Antiphospholipid Antibodies Modify the Prognostic Value of Baseline Platelet Count for Clinical Outcomes After Ischemic Stroke.

BACKGROUND: Antiphospholipid antibodies (aPLs) have been reported to be involved in platelet-mediated thrombosis and inflammation, but the impact on the prognosis of ischemic stroke remains unclear. We aimed to examine whether the association between baseline platelet count (PLT) and long-term clinical outcomes within 2 years after ischemic stroke onset is modulated by aPLs. METHODS AND RESULTS: A total of 2938 patients with ischemic stroke were included in this prospective cohort study. Cox proportional hazards regression models were used to assess the association between the baseline PLT stratified by aPLs status and 2-year clinical outcomes after stroke onset, and an interaction effect between PLT and aPLs on clinical outcomes was tested by likelihood ratio test. There was a significant interaction effect of aPLs and PLT on recurrent stroke (Pinteraction=0.002) and cardiovascular events (Pinteraction=0.001) within 2 years after stroke onset. After multivariate adjustment, high PLT was associated with increased risks of recurrent stroke (hazard ratio [HR], 2.78 [95% CI, 1.03-7.45]; Ptrend=0.039) and cardiovascular events (HR, 2.58 [95% CI, 1.12-5.90]; Ptrend=0.024) when 2 extreme tertiles were compared among patients with aPL positive, but not among those with aPL negative. CONCLUSIONS: The aPLs had a modifying effect on the association between PLT and clinical outcomes within 2 years after ischemic stroke onset. Increased PLT was associated with recurrent stroke and cardiovascular events after ischemic stroke onset among patients with aPL positive, but not in those with aPL negative.

Serum Soluble Corin and Long-Term Clinical Outcomes After Acute Ischemic Stroke.

BACKGROUND: Corin plays important roles in the regulation of blood volume and pressure and cardiac function by activating natriuretic peptide pathway, exerting multiple cardioprotective effects. But the impacts of soluble corin on clinical outcomes after ischemic stroke are unclear. We aimed to investigate the associations between serum soluble corin and long-term clinical outcomes after acute ischemic stroke. METHODS AND RESULTS: We measured the concentrations of serum soluble corin in 3162 participants (2010 men and 1152 women) from the China Antihypertensive Trial in Acute Ischemic Stroke. The clinical outcomes were recurrent stroke, cardiovascular events, all-cause mortality, and unfavorable functional outcome within 24 months after stroke. Risk reclassification for study clinical outcomes of models with soluble corin were evaluated. Serum soluble corin was inversely associated with recurrent stroke, cardiovascular events, and unfavorable functional outcome after ischemic stroke. After adjusting for multiple covariates, each additional SD of log-corin was associated with a 21% (95% CI, 11-30), 16% (95% CI, 6-26), and 12% (95% CI, 3-21) decreased risk for recurrent stroke, cardiovascular events, and unfavorable functional outcome, respectively. Furthermore, the addition of soluble corin to the basic model with conventional risk factors significantly improved risk discrimination for recurrent stroke, cardiovascular events, and the composite outcome of all-cause mortality and cardiovascular events, as shown by C-statistics (all P<0.05). CONCLUSIONS: Serum soluble corin was associated with decreased risks of long-term clinical outcomes, and may be a promising prognostic biomarker for risk stratification in patients with acute ischemic stroke.

Sex-specific associations between total and regional Fat-to-muscle Mass ratio and cardiometabolic risk: findings from the China National Health Survey.

BACKGROUND: The fat-to-muscle mass ratio (FMR), integrating the antagonistic effects of fat and muscle mass, has been suggested as a valuable indicator to assess cardiometabolic health independent of overall adiposity. However, the specific associations of total and regional FMR with cardiometabolic risk are poorly understood. We aimed to examine sex-specific associations of total and regional FMR with single and clustered cardiometabolic risk factors (CRFs). METHODS: 13,505 participants aged 20 years and above were included in the cross-sectional study. Fat mass and muscle mass were assessed using a bioelectrical impedance analysis device. FMR was estimated as fat mass divided by muscle mass in corresponding body parts (whole body, arm, leg, and trunk). Clustered CRFs was defined as the presence of two or more risk factors, including hypertension, elevated blood glucose, dyslipidemia, insulin resistance (IR), and hyperuricemia. IR was assessed by the triglyceride glucose (TyG) index. Multivariable logistic regression models were applied to explore the associations of FMR in the whole body and body parts with single and clustered CRFs. RESULTS: The odds ratios (ORs) increased significantly for all single and clustered CRFs with the per quartile increase of total and regional FMR in both sexes (P for trend < 0.001), following adjustment for confounders. Among the regional parts, FMRs of the legs presented the strongest associations for clustered CRFs in both men and women, with adjusted OR of 8.54 (95% confidence interval (CI): 7.12-10.24) and 4.92 (95% CI: 4.24-5.71), respectively. Significant interactions (P for interaction < 0.05) were identified between age and FMRs across different body parts, as well as between BMI status and FMRs in different regions for clustered CRFs. Restricted cubic splines revealed significant non-linear relationships between FMRs of different body parts and clustered CRFs in both sexes (P for nonlinear < 0.05). CONCLUSIONS: FMRs in the whole body and different regions were significantly associated with single and clustered CRFs in the general Chinese population. The association between FMR and clustered CRFs was more pronounced in youngers than in the elderly.

Early vs Delayed Antihypertensive Treatment in Acute Single Subcortical Infarction: A Secondary Analysis of the CATIS-2 Randomized Clinical Trial.

Importance: The China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) suggests that early antihypertensive treatment did not reduce the risk of dependency or death in acute ischemic stroke (AIS), compared with delayed treatment. Single subcortical infarction (SSI) is an important stroke subtype, and the association of antihypertensive timing with clinical outcomes is unclear. Objective: To investigate the association of early vs delayed antihypertensive treatment with clinical outcomes in patients with SSI, stratified by the presence of parent artery disease (PAD) stenosis. Design, Setting, and Participants: This secondary analysis of the CATIS-2 randomized clinical trial included 106 hospitals in China between June 2018 and July 2022. In CATIS-2, patients with AIS within 24 to 48 hours of symptoms onset and elevated systolic blood pressure were eligible. Patients with SSI detected in diffusion-weighted imaging were included in the current post hoc subgroup analysis. Patients were grouped into (1) SSI with PAD stenosis and (2) SSI without PAD stenosis. Statistical analysis was performed from July 2023 to May 2024. Exposures: Early (immediate) vs delayed (starting on day 8) antihypertensive therapy. Main Outcome and Measure: Primary outcome was the combination of functional dependency or death (modified Rankin Scale score ≥3) at 90 days. Results: Among 997 patients with SSI in CATIS-2 (mean [SD] age, 62.4 [9.8] years; 612 [61.4%] men), 116 (11.6%) had SSI with PAD and 881 (88.4%) had SSI without PAD. There was no significant difference in the primary outcome between early and delayed antihypertensive treatment groups among all patients with SSI (8.8% vs 7.1%; OR, 1.25 [95% CI, 0.79-1.99]; P = .34). Among patients with SSI with PAD, early antihypertensive treatment was associated with increased risk of the primary outcome compared with delayed treatment (23.4% vs 7.7%; OR, 3.67 [95% CI, 1.14-11.86]; P = .03); this finding was not observed in patients with SSI without PAD (6.6% vs 7.1%; OR, 0.93 [95% CI, 0.55-1.57]; P = .77). Significant interaction with treatment and presence of PAD stenosis was detected for the primary outcome (P for interaction = .04). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, early antihypertensive treatment was associated with an increased risk of functional dependency or death at 90 days among patients with SSI and coexisting PAD stenosis, compared with delayed antihypertensive treatment. Further studies are warranted for individualized BP management in patients with SSI by the presence of PAD. Trial Registration: ClinicalTrials.gov Identifier: NCT03479554.

The association of early life factors with depression and anxiety in adults aged 40-69 years: a population-based cohort study.

This study was aimed to explore the longitudinal association of five early life factors (breastfeeding, maternal smoking around birth, birth weight, being born in a multiple birth, and adoption) during the in-utero, perinatal, and early childhood development stages with incidence of depression and anxiety in adults aged 40-69 years. We used data from the UK biobank, 5,02,394 participants aged 40-69 years were recruited between 2006 and 2010. Participants provided information on early life exposures through touchscreen questionnaires or verbal interviews at baseline. The primary outcomes, depression, and anxiety, were defined according to the International Classification of Diseases, 10th Revision. Hazard ratios (HR) and 95% confidence intervals (CI) for each factor were reported. During a median follow-up of 13.6 years, 16,502 (3.55%) participants developed depression, and 15,507 (3.33%) developed anxiety. After adjusting for potential confounders, increased risk of depression was found to be significantly associated with non-breastfeeding (HR, 1.08; 95% CI, 1.04-1.13), maternal smoking around birth (HR, 1.19; 95% CI, 1.14-1.23), being born in multiple births (HR, 1.16; 95% CI, 1.05-1.27), low birth weight (HR, 1.14; 95% CI, 1.07-1.22), and being an adoptee (HR, 1.42; 95% CI, 1.28-1.58). Increased risk of anxiety was associated with non-breastfeeding (HR, 1.09; 95% CI, 1.04-1.13), maternal smoking around birth (HR, 1.11; 95% CI, 1.07-1.16), being born in a multiple births (HR, 1.05; 95% CI, 0.95-1.17), low birth weight (HR, 1.12; 95% CI, 1.05-1.20), and being an adoptee (HR, 1.25; 95% CI, 1.10-1.41). Each of these five early life factors can be considered as early life risk factors for incident depression and anxiety in adulthood independently. The dose-response relationship was also observed, suggesting that with an increase in the number of early life risk factors, the likelihood of experiencing depression and anxiety also increased. These findings highlighted the imperative consideration of early life factors in comprehending the susceptibility to mental health disorders later in life, including non-breastfeeding, maternal smoking around birth, being born in multiple births, low birth weight, and being an adoptee.

Associations of muscle mass, strength, and quality with diabetes and the mediating role of inflammation in two National surveys from China and the United states.

AIMS: The evidence for joint and independent associations of low muscle mass and low muscle strength with diabetes is limited and mixed. The study aimed to determine the associations of muscle parameters (muscle mass, strength, quality, and sarcopenia) and sarcopenia obesity with diabetes, and the previously unstudied mediating effect of inflammation. MATERIALS AND METHODS: A total of 13,420 adults from the 2023 China National Health Survey (CNHS) and 5,380 adults from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) were included in this study. Muscle mass was determined using bioelectrical impedance analysis (BIA) in the CNHS, and whole-body dual X-ray absorptiometry (DXA) in the NHANES. Muscle strength was assessed using digital hand dynamometer. Multivariate logistic regression models were used to evaluate the associations of muscle parameters and sarcopenia obesity with diabetes. Inflammatory status was assessed using blood cell counts and two systemic inflammation indices (platelet-to-lymphocyte ratio (PLR) and system inflammation response index (SIRI)). Mediation analysis was conducted to examine inflammation's role in these associations. RESULTS: Low muscle mass and strength were independently related to diabetes. Low muscle quality was associated with elevated diabetes risk. Sarcopenia has a stronger association with diabetes compared to low muscle strength alone or mass alone (CNHS, odds ratio (OR) = 1.93, 95 % confidence interval (CI):1.64-2.27; NHANES, OR = 3.80, 95 %CI:2.58-5.58). Participants with sarcopenia obesity exhibit a higher risk of diabetes than those with obesity or sarcopenia alone (CNHS, OR = 2.21, 95 %CI:1.72-2.84; NHANES, OR = 6.06, 95 %CI:3.64-10.08). Associations between muscle parameters and diabetes were partially mediated by inflammation (mediation proportion: 1.99 %-36.64 %, P < 0.05). CONCLUSION: Low muscle mass and muscle strength are independently or jointly associated with diabetes, and inflammation might be a potential mechanism underlying this association. Furthermore, the synergistic effects of sarcopenia and obesity could significantly increase diabetes risk.

Plasma Polyamines and Short-Term Adverse Outcomes Among Patients With Ischemic Stroke: A Prospective Cohort Study.

BACKGROUND: Polyamines have been reported to be associated with neurological function, but the associations between polyamines and the prognosis of ischemic stroke remain unclear. We aimed to prospectively investigate whether elevated plasma polyamine levels are associated with adverse outcomes in patients with ischemic stroke. METHODS AND RESULTS: Plasma polyamine levels were measured at admission in 3570 patients with acute ischemic stroke, and clinical outcomes were assessed at 3 months after stroke onset. The primary outcome was a composite outcome of death and major disability (modified Rankin Scale score≥3), and secondary outcomes included the individual outcomes of death and major disability. During a 3-month follow-up period, 877 participants (25.1%) experienced the primary outcome. Increased putrescines were associated with a decreased risk of the primary outcome (the highest versus the lowest tertile: odds ratio, 0.72 [95% CI, 0.58-0.91]; P=0.005) and major disability (odds ratio, 0.59 [95% CI, 0.47-0.74]; P<0.001). Conversely, increased spermidines were associated with an increased risk of death (hazard ratio, 1.86 [95% CI, 1.10-3.14]; P=0.020), and increased spermines were associated with an increased risk of the primary outcome (odds ratio, 1.36 [95% CI, 1.08-1.71]; P=0.009) and major disability (odds ratio, 1.27 [95% CI, 1.01-1.59]; P=0.041). CONCLUSIONS: Among patients with ischemic stroke, high plasma putrescine levels were associated with a decreased risk of adverse outcomes, whereas high plasma spermidine and spermine levels were associated with an increased risk of adverse outcomes. Further studies are needed to investigate whether targeting these polyamines can improve the prognosis of patients with ischemic stroke. REGISTRATION: https://clinicaltrials.gov. Identifier: NCT01840072.

Serum brain derived neurotrophic factor levels and post-stroke depression in ischemic stroke patients.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is crucial for neuronal survival and may be implicated in the pathophysiological process of depression. This study aimed to prospectively investigate the association between serum BDNF and post-stroke depression (PSD) at 3 months in a multicenter cohort study. METHODS: A total of 611 ischemic stroke patients with serum BDNF measurements from the China Antihypertensive Trial in Acute Ischemic Stroke were included in this analysis. We used the 24-item Hamilton Depression Rating Scale to assess depression status at 3 months after ischemic stroke, and PSD was defined as a score of ≥8. RESULTS: Baseline serum BDNF was inversely associated with the risk of depression after ischemic stroke. The multivariable-adjusted odds ratio of PSD for the highest tertile of BDNF was 0.53 (95 % confidence interval, 0.34-0.82; P for trend = 0.004) compared with the lowest tertile. Multivariable-adjusted spline regression model also showed a linear does-response association between serum BDNF levels and PSD at 3 months (P for linearity = 0.006). In addition, adding serum BDNF to conventional risk factors significantly improved the risk reclassification of PSD (net reclassification improvement: 16.98 %, P = 0.039; integrated discrimination index: 0.93 %, P = 0.026). LIMITATIONS: All patients in this study were Chinese, so our findings should be applied to other populations cautiously. CONCLUSIONS: Higher serum BDNF levels at baseline were significantly associated with a decreased risk of PSD at 3 months, suggesting that BDNF might be a valuable predictive biomarker and potential therapeutic target for PSD among ischemic stroke patients.

Twenty-four-hour blood pressure trajectories and clinical outcomes in patients who had an acute ischaemic stroke.

OBJECTIVE: The management of blood pressure (BP) in acute ischaemic stroke remains a subject of controversy. This investigation aimed to explore the relationship between 24-hour BP patterns following ischaemic stroke and clinical outcomes. METHODS: A cohort of 4069 patients who had an acute ischaemic stroke from 26 hospitals was examined. Five systolic BP trajectories were identified by using latent mixture modelling: trajectory category 5 (190-170 mm Hg), trajectory category 4 (180-140 mm Hg), trajectory category 3 (170-160 mm Hg), trajectory category 2 (155-145 mm Hg) and trajectory category 1 (150-130 mm Hg). The primary outcome was a composite outcome of death and major disability at 3 months poststroke. RESULTS: Patients with trajectory category 5 exhibited the highest risk, while those with trajectory category 1 had the lowest risk of adverse outcomes at 3-month follow-up. Compared with the patients in the trajectory category 5, adjusted ORs (95% CIs) for the primary outcome were 0.79 (0.58 to 1.10), 0.70 (0.53 to 0.93), 0.64 (0.47 to 0.86) and 0.47 (0.33 to 0.66) among patients in trajectory category 4, trajectory category 3, trajectory category 2 and trajectory category 1, respectively. Similar trends were observed for death, vascular events and the composite outcome of death and vascular events. CONCLUSION: Patients with persistently high BP at 180 mm Hg within 24 hours of ischaemic stroke onset had the highest risk, while those maintaining stable BP at a moderate-low level (150 mm Hg) or even a low level (137 mm Hg) had more favourable outcomes.

Association of Cardiac Biomarkers in Combination With Cognitive Impairment After Acute Ischemic Stroke.

BACKGROUND: Poststroke cognitive impairment is a severe and common clinical complication that constitutes a substantial global health burden. We aimed to evaluate the association of 3 cardiac biomarkers in combination with poststroke cognitive impairment and their prognostic significance. METHODS AND RESULTS: This prospective study included 566 patients with ischemic stroke. Cardiac biomarkers, including sST2 (soluble suppression of tumorigenicity-2 receptor), GDF-15 (growth differentiation factor-15), and NT-proBNP (N-terminal pro-B-type natriuretic peptide), were measured. Cognitive impairment was defined as a Mini-Mental State Examination score of <27 or a Montreal Cognitive Assessment score of <25 at 3 months after ischemic stroke. Odds of cognitive impairment 3 months after ischemic stroke increased with the number of elevated cardiac biomarkers (sST2, GDF-15, and NT-proBNP; Ptrend<0.001). The multivariable adjusted odds ratios (95% CIs) of cognitive impairment defined by the Mini-Mental State Examination and Montreal Cognitive Assessment were 2.45 (1.48-4.07) and 1.86 (1.10-3.14) for the participants with ≥2 elevated cardiac biomarkers, respectively, compared with those without any elevated cardiac biomarker. Additionally, higher cardiac biomarker scores were associated with an increased risk of cognitive impairment (Ptrend<0.05). Simultaneously adding all 3 cardiac biomarkers to the basic model with traditional risk factors significantly improved the risk prediction of Mini-Mental State Examination-defined cognitive impairment (net reclassification improvement=34.99%, P<0.001; integrated discrimination index=2.67%, P<0.001). Similar findings were observed using the Montreal Cognitive Assessment scores. CONCLUSIONS: An increased number of elevated novel cardiac biomarkers were associated with an increased odds of poststroke cognitive impairment, suggesting that a combination of these cardiac biomarkers may improve the risk prediction of cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

High-Serum Brain-Derived Neurotrophic Factor Levels Are Associated With Decreased Risk of Poststroke Cognitive Impairment.

BACKGROUND: BDNF (brain-derived neurotrophic factor) is widely implicated in the pathophysiological process of stroke, but the effect of BDNF on poststroke cognitive impairment (PSCI) remains unclear. We aimed to investigate the association between baseline serum BDNF and the risk of PSCI at 3 months in a multicenter study based on a preplanned ancillary study of the CATIS trial (China Antihypertensive Trial in Acute Ischemic Stroke). METHODS: We examined serum BDNF levels at baseline and used the Mini-Mental State Examination and Montreal Cognitive Assessment to evaluate cognitive function at 3-month follow-up after ischemic stroke. PSCI was defined as Mini-Mental State Examination score <27 or Montreal Cognitive Assessment score <25. Logistic regression analyses were performed to evaluate the association between serum BDNF and the risk of 3-month PSCI. RESULTS: In this ancillary study, a total of 660 patients with ischemic stroke with hypertension were included, and 593 patients (mean age, 59.90±10.44 years; 410 males and 183 females) were finally included in this analysis. According to mini-mental state examination score, after adjustment for age, sex, education, baseline National Institutes of Health Stroke Scale score, APOE ɛ4 carriers, and other potential confounders, the odds ratio of PSCI for the highest tertile of BDNF was 0.60 ([95% CI, 0.39-0.94]; P=0.024) compared with the lowest tertile. Multiple-adjusted spline regression model showed a linear association of serum BDNF levels with PSCI at 3 months (P value for linearity=0.010). Adding serum BDNF to conventional prognostic factors slightly improved the risk reclassification of PSCI (net reclassification improvement: 27.46%, P=0.001; integrated discrimination index: 1.02%, P=0.015). Similar significant findings were observed when PSCI was defined by the Montreal Cognitive Assessment score. CONCLUSIONS: Elevated serum BDNF levels were associated with a decreased risk of PSCI at 3 months, suggesting that serum BDNF might be a potential predictive biomarker for PSCI among patients with ischemic stroke with hypertension.

Efficacy of Immediate Antihypertensive Treatment in Patients With Acute Ischemic Stroke With Different Blood Pressure Genetic Variants.

BACKGROUND: It remains unclear whether blood pressure (BP) genetic variants could modify the efficacy of immediate antihypertensive treatment after acute ischemic stroke. We conducted a secondary analysis of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) to investigate the effect of early antihypertensive treatment on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. METHODS: The CATIS randomized 4071 patients with acute ischemic stroke with elevated systolic BP to receive antihypertensive treatment or discontinue all antihypertensive agents during hospitalization. Randomization was conducted centrally and was stratified by participating hospitals and use of antihypertensive medications. Five BP-associated single nucleotide polymorphisms (rs16849225, rs17030613, rs1173766, rs6825911, and rs35444 in FIGN-GRB14, ST7L-CAPZA1, NPR3, ENPEP, and near TBX3, respectively) were genotyped among 2590 patients. The primary outcome was a combination of death and major disability at 14 days or hospital discharge. A weighted BP genetic risk score was constructed by the 5 single nucleotide polymorphisms. RESULTS: At 14 days or hospital discharge, the primary outcome was not significantly different between antihypertensive treatment and control groups based on genotype subgroups for all 5 single nucleotide polymorphisms (all P>0.05 for interaction). In addition, the BP genetic risk score did not modify the effect of antihypertensive treatment. The odds ratios (95% CIs) for the primary outcome were 0.95 (0.71-1.26), 1.08 (0.80-1.44), and 0.91 (0.69-1.22) in patients with low, intermediate, and high BP genetic risk score, respectively (P=0.88 for interaction). CONCLUSIONS: Early antihypertensive treatment had a neutral effect on clinical outcomes among patients with acute ischemic stroke according to 5 BP-associated genetic variants. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Emergency Physician-performed Echocardiogram in Non-ST Elevation Acute Coronary Syndrome Patients Requiring Coronary Intervention.

Introduction: Identification of patients not meeting catheterization laboratory activation criteria by electrocardiogram (ECG) but who would benefit from early coronary intervention remains challenging in the emergency department (ED). The purpose of this study was to evaluate whether emergency physician (EP)-performed point-of-care transthoracic echocardiography (POC TTE) could help identify patients who required coronary intervention within this population. Methods: This was a retrospective observational cohort study of adult patients who presented to two EDs between 2018-2020. Patients were included if they received a POC TTE and underwent diagnostic coronary angiography within 72 hours of ED presentation. We excluded patients meeting catheterization laboratory activation criteria on initial ED ECG. Ultrasound studies were independently reviewed for presence of regional wall motion abnormalities (RWMA) by two blinded ultrasound fellowship-trained EPs. We then calculated test characteristics for coronary intervention. Results: Of the 221 patient encounters meeting inclusion criteria, 104 (47%) received coronary intervention or coronary artery bypass grafting (CABG) referral. Overall prevalence of RWMA on POC TTE was 35% (95% confidence interval [CI] 29-42%). Presence of RWMA had 38% (95% CI 29-49%) sensitivity and 68% (95% CI 58-76%) specificity for coronary intervention/CABG referral. Presence of "new" RWMA (presence on EP-performed POC TTE and prior normal echocardiogram) had 43% (95% CI 10-82%) sensitivity and 93% (95% CI 66-100%) specificity for coronary intervention/CABG referral. The EP-performed POC TTE interpretation of RWMA had 57% (95% CI 47-67%) sensitivity and 96% (95% CI 87-100%) specificity for presence of RWMA on subsequent cardiology echocardiogram during the same admission. Conclusion: Presence of RWMA on EP-performed POC TTE had limited sensitivity or specificity for coronary intervention or referral to CABG. The observed specificity appeared to trend higher in subjects with a prior echocardiogram demonstrating absence of RWMA, although a larger sample size will be required to confirm this finding. The EP-performed POC TTE RWMA had high specificity for presence of RWMA on subsequent cardiology echocardiogram. Further evaluation of the diagnostic performance of new RWMA on EP-performed POC TTE with a dedicated cohort is warranted.

One-Year Disability Trajectories and Long-Term Cardiovascular Events, Recurrent Stroke, and Mortality After Ischemic Stroke.

BACKGROUND: Patients with stroke are often affected by varying degrees of functional disability and have different evolution patterns in functional disability. However, little is known about the predictive usefulness of disability changes after stroke. We aimed to describe 1-year disability trajectories and to assess the associations of longitudinal disability trajectories with 24-month clinical outcomes after ischemic stroke. METHODS AND RESULTS: A total of 3533 patients with ischemic stroke from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) were studied. Distinct trajectories of disability were identified by the group-based trajectory model, as measured by modified Rankin Scale score within 12 months. Cox proportional hazards regression models were used to examine the associations of disability trajectories with 24-month cardiovascular events and all-cause mortality. We identified 4 distinct disability trajectories: no significant disability (562 participants [15.9%]), slight disability to recovery (1575 participants [44.6%]), severe to moderate disability (1087 participants [30.8%]), and persistent severe disability (309 participants [8.7%]). Compared with no significant disability trajectory, the multivariable adjusted hazard ratios (95% CIs) of patients within the persistent heavy-severe trajectory were 2.63 (1.20-5.76) for cardiovascular events, 2.55 (1.12-5.79) for recurrent stroke, and 6.10 (2.22-16.72) for all-cause mortality; notably, the hazard ratios (95% CIs) for patients within the severe to moderate disability trajectory were 1.99 (1.01-3.94) for cardiovascular events and 1.85 (1.03-3.33) for the composite outcome of cardiovascular events and all-cause mortality. CONCLUSIONS: Functional disability trajectories within 12 months after stroke onset were associated with the risk of 24-month adverse outcomes. Patients with persistent severe disability or severe to moderate disability had higher risk of cardiovascular events and all-cause mortality. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Association of Pulse Pressure Fluctuation During Hospitalization With Adverse Outcomes Within 3 Months After Ischemic Stroke.

BACKGROUND: Pulse pressure (PP) depends on heart function and arterial wall elasticity, which is closely related to the incidence of ischemic stroke. However, the association of PP fluctuation during hospitalization with adverse outcomes after ischemic stroke remains unclear. METHODS: The present study included 3,971 patients with ischemic stroke. The primary outcome was the composite outcome of death or vascular events within 3 months after ischemic stroke. PP fluctuation was reflected by successive variation of PP (PP-SV). RESULTS: The cumulative incidence rates of the primary outcome were the highest in the patients in the highest quartiles of PP-SV (P < 0.05). The multivariable-adjusted hazard ratios (95% confidence intervals) of the primary outcome in the highest quartiles were 1.86 (1.03-3.38) for death or vascular events, and 2.15 (1.06-4.37) for vascular events (all Ptrend < 0.05). Multivariable-adjusted restricted cubic spline analyses showed linear associations of PP-SV during hospitalization with the primary outcome (P for linearity <0.05). CONCLUSIONS: Large PP fluctuation during hospitalization was associated with increased risks of adverse outcomes within 3 months after ischemic stroke, which provided valuable new insight for blood pressure management in the acute phase of ischemic stroke. Controlling PP fluctuation may be contributing to improving prognosis after ischemic stroke.

The efficacy of artificial(nonbiological)extracorporeal liver support system for primary biliary cholangitis and the effect of this therapy on prognosis / 实用医学杂志

Objective To evaluate the clinical efficacy of plasma exchange(PE)and double plasma molecular absorption system(DPMAS)in the treatment of primary biliary cholangitis(PBC)and the effect of this therapy on prognosis.Methods The clinical data on 526 PBC patients in our hospital from December 2013 to January 2022 were retrospectively analyzed.The patients were divided into different groups according to different therapies and then matched with propensity.The changes in symptoms,laboratory indexes and MELD scores were compared between two groups before and after treatment,and the clinical efficacy of artificial liver treatment for PBC patients was assessed.The effect of this treatment on the survival outcomes in these patients via comparing the cumulative survival rates at 3,6 and 12 months between the two groups.Results The efficiency was better in the group with artificial liver treatment in addition medical therapy than the group with medical treatment alone,the difference was statistically significant(76.7%vs.55.8%,χ2 = 4.214,and P = 0.040).Cox proportional risk regression showed that TBIL was an independent risk factor affecting the 3-,6-,or 12-month survival in PBC patients.Conclusions Artificial liver support system can effectively relieve symptoms,reduce levels of ALT,AST and TBIL,improve blood coagula-tion function,and lower MELD scores in PBC patients.This therapy revealed a trend of improvement in 3-,6-,or 12-month survival outcomes.

FAM3A Deficiency - Induced Mitochondrial Dysfunction Underlies Post-Infarct Mortality and Heart Failure.

Mitochondrial protein sequence similarity 3 gene family member A (FAM3A) plays important roles in the electron transfer chain, while its functions in the heart are still unknown. This study aims to explore the roles and mechanisms of FAM3A after myocardial infarction (MI). FAM3A-deficient (Fam3a-/-) mice were implemented with MI injury and showed lower survival rates at 4 weeks as well as decreased cardiac systolic function. Isolated cardiomyocytes of Fam3a-/- mice showed reduced basal, ATP-linked respiration and respiratory reserve compared to that of wild-type mice. Transmission electron microscopy studies showed Fam3a-/- mice had a larger size and elevated density of mitochondria. FAM3A deficiency also induced elevated mitochondrial Ca2+, higher opening level of mPTP, lower mitochondrial membrane potential and elevated apoptotic rates. Further analyses demonstrated that mitochondrial dynamics protein Opa1 contributed to the effects of FAM3A in cardiomyocytes. Our study discloses the important roles of mitochondrial protein FAM3A in the heart.

Prognostic significance of plasma SDF-1 in acute ischemic stroke patients with diabetes mellitus: the CATIS trial.

BACKGROUND AND OBJECTIVES: Evidence on the associations between baseline stromal cell-derived factor (SDF)-1 and clinical outcomes in acute ischemic stroke patients is lacking. The present study aimed to examine the relationship between plasma SDF-1 levels and clinical outcomes based on a large multicenter study of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). METHODS: Secondary analysis was conducted among 3,255 participants from the CATIS trial with a baseline measurement of plasma SDF-1 levels. We evaluated the associations between plasma SDF-1 levels and one-year recurrent stroke, cardiovascular events, and all-cause mortality using Cox regression models. We further investigated the prognostic effect of SDF-1 on clinical outcomes in patients with different characteristics. RESULTS: Higher plasma SDF-1 levels were not associated with recurrent stroke, cardiovascular events, and all-cause mortality at one-year after ischemic stroke (all P trend ≥ 0.05). There were significant interactions between plasma SDF-1 levels and history of diabetes mellitus on recurrent stroke (P = 0.005), cardiovascular events (P = 0.007) and all-cause mortality (P = 0.04) at one year. In patients with diabetes mellitus, plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events after adjustment for confounders. For example, 1-SD higher log-SDF-1 was associated with a hazard ratio (95% confidence interval) of 1.65 (1.18-2.32) for recurrent stroke and 1.47 (1.08-1.99) for the cardiovascular events, but not all-cause mortality 1.36 (0.96-1.93) at one year. However, there were no associations between plasma SDF-1 and clinical outcomes in patients without diabetes mellitus (all P > 0.05). The addition of plasma SDF-1 to the conventional risk factors model significantly improved the risk prediction of all outcomes. Similarly, findings between elevated SDF-1 levels and two-year outcomes were found only in patients with diabetes mellitus. CONCLUSIONS: Elevated plasma SDF-1 was significantly associated with an increased risk of recurrent stroke and cardiovascular events only in ischemic patients with diabetes mellitus.

Blood pressure control and antihypertensive medication use after discharge and prognosis of ischemic stroke.

OBJECTIVE: To investigate the effect of consistently blood pressure (BP) control status after discharge on adverse clinical outcomes among ischemic stroke (IS) patients. METHODS: Three thousand, four hundred and six acute IS patients were included and followed up at 3 months, 12 months, and 24 months after stroke. Study outcomes were defined as death, vascular events and composite of death or vascular events. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confident interval (CI) of death and the composite outcome of death or vascular events associated with BP control and antihypertensive medication use. RESULTS: The multivariable adjusted HRs were 0.22 [95% confidence interval (CI): 0.09-0.57] for death and 0.60 (95% CI: 0.39-0.97) for the composite outcome of death or vascular events among participants with consistently controlled BP compared with those with consistently uncontrolled BP. The participants with both consistently controlled BP and regular use of antihypertensive medication had the lowest risks of death [hazard ratio (HR): 0.18, 95% CI: 0.04-0.75] and composite outcome of death or vascular events (HR: 0.54, 95% CI: 0.29-0.98) in comparison with those with both uncontrolled BP and irregular use of antihypertensive medication. DISCUSSION: Continuous BP control and regular use of antihypertensive medications after discharge can decrease the risks of death and composite outcome of death or vascular events among IS patients, suggesting the importance of continuous BP control and regular use of antihypertensive medications after discharge for improving prognosis of IS.