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: https://www.clinicaltrials.gov; Unique identifier: NCT04078737.

Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA.

BACKGROUND: Comparisons between ticagrelor and clopidogrel for the secondary prevention of stroke in CYP2C19 loss-of-function carriers have not been extensively performed. METHODS: We conducted a randomized, double-blind, placebo-controlled trial at 202 centers in China involving patients with a minor ischemic stroke or transient ischemic attack (TIA) who carried CYP2C19 loss-of-function alleles. Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive ticagrelor (180 mg on day 1 followed by 90 mg twice daily on days 2 through 90) and placebo clopidogrel or to receive clopidogrel (300 mg on day 1 followed by 75 mg once daily on days 2 through 90) and placebo ticagrelor; both groups received aspirin for 21 days. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days. RESULTS: A total of 11,255 patients were screened and 6412 patients were enrolled, with 3205 assigned to the ticagrelor group and 3207 to the clopidogrel group. The median age of the patients was 64.8 years, and 33.8% were women; 98.0% belonged to the Han Chinese ethnic group. Stroke occurred within 90 days in 191 patients (6.0%) in the ticagrelor group and 243 patients (7.6%) in the clopidogrel group (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P = 0.008). Secondary outcomes were generally in the same direction as the primary outcome. Severe or moderate bleeding occurred in 9 patients (0.3%) in the ticagrelor group and in 11 patients (0.3%) in the clopidogrel group; any bleeding occurred in 170 patients (5.3%) and 80 patients (2.5%), respectively. CONCLUSIONS: Among Chinese patients with minor ischemic stroke or TIA who were carriers of CYP2C19 loss-of-function alleles, the risk of stroke at 90 days was modestly lower with ticagrelor than with clopidogrel. The risk of severe or moderate bleeding did not differ between the two treatment groups, but ticagrelor was associated with more total bleeding events than clopidogrel. (Funded by the Ministry of Science and Technology of the People's Republic of China and others; CHANCE-2 ClinicalTrials.gov number, NCT04078737.).

Association between BMI-based metabolic phenotypes and prevalence of intracranial atherosclerotic stenosis: a cross-sectional study.

BACKGROUND: Obesity and metabolic syndrome (MetS) have been acknowledged to commonly co-exist and lead to increased risks of stroke, whereas the association between various BMI-based metabolic phenotypes and development of intracranial atherosclerotic stenosis (ICAS) remained controversial. METHODS: A total of 5355 participants were included from the Asymptomatic Polyvascular Abnormalities Community (APAC) study. Participants were categorized into six groups according to their body mass index (BMI) and MetS status. ICAS was assessed using transcranial Doppler (TCD) Ultrasonography. Logistic regression was employed to evaluate the association between BMI-based metabolic phenotypes and ICAS. RESULTS: 704 participants were diagnosed with ICAS. Compared to the metabolic healthy normal weight (MH-NW) group, the metabolic unhealthy normal weight (MUH-NW) group demonstrated a higher risk of ICAS (full-adjusted odds ratio [OR], 1.91; 95% confidence interval [CI], 1.42-2.57), while no significant association was observed in the metabolic unhealthy obesity (MUO) group (full-adjusted OR, 1.07; 95% CI, 0.70-1.65) and other metabolic healthy groups regardless of BMI. The results were consistent across gender, age, smoking, alcohol intake, and physical activity subgroups. CONCLUSION: The present study suggested that MUH-NW individuals had a significant association with increased risk of ICAS compared with MH-NW individuals.

Association of obesity with cardiovascular disease in the absence of traditional risk factors.

BACKGROUND: The association between obesity and cardiovascular disease (CVD) in people without traditional CVD risk factors is unclear. This study aimed to investigate the association of obesity with CVD and its subtypes in people without traditional CVD risk factors. METHODS: Based on the Kailuan cohort study, the included participants were divided into different groups according to levels of body mass index (BMI) and waist height ratio (WHtR), respectively. Multivariate Cox proportional hazard models were used to evaluate the associations. RESULTS: This study included 31,955 participants [men 63.99%; mean age (48.14 ± 3.33) years]. During a median follow-up period of 12.97 (interquartile range: 12.68-13.17) years, 1298 cases of CVD were observed. Compared with the normal BMI group, the hazard ratios (HRs) for CVD, stroke, and myocardial infarction (MI) in the BMI obese group were 1.31 (95% confidence interval [CI] 1.11-1.55), 1.21 (95%CI 1.01-1.46), 1.62 (95%CI 1.13-2.33), respectively. Compared with the WHtR non-obese group, the HRs for CVD, stroke, and MI in the obese group were 1.25(95%CI 1.11-1.41), 1.18 (95%CI 1.03-1.34), 1.57 (95%CI 1.18-2.09), respectively. There was an interaction between age and WHtR (P for interaction was 0.043). The association between WHtR and CVD was stronger in people under 60 years old, with a HR of 1.44 (95%CI 1.24-1.67). CONCLUSION: We found that obesity increased the risk of CVD in people without traditional CVD risk factors. The association of WHtR with CVD was stronger in people under 60 years old.

Association of Stroke With Metabolic Dysfunction-Associated Fatty Liver Disease With and Without CKD.

RATIONALE & OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD), a risk factor for stroke and all-cause mortality, is highly prevalent among patients with chronic kidney disease (CKD), but it is unclear whether the association of MAFLD with stroke and all-cause mortality differs within and outside of the setting of CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We enrolled 95,353 participants from the Kailuan Cohort Study, among whom 35,749 had CKD at baseline or developed CKD during the follow-up period, and 59,604 individuals who had no CKD at baseline or during the follow-up period. EXPOSURE: MAFLD. OUTCOME: Stroke (ischemic stroke, hemorrhagic stroke), all-cause mortality. ANALYTICAL APPROACH: Adjusted Cox regression models were used to estimate the influence of MAFLD on stroke outcomes within the subgroups defined by the presence of CKD. RESULTS: After a median follow-up of 12.8 years, 6,140 strokes (6.4%) and 11,975 deaths from any cause (12.6%) occurred. After adjusting for potential confounders, MAFLD was associated with an increased incidence of stroke among the participants with CKD (HR, 1.34 [95% CI, 1.23-1.45]) but not among those without CKD (HR, 1.05 [95% CI, 0.97-1.15]; Pinteraction<0.001). This association was principally related to ischemic stroke (HR, 1.38 [95% CI, 1.26-1.51]) and not hemorrhagic stroke (HR, 1.04 [95% CI, 0.85-1.26]). No association was found between MAFLD and all-cause mortality in the participants with CKD (HR,1.04 [95% CI, 0.98-1.10]) or those without CKD (HR,1.03 [95% CI, 0.97-1.09]). Among the participants with CKD, compared with non-MAFLD, MAFLD with diabetes (HR,1.36 [95% CI, 1.23-1.50]) or overweight/obesity (HR,1.30 [95% CI, 1.14-1.50]) was associated with a higher risk of stroke whereas MAFLD without overweight/obesity or diabetes was not associated with a higher risk (HR,1.08 [95% CI, 0.81-1.43]). LIMITATIONS: This was an observational study and included individuals with CKD who had a relatively high estimated glomerular filtration rate. CONCLUSIONS: MAFLD was associated with an increased risk of stroke in individuals with CKD but not in those without CKD. PLAIN-LANGUAGE SUMMARY: Metabolic dysfunction-associated fatty liver disease (MAFLD), which is recognized as a risk factor for stroke in the general population, is highly prevalent among individuals with chronic kidney disease (CKD). However, the impact of MAFLD on the risk of stroke in patients with CKD remains uncertain. We investigated the association of MAFLD with stroke in individuals with and without CKD. Our analysis revealed that MAFLD was associated with a significantly increased risk of stroke in individuals with CKD, and the magnitude of this increased risk was greater in the setting of CKD. These findings highlight the need for increased attention to MAFLD in patients with CKD and emphasize that addressing and preventing MAFLD in this population may contribute to reduced morbidity from stroke.

Genotype-Guided Dual Antiplatelet Use for Transient Ischemic Attack and Minor Stroke by Imaging Status: Subgroup Analysis of the CHANCE-2 Trial.

OBJECTIVE: This study was performed to investigate whether ticagrelor/aspirin versus clopidogrel/aspirin can further reduce the residual risk of stroke recurrence in patients with positive diffusion-weighted imaging (DWI) in the High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial. METHODS: Patients with DWI data in the CHANCE-2 trial were included and divided into those with and without acute infarction according to their DWI findings. The primary efficacy outcome and safety outcome were stroke recurrence and moderate to severe bleeding within 3 months of follow-up, respectively. RESULTS: Of the 6,412 patients enrolled in the CHANCE-2 trial, 5,796 (90.4%) patients with DWI data were included in the subgroup analysis. A total of 4,369 patients (75.4%) had an acute infarction on DWI. Patients with positive DWI had higher risk of recurrent stroke (8.1%) than those without infarction (2.2%) within 3-month follow-up. Compared with clopidogrel/aspirin, ticagrelor/aspirin was associated with lower risk of stroke in patients with positive DWI (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.52-0.80, p < 0.001) than in those negative DWI (HR = 1.22, 95% CI = 0.55-2.72, p = 0.63), with a significant interaction association (p for interaction = 0.049). The risk of moderate to severe bleeding was similar between ticagrelor/aspirin and clopidogrel/aspirin treatment in the different groups. INTERPRETATION: Our study demonstrates that imaging evaluation should be emphasized before targeting the best candidates for genotype-guided dual antiplatelet therapy in future clinical research and practice. ANN NEUROL 2023;93:783-792.

Association of triglyceride-glucose index and its related parameters with atherosclerotic cardiovascular disease: evidence from a 15-year follow-up of Kailuan cohort.

BACKGROUND: Triglyceride glucose (TyG) index and its related parameters have been introduced as cost-effective surrogate indicators of insulin resistance, while prospective evidence of their effects on atherosclerotic cardiovascular disease (ASCVD) remained scattered and inconsistent. We aimed to evaluate the association of TyG and its related parameters with new-onset ASCVD, and the predictive capacity were further compared. METHOD: A total of 95,342 ASCVD-free participants were enrolled from the Kailuan study. TyG and its related parameters were defined by fasting blood glucose, triglyceride, body mass index (BMI), waist circumstance (WC) and waist-to-height ratio (WHtR). The primary outcome was incident ASCVD, comprising myocardial infarction (MI) and ischemic stroke (IS). Cox proportional hazard models and restricted cubic spline (RCS) analyses were adopted to investigate the association between each index and ASCVD. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used for comparison of their predictive value for ASCVD. RESULTS: During a median follow-up of 15.0 years, 8,031 new cases of ASCVD were identified. The incidence rate of ASCVD increased along with elevated levels of each index, and the relationships were found to be nonlinear in the RCS analyses. The hazard ratio (HR) and 95% confidence interval (95% CI) for ASCVD was 1.39 (1.35, 1.43), 1.46 (1.41, 1.50), 1.50 (1.46, 1.55), and 1.52 (1.48, 1.57) per 1 IQR increase of baseline TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively, and the association were more pronounced for females and younger individuals aged < 60 years (Pfor interaction<0.05). Using the updated mean or time-varying measurements instead of baseline indicators did not significantly alter the primary findings. Additionally, TyG-WC and TyG-WHtR showed better performance in predicting risk of ASCVD than TyG, with the IDI (95% CI) of 0.004 (0.001, 0.004) and 0.004 (0.001, 0.004) and the category-free NRI (95% CI) of 0.120 (0.025, 0.138) and 0.143 (0.032, 0.166), respectively. Similar findings were observed for MI and IS. CONCLUSIONS: Both the TyG index and its related parameters were significantly and positively associated with ASCVD. TyG-WC and TyG-WHtR had better performance in predicting incident ASCVD than TyG, which might be more suitable indices for risk stratification and enhance the primary prevention of ASCVD.

Longitudinal cardiovascular health measured by life's essential 8 metrics with incident diabetes: A 13-year prospective cohort study.

AIMS: To investigate the associations of baseline and longitudinal cardiovascular health (CVH) measured by 'Life's Essential 8' (LE8) metrics with the risk of diabetes in Chinese people with normoglycaemia or prediabetes. MATERIALS AND METHODS: A total 86,149 participants without diabetes were enroled from the Kailuan study and were stratified by baseline glycaemic status (normoglycaemia or prediabetes). Cardiovascular health score ranged from 0 to 100 points was categorised into low (0-49), middle (50-79), and high (80-100) CVH status. Cox regressions were used to assess the associations of baseline and time-updated CVH status with incident diabetes in the overall cohort and across baseline glycaemic statuses. RESULTS: During a median follow-up of 12.94 (interquartile rage: 12.48-13.16) years, we identified 13,097 (15.20%) cases of incident diabetes. Baseline and time-updated high CVH status was associated with a lower risk of diabetes, the corresponding hazard ratio (HR) versus low CVH status was 0.27 (95% confidence interval [CI], 0.23-0.31) and 0.26 (95% CI, 0.23-0.30) in the overall cohort, respectively. Additionally, the effect of high CVH on diabetes was more prominent in participants with normoglycaemia than those with prediabetes (P < 0.0001), with an HR of 0.26 (95% CI, 0.22-0.31) versus 0.50 (95% CI, 0.41-0.62) for baseline CVH, and 0.25 (95% CI, 0.21-0.30) versus 0.39 (95% CI, 0.32-0.48) for time-updated CVH. CONCLUSIONS: Elevated baseline and longitudinal CVH score assessed by LE8 metrics is associated with a lower risk of subsequent diabetes, especially in normoglycaemic adults.

Plasma sACE-2 and risk of recurrent stroke: a nested case-control analysis.

Introduction The angiotensin-converting enzyme-2 (ACE-2) and its shedding product [soluble ACE-2 (sACE-2)] are implicated in adverse cardiovascular outcomes. However, the relationship between sACE-2 and stroke recurrence is unknown. Herein, we examined the relationship of sACE-2 with stroke recurrence in patients with ischemic stroke or transient ischemic attack (TIA). Methods Data were obtained from the Third China National Stroke Registry (CNSR-Ⅲ). Eligible cases consisted of 494 patients who developed recurrent stroke within 1-year follow-up, 494 controls were selected using age- and sex- matched with a 1:1 case-control ratio. Conditional logistic regressions were used to evaluate the association between sACE-2 and recurrent stroke. The main outcomes were recurrent stroke within 1 year. Results Among 988 patients included in this study, the median (interquartile range) of sACE-2 was 25.17 (12.29-45.56) ng/mL. After adjustment for conventional confounding factors, the odds ratio with 95% confidence interval in the highest quartile versus the lowest quartile was 1.68 (1.12-2.53) for recurrent stroke within 1-year follow-up. Subgroup analysis showed that the association between elevated plasma level of sACE-2 and stroke recurrence was significant in patients with higher systemic inflammation, as indicated by high sensitivity C reactive protein (hsCRP) ≥ 2 mg/L (adjusted OR: 2.33 [95% CI, 1.15-4.72]) and neutrophil (NEUT) counts ≥ median (adjusted OR: 2.66 [95% CI, 1.35-5.23]), but not significant in patients with lower systemic inflammation. Discussion Elevated plasma sACE-2 concentration was associated with increased risk of recurrent stroke.

Differential effect of ticagrelor versus clopidogrel by homocysteine levels on risk of recurrent stroke: a post hoc analysis of the CHANCE-2 trial.

BACKGROUND: Elevated homocysteine levels are associated with increased blood coagulation and platelet activity and may modulate the response to antiplatelet therapies. We aimed to investigate the effects of homocysteine levels on the efficacy and safety of ticagrelor-acetylsalicylic acid (ASA) versus clopidogrel-ASA among patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles. METHODS: We conducted a post hoc analysis of the CHANCE-2 (The Clopidogrel in High-risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial. Participants were randomly assigned to treatment with ticagrelor-ASA or clopidogrel-ASA. We categorized participants into groups with elevated and non-elevated homocysteine levels, based on the median level. The primary efficacy outcome was recurrent stroke within 90-day follow-up. The primary safety outcome was severe or moderate bleeding within 90 days. RESULTS: A total of 2740 participants were randomly assigned to receive ticagrelor-ASA and 2700 to receive clopidogrel-ASA. Use of ticagrelor-ASA was associated with a reduced risk of recurrent stroke among participants with elevated homocysteine levels (74 [5.3%] v. 119 [8.5%]; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.45-0.81), but not among those with non-elevated levels (86 [6.4%] v. 87 [6.7%]; HR 0.97, 95% CI 0.71-1.32; p = 0.04 for interaction). When analyzed as a continuous variable, the benefits of ticagrelor-ASA with regard to recurrent stroke increased as homocysteine levels increased (p = 0.04 for interaction). No significant interaction between homocysteine levels and treatment with regard to severe or moderate bleeding was observed (p = 0.7 for interaction). We found a significant interaction between homocysteine levels and therapy with regard to recurrent stroke in females (p = 0.04 for interaction) but not males. INTERPRETATION: In comparison with clopidogrel-ASA, ticagrelor-ASA conferred more benefit to patients with elevated homocysteine levels, particularly to female patients, in this secondary analysis of a randomized controlled trial involving patients with minor ischemic stroke or TIA. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT04078737.

Two cases of venous thromboembolism in siblings after splenectomy due to a novel PROC gene mutation.

BACKGROUND: Venous thromboembolism(VTE)is a common multifactorial disease. Anticoagulant protein deficiency is the most usual hereditary thrombophilia in the Chinese people, which includes protein C(PC), protein S and antithrombin deficiencies. CASE PRESENTATION: A retrospective analysis was conducted on clinical manifestations, laboratory tests, genetic information, and other relevant data of siblings diagnosed with VTE in 2020 at the Department of Pediatrics of Shenzhen Second People's Hospital. The proband, a 12-year-old female, was admitted to the hospital in December 2020 with a complaint of pain in the left lower limb for four days. The examination found that the PC activity was 53%, and B-ultrasound showed bilateral thrombosis of the great saphenous vein in the thigh segment. The proband's younger brother, a 10-year-old male, was admitted to the hospital in January 2021 due to right lower limb pain for two weeks. PC activity is 40%. B-ultrasound showed superficial venous thrombosis in the left lower limb and upper limb. Both siblings suffered from thalassemia and underwent splenectomy before recurrent thrombosis occurred. The proband's mother was asymptomatic, and her PC activity was 45%. Both cases were treated with warfarin anticoagulation, and their symptoms improved. The proband's mother was found to have a heterozygous mutation at this locus through Sanger sequencing. CONCLUSION: Protein C deficiency should be considered for venous thromboembolism in childhood. The heterozygous mutation 1204 A > G in PROC exon 9 in this family is reported for the first time.

Early onset of hyperuricemia is associated with the risk of nonalcoholic fatty liver disease across life course.

BACKGROUND AND AIM: Hyperuricemia is associated with nonalcoholic fatty liver disease (NAFLD), whereas whether the association differed by hyperuricemia onset age remained unclear. This study sought to investigate the associations of hyperuricemia onset age with the risk of incident NAFLD across adulthood. METHODS AND RESULTS: Based on Kailuan prospective cohort, our analysis comprised 3318 new-onset hyperuricemia cases from 2006 to 2015 and 3318 age- and sex-matched controls who were randomly selected from the general population. The risk of NAFLD across the onset age groups (<45, 45-54, 55-64, and ≥65 years) were compared using multivariable-adjusted Cox regression models. During a median follow-up of 6.78 years, 744 (22.42%) hyperuricemia participants and 586 (17.66%) normouricemia participants were diagnosed with incident NAFLD. After adjusted for potential confounders, the risk of NAFLD was gradually attenuated with each decade increase in hyperuricemia onset age. The adjusted hazard ratio (95% confidence interval) was 1.62 (1.33-1.97) for hyperuricemia onset age <45 years, 1.26 (1.01-1.57) for age of 45-54 years, 1.24 (1.00-1.59) for age of 55-64 years, and 1.19 (0.90-1.71) for age ≥65 years, respectively. The trend remained robust among the multiple sensitivity analyses. CONCLUSIONS: The relative risk of incident NAFLD differed across hyperuricemia onset age-group, and the association was more evident in those with a younger age of hyperuricemia onset, highlighting the importance of performing early strategies on the prevention of NAFLD.

Association of hyperuricemia with risk of cardiovascular disease according to the number of risk factors within target range.

BACKGROUND AND AIMS: Risk factor modification may decrease the risk of cardiovascular disease (CVD). Whether risk factor modification can mitigate the effect of hyperuricemia on CVD is unclear. This study aimed to investigate the risk of CVD among individuals with hyperuricemia, according to risk factors on target, compared with controls without hyperuricemia. METHODS AND RESULTS: This prospective study included 91,722 participants free of CVD at baseline (2006-2007) of the Kailuan study. Individuals with hyperuricemia were categorized according to the number of seven selected risk factors within the guideline-recommended target range (nonsmoking, physical activity, healthy diet, guideline-recommended levels of body mass index, blood pressure, fasting blood glucose, and total cholesterol). During a median follow-up of 13.00 years, 671 out of 6740 individuals (9.96%) with hyperuricemia and 6301 out of 84,982 control subjects (7.41%) had incident CVD. Compared with control subjects without hyperuricemia, individuals with hyperuricemia who had 4 or 5 to 7 risk factors on target had no significant excess CVD risk, the hazard ratio (HR) (95% confidence internal [CI]) was 0.93 (0.79-1.10) and 0.88 (0.71-1.10), respectively. Among individuals with hyperuricemia, excess CVD risk decreased stepwise for a higher number of risk factors on target, the HR of CVD associated with per additional risk factor within target range was 0.82 (95% CI, 0.77-0.87). Similar results were yielded for CVD subtypes. CONCLUSIONS: Among individuals with hyperuricemia, excess CVD risk decreased stepwise for a higher number of risk factors within target.

Low LDL-C/HDL-C Ratio is Associated with Poor Clinical Outcome After Intracerebral Hemorrhage: A Retrospective Analysis of Multicenter, Prospective Cohort Data in China.

BACKGROUND: The association between low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio and the clinical outcomes of acute intracranial hemorrhage (ICH) remains unclear. In this study, we attempt to investigate whether low LDL-C/HDL-C ratio is associated with poor clinical outcomes in patients with ICH. METHODS: The database was collected from a multicenter, prospective, observational cohort study, conducted in 13 hospitals in Beijing from January 2014 to September 2016. A total of 1,964 patients with ICH were initially screened in our database. Next, we selected patients with admission serum lipid information for retrospective analysis. Patients were categorized into four groups based on LDL-C/HDL-C ratio quartiles. The main outcomes were 30-day and 90-day poor functional outcome, which is defined as modified Rankin Scale score of 3 to 6, and 90-day all-cause death. Logistic regression was used to assess the association between LDL-C/HDL-C ratio and 30-day or 90-day poor functional outcome. Kaplan-Meier survival analysis and Cox regression were used to assess the association between LDL-C/HDL-C ratio and 90-day all-cause death. Restricted cubic splines were used to explore the nonlinear association between LDL-C/HDL-C ratio and the outcome of patients with ICH. RESULTS: A total of 491 patients with spontaneous ICH were finally enrolled in our study. The mean age was 57.6 years old, and 72.1% (357/491) were men. After adjustment for confounders, patients in the lowest LDL-C/HDL-C quartile (< 1.74) had a significantly higher risk of 30-day and 90-day poor functional outcome compared with those in the highest quartile (> 3.16; 30-day: adjusted odds ratio 3.61, 95% confidence interval 1.68-7.72; 90-day: adjusted odds ratio 2.82, 95% confidence interval 1.33-5.95). Restricted cubic splines depicted a nonlinear association between LDL-C/HDL-C ratio and 90-day poor functional outcomes, indicating LDL-C/HDL-C ratio of 3.1-3.5 was correlated with better 90-day functional outcome. However, no significant correlation was found between low LDL-C/HDL-C ratio and 90-day all-cause death. CONCLUSIONS: Lower LDL-C/HDL-C ratio (< 1.74) is independently associated with an increased risk of poor functional outcome in patients with ICH. In the population of patients whom we studied, there is a nonlinear association between LDL-C/HDL-C ratio and 90-day poor functional outcome, and patients with an LDL-C/HDL-C ratio of 3.1 to 3.5 tend to have the lowest risk of 90-day poor functional outcome.

Systemic Immune-Inflammation Response is Associated with Futile Recanalization After Endovascular Treatment.

BACKGROUND: Frequent incidence of futile recanalization decreases the benefit of endovascular treatment (EVT) in acute ischemic stroke. We hypothesized that the inflammation and immune response after ischemic are associated with futile recanalization. We aimed to investigate the correlation of admission systemic immune-inflammation index (SII) with futile recanalization post EVT. METHODS: Patients with successful recanalization (modified Thrombolysis in Cerebral Ischemia angiographic score 2b-3) and maintained artery recanalized after 24 h of EVT were chosen from a prospective nationwide registry study. Futile recanalization was defined as a poor functional outcome (modified Rankin Scale score 3-6) at 90 days, irrespective of a successful recanalization. At admission, SII was calculated as (platelet count × neutrophil count)/lymphocyte count/100. Logistic regression analysis helped to test the relationship of SII with futile recanalization. RESULTS: Among the 1,002 patients included, futile recanalization occurred in 508 (50.70%). No matter whether tested as quartiles or continuous variables, SII was significantly associated with futile recanalization (P < 0.05), and for every one standard deviation increase of SII, the risk of futile recanalization elevated by 22.3% (odds ratio 1.223, 95% confidence interval 1.053-1.444, P = 0.0093). Moreover, no significant interactions could be observed between SII or SII quartiles and age, baseline National Institutes of Health Stroke Scale scores, onset-to-recanalization time, and modified Thrombolysis in Cerebral Ischemia angiographic scores (all P for interaction > 0.05). CONCLUSIONS: Early SII elevation was associated with an increased risk of futile recanalization among patients with EVT. Our results indicated that therapeutic drug targeting hyperreactive immune-inflammation response might be helpful for reducing the incidence of futile recanalization.

Association between the C-reactive protein to albumin ratio and poor clinical outcome in patients with spontaneous intracerebral hemorrhage.

BACKGROUND: The C-reactive protein-to-albumin ratio (CAR) is a novel prognostic biomarker of systemic inflammation and nutritional status. The association between CAR and the long-term outcome of spontaneous intracerebral hemorrhage (ICH) remains unclear. METHODS: From January 2014 to September 2016, 497 patients with spontaneous ICH were enrolled in our study from 13 hospitals in Beijing. According to the CAR quartiles, patients were classified into four groups (Q1-Q4). Logistic regression was applied to analyze the relationship between different CAR levels and main outcome (90-day and 1-year mRS 4-6). Restricted cubic splines and receiver operating characteristic (ROC) curves of CAR for poor clinical outcomes were assessed. RESULTS: In the multivariate logistic regression model, compared with the lowest quartile of CAR, the adjusted odds ratios of the Q2, Q3, and Q4 group for 90-day mRS score of 4-6 were 3.64 (1.61-8.23), 3.83 (1.67-8.77), and 8.91 (3.85-20.64). In terms of 1-year mRS score of 4-6, compared with the lowest quartile of CAR, the adjusted odds ratios of the Q3 and Q4 group were 3.31 (1.33-8.22) and 6.87 (2.81-16.78). CONCLUSIONS: A high CAR level was associated with a high risk of long-term adverse prognosis in patients with ICH, and the risk of ICH poor outcome increased steadily with CAR rising in a certain range, and maintained in a high level thereafter.

Outcomes of antiplatelet therapy before endovascular treatment of acute large vessel occlusion: Data from the ANGEL-ACT registry.

OBJECTIVES: To investigate whether single or dual antiplatelet therapy (SAPT or DAPT) within 24 hours before endovascular treatment (EVT) could improve the clinical outcomes of patients with large vessel occlusion (LVO). METHODS: Patients from the ANGEL-ACT registry were divided into antiplatelet therapy (APT) and non-APT groups. The APT group was divided into SAPT and DAPT groups. Outcome measurement included 90-day modified Rankin Scale (mRS) distribution, change in the NIHSS at 7 days or discharge, number of passes, modified first pass effect (mFPE), symptomatic intracranial hemorrhage (SICH), and mortality within 90 days. To compare the outcomes, we performed multivariable analyses by adjusting for the propensity score calculated by the logistic regression model. RESULTS: Of 1611 patients, 1349 were in the non-APT group, while 262 (16.3 %) were in the APT group (122 [46.6 %] received SAPT, 140 [53.4 %] received DAPT). APT, SAPT or DAPT were not associated with a shift to better outcomes (non-APT vs. APT, 3[0-5] vs. 3[0-5], common odds ratio [OR], 1.04, 95 %confidence interval [CI]:0.82-1.34, P = 0.734). DAPT was associated with mFPE (OR,2.05, 95 %CI:1.39-3.01, P<0.001), more NIHSS reduction at 7 days or discharge (ß, -2.13, 95 %CI: -4.02--0.24, P = 0.028), lower number of passes (ß, -0.40, 95 %CI: -0.68--0.12, P=0.006), and shorter procedure duration (ß, -12.4, 95 %CI: -23.74--1.05, P = 0.032) without increasing odds of successful recanalization, PH within 24 hours and mortality with 90 days . CONCLUSIONS: APT before MT for AIS due to LVO does not affect clinical outcome in 90 days despite a tendency to reduce MT procedure time and number of passes. APT before MT in LVO does not increase SICH or mortality rates.

Association of baseline blood pressure and outcomes in etiology subtypes of large vessel occlusion stroke: Data from ANGEL-ACT registry.

BACKGROUND: Blood pressure (BP) management at the initial stage of stroke caused by large-vessel occlusion (LVO) remains challenging. We assessed the association between baseline BP and clinical and safety outcomes of endovascular treatment (EVT) in different stroke etiologies. METHODS: Patients with acute ischemic stroke and anterior circulation LVO were screened from a prospective, multicenter registry of EVT from November 2017 to March 2019. The primary outcome was poor 90-day outcome (modified Rankin Scale score 3-6). The safety outcome was 24 h post-procedure parenchymal hematoma (PH). The Trial of Org 101072 in Acute Stroke Treatment criteria were used for etiologic stroke classification. Restricted cubic spline and binary logistic regression analysis were performed to examine the association between study outcomes and natural log-transformed BP. RESULTS: In subgroup analyses, a U-shaped correlation existed between baseline mean arterial pressure (MAP) and poor outcome in large-artery atherosclerosis stroke only. Higher MAP was an independent risk factor compared with a central reference value (≥ 133 mm Hg vs 96-115 mm Hg; adjusted OR [aOR], 2.50; 95 % CI, 1.09 to 5.71, P = 0.030). Whereas elevated MAP was associated with PH (aOR, 1.58; 95 % CI 1.04 to 2.39, P = 0.030 for a ln10-unit increase in natural log-transformed MAP) in the range <110 mm Hg exclusively for cardioembolic stroke. CONCLUSION: Whether it is cause or epiphenomenon, baseline BP was associated with 90-day outcome in large-artery atherosclerosis stroke, whereas in cardioembolic stroke baseline BP was correlated with post-procedure PH within a certain range. Identifying these features based on etiological subtypes may offer a reference for BP management in acute LVO stroke.

Effectiveness of decision aids on critically ill patients' outcomes and family members' knowledge, anxiety, depression and decisional conflict: A systematic review and meta-analysis.

BACKGROUND: Decision aids (DAs) have been proposed to support patients and families with disease information processing and decision-making, but their effectiveness for critically ill patients and their families is incompletely understood. AIM: To systematically synthesize evidence on the effectiveness of the DAs on the prognosis of critically ill patients and knowledge, anxiety, depression and decisional conflict of their family members. STUDY DESIGN: Systematic review and meta-analysis. We conducted a systematic search of literature using PubMed, Embase, Cochrane Library, Web of Science, Cumulative Index to Nursing and Allied Health Literature database, Scopus, PsycNet, CNKI and Wanfang Database from the inception of the databases until May 2023 to identify randomized clinical trials (RCTs) describing DAs interventions targeted at adult intensive care unit (ICU) patients or their families. We also searched grey literature in four databases: Chinese Clinical Trials Registry, Chinese Cochrane Center, Open Grey and GreyNet International. RESULTS: Seven RCTs were included in the review. Meta-analysis identified longer hospital length of stay (LOS) among all patients compared with usual care (mean difference [MD] = 5.64 days, 95% confidence interval, CI [0.29, 10.98], p = .04), but not in surviving patients (MD = 2.09 days, 95% CI [-3.70, 7.89], p = .48). However, there was no evidence of an effect of DAs on hospital mortality (RR = 1.25, 95% CI [0.92, 1.70], p = .15), ICU LOS (MD = 3.77 days, 95% CI [-0.17, 7.70], p = .06) and length of mechanical ventilation (MD = 0.88 days, 95% CI [-2.22, 3.97], p = .58). DAs led to a statistically significant improvement in family members' knowledge (standard mean difference = 0.84, 95% CI [0.12, 1.56], p = .02). We found no significant effect of DAs on anxiety, depression, post-traumatic stress disorder, decisional conflict and quality of communication of family members. CONCLUSIONS: This review provides effective evidence that DAs can potentially improve the knowledge level of family members while prolonging the hospital LOS among critically ill patients. RELEVANCE TO CLINICAL PRACTICE: Well-designed large-scale studies with DAs tailored to the individuals' preferences and existing cultural values are warranted.

Stroke Recurrence and Antiplatelets in Posterior Versus Anterior Circulation Minor Stroke or Transient Ischemic Attack.

BACKGROUND: It is unclear whether infarct location affects stroke recurrence after index ischemic stroke. We aimed to compare the risk of stroke recurrence and the responses to dual antiplatelets with ticagrelor-aspirin versus clopidogrel-aspirin between patients with posterior circulation infarct (PCI) and those with anterior circulation infarct (ACI) after minor stroke or transient ischemic attack. METHODS: Data were obtained from the double-blind CHANCE-2 trial (Ticagrelor or Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II), which was conducted across 202 centers in China from September 2019 to March 2021. Patients with positive diffusion-weighted imaging were included and classified into PCI and ACI groups according to the hyperintense lesions on diffusion-weighted imaging. The primary efficacy and safety outcomes were a new stroke and severe or moderate bleeding within 90 days, respectively. RESULTS: A total of 4168 patients were included in this substudy, with 1427 PCI and 2741 ACI. During the 90-day follow-up, the risk of stroke recurrence in patients with PCI was similar to that with ACI (7.4% versus 8.3%; adjusted hazard ratio, 1.01 [95% CI, 0.79-1.29]; P=0.94). In comparison with clopidogrel-aspirin, ticagrelor-aspirin significantly reduced the risk of stroke recurrence in both the PCI (hazard ratio, 0.59 [95% CI, 0.40-0.89]; P=0.01) and ACI groups (hazard ratio, 0.65 [95% CI, 0.50-0.85]; P=0.002). There was no treatment-by-infarct location interaction (P value for interaction, 0.92). The risk of severe or moderate bleeding was similar between PCI and ACI patients (P=0.19). However, the risk of any bleeding increased on ticagrelor-aspirin than clopidogrel-aspirin treatment in PCI and ACI patients (P=0.02 and 0.002, respectively). CONCLUSIONS: Our study demonstrated that stroke recurrence was similar between PCI and ACI in patients with minor stroke or transient ischemic attack. Additionally, ticagrelor-aspirin was superior to clopidogrel-aspirin in reducing the risk of stroke within 90 days in both PCI and ACI patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04078737.