTS: A total of 388,823 cerebrovascular deaths were included. Monotonous increases were observed for mortality of all cerebrovascular diseases except for hemorrhagic stroke. A 10 µg/m3 rise in PM2.5 was related to rises of 1.35% [95% confidence interval (CI): 1.04%, 1.66%] in mortality of all cerebrovascular diseases, 1.84% (95% CI: 1.25%, 2.44%) in ischemic stroke, 1.53% (95% CI: 1.07%, 1.99%) in cerebrovascular sequelae and 1.56% (95% CI: 1.08%, 2.05%) in ischemic stroke sequelae. The excess risk estimates per each 10 µg/m3 rise in PM2.5-10 were 1.47% (95% CI: 1.10%, 1.84%), 1.53% (95% CI: 0.83%, 2.24%), 1.93% (95% CI: 1.38%, 2.49%) and 2.22% (95% CI: 1.64%, 2.81%), respectively. The associations of both pollutants with all cerebrovascular outcomes were robust after controlling for co-pollutants. The associations were greater in females, individuals > 80 years, and during the warm season. CONCLUSIONS: Short-term exposures to both PM2.5 and PM2.5-10 may independently increase the mortality risk of cerebrovascular diseases, particularly of ischemic stroke and stroke sequelae.

Prenatal and postnatal early life exposure to greenness and particulate matter of different size fractions in relation to childhood rhinitis - A multi-center study in China.

The impact of early life exposure to residential greenness on childhood rhinitis and its interaction with particulate matter (PM) of different size fractions remain inconsistent. Herein, we recruited 40,486 preschool children from randomly selected daycare centers in 7 cities in China from 2019 to 2020, and estimated exposure to residential greenness by the normalized difference vegetation index (NDVI) with a 500 m buffer. Exposure to ambient PM (PM1, PM2.5, and PM10) was evaluated using a satellite-based prediction model (daily, at a resolution of 1 km × 1 km). By mixed-effect logistic regression, NDVI values during pregnancy, in the first (0-1 year old) and the second (1-2 years old) year of life were negatively associated with lifetime rhinitis (LR) and current rhinitis (CR) (P < 0.001). PM in the same time windows was associated with increased risks of LR and CR in children, with smaller size fraction of PM showing greater associations. The negative associations between prenatal and postnatal NDVI and LR and CR in preschool children remained robust after adjusting for concomitant exposure to PM, whereas the associations of postnatal NDVI and rhinitis showed significant interactions with PM. At lower levels of PM, postnatal NDVI remained negatively associated with rhinitis and was partly mediated by PM (10.0-40.9 %), while at higher levels of PM, the negative associations disappeared or even turned positive. The cut-off levels of PM were identified for each size fraction of PM. In conclusion, prenatal exposure to greenness had robust impacts in lowering the risk of childhood rhinitis, while postnatal exposure to greenness depended on the co-exposure levels to PM. This study revealed the complex interplay of greenness and PM on rhinitis in children. The exposure time window in prenatal or postnatal period and postnatal concomitant PM levels played important roles in influencing the associations between greenness, PM and rhinitis.

Association of exposure to ultraviolet radiation and warm-season ozone air pollution with incident age-related macular degeneration: A nationwide cohort study in China.

BACKGROUND: As the leading cause of blindness, age-related macular degeneration (AMD) performs an adverse impact on human health and disability. AMD have been reported to be associated with environmental factors; however, the association between ultraviolet (UV) radiation, warm-season ambient ozone pollution, and incident AMD remains unclear. METHODS: In this study, 19,707 participants without AMD at baseline were included from a nationwide longitudinal cohort in China. UV radiation and warm-season ozone exposure were evaluated through satellite-based models. Incident AMD was diagnosed via ophthalmological fundus images. Cox proportional hazard regression models were employed to explore the association of UV radiation and warm-season ozone with incident AMD, and the hazard ratios (HRs) and 95 % confidence intervals (CIs) were reported. RESULTS: During 312,935 person-month of follow-up, 3774 participants developed to AMD. High exposure to both UV radiation and warm-season ozone was associated with increasing risk of incident AMD, with HRs and 95 % CIs of 1.32 (1.23, 1.41) and 1.20 (1.11, 1.29) in two-exposure models, respectively. Moreover, negative interaction between UV radiation and warm-season ozone was identified, and it was found that exposure to high UV radiation and low ozone presented the highest hazard for AMD. Subgroup analyses showed that the UV-AMD association was stronger in southern China, while the ozone-AMD association was greater in northern China and rural areas. CONCLUSION: Our study provides the first epidemiological evidence that both UV radiation and warm-season ozone would elevate the risk of incident AMD, and the hazard of higher UV radiation may be attenuated by exposure to ozone. Strategies for decreasing AMD burden should jointly consider environmental exposures and geographic locations.

Efficacy and safety of Ferrous iron on the prevention of Vascular cOgnitive impaiRment among patients with cerebral Infarction/TIA (FAVORITE): rationale and design of a multicentre randomised trial.

BACKGROUND: The incidence of vascular cognitive impairment (VCI) is high in patients suffering from ischaemic stroke or transient ischaemic attack (TIA) or with vascular risk factors. Effective prevention strategies for VCI remain limited. Anaemia or low haemoglobin was found as an independent risk factor for adverse outcomes after acute stroke. Anaemia or low haemoglobin was possibly associated with an increased risk of poststroke cognitive impairment. Whether supplement of ferrous iron to correct anaemia reduces the risk of VCI and improves adverse outcomes in patients with ischaemic cerebrovascular disease remains uncertain. AIM: We aim to introduce the design and rationale of the safety and efficacy of Ferrous iron on the prevention of Vascular cOgnitive impaiRment in patients with cerebral Infarction or TIA (FAVORITE) trial. DESIGN: FAVORITE is a randomised, placebo-controlled, double-blind, multicentre trial that compares supplement of ferrous iron with placebo for recent minor stroke/TIA patients complicated with mild anaemia or iron deficiency: Ferrous succinate sustained-release tablet 0.2 g (corresponding to 70 mg of elemental iron) once daily after or during breakfast for 12 weeks or placebo with much the same colour, smell and size as ferrous iron once daily during or after breakfast for 12 weeks. All paticipants will be followed within the next year. STUDY OUTCOMES: The primary effective outcome is the incidence of VCI at 3 months after randomisation and the primary safety outcome includes any gastrointestinal adverse event during 3 months. DISCUSSION: The FAVORITE trial will clarify whether supplement of ferrous iron to correct low haemoglobin reduces the risk of VCI in patients with recent ischaemic stroke or TIA complicated with mild anaemia or iron deficiency compared with placebo. TRIAL REGISTRATION NUMBER: NCT03891277.

Cluster analysis of clinical phenotypes in idiopathic inflammatory myopathy patients complicated with cardiac involvement.

OBJECTIVE: This study aimed to classify idiopathic inflammatory myopathy (IIM) patients with cardiac involvement (IIM-CI) into different categories based on their clinical phenotypes via cluster analysis and to explore their differences in outcomes. METHODS: IIM-CI patients admitted to Peking Union Medical College Hospital from January 2015 to June 2021 were retrieved. The clinical data, laboratory examinations, and treatment were retrospectively reviewed, and the outcome was traced. A second-order clustering method was employed for categorization. RESULTS: A total of 88 IIM-CI patients were enrolled in this study and were classified into two categories through cluster analysis. Category I consisted of patients who exhibited distinct cardiac structural and functional changes, such as enlargement of atriums and/or ventricles, along with the remarkable heart insufficiency biomarkers, whereas patients of category II displayed more widely systemic injuries and intensive skeletal muscle weakness. In comparison, pulmonary hypertension (58.8% vs 16.7%, p < 0.01), arrhythmia (82.4% vs 27.8%, p < 0.01), and positive serum anti-mitochondrial-M2 antibody (52.9% vs 5.6%, p < 0.01) were more prevalent in category I than in category II, and serum N-terminal pro-B-type natriuretic peptide levels (1703.5 pg/L vs 364.0 pg/L, p = 0.02) were significantly elevated in category I, whereas skeletal muscle weakness (50.0% vs 74.1%, p = 0.02), interstitial lung disease (20.6% vs 63.0%, p < 0.01), skin rash (11.8% vs 48.1%, p < 0.01), arthralgia (2.9% vs 27.8%, p < 0.01), fever (2.9% vs 27.8%, p < 0.01), and dysphagia (2.9% vs 22.2%, p < 0.01) were more common in category II patients. Heart failure was the primary cause of death in category I, but severe pneumonia was predominantly responsible for deaths in category II. CONCLUSION: Two categories of IIM-CI were identified based on clinical features with distinctive characteristics. Two categories exhibited differences in clinical manifestations, autoantibody profiles, and the primary cause of death.

Immediate- or Delayed-Intensive Statin in Acute Cerebral Ischemia: The INSPIRES Randomized Clinical Trial.

Importance: Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis. Objective: To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022. The trial was conducted at 222 hospitals in China. Patients aged 35 to 80 years with mild ischemic stroke or high-risk TIA of presumed atherosclerosis within 72 hours of symptom onset were assessed. Interventions: Patients were randomly assigned to receive immediate-intensive atorvastatin (80 mg daily on days 1-21; 40 mg daily on days 22-90) or 3-day delayed treatment (placebo for days 1-3, followed by placebo and atorvastatin, 40 mg daily on days 4-21, and then atorvastatin, 40 mg daily on days 22-90). Main Outcomes and Measures: The primary efficacy outcome was new stroke within 90 days, and a secondary efficacy outcome was poor functional outcome. Moderate to severe bleeding was the primary safety outcome. Results: A total of 11 431 patients were assessed for eligibility, and 6100 patients (median [IQR] age, 65 [57-71] years; 3915 men [64.2%]) were enrolled, with 3050 assigned to each treatment group. Within 90 days, new stroke occurred in 245 patients (8.1%) in the immediate-intensive statin group and 256 patients (8.4%) in the delayed group (hazard ratio, 0.95; 95% CI, 0.80-1.13). Poor functional outcome occurred in 299 patients (9.8%) and 348 patients (11.4%) in the immediate-intensive and delayed-intensive statin groups, respectively (odds ratio, 0.83; 95% CI, 0.71-0.98). Moderate to severe bleeding occurred in 23 of 3050 patients (0.8%) and 17 of 3050 patients (0.6%), in the immediate-intensive and delayed-intensive statin groups, respectively. Conclusions and Relevance: Immediate-intensive statin initiated within 72 hours did not reduce the risk of stroke within 90 days and may be associated with improved functional outcomes without significant difference in moderate to severe bleeding, compared with 3-day delayed-intensive statin in Chinese patients with acute mild ischemic stroke or TIA from atherosclerosis. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.

The FAITHS2 Model Predicts Functional Disability in Patients With Acute Ischemic Stroke.

The present study aimed to develop a model to predict functional disability at 3 months in patients with acute ischemic stroke (AIS) (n = 5,406). The primary outcome was functional disability (modified Rankin Scale [mRS] >2) at 3 months. A prediction model including blood biomarkers was developed based on a multivariable logistic regression model, which was internally validated by the 100-time bootstrap method. A nomogram and a web-based calculator were developed for usage in clinical practice. At 3 months, 11% (638/5,406) of the patients had functional disability. Seven independent predictors of functional disability at 3 months were incorporated into the FAITHS2 model (fasting plasma glucose, age, interleukin-6, stroke history, National Institute of Health Stroke Scale [NIHSS] at admission, sex, and systolic blood pressure). The Area Under Curves (AUCs) were 0.814 (95% confidence interval [CI] 0.796-0.832) and 0.808 (95% CI 0.806-0.810), and the Brier scores were 0.088 ± 0.214 and 0.089 ± 0.003 for the derivation cohort and internal validation, respectively, showing optimal performance of the model. The FAITHS2 model has excellent potential to be a dependable application for individualized clinical decision making.

Long-Term Exposure to Fine Particulate Matter and Fasting Blood Glucose and Diabetes in 20 Million Chinese Women of Reproductive Age.

OBJECTIVE: Evidence of the associations between fine particulate matter (PM2.5) and diabetes risk from women of reproductive age, in whom diabetes may have adverse long-term health effects for both themselves and future generations, remains scarce. We therefore examined the associations of long-term PM2.5 exposure with fasting blood glucose (FBG) level and diabetes risk in women of reproductive age in China. RESEARCH DESIGN AND METHODS: This study included 20,076,032 women age 20-49 years participating in the National Free Preconception Health Examination Project in China between 2010 and 2015. PM2.5 was estimated using a satellite-based model. Multivariate linear and logistic regression models were used to examine the associations of PM2.5 exposure with FBG level and diabetes risk, respectively. Diabetes burden attributable to PM2.5 was estimated using attributable fraction (AF) and attributable number. RESULTS: PM2.5 showed monotonic relationships with elevated FBG level and diabetes risk. Each interquartile range (27 µg/m3) increase in 3-year average PM2.5 concentration was associated with a 0.078-mmol/L (95% CI 0.077, 0.079) increase in FBG and 18% (95% CI 16%, 19%) higher risk of diabetes. The AF attributed to PM2.5 exposure exceeding 5 µg/m3 was 29.0% (95% CI 27.5%, 30.5%), corresponding to an additional 78.6 thousand (95% CI 74.5, 82.6) diabetes cases. Subgroup analyses showed more pronounced diabetes risks in those who were overweight or obese, age >35 years, less educated, of minority ethnicity, registered as a rural household, and residing in western China. CONCLUSIONS: We found long-term PM2.5 exposure was associated with higher diabetes risk in women of reproductive age in China.

Derivation and Validation of a Scoring System for Predicting Poor Outcome After Posterior Circulation Ischemic Stroke in China.

BACKGROUND AND OBJECTIVES: Guidelines for posterior circulation ischemic stroke (PCIS) treatment are lacking and outcome prediction is crucial for patients and clinicians. We aimed to develop and validate a prognostic score to predict the poor outcome for patients with PCIS. METHODS: The score was developed from a prospective derivation cohort named the Third China National Stroke Registry (August 2015-March 2018) and validated in a spatiotemporal independent validation cohort (December 2017-March 2023) in China. Patients with PCIS with acute infarctions defined as hyperintense lesions on diffusion-weighted imaging were included in this study. The poor outcome was measured as modified Rankin scale (mRS) score 3-6 at 3 months after PCIS. Multivariable logistic regression analysis was used to identify predictors for poor outcome. The prognostic score, namely PCIS Outcome Score (PCISOS), was developed by assigning points to variables based on their relative ß-coefficients in the logistic model. RESULTS: The PCISOS was derived from 3,294 patients (median age 62 [interquartile range (IQR) 55-70] years; 2,250 [68.3%] men) and validated in 501 patients (median age 61 [IQR 53-68] years; 404 [80.6%] men). Among them, 384 (11.7%) and 64 (12.8%) had poor outcome 3 months after stroke in respective cohorts. Age, mRS before admission, NIH Stroke Scale on admission, ischemic stroke history, infarction distribution, basilar artery, and posterior cerebral artery stenosis or occlusion were identified as independent predictors for poor outcome and included in PCISOS. This easy-to-use integer scoring system identified a marked risk gradient between 4 risk groups. PCISOS performed better than previous scores, with an excellent discrimination (C statistic) of 0.80 (95% CI 0.77-0.83) in the derivation cohort and 0.81 (95% CI 0.77-0.84) in the validation cohort. Calibration test showed high agreement between the predicted and observed outcomes in both cohorts. DISCUSSION: PCISOS can be applied for patients with PCIS with acute infarctions to predict functional outcome at 3 months post-PCIS. This simple tool helps clinicians to identify patients with PCIS with higher risk of poor outcome and provides reliable outcome expectations for patients. This information might be used for personalized rehabilitation plan and patient selection for future clinical trials to reduce disability and mortality.

Particulate matter pollution, polygenic risk score and mosaic loss of chromosome Y in middle-aged and older men from the Dongfeng-Tongji cohort study.

Mosaic loss of chromosome Y (mLOY) is the most common somatic alteration as men aging and may reflect genome instability. PM exposure is a major health concern worldwide, but its effects with genetic factors on mLOY has never been investigated. Here we explored the associations of PM2.5 and PM10 exposure with mLOY of 10,158 males measured via signal intensity of 2186 probes in male-specific chromosome-Y region from Illumina array data. The interactive and joint effects of PM2.5 and PM10 with genetic factors and smoking on mLOY were further evaluated. Compared with the lowest tertiles of PM2.5 levels in each exposure window, the highest tertiles in the same day, 7-, 14-, 21-, and 28-day showed a 0.005, 0.006, 0.007, 0.007, and 0.006 decrease in mLRR-Y, respectively (all P < 0.05), with adjustment for age, BMI, smoking pack-years, alcohol drinking status, physical activity, education levels, season of blood draw, and experimental batch. Such adverse effects were also observed in PM10-mLOY associations. Moreover, the unweighted and weighted PRS presented significant negative associations with mLRR-Y (both P < 0.001). Participants with high PRS and high PM2.5 or PM10 exposure in the 28-day separately showed a 0.018 or 0.019 lower mLRR-Y level [ß (95 %CI) = -0.018 (-0.023, -0.012) and - 0.019 (-0.025, -0.014), respectively, both P < 0.001], when compared to those with low PRS and low PM2.5 or PM10 exposure. We also observed joint effects of PM with smoking on exacerbated mLOY. This large study is the first to elucidate the impacts of PM2.5 exposure on mLOY, and provides key evidence regarding the interactive and joint effects of PM with genetic factors on mLOY, which may promote understanding of mLOY development, further modifying and increasing healthy aging in males.

Rehabilitation with brain-computer interface and upper limb motor function in ischemic stroke: A randomized controlled trial.

BACKGROUND: Upper limb motor dysfunction is a major problem in the rehabilitation of patients with stroke. Brain-computer interface (BCI) is a kind of communication system that converts the "ideas" in the brain into instructions and has been used in stroke rehabilitation. This study aimed to investigate the efficacy and safety of BCI in rehabilitation training on upper limb motor function among patients with ischemic stroke. METHODS: This was an investigator-initiated, multicenter, randomized, open-label, blank-controlled clinical trial with blinded outcome assessment conducted at 17 centers in China. Patients were assigned in a 1:1 ratio to the BCI group or the control group based on traditional rehabilitation training. The primary efficacy outcome is the difference in improvement of the Fugl-Meyer Assessment upper extremity (FMA-UE) score between two groups at month 1 after randomization. The safety outcomes were any adverse events within 3 months. FINDINGS: A total of 296 patients with ischemic stroke were enrolled and randomly allocated to the BCI group (n = 150) and the control group (n = 146). The primary efficacy outcomes of FMA-UE score change from baseline to 1 month were 13.17 (95% confidence interval [CI], 11.56-14.79) in the BCI group and 9.83 (95% CI, 8.19-11.47) in the control group (mean difference between groups was 3.35; 95% CI, 1.05-5.65; p = 0.0045). Adverse events occurred in 33 patients (22.00%) in the BCI group and in 31 patients (21.23%) in the control group. CONCLUSIONS: BCI rehabilitation training can further improve upper limb motor function based on traditional rehabilitation training in patients with ischemic stroke. This study was registered at ClinicalTrials.gov: NCT04387474. FUNDING: This work was supported by the National Key R&D Program of China (2018YFC1312903), the National Key Research and Development Program of China (2022YFC3600600), the Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University (CCMU2022ZKYXZ009), the Beijing Natural Science Foundation Haidian original innovation joint fund (L222123), the Fund for Young Talents of Beijing Medical Management Center (QML20230505), and the high-level public health talents (xuekegugan-02-47).