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.

Gender difference in association between diabetes mellitus and all-cause mortality in atrial fibrillation patients.

OBJECTIVE: There may be gender difference in correlation of diabetes mellitus (DM) and cardiovascular events. We attempt to investigate whether there is gender-heterogeneity in one-year outcomes of atrial fibrillation (AF) patients with DM or not. METHODS: Patients who were diagnosed with AF admitted to the emergency departments in the Chinese AF Multicenter Registry study were enrolled. Basic demographics information, initial Blood Pressure and heart rate, medical histories, and treatments of each patient were collected. Follow-up was carried out with a mean duration of one year. The primary endpoint was all-cause mortality and systemic embolism. RESULTS: A total of 2016 patients were selected from September 2008 and April 2011. All-cause mortality was significantly higher in male AF patients with DM than those without (21.8 % & 13.6 %, P = 0.014). Cox regression analysis showed that there was an interaction between gender and DM for one-year all-cause mortality (P = 0.049). DM was significantly associated with one-year all-cause mortality regardless of univariate analysis (HR = 1.436, 95%CI:1.079-1.911, P = 0.013) or multivariate analysis (HR = 1.418, 95%CI: 1.059-1.899, P = 0.019). For male patients with AF, DM was significantly associated with one-year all-cause mortality (P = 0.048), but not for female patients with AF (P = 0.362). CONCLUSION: DM was independently associated with one-year all-cause mortality in the entire cohort of AF patients. This association was found mainly in male patients with AF, but not in female patients. DM management programs may need to reflect gender difference.

Clinical characteristics and thrombotic risk of atrial fibrillation with obstructive sleep apnea: results from a multi-center atrial fibrillation registry study.

BACKGROUND: Sleep apnea is a risk factor for atrial fibrillation (AF) but it is underdiagnosed. Whether obstructive sleep apnea (OSA) is correlated with thrombotic risk in AF remains unclear. The aim of the present study was to analyze the clinical characteristics and assess the thrombotic risk of AF with OSA. METHODS: In the present registry study,1990 consecutive patients with AF from 20 centers were enrolled. The patients were divided into 2 groups depending on whether they presented with both AF and OSA. All the patients were followed up for 1 year to evaluate the incidences of stroke and non-central nervous system (CNS) embolism. RESULTS: Of the 1990 AF patients, 70 (3.5%) and 1920 (96.5%) patients were in the OSA group and non-OSA group, respectively. The results of the multivariate logistic model analysis showed that male sex, body mass index (BMI), smoking, and major bleeding history were independent risk factors for patients with AF and OSA. The comparison of the Kaplan-Meier curves using the log-rank test revealed that AF with OSA was correlated with an increased risk of non-CNS embolism (p < 0.01). After multivariate adjustments were performed, OSA remained an independent risk factor for non-CNS embolism (HR 5.42, 95% CI 1.34-22.01, p = 0.02), but was not correlated with the risk of stroke in patients with AF. CONCLUSIONS: The present study revealed that male sex, high BMI values, smoking, and major bleeding history were independent risk factors for patients with AF and OSA. Moreover, OSA was an independent risk factor for non-CNS embolism in AF. Our results indicate that non-CNS embolism requires focus in patients with AF and OSA.

Corrigendum: Multimorbidity and Polypharmacy in Chinese Emergency Department Patients With Atrial Fibrillation and Impacts on Clinical Outcomes.

[This corrects the article DOI: 10.3389/fcvm.2022.806234.].

Impact of renin-angiotensin-aldosterone-system inhibitor drugs on mortality in patients with atrial fibrillation and hypertension.

BACKGROUND: Renin-angiotensin-aldosterone-system inhibitors markedly play an active role in the primary prevention of atrial fibrillation (AF), but the impact of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) on the mortality of patients with AF remains unclear. This study aimed to examine the relationship between treatment with ACEIs or ARBs and mortality in emergency department (ED) patients with AF and hypertension. METHODS: This multicenter study enrolled 2016 ED patients from September 2008 to April 2011; 1110 patients with AF and hypertension were analyzed. Patients were grouped according to whether they were treated with ACEI/ARB or not and completed a 1-year follow-up to evaluate outcomes including all-cause death, cardiovascular death, stroke, and major adverse events (MAEs). RESULTS: Among the 1110 patients with AF and hypertension, 574 (51.7%) received ACEI/ARB treatment. During the 1-year follow-up, 169 all-cause deaths (15.2%) and 100 cardiovascular deaths (9.0%) occurred, while 98 strokes (8.8%) and 255 MAEs (23.0%) occurred. According to the multivariate Cox regression analysis, ACEI/ARB therapy was significantly associated with a reduced risk of all-cause death (HR, 0.605; 95% CI 0.431-0.849; P = 0.004). Moreover, ACEI/ARB therapy was independently associated with a reduced risk of cardiovascular death (HR 0.585; 95% CI 0.372-0.921; P = 0.020) and MAEs (HR 0.651, 95% CI 0.496-0.855, P = 0.002) after adjusting for other risk factors. CONCLUSIONS: Our results revealed that ACEI/ARB therapy was independently associated with a reduced risk of all-cause death, cardiovascular death, and MAEs in ED patients with AF and hypertension. These results provide evidence for a tertiary preventive treatment for patients with AF and hypertension.

Evolving Antithrombotic Treatment Patterns for Patients With Nonvalvular Atrial Fibrillation and Acute Coronary Syndrome or Underwent Percutaneous Coronary Intervention in China: A Cross-Sectional Study.

Objective: Antithrombotic therapy in patients with nonvalvular atrial fibrillation (NVAF) concomitant with the acute coronary syndrome (ACS) or underwent percutaneous coronary intervention (PCI) is challenging and has evolved in recent years. However, real-world data on this issue about antithrombotic regimens at discharge and its evolving trend were relatively scarce, especially in China. Methods: A total of 2,182 patients with NVAF and ACS/PCI were enrolled from 2017 to 2019. A total of 1,979 patients were finally analyzed and divided in three sequential cohorts: cohort 1 (2017), n = 674; cohort 2 (2018), n = 793; and cohort 3 (2019), n = 512. Baseline characteristics and antithrombotic therapy at discharge were analyzed by cohort. Results: In our cross-sectional study, the majority of patients (59.6%) received dual antiplatelet therapy (DAPT). Over the 3 years, DAPT prescription reduced from nearly 70% to <50% (P trend < 0.001), while triple therapy (TT)/double therapy (DT) increased from 27.2 to 50.0% (P trend < 0.001). This trend was also seen in different subgroups stratified by CHA2DS2-VASc score, HAS-BLED score, coronary artery disease type, or management type, and was validated after multivariate adjustment. Persistent atrial fibrillation and history of congestive heart failure, hypertension, diabetes mellitus, and stroke/transient ischemic attack/systemic embolism were the independent predictors of TT/DT use, while ACS, PCI, or advanced chronic kidney disease was related with more DAPT prescription. Conclusion: There is a shift of antithrombotic regime at discharge for patients with NVAF with recent ACS/PCI with reducing DAPT prescription and increasing TT/DT prescription. While the appropriate antithrombotic regimen for patients with NVAF having ACS/PCI is still underused in China.

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 value of the stress hyperglycemia ratio in patients with acute ST-segment elevation myocardial infarction: insights from a multi-center observational study.

BACKGROUND: Stress hyperglycemia is a strong predictor of adverse outcomes in patients with acute myocardial infarction (AMI). Recently, the stress hyperglycemia ratio (SHR) has been designed as an index to identify acute hyperglycemia with true risk; however, data regarding the impact of SHR on the prognosis of ST-segment elevation myocardial infarction (STEMI) remains limited. This study aimed to evaluate the predictive value of the SHR in patients with acute STEMI and to assess whether it can improve the predictive efficiency of the Thrombolysis in Myocardial Infarction (TIMI) risk score. METHODS: This study included 7476 consecutive patients diagnosed with acute STEMI across 274 emergency centers. After excluding 2052 patients due to incomplete data, 5417 patients were included in the final analysis. Patients were divided into three groups according to SHR tertiles (SHR1, SHR2, and SHR3) and were further categorized based on diabetes status. All patients were followed up for major cardiovascular adverse events (MACEs) and all-cause mortality. RESULTS: After 30 days of follow-up, 1547 MACEs (28.6%) and 789 all-cause deaths (14.6%) occurred. The incidence of MACEs was highest among patients in the SHR3 group with diabetes mellitus (DM) (42.6%). Kaplan-Meier curves demonstrated that patients with SHR3 and DM also had the highest risk for MACEs when compared with other groups (p < 0.001). Moreover, C-statistics improved significantly when SHR3 was added into the original model: the ΔC-statistics (95% confidence interval) were 0.008 (0.000-0.013) in the total population, 0.010 (0.003-0.017) in the DM group, and 0.007 (0.002-0.013) in the non-DM group (all p < 0.05). In the receiver operating characteristic analysis, the area under the curve (AUC) for the original TIMI risk score for all-cause death was 0.760. When an SHR3 value of 1 point was used to replace the history of DM, hypertension, or angina in the original TIMI risk score, the Delong test revealed significant improvements in the AUC value (∆AUC of 0.009, p < 0.05), especially in the DM group (∆AUC of 0.010, p < 0.05). CONCLUSION: The current results suggest that SHR is independently related to the risks of MACEs and mortality in patients with STEMI. Furthermore, SHR may aid in improving the predictive efficiency of the TIMI risk score in patients with STEMI, especially those with DM.

Relationship between creatinine clearance and clinical outcomes in Chinese emergency patients with atrial fibrillation.

BACKGROUND: Few real-world data on the relation between creatinine clearance (CrCl) and adverse clinical outcomes in Chinese emergency department (ED) patients with nonvalvular atrial fibrillation (AF). METHODS: In this prospective, observational, multicenter AF study, enrolled AF patients presenting to an ED at 20 hospitals in China from November 2008 to October 2011, with a follow-up of 12 month. A total of 863 AF patients with CrCl data were analyzed, and patients were categorized as CrCl ≥ 80, 50 ≤ CrCl < 80, 30 ≤ CrCl < 50, and CrCl < 30(ml/min). Outcomes of analyses were all-cause death, cardiovascular death, thromboembolism (TE), and major bleeding. RESULTS: Among the whole patients, 126(14.6%) patients died during 12-month follow-up, 53(40.2%) among CrCl < 30 ml/min group, and 48(16.2%), 22(6.5%), and 3(3.2%) among 30 ≤ CrCl50, 50 ≤ Crl < 80, and CrCl ≥ 80 ml/min groups, respectively (p < 0.001). Cardiovascular death and TE rates also increased with decreasing CrCl. On multivariate analysis, patients with CrCl < 30 ml/min were associated with higher risks of all-cause death (HR 5.567; 95%CI1.618-19.876; p = .007) and higher cardiovascular death (HR11.939; 95%CI1.439-99.031; p = .022) as compared with CrCl≥80 ml/min category. Nevertheless, for TE and major bleeding risk, CrCl groups showed no significant difference after adjustment for variables in CHA2 DS2 -VASc score and status of warfarin prescription in our cohort. CONCLUSIONS: In Chinese ED nonvalvular AF patients, incidence rates of death increased with reducing CrCl across the whole range of renal function. CrCl < 30 ml/min was associated with all-cause death, cardiovascular death, but not for TE and major bleeding.

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.

Multimorbidity and Polypharmacy in Chinese Emergency Department Patients With Atrial Fibrillation and Impacts on Clinical Outcomes.

BACKGROUND AND OBJECTS: Few studies focus on multimorbidity and polypharmacy in Chinese atrial fibrillation (AF) patients. We examined the impact of multimorbidity, polypharmacy, and treatment strategies on outcomes in Chinese emergency department (ED)AF patients. We also assessed factors associated with vitamin K antagonist (VKA) non-use in AF patients with multimorbidity or polypharmacy. METHODS: 2015 AF patients who presented to emergency department (ED) were enrolled from Nov 2008 to Oct 2011, mean follow-up of 12-months. Cox regressions were performed to identify the impact of multimorbidity and polypharmacy on clinical outcomes. RESULTS: Six hundred and sixty-five patients in low morbidity group (≤1 comorbidity), 608 patients in moderate morbidity group (2 comorbidities), 742 patients in high morbidity group (≥3 comorbidities). Five hundred and seventy patients (28.3%) had polypharmacy (≥5 medications). High and moderate morbidity groups were significantly associated with a higher risk of all-cause death (HR 2.083, 95%CI 1.482-2.929; HR 1.713, 95%CI 1.198-2.449), CV death (HR 2.457, 95%CI 1.526-3.954; HR 1.974, 95%CI 1.206-3.232) and major bleeding (HR 4.126, 95%CI 1.022-16.664; HR 6.142, 95%CI 1.6789-22.369) compared with low morbidity group. In VKA subgroup, only high morbidity group was associated with a higher risk of all-cause death (HR 2.521, 95%CI 1.482-2.929), but not significantly in other events. For polypharmacy category, there were no significant statistics among these endpoints. Coronary artery disease (CAD), hypertension, chronic obstructive pulmonary disease, and antiplatelet therapy were independent predictors for VKA non-use in whole cohort, and patients with multimorbidity. CAD and antiplatelet therapy were independent predictors for VKA non-use in patients with polypharmacy. CONCLUSION: Multimorbidity was associated with worse outcomes in Chinese ED AF patients. Polypharmacy showed no significant statistics among these outcomes. CAD and antiplatelet therapy were independent risk factors of VKA non-use in Chinese ED AF patients with multimorbidity or polypharmacy.

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.

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.

Impact of Baseline Neutrophil-to-Lymphocyte Ratio on Long-Term Prognosis in Patients With Atrial Fibrillation.

We performed a retrospective analysis involving 1269 patients with atrial fibrillation (AF) to evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) on long-term outcomes. The primary outcomes were all-cause mortality and combined end point events (CEEs). Cox proportional hazards regression analysis and net reclassification improvement (NRI) analysis were performed. During a median follow-up of 3.32 years, 285 deaths and 376 CEEs occurred. With the elevation of the NLR, the incidence of all-cause mortality (2.77, 4.14, 6.12, and 12.18/100 person-years) and CEEs (4.19, 7.40, 8.03, and 15.22/100 person-years) significantly increased. Multivariate Cox analysis indicated that the highest NLR quartile was independently associated with the incidence of all-cause mortality (hazard ratio [HR] = 1.77, 95% CI: 1.19-2.65) and CEEs (HR = 1.66, 95% CI: 1.18-2.33). When the NLR was analyzed as a continuous variable, a 1-unit increment in log NLR was related to 134% increased risk of all-cause mortality and 119% increased risk of CEEs. Net reclassification improvement analysis revealed that NLR significantly improved risk stratification for all-cause death and CEEs by 15.0% and 9.6%, respectively. Neutrophil-to-lymphocyte ratio could be an independent predictor of long-term outcomes in patients with AF.

Association between body mass index and mortality in atrial fibrillation patients with and without diabetes mellitus: Insights from a multicenter registry study in China.

BACKGROUND AND AIMS: The aim of this study was to evaluate the association between body mass index (BMI) and mortality in atrial fibrillation (AF) patients with and without diabetes mellitus (DM). METHODS AND RESULTS: A total of 1991 AF patients were enrolled and divided into two groups according to whether they have DM at recruitment. Baseline information was collected and a mean follow-up of 1 year was carried out. The primary outcome was defined as all-cause mortality with the secondary outcomes including cardiovascular mortality, stroke and major adverse events (MAEs). Univariable and multivariable Cox regression were performed to estimate the association between BMI and 1-year outcomes in AF patients with and without DM. 309 patients with AF (15.5%) had comorbid DM at baseline. Patients with DM were more likely to have cardiovascular comorbidities, receive relevant medications but carry worse 1-year outcomes. Multivariable Cox regressions indicated that elevated BMI was related with reduced risk of all-cause mortality, cardiovascular mortality and major adverse events. Compared to normal weight, overweight [HR (95% CI): 0.548 (0.405-0.741), p < 0.001] and obesity [HR (95% CI): 0.541 (0.326-0.898), p = 0.018] were significantly related with decreased all-cause mortality for the entire cohort. Remarkably reduced all-cause mortality in the overweight [HR (95% CI): 0.497 (0.347-0.711), p < 0.001] and obesity groups [HR (95% CI): 0.405 (0.205-0.800), p = 0.009] could also be detected in AF patients without DM, but not in those with DM. CONCLUSION: Elevated BMI was associated with reduced mortality in patients with AF. This association was modified by DM. The obesity paradox confined to AF patients without DM, but could not be generalized to those with DM.