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.

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.

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.

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.

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.

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.

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.

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.

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.

The efficacy and safety of CYP2C19 genotype-guided antiplatelet therapy compared with conventional antiplatelet therapy in patients with acute coronary syndrome or undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials.

Cytochrome P450 (CYP) 2C19 genotype is closely associated with the metabolism and efficacy of clopidogrel, thereby having an important impact on clinical outcomes of patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). This study aimed to evaluate the efficacy and safety of CYP2C19 genotype-guided antiplatelet therapy in patients with ACS or undergoing PCI. PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov were searched to identify randomized controlled trials (RCTs) comparing CYP2C19 genotype-guided antiplatelet therapy with conventional therapy in patients with ACS or undergoing PCI. Eight RCTs involving 6708 patients were included in this meta-analysis. CYP2C19 genotype-guided antiplatelet therapy was slightly superior to the conventional antiplatelet therapy in reducing the risk of MACE [RR(95%CI): 0.71(0.51-0.98), p = .04]. Meanwhile, the genotype-guided therapy group had significantly lower incidence of myocardial infarction [RR(95%CI): 0.56(0.40-0.78), p < .01], but similar risk of all-cause mortality, cardiovascular mortality, stent thrombosis, urgent revascularization and stroke compared to the conventional therapy group. Incidences of major/minor bleeding and major bleeding were comparable between the two groups. In patients with ACS or undergoing PCI, CYP2C19 genotype-guided antiplatelet therapy displayed benefit over conventional antiplatelet therapy in reducing the risk of MACE and myocardial infarction, without increasing bleeding risk. Further RCTs are needed to provide more evidences for CYP2C19 genotype-guided antiplatelet therapy.

Increased mortality in patients with secondary diagnosis of atrial fibrillation: Report from Chinese AF registry.

BACKGROUND: The relationship between mortality and the primary diagnosis in AF patients is poorly recognized. The purpose of the study is to compare the differences on mortality in patients with a primary or secondary diagnosis of AF and to identify risk factors amenable to treatment. METHODS: This was a prospective cohort study using data from the Chinese AF registry. For admitted patients, a follow-up was completed to obtain the outcomes during 1 year. RESULTS: A total of 2015 patients with confirmed AF were included. AF was the primary diagnosis in 40.9% (n = 825) of them. 78.9% (n = 939) of the secondary AF diagnosis patients and 55.5% (n = 458) of the primary AF diagnosis patients were sustained AF. Compared with primary AF diagnosis group, the secondary AF diagnosis group was older with more comorbidities. At 1 year, the unadjusted mortality was much higher in the secondary AF diagnosis groups compared with the primary AF diagnosis groups. In Cox regression analysis with adjustment for confounding factors, patients with secondary AF diagnosis were associated with an increased mortality (relative risk 1.723; 95% CI: 1.283 to 2.315, p < .001). On multivariate analysis, age ≥ 75, LVSD, COPD, and diabetes were independent predictors of mortality in patients with primary AF diagnosis, while for the secondary AF diagnosis group, the risk factors were age ≥ 75, heart failure, and previous history of stroke. CONCLUSIONS: Patients presenting to ED with secondary diagnosis of AF were suffering from higher mortality risks compared with primary AF diagnosis patients. Physicians should distinguish these two groups in clinical practice.

Long-term treatment with ivabradine in transgenic atrial fibrillation mice counteracts hyperpolarization-activated cyclic nucleotide gated channel overexpression.

INTRODUCTION: Recent studies have demonstrated that ivabradine (IVA), is a selective inhibitor of funny current (If) and exerts antiarrhythmic effects in the settings of various diseases such as heart failure and myocardial ischemia. However, little is known regarding the effects of long-term IVA treatment on If current and hyperpolarization-activated cyclic nucleotide gated (HCN) channel overexpression. METHODS AND RESULTS: We investigated both the If current and HCN channel expression in wild-type (WT) mice and transgenic (TG) atrial fibrillation (AF) mice (heart-specific overexpressing of (pro) renin receptor TG mice) and examined the effects of IVA on the If current and HCN channel expression, and whether those effects were sufficient to prevent an AF episode. Compared with WT mice, the If current density (at -170 mV: TG, -39.6 ± 4.6 pA/pF; WT, -26.9 ± 3.0 pA/pF; P < 0.001) and activation kinetics (V1/2 : TG, -109.45 ± 1.35 mV; WT, -128.20 ± 1.65 mV), as well as HCN2 and HCN4 messenger RNA expression and HCN4 protein expression were significantly increased in the atrial myocytes of TG mice. After 4 months of IVA treatment (7 mg/kg per day orally) the effects of IVA on TG AF mice were accompanied by the inhibition of upregulation of HCN2 and HCN4 protein expression in atrial tissue, and then resulted in a uniform If loss of function. Furthermore, we observed that ivabradine significantly decreased the incidence of AF in the TG mice (41.2% in TG mice, 16.7% in TG + IVA mice; P < 0.01). CONCLUSION: IVA reduced the incidence of AF in mice, and the antiarrhythmic effects of IVA are not limited to heart rate reduction, as they partially counteract HCN overexpression and reverse electrophysiological cardiac remodeling by attenuating If gain-of-function.

Predictors of digoxin use and risk of mortality in ED patients with atrial fibrillation.

OBJECTIVES: The aim of this study was to evaluate factors of digoxin use and its relation to mortality in ED patients with atrial fibrillation (AF). METHODS: The Chinese AF registry enrolled 2016 AF patients from 20 representative EDs, and the period of study was one year. Predictors of digoxin use and its relation to mortality were assessed by logistic and Cox regression analyses. RESULTS: Digoxin was assigned in 609 patients (30.6%), and younger age, lower body mass index values, and existence of permanent AF, heart failure (HF), chronic obstructive pulmonary disease, and valvular heart disease were identified to be factors associated with digoxin use. During the follow-up, compared to patients without digoxin therapy, digoxin-treated patients had significantly higher risk of all-cause death (17.2% vs. 13.0%, P=0.012) and cardiovascular death (15.1% vs. 6.7%, P<0.001), but similar risk of sudden cardiac death (1.1% vs. 0.7%, P=0.341). However, after adjustment for related covariates, digoxin use was no longer notably associated with increased all-cause mortality (hazards ratio [HR] 0.973, 95% confidence interval [CI] 0.718-1.318) and cardiovascular death (HR 1.313, 95% CI 0.905-1.906). Besides, neutral associations of digoxin treatment to mortality were obtained in relevant subgroups, with no interactions observed between digoxin and gender, HF, valvular heart disease, or concomitant warfarin treatment in mortality risk. CONCLUSIONS: In ED patients with AF, digoxin was more frequently assigned to vulnerable patients with concomitant HF or valvular heart disease, and digoxin use was not related to a significantly increased risk of mortality.

The expression of Ubc9 and the intensity of SERCA2a-SUMOylation were reduced in diet-induced obese rats and partially restored by trimetazidine.

BACKGROUND: Reduced expression of sarcoplasmic reticulum calcium-transporting ATPase isoform 2a (SERCA2a) has been shown to play a significant role in the cardiac dysfunction of obese animal models. It was reported recently that SUMOylation enhances the stability and activity of SERCA2a. We hypothesized that SERCA2a-SUMOylation might be involved in obesity-mediated reduction of SERCA2a. METHOD AND RESULTS: Trimetazidine (TMZ), the drug that inhibits fatty acid oxidation, was used in diet-induced obese (DIO) rats and palmitic acid (PA)-treated cardiomyocytes. The intensity of SERCA2a-SUMOylation and proteins involved in SERCA2a-SUMOylation were investigated in vivo and in vitro. DIO rats presented cardiac dysfunction, which was alleviated by TMZ treatment. Reductions of SERCA2a protein and the intensity of SERCA2a-SUMOylation were observed in DIO rats and PA-treated cardiomyocytes. These reductions were partially restored by TMZ. However, TMZ itself did not alter the intensity of SERCA2a-SUMOylation in control cardiomyocytes. The variations of protein and messenger RNA levels of Ubiquitin carrier protein 9 are in accordance with the intensity of SERCA2a-SUMOylation. Whereas the other proteins involved in SERCA2a-SUMOylation were not changed by DIO and PA. CONCLUSIONS: TMZ alleviates the DIO- and PA-induced reductions of SERCA2a-SUMOylation. Ubiquitin carrier protein 9 is involved in the reductions.

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.

[Analysis of risk factors for all cause-mortality in Chinese emergency atrial fibrillation patients].

OBJECTIVE: To explore the independent risk factors associated with one-year mortality in patients with atrial fibrillation (AF). METHODS: This study consecutively enrolled AF patients presenting to an emergency department at 20 Chinese hospitals from November 2008 to October 2011. Their baseline data and therapies were recorded. They were followed up for one year. Their major cardiovascular outcomes were recorded. And the predictors of one-year mortality were identified by uni- and multi-variate Cox regression analysis with baseline, therapy variables and follow-up therapy variables. RESULTS: The one-year all-cause mortality was 13.8% among a total of 2016 AF patients. They were divided into mortality group (A, n = 279) and survival group (B, n = 1737). The baseline data of two groups were analyzed. The group A patients were older ((76.1 ± 11.6) vs (67.2 ± 13.1) years, P < 0.01) and had smaller body mass index compared with group B ((23.7 ± 3.6) vs (22.3 ± 3.4) kg/m(2), P < 0.01); the proportion of permanent AF and CHADS2 score ≥ 2 points was higher in the group A (71.8% vs 47.5%, P < 0.01). History of heart failure, previous stroke, left ventricular systolic dysfunction, diabetes, dementia and chronic obstructive pulmonary disease (COPD) were in a higher proportion of group A (51.2% vs 35.1%, 26.3% vs 17.6%, 26.7% vs 17.9%, 21.0% vs 14.6%, 6.0% vs 1.6%, 21.4% vs 10.1%, all P < 0.01). With regards to drug treatment, usage of diuretics, digoxin and other anticoagulants (heparin, etc), the values were greater in group A (50.9% vs 42.2%, 41.3% vs 34.7%, 10.0% vs 5.9%, all P < 0.01). The Kaplan-Meier survival curves showed that the mortality rate increased along with rising CHADS2 score. Multi-variate Cox regression analysis showed that age (HR = 1.053, 95%CI: 1.040-1.066), permanent AF (HR = 1.374, 95%CI: 1.003-1.883), history of heart failure (HR = 1.385, 95%CI: 1.009-1.901), previous stroke (HR = 1.345, 95%CI: 1.009-1.795), COPD (HR = 1.379, 95%CI: 1.030-1.848), unused angiotensin II receptor blocker (ARB) (HR = 1.955, 95%CI: 1.349-2.832), aspirin unused (HR = 1.770, 95%CI: 1.375-2.278) and warfarin unused (HR = 3.262, 95%CI:1.824-5.834) were independent risk factors for one-year mortality of AF patients. CONCLUSION: Age, history of heart failure, previous stroke, COPD history, ARB unused, aspirin and warfarin unused are independent risk factors for one-year all-cause mortality of AF patients.

[The impact of hypertension history and baseline blood pressure levels on the cardiovascular outcomes in Chinese emergency atrial fibrillation patients].

OBJECTIVE: To explore the impact of hypertension history and baseline blood pressure levels on cardiovascular outcomes in Chinese emergency atrial fibrillation patients during 1 year follow-up. METHODS: This prospective study consecutively enrolled patients presenting to an emergency department with atrial fibrillation from 20 hospitals in China during November 2008 to October 2011. Baseline data and treatment regimen were recorded, all patients were followed up for one year, and major cardiovascular events (MACE including cardiovascular death, stroke, myocardial infarction, and non central nervous systemic embolism) were recorded. Patients were divided into hypertension history group and non-hypertension history group. Univariate Cox analysis was evaluated hypertension history, baseline blood pressure on major cardiovascular events. Multivariate Cox analysis recognized risk factors for major cardiovascular events. RESULTS: A total of 2016 atrial fibrillation patients were enrolled, and the average systolic blood pressure and diastolic blood pressure were (131.9 ± 23.3)mm Hg(1 mm Hg = 0.133kPa), (79.9 ± 14.7)mm Hg respectively. 1118 patients (55.5%) had a history of hypertension, and about 91.1% hypertension patient received antihypertensive treatment. Major cardiovascular events occurred in 314 cases (15.6%) among 1 year follow up, and 191 cases (17.1%) among hypertension group and 123 cases (13.7%) among non-hypertension group. Univariate Cox regression analysis of prognostic factors for major cardiovascular events showed that hypertension history and baseline systemic blood pressure were risk factors (HR = 1.269, 95%CI: 1.012-1.592, P = 0.039; HR = 1.005, 95%CI: 1.000-1.010, P = 0.042). Multivariate Cox regression model analysis, adjusted others risk factors, showed that hypertension history, baseline systolic pressure levels, and baseline diastolic blood pressure did not have independent predictive value for major cardiovascular events. Moreover, multivariate Cox regression analysis showed that age, history of heart failure, history of stroke were independent prognostic factor for one year follow-up of major cardiovascular events in atrial fibrillation patients. CONCLUSION: Age, history of heart failure, history of stroke were independent predictor for 1 year major cardiovascular events in Chinese emergency atrial fibrillation patients.

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.

[Comparison on therapeutic approach and short-term outcomes between male and female patients with ST-segment elevation myocardial infarction].

OBJECTIVE: To compare the differences on therapeutic approach and short-term outcomes between male and female patients with ST-elevation myocardial infarction (STEMI). METHODS: Data of Chinese STEMI patients were retrospectively analyzed from a global multicenter clinical trial of reviparin and metabolic modulation in acute myocardial infarction treatment evaluation (CREATE). The patients were divided into two groups according to gender and difference on demographic, baseline clinical characteristics at admission, reperfusion and drug therapy and 30-day all-cause mortality, re-infarction, stroke, hemorrhage, heart failure and combined end points were compared. RESULTS: Of the 7431 patients, 29.1% were female. Female patients were older than male patients [(68.2 ± 9.1) years vs. (60.3 ± 12.1) years]. On admission, heart rate, diastolic blood pressure and Killip class were higher and the delay between onset of chest pain and arrival at hospital was longer in female patients than in male patients (all P < 0.01). Male patients often presented MI in anterior leads while female patients often presented MI in inferior and lateral leads. History of diabetes mellitus, hypertension and heart failure was significantly higher in female than in male patients (all P < 0.01). Incidence of high blood glucose was higher in female while high blood potassium was higher in male patients (P < 0.01). Rate of reperfusion therapy was lower and the use aspirin and diuretic was more frequent in female patients than in male patients, while frequency of clopidogrel, Glycoprotein IIb/IIIa receptor inhibitor, ß-blockers, angiotensin converting enzyme inhibitor, lipid-lowering drug use was significantly higher in male than in female patients (all P < 0.01). Multivariate logistic regression analysis showed that female gender was a predictor for less PCI therapy (P < 0.01). Thirty-day all cause mortality (OR = 1.425, 95%CI: 1.163 - 1.747, P < 0.01) and combined end points (OR = 1.193, 95%CI: 1.010 - 1.410, P = 0.04) were significantly higher in female patients than in male patients. CONCLUSIONS: There are gender-related differences on therapeutic approach and short-term outcome in Chinese STEMI patients. The unfavorable demographic and baseline clinical profile could partially explain the less reperfusion therapy rate and worse prognosis in female patients.

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.].