Association between adherence to life's simple 7 metrics and risk of obstructive sleep apnea among adults in the United States.

BACKGROUND: We aimed to explore the impact of adherence to Life's Simple 7 (LS7) metrics on risk of obstructive sleep apnea (OSA), and the impact of inflammation on the association, in adults in the United States. METHODS: Data from 13,825 community-dwelling adults aged ≥ 20 years recruited in the National Health and Nutrition Examination Surveys (NHANES) 2005-2008, 2015-2018 was analyzed. The LS7 score was calculated based on the AHA definition of LS7 metrics. The diagnosis of OSA was based on self-reported symptoms of sleep disturbance using a standard questionnaire. The Multivariable Apnea Prediction (MAP) Index score was also calculated to assess the risk of OSA. Log-binominal regression and negative binomial regression were performed to estimate the associations between LS7 and OSA and MAP index, with odds ratios (ORs) and prevalence ratios (PRs) and their 95% confidence intervals (CIs) calculated. Mediation analysis was performed to estimate the mediating effects of inflammatory indicators on the associations. RESULTS: A total of 4473 participants (32.4%) had OSA, and the mean MAP index was 0.39. In fully adjusted log-binominal regression models, with total score < 6 as the reference, the ORs (95% CIs) for risk of OSA were 0.90 (0.73, 1.10), 0.76 (0.65, 0.89), 0.78 (0.64, 0.95), and 0.45 (0.38, 0.54) for total score = 6, total score = 7, total score = 8, and total score > 8, respectively (P for trend < 0.001). When LS7 score was analyzed as a continuous variable, each 1-point increase in LS7 score was associated with a 15% decrease in OSA risk (P < 0.001). In negative binominal regression models, the adjusted PRs (95% CIs) for the MAP index were 0.93 (0.90, 0.97), 0.87 (0.84, 0.91), 0.80 (0.77, 0.84), and 0.55 (0.53, 0.57) for total score = 6, total score = 7, total score = 8, and total score > 8, respectively (P for trend < 0.001). For each 1-point increase in LS7 score, the risk of OSA decreased by 13% (P < 0.001). Consistent results were observed in subgroup analysis. Mediation analysis indicated that inflammatory factors, including blood cell count, neutrophil count, and C-reactive protein, positively mediated the association of LS7 with OSA, with a mediation proportion of 0.022 (P = 0.04), 0.02 (P = 0.04), and 0.02 (P = 0.02), respectively. CONCLUSIONS: In a nationally representative sample of US adults, adherence to LS7 metrics was independently associated with reduced OSA risk. Inflammation plays a mediating role in the association between LS7 and OSA.

The Application of Artificial Intelligence in Atrial Fibrillation Patients: From Detection to Treatment.

Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. Although the guidelines for AF have been updated in recent years, its gradual onset and associated risk of stroke pose challenges for both patients and cardiologists in real-world practice. Artificial intelligence (AI) is a powerful tool in image analysis, data processing, and for establishing models. It has been widely applied in various medical fields, including AF. In this review, we focus on the progress and knowledge gap regarding the use of AI in AF patients and highlight its potential throughout the entire cycle of AF management, from detection to drug treatment. More evidence is needed to demonstrate its ability to improve prognosis through high-quality randomized controlled trials.

Rate control or rhythm control in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention.

Background: Restoring and maintaining sinus rhythm in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) has been studied in clinical trials to reduce symptoms and improve quality of life. Limited data exist on the effectiveness of rate or rhythm control therapy in these patients. Methods: Consecutive patients with AF and ACS or referred for PCI were prospectively recruited in Fuwai Hospital during 2017-2020. The primary endpoints were all-cause death and major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular mortality, myocardial infarction, ischemic stroke, non-central nervous system embolism and ischemia-driven revascularization. Kaplan-Meier curves and Cox regressions were performed to evaluate the association between rhythm/rate control and subsequent outcomes. For the primary endpoints, we used the Benjamini-Hochberg correction for multiple comparisons. Results: A total of 1499 patients with AF and ACS or undergoing PCI were included, with a median follow-up of 34.7 months. Compared to non-rate control, rate control strategy reduced the risk of subsequent MACCEs (adjusted HR, 0.320; 95 % CI 0.220-0.466; p <0.001; *p <0.002) and all-cause death (adjusted HR, 0.148; 95 % CI 0.093-0.236; p <0.001; *p <0.002). Similar trends were observed across all predefined subgroups (p <0.001). In the final multivariate model, rhythm control was not associated with a lower subsequent MACCEs but significantly improved all-cause mortality compared to non-rhythm control (adjusted HR, 0.546; 95 % CI 0.313-0.951; p =0.033; *p =0.044). Conclusions: In this real-world study, rate control strategy was associated with lower risk of MACCEs and all-cause death in AF and ACS or undergoing PCI. Besides, management with rhythm control strategy may improve all-cause mortality.

Characterization of linoleate dioxygenases in basidiomycetes and the functional role of CcLdo1 in regulating fruiting body development in Coprinopsis cinerea.

Coprinopsis cinerea, a model fungus, is utilized for investigating the developmental mechanisms of basidiomycetes. The development of basidiomycetes is a highly organized process that requires coordination among genetic, environmental, and physiological factors. Oxylipins, a class of widely distributed signaling molecules, play crucial roles in fungal biology. Among oxylipins, the sexual pheromone-inducing factors (psi factors) have been identified as key regulators of the balance between asexual and sexual spore development in Ascomycetes. Linoleate dioxygenases are enzymes involved in the biosynthesis of psi factors, yet their specific physiological functions in basidiomycete development remain unclear. In this study, linoleate dioxygenases in basidiomycetes were identified and characterized. Phylogenetic analysis revealed that linoleate dioxygenases from Basidiomycota formed a distinct clade, with linoleate dioxygenases from Agaricomycetes segregating into three groups and those from Ustilaginomycetes forming a separate group. Both basidiomycete and ascomycete linoleate dioxygenases shared two characteristic domains: the N-terminal of linoleate dioxygenase domain and the C-terminal of cytochrome P450 domain. While the linoleate dioxygenase domains exhibited similarity between basidiomycetes and ascomycetes, the cytochrome P450 domains displayed high diversity in key sites. Furthermore, the gene encoding the linoleate dioxygenase Ccldo1 in C. cinerea was knocked out, resulting in a significant increase in fruiting body formation without affecting asexual conidia production. This observation suggests that secondary metabolites synthesized by CcLdo1 negatively regulate the sexual reproduction process in C. cinerea while not influencing the asexual reproductive process. This study represents the first identification of a gene involved in secondary metabolite synthesis that regulates basidiocarp development in a basidiomycete.

The Mechanism of Inhomogeneous Mass Transfer Process of Separators in Lithium-Ion Batteries.

The liquid-phase mass transport is the key factor affecting battery stability. The influencing mechanism of liquid-phase mass transport in the separators is still not clear, the internal environment being a complex multi-field during the service life of lithium-ion batteries. The liquid-phase mass transport in the separators is related to the microstructure of the separator and the physicochemical properties of electrolytes. Here, in-situ local electrochemical impedance spectra were developed to investigate local inhomogeneities in the mass transfer process of lithium-ion batteries. The geometric microstructure of the separator significantly impacts the mass transfer process, with a reduction in porosity leading to increased overpotentials. A competitive relationship among porosity, tortuosity, and membrane thickness in the geometric parameters of the separator were established, resulting in a peak of polarization. The resistance of the liquid-phase mass transfer process is positively correlated with the viscosity of the electrolyte, hindering ion migration due to high viscosity. Polarization is closely related to the electrochemical performance, so a phase diagram of battery performance and inhomogeneous mass transfer was developed to guide the design of the battery. This study provides a foundation for the development of high stability lithium-ion batteries.

Effect of musical expertise on the perception of duration and pitch in language: A cross-linguistic study.

This study adopts a cross-linguistic perspective and investigates how musical expertise affects the perception of duration and pitch in language. Native speakers of Chinese (N = 44) and Estonian (N = 46), each group subdivided into musicians and non-musicians, participated in a mismatch negativity (MMN) experiment where they passively listened to both Chinese and Estonian stimuli, followed by a behavioral experiment where they attentively discriminated the stimuli in the non-native language (i.e., Chinese to Estonian participants and Estonian to Chinese participants). In both experiments, stimuli of duration change, pitch change, and duration plus pitch change were discriminated. We found higher behavioral sensitivity among Chinese musicians than non-musicians in perceiving the duration change in Estonian and higher behavioral sensitivity among Estonian musicians than non-musicians in perceiving all types of changes in Chinese, but no corresponding effect was found in the MMN results, which suggests a more salient effect of musical expertise on foreign language processing when attention is required. Secondly, Chinese musicians did not outperform non-musicians in attentively discriminating the pitch-related stimuli in Estonian, suggesting that musical expertise can be overridden by tonal language experience when perceiving foreign linguistic pitch, especially when an attentive discrimination task is administered. Thirdly, we found larger MMN among Chinese and Estonian musicians than their non-musician counterparts in perceiving the largest deviant (i.e., duration plus pitch) in their native language. Taken together, our results demonstrate a positive effect of musical expertise on language processing.

The efficacy and safety of direct oral anticoagulants compared with vitamin K antagonist in patients with hypertrophic cardiomyopathy and atrial fibrillation.

BACKGROUND: The benefit-risk profile of direct oral anticoagulants (DOAC) therapy in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) has not been well established yet. This study aimed to evaluate the efficacy and safety of DOAC compared with vitamin K antagonists (VKA) in patients with HCM and AF. METHODS: PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov were searched to identify studies comparing DOAC with VKA in patients with HCM and AF. The primary endpoint was thromboembolic events. The relative risks and standard errors were pooled by random-effect models using the generic inverse variance method. RESULTS: Seven observational studies involving 9395 patients were included in this meta-analysis. Compared to the VKA group, the DOAC group displayed a similar risk of thromboembolic events [RR (95%CI): 0.93 (0.73-1.20), p = 0.59] and ischemic stroke [RR (95%CI): 0.65 (0.33-1.28), p = 0.22]. The incidence of major bleeding was comparable between the two groups [RR (95%CI): 0.75 (0.49-1.15), p = 0.19]. Meanwhile, DOAC therapy was superior to VKA therapy in reducing the incidences of all-cause death [RR (95%CI): 0.44 (0.35-0.55), p < 0.001], cardiovascular death [RR (95%CI): 0.41 (0.22-0.75), p = 0.004], and intracranial hemorrhage [RR (95%CI): 0.42 (0.24-0.74), p = 0.003]. CONCLUSION: In patients with HCM and AF, DOAC therapy was similar to VKA therapy in reducing the risk of thromboembolic events, without increasing bleeding risk. In addition, the DOAC group displayed significant advantages in reducing mortality and intracranial hemorrhage compared with the VKA group. Further randomized controlled trials are needed to provide more evidence for DOAC therapy in this population.

Impact of hemoglobin adducts of ethylene oxide on the prevalence and prognosis of chronic kidney disease in US adults: an analysis from NHANES 2013-2016.

Animal experiments have shown that high exposure to ethylene oxide (EO) can cause multiple system damages including the renal system. Recent studies have reported associations between exposure to EO and cancer, dyslipidemia, diabetes, and cardiovascular disease. However, the impact of exposure to EO on the prevalence and prognosis of chronic kidney disease (CKD) in humans is scarcely investigated. The study was designed to investigate the associations between EO exposure and incidence and prognosis of CKD among 2900 US adults. Exposure to EO was measured by detecting the levels of hemoglobin adducts of EO (HbEO). The diagnosis of CKD was made according to an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) > 30 mg/g. Prognosis of CKD was assessed based on the evaluation system initiated by KDIGO that consists of eGFR and UACR. Survey-weighted generalized linear models and proportional odds models were constructed to assess the associations between HbEO and prevalence and prognosis of CKD, with odds ratios (ORs) and proportional odds ratios (PORs) and their 95% confidence intervals (CIs) reported, respectively. Restricted cubic spline (RCS) function was performed to depict the correlation between HbEO and CKD. The weighted median (interquartile range) of HbEO was 31.3 (23.1-60.3) pmol/g Hb. A total of 491 participants (16.9%) were diagnosed with CKD, and 153 participants (5.31%) were identified to be at high or very high risk. Referred to the first tertile of HbEO, the adjusted ORs (95% CIs) for CKD in the second and third tertile were 1.46 (0.85, 2.50) and 1.69 (1.00, 2.85), and the adjusted PORs (95% CIs) for prognosis of CKD in the second and third tertile were 1.37 (0.94, 1.99) and 1.58 (1.10, 2.26). When HbEO was analyzed as a continuous variable, the adjusted OR (95% CI) for CKD and POR (95% CI for prognosis of CKD were 1.24 (0.97, 1.58) and 1.22 (1.01, 1.47), respectively. RCS analysis revealed a non-linear positive correlation between HbEO and prevalence of CKD (P for nonlinearity < 0.05). Subgroup analysis indicated smoking status had a significant impact on this association, which remained significant among never smokers but lost significance among smokers. Among US adults, increased EO exposure was independently related to increased CKD prevalence and poor CKD outcomes, which was established in never smokers but not among ever smokers.

Association between Plasma Big Endothelin-1 Level and The Severity of Coronary Artery Disease in Patients with Non-ST Segment-Elevated Myocardial Infarction. / Associação entre Nível de Big Endotelina-1 Plasmática e a Gravidade da Doença Arterial Coronariana em Pacientes com Infarto do Miocárdio sem Supradesnivelamento do Segmento ST.

BACKGROUND: Early risk stratification with simple biomarkers is essential in patients with non-ST segment-elevation myocardial infarction (NSTEMI). OBJECTIVE: This study aimed to evaluate the association between plasma big endothelin-1 (ET-1) level and the SYNTAX score (SS) in patients with NSTEMI. METHODS: A total of 766 patients with NSTEMI undergoing coronary angiography were recruited. Patients were divided into three groups: low SS (≤22), intermediate SS (23-32), and high SS (>32). Spearman correlation, smooth curve fitting, logistic regression, and receiver operating characteristic (ROC) curve analysis were performed to evaluate the association between plasma big ET-1 level and the SS. A p-value <0.05 was considered statistically significant. RESULTS: There was a significant correlation between the big ET-1 and the SS (r=0.378, p<0.001). The smoothing curve indicated a positive correlation between the plasma big ET-1 level and the SS. The ROC curve analysis showed that the area under the curve was 0.695 (0.661-0.727) and the optimal cutoff of plasma big ET-1 level was 0.35pmol/l. Logistic regression showed that elevated big ET-1 was an independent predictor of intermediate-high SS in patients with NSTEMI, whether entered as a continuous variable [OR (95% CI): 1.110 (1.053-1.170), p<0.001] or as a categorical variable [OR (95% CI): 2.962 (2.073-4.233), p<0.001]. CONCLUSION: In patients with NSTEMI, the plasma big ET-1 level was significantly correlated with the SS. Elevated plasma big ET-1 level was an independent predictor for intermediate-high SS.

FUNDAMENTO: A estratificação de risco precoce com biomarcadores simples é essencial em pacientes com infarto do miocárdio sem supradesnivelamento do segmento ST (IAMSSST). OBJETIVO: Este estudo tem o objetivo de avaliar a associação entre nível de big endotelina-1 plasmática (ET-1) e o escore SYNTAX (SS) em pacientes com IAMSSST. MÉTODOS: Foram recrutados 766 pacientes com IAMSSST que passaram por angiografia coronária. Os pacientes foram divididos em três grupos: SS baixo (≤22), SS intermediário (23-32), e SS alto (>32). A correlação de Spearman, o ajuste de curva suave, a regressão logística, e a análise de curva característica de operação do receptor (ROC) foram realizados para avaliar a associação entre o nível de big ET-1 plasmática e o SS. Um p-valor <0.05 foi considerado estatisticamente significativo. RESULTADOS: Foi identificada uma correlação significativa entre a big ET-1 e o SS (r=0,378, p<0,001). A curva suavizada indicou uma correlação positiva entre o nível de big ET-1 plasmática e o SS. A análise de curva ROC demonstrou que a área sob a curva foi de 0,695 (0,661-0,727) e o ponto de corte ideal do nível de big ET-1 plasmática foi de 0,35 pmol/l. A regressão logística demonstrou que a big ET-1 elevada era um preditor independente de SS intermediário a alto em pacientes com IAMSSST, seja como variável contínua [RC (IC 95%: 1,110 (1,053-1,170), p<0,001] ou como variável categórica [RC (IC 95%: 2,962 (2,073-4,233), p<0,001]. CONCLUSÃO: Em pacientes com IAMSSST, o nível de big ET-1 plasmática estava significativamente correlacionado ao SS. O nível de big ET-1 plasmática elevado foi um preditor independente para SS intermediário a alto.

Associação entre Nível de Big Endotelina-1 Plasmática e a Gravidade da Doença Arterial Coronariana em Pacientes com Infarto do Miocárdio sem Supradesnivelamento do Segmento ST / Association between Plasma Big Endothelin-1 Level and The Severity of Coronary Artery Disease in Patients with Non-ST Segment-Elevated Myocardial Infarction

Resumo Fundamento A estratificação de risco precoce com biomarcadores simples é essencial em pacientes com infarto do miocárdio sem supradesnivelamento do segmento ST (IAMSSST). Objetivo Este estudo tem o objetivo de avaliar a associação entre nível de big endotelina-1 plasmática (ET-1) e o escore SYNTAX (SS) em pacientes com IAMSSST. Métodos Foram recrutados 766 pacientes com IAMSSST que passaram por angiografia coronária. Os pacientes foram divididos em três grupos: SS baixo (≤22), SS intermediário (23-32), e SS alto (>32). A correlação de Spearman, o ajuste de curva suave, a regressão logística, e a análise de curva característica de operação do receptor (ROC) foram realizados para avaliar a associação entre o nível de big ET-1 plasmática e o SS. Um p-valor <0.05 foi considerado estatisticamente significativo. Resultados Foi identificada uma correlação significativa entre a big ET-1 e o SS (r=0,378, p<0,001). A curva suavizada indicou uma correlação positiva entre o nível de big ET-1 plasmática e o SS. A análise de curva ROC demonstrou que a área sob a curva foi de 0,695 (0,661-0,727) e o ponto de corte ideal do nível de big ET-1 plasmática foi de 0,35 pmol/l. A regressão logística demonstrou que a big ET-1 elevada era um preditor independente de SS intermediário a alto em pacientes com IAMSSST, seja como variável contínua [RC (IC 95%: 1,110 (1,053-1,170), p<0,001] ou como variável categórica [RC (IC 95%: 2,962 (2,073-4,233), p<0,001]. Conclusão Em pacientes com IAMSSST, o nível de big ET-1 plasmática estava significativamente correlacionado ao SS. O nível de big ET-1 plasmática elevado foi um preditor independente para SS intermediário a alto.

Abstract Background Early risk stratification with simple biomarkers is essential in patients with non-ST segment-elevation myocardial infarction (NSTEMI). Objective This study aimed to evaluate the association between plasma big endothelin-1 (ET-1) level and the SYNTAX score (SS) in patients with NSTEMI. Methods A total of 766 patients with NSTEMI undergoing coronary angiography were recruited. Patients were divided into three groups: low SS (≤22), intermediate SS (23-32), and high SS (>32). Spearman correlation, smooth curve fitting, logistic regression, and receiver operating characteristic (ROC) curve analysis were performed to evaluate the association between plasma big ET-1 level and the SS. A p-value <0.05 was considered statistically significant. Results There was a significant correlation between the big ET-1 and the SS (r=0.378, p<0.001). The smoothing curve indicated a positive correlation between the plasma big ET-1 level and the SS. The ROC curve analysis showed that the area under the curve was 0.695 (0.661-0.727) and the optimal cutoff of plasma big ET-1 level was 0.35pmol/l. Logistic regression showed that elevated big ET-1 was an independent predictor of intermediate-high SS in patients with NSTEMI, whether entered as a continuous variable [OR (95% CI): 1.110 (1.053-1.170), p<0.001] or as a categorical variable [OR (95% CI): 2.962 (2.073-4.233), p<0.001]. Conclusion In patients with NSTEMI, the plasma big ET-1 level was significantly correlated with the SS. Elevated plasma big ET-1 level was an independent predictor for intermediate-high SS.

Impact of glycemic gap on 30-day adverse outcomes in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND AND AIMS: Stress-induced hyperglycemia (SIH) generally occurs in critical illness. Recently, glycemic gap (GAP) has been considered to be a superior indicator of SIH. However, data on the association between GAP and prognosis in ST-segment elevation myocardial infarction (STEMI) is limited. This observational study aimed to estimate the prognostic value of GAPmean, defined as the difference between mean blood glucose level (MGL) within 24 h after admission and A1c-derived average glucose (ADAG), in patients with acute STEMI. METHODS: A total of 4952 patients with acute STEMI were included in the final analysis, and they were divided into four groups according to GAPmean quartiles and diabetes mellitus (DM). The primary outcomes were all-cause mortality and major adverse cardiovascular events (MACEs). Cox proportional hazards regression analysis and net reclassification improvement (NRI) analysis were performed. RESULTS: At 30 days of follow-up, 324 (6.5%) deaths and 569 (11.5%) MACEs occurred. With the elevation of GAPmean, the incidence of all-cause mortality (4.0%, 5.6%, 6.5%, and 10.1%) and MACEs (7.3%, 9.6%, 11.4%, and 17.7%) significantly increased. Receiver operating characteristic curve analysis demonstrated that GAPmean was superior to admission blood glucose (ABG) and GAPadm (defined as the difference between ABG and ADAG) to detect adverse outcomes. Multivariate Cox regression analysis revealed that elevated GAPmean was independently associated with all-cause death and MACEs. With the first quartile as a reference, the hazards ratios (HRs) for all-cause death in the second, third, and fourth quartiles were 1.49 (95% CI 1.02-2.18), 1.58 (95% CI 1.09-2.30), and 2.11 (95% CI 1.48-3.02), respectively, and the HRs for MACEs were 1.40 (95% CI 1.05-1.86), 1.60 (95% CI 1.21-2.11), and 2.17 (95% CI 1.66-2.83), respectively, which were independent of DM status. Continuous NRI analysis revealed that GAPmean significantly improved risk stratification for all-cause mortality and MACEs by 21.6% and 19.8%, respectively. CONCLUSIONS: The glycemic gap between MGL within 24 h after admission and ADAG was independently associated with 30-day all-cause mortality and MACEs in patients with acute STEMI, which was not affected by DM status. Further, the glycemic gap provided incremental accuracy in the risk stratification of STEMI.

Implicit Causality and Pronoun Resolution in Intersubjective Discourse Relations.

Interpersonal verbs like disappoint and praise in Lucy disappointed/praised Mary because she… bias the potential cause of the event to one of the antecedent noun phrases (henceforth NPs) (e.g., Lucy for disappoint whereas Mary for praise). Using Chinese as its materials, this study investigated how verb-based implicit causality affects online pronoun resolution in backward concession (e.g., Lucy disappointed/praised Mary although she…), an intersubjective discourse relation where the subordinate although-clause forms an indirect relationship with the preceding main clause. Experiment 1 was a baseline experiment with the typical structure where implicit causality is found to be effective, i.e., backward causality. Results showed a clear modulation effect of implicit causality on pronoun resolution such that as verb bias strength decreases, participants were faster in processing sentences that disambiguate the pronoun to the verb-inconsistent NP. However, this modulation effect was not observed in Experiment 2 where we used the same verbs but replaced because with although. There was no preference for the pronoun to be disambiguated toward the verb-consistent NP or the verb-inconsistent NP in backward concession. The results of Experiments 1 and 2 were replicated in Experiment 3 where we directly compared causal and concessive relations. We suggest that the absent effect of verb-based implicit causality in backward concession could be attributed to the intersubjective nature of the concessive relation. Discourse devices such as although indicate speakers' subjective perspective and comprehenders are able to quickly accommodate the speaker's point of view during online discourse processing.

Plasma Big Endothelin-1 Levels and Long-Term Outcomes in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention.

Background: This study aimed to evaluate the association between plasma big ET-1 levels and long-term outcomes in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). Methods: A total of 930 patients were enrolled and followed up for a median duration of 2.3 years. According to the optimal cutoff of big ET-1 for predicting all-cause death, these patients were divided into two groups. The primary endpoints were all-cause death and net adverse clinical events (NACE). The secondary endpoints included cardiovascular death, major adverse cardiovascular events (MACE), BARC class ≥ 3 bleeding, and BARC class ≥ 2 bleeding. Cox regressions were performed to evaluate the association between big ET-1 and outcomes. Results: Based on the optimal cutoff of 0.54 pmol/l, 309 patients (33.2%) had high big ET-1 levels at baseline. Compared to the low big ET-1 group, patients in the high big ET-1 group tended to have more comorbidities, impaired cardiac function, elevated inflammatory levels, and worse prognosis. Univariable and multivariable Cox regressions indicated that big ET-1 ≥ 0.54 pmol/l was associated with increased incidences of all-cause death [HR (95%CI):1.73 (1.10-2.71), p = 0.018], NACE [HR (95%CI):1.63 (1.23-2.16), p = 0.001], cardiovascular death [HR (95%CI):1.72 (1.01-2.92), p = 0.046], MACE [HR (95%CI):1.60 (1.19-2.16), p = 0.002], BARC class ≥ 3 [HR (95%CI):2.21 (1.16-4.22), p = 0.016], and BARC class ≥ 2 bleeding [HR (95%CI):1.91 (1.36-2.70), p < 0.001]. Subgroup analysis indicated consistent relationships between the big ET-1 ≥ 0.54 pmol/l and the primary endpoints. Conclusion: Elevated plasma big ET-1 levels were independently associated with increased risk of all-cause death, NACE, cardiovascular death, MACE, BARC class ≥ 3 bleeding, and BARC class ≥ 2 bleeding in patients with AF and ACS or undergoing PCI.

Predictive performance of different bleeding risk scores in patients with atrial fibrillation and acute coronary syndrome or undergoing percutaneous coronary intervention.

This study aims to evaluate the predictive values of the HAS-BLED, ORBIT, ATRIA, REACH, PARIS, and PRECISE-DAPT scores in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) who received both anticoagulant and antiplatelet therapy. 930 patients were consecutively recruited and followed up for 1 year. The primary endpoints were BARC class ≥3 bleeding and BARC class ≥2 bleeding. BARC class ≥3 bleeding occurred in 36 patients(3.9%), while BARC class ≥2 bleeding was seen in 134 patients (14.4%). The predictive performance of the HAS-BLED score for BARC class ≥3 bleeding was unsatisfactory (c-statistic = 0.575). The discrimination of the ATRIA, ORBIT, PARIS, and PRECISE-DAPT scores was also low-to-moderate. The REACH score was useless in bleeding risk stratification for this population. Multivariable logistic regression indicated that previous bleeding events and hemoglobin were two independent predictors of BARC class ≥3 bleeding. Compared to the HAS-BLED score, the model constructed by previous bleeding events and hemoglobin displayed a significant improvement in bleeding risk prediction [c-statistics: 0.704 vs. 0.575 (p = .008), NRI = 0.662,IDI = 0.049]. In patients with AF and ACS or undergoing PCI who received anticoagulant+antiplatelet therapy, the HAS-BLED, ORBIT, ATRIA, REACH, PARIS, and PRECISE-DAPT scores displayed only low-to-moderate performance in predicting BARC class≥3 bleeding. Future studies are required to develop more reliable scoring systems for bleeding risk evaluation in this population.

Validation of the Academic Research Consortium for High Bleeding Risk criteria in Chinese patients with atrial fibrillation and acute coronary syndrome or undergoing percutaneous coronary intervention.

BACKGROUND: This study aims to validate the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria in Chinese patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) who received both oral anticoagulants (OAC) and antiplatelet therapy (APT). METHODS: 930 consecutive patients with AF and ACS or undergoing PCI receiving both OAC and APT were recruited and followed up for 1 year. The primary endpoint was BARC type 3 or 5 bleeding. The secondary endpoints included BARC type 2, 3, or 5 bleeding, TIMI major bleeding, TIMI major or minor bleeding, and major adverse cardiovascular events (a composite of all-cause death, stroke, non-central nervous system embolism, myocardial infarction, definite or probable stent thrombosis, and target vessel revascularization). Cox regressions were performed to evaluate the association between the ARC-HBR score and outcomes. Discrimination was evaluated through analysis of the receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Compared to patients with no HBR other than OAC, patients with HBR besides OAC tended to have more comorbidities and worse outcomes. The ARC-HBR score was significantly associated with the primary and secondary endpoints, both as a continuous variable and as a categorical variable. The ARC-HBR score performed better than the HAS-BLED score (c-statistic: 0.692 vs. 0.575, NRI = 0.313, IDI = 0.061) and the PRECISE-DAPT score (c-statistic: 0.692 vs. 0.616, NRI = 0.393, IDI = 0.049). CONCLUSIONS: In patients with AF and ACS or undergoing PCI receiving both OAC and APT, the ARC-HBR score was a significant predictor of 1-year bleeding and ischemic endpoints. The ARC-HBR score performed better than the HAS-BLED score and the PRECISE-DAPT score in BARC type 3 or 5 bleeding prediction.

Performance of the REACH, PARIS, BleeMACS, and PRECISE-DAPT scores for predicting 1-year bleeding events in patients undergoing coronary drug-eluting stent implantation.

This study aimed to evaluate the predictive performance of the REACH, PARIS, BleeMACS, and PRECISE-DAPT scores in Chinese patients undergoing coronary drug-eluting stent (DES) implantation. A total of 1911 patients undergoing coronary DES implantation were consecutively recruited and followed up for 1 year. The primary endpoints were BARC type 3 or 5 bleeding and BARC type 2,3, or 5 bleeding. The BleeMACS score and the PRECISE-DAPT score were significantly associated with 1-year incidence of BARC type 3 or 5 bleeding, but not BARC type 2, 3, or 5 bleeding. The discrimination of the PRECISE-DAPT score was moderate for BARC type 3 or 5 bleeding (c-statistic = 0.633), while those of the REACH (c-statistic = 0.533), PARIS (c-statistic = 0.553), and BleeMACS scores (c-statistic = 0.613) were relatively low. However, the analysis of c-statistic, NRI, and IDI detected no significant discrimination improvement of the PRECISE-DAPT score for BARC type 3 or 5 bleeding compared to the other three scores. The calibrations of the PRECISE-DAPT and BleeMACS scores were modest (Hosmer-Lemeshow test p > .05). Decision curve analysis indicated net benefit of the PRECISE-DAPT score in bleeding risk evaluation. In conclusion, the PRECISE-DAPT score performed moderately in predicting BARC type 3 or 5 bleeding, while the discriminative capacities of the REACH, PARIS, BleeMACS scores were relatively low in patients undergoing DES implantation. But no significant discrimination improvement of the PRECISE-DAPT score compared to the other scores could be detected. Further studies are required to develop standardized bleeding risk scores for this population.

Utility of a pharmacogenetic-driven algorithm in guiding dual antiplatelet therapy for patients undergoing coronary drug-eluting stent implantation in China.

PURPOSES: The POPular Risk Score (PRiS), a pharmacogenetic-driven algorithm consisting of CYP2C19 genotype, platelet reactivity, and clinical risk factors, is developed to evaluate ischemic risk and guide dual antiplatelet therapy (DAPT). This study aimed to evaluate the efficacy and safety of DAPT in accordance with the PRiS in patients undergoing drug-eluting stent (DES) implantation. METHODS: A total of 1757 patients recruited in this cohort study were divided into four groups according to the PRiS and type of P2Y12 receptor inhibitor treatment at discharge. The primary endpoint was major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis, and target vessel revascularization) during 1-year follow-up. The safety endpoints were defined by Bleeding Academic Research Consortium (BARC) criteria as major bleeding (BARC 3a, 3b, 3c, and 5) and clinically relevant bleeding (BARC 2, 3a, 3b, 3c, and 5). RESULTS: Among 1046 patients with PRiS < 2 and 711 patients with PRiS ≥ 2, 34.2% and 38.3% of them were treated with ticagrelor, respectively. The PRiS ≥ 2 was an independent predictor for the 1-year incidence of MACE (HR(95%CI): 2.09 (1.37-3.20), p = 0.001). Multivariable Cox regression indicated that in the PRiS ≥ 2 group, ticagrelor was superior to clopidogrel in reducing the risk of MACE (HR(95%CI): 0.53 (0.29-0.98), p = 0.042), without increasing the bleeding risk. On the other hand, in the PRiS < 2 group, clopidogrel treatment was related to a remarkably lower rate of BARC class ≥ 2 bleeding (HR(95%CI): 0.39 (0.20-0.72), p = 0.003), but comparable incidences of MACE and BARC class ≥ 3 bleeding during 1-year follow-up. Similar associations between P2Y12 receptor inhibitors and 1-year endpoints in the PRiS < 2 and PRiS ≥ 2 group could also be identified in propensity score-weighted analysis and propensity score-matched analysis. CONCLUSION: Tailored DAPT based on the PRiS could assist in improving the prognosis of patients undergoing DES implantation. Further randomized controlled trials are required to provide more evidence for PRiS-guided DAPT.

Clinical Application of CHA2DS2-VASc versus GRACE Scores for Assessing the Risk of Long-term Ischemic Events in Atrial Fibrillation and Acute Coronary Syndrome or PCI.

Background: Early risk stratification of patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) has relevant implication for individualized management strategies. The CHA 2 DS 2 -VASc and GRACE ACS risk model are well-established risk stratification systems. We aimed to assess their prognostic performance in AF patients with ACS or PCI. Methods: Consecutive patients with AF and ACS or referred for PCI were prospectively recruited and followed up for 3 years. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular mortality, myocardial infarction, ischemic stroke, systemic embolism and ischemia-driven revascularization. Results: Higher CHA 2 DS 2 -VASc (HR [hazard ratio] 1.184, 95% CI 1.091-1.284) and GRACE at discharge score (HR 1.009, 95% CI 1.004-1.014) were independently associated with increased risk of MACCEs. The CHA 2 DS 2 -VASc (c-statistics: 0.677) and GRACE at discharge (c-statistics: 0.699) demonstrated comparable discriminative capacity for MACCEs (p = 0.281) while GRACE at admission provided relatively lower discrimination (c-statistics: 0.629, p vs. CHA 2 DS 2 -VASc = 0.041). For predicting all-cause mortality, three models displayed good discriminative capacity (c-statistics: 0.750 for CHA 2 DS 2 -VASc, 0.775 for GRACE at admission, 0.846 for GRACE at discharge). A significant discrimination improvement of GRACE at discharge compared to CHA 2 DS 2 -VASc was detected (NRI = 45.13%). Conclusions: In the setting of coexistence of AF and ACS or PCI, CHA 2 DS 2 -VASc and GRACE at discharge score were independently associated with an increased risk of MACCEs. The GRACE at discharge performed better in predicting all-cause mortality.

Processing Mandarin Tone 3 Sandhi at the Morphosyntactic Interface: Reduplication and Lexical Compounds.

Mandarin tone 3 sandhi is a phonological alternation in which the initial tone 3 (i.e., low tone) syllable changes to a tone 2 (i.e., rising tone) when followed by another tone 3. The present study used a cross-modal syllable-morpheme matching experiment to examine how native speakers process the sandhi sequences derived from verb reduplication and compounding, respectively. Embedded in a visually-presented sentential context, a disyllabic sequence containing a sandhi target was displayed simultaneously with a monosyllabic audio, either a tone 1 (i.e., high-level tone), tone 2 (i.e., rising tone) or tone 3 (i.e., low tone), and participants judged whether the audio syllable matched the visual morpheme. Results showed that the tone 3 sandhi was processed differently in the two constructions. The underlying tone and the surface tone were co-activated and competed with each other in sandhi compounds whereas predominant activation of the underlying tone, over the surface tone, was observed in reduplication. The processing of tone 3 sandhi offers support for distinctive morphological structures: a lexical compound is represented both as a whole-word unit and as a combination of two individual morphemes whereas a verb reduplication is represented and accessed as a monomorphemic unit in the mental lexicon.

Type of atrial fibrillation and outcomes in patients without oral anticoagulants.

BACKGROUND: The effect of type of atrial fibrillation (AF) on adverse outcomes in Chinese patients without oral anticoagulants (OAC) was controversial. HYPOTHESIS: The type of AF associated with adverse outcomes in Chinese patients without OAC. METHODS: A total of 1358 AF patients without OAC from a multicenter, prospective, observational study was included for analysis. Univariable and multivariable Cox regression models were utilized. Net reclassification improvement analysis was performed for the assessment of risk prediction models. RESULTS: There were 896(66%) patients enrolled with non-paroxysmal AF (NPAF) and 462(34%) with paroxysmal AF (PAF). The median age was 70.9 ± 12.6 years, and 682 patients (50.2%) were female. During 1 year of follow-up, 215(16.4%) patients died, and 107 (8.1%) patients experienced thromboembolic events. Compared with the PAF group, NPAF group had a notably higher incidence of all-cause mortality (20.2% vs. 9.4%, p < .001), thromboembolism (10.5% vs. 3.8%, p < .001). After multivariable adjustment, NPAF was a strong predictor of thromboembolism (HR 2.594, 95%CI 1.534-4.386; p < .001), all-cause death (HR 1.648, 95%CI 1.153-2.355; p = .006). Net reclassification improvement analysis indicated that the addition of NPAF to the CHA2 DS2 -VASc score allowed an improvement of 0.37 in risk prediction for thromboembolic events (95% CI 0.21-0.53; p < .001). CONCLUSIONS: In Chinese AF patients who were not on OAC, NPAF was an independent predictor of thromboembolism and mortality. The addition of NPAF to the CHA2 DS2 -VASc score allowed an improvement in the accuracy of the prediction of thromboembolic events.