Genetic Predisposition of Anti-Cytomegalovirus Immunoglobulin G Levels and the Risk of 9 Cardiovascular Diseases.

Background: Accumulating evidence has indicated that persistent human cytomegalovirus (HCMV) infection is associated with several cardiovascular diseases including atherosclerosis and coronary artery disease. However, whether there is a causal association between the level of anti-HCMV immune response and the risk of cardiovascular diseases remains unknown. Methods: Single-nucleotide polymorphisms associated with anti-cytomegalovirus immunoglobulin (Ig) G levels were used as instrumental variables to estimate the causal effect of anti-cytomegalovirus IgG levels on 9 cardiovascular diseases (including atrial fibrillation, coronary artery disease, hypertension, heart failure, peripheral artery disease, pulmonary embolism, deep vein thrombosis of the lower extremities, rheumatic valve diseases, and non-rheumatic valve diseases). For each cardiovascular disease, Mendelian randomization (MR) analyses were performed. Inverse variance-weighted meta-analysis (IVW) with a random-effects model was used as a principal analysis. In addition to this, the weighted median approach and MR-Egger method were used for further sensitivity analysis. Results: In the IVW analysis, genetically predicted anti-cytomegalovirus IgG levels were suggestively associated with coronary artery disease with an odds ratio (OR) of 1.076 [95% CI, 1.009-1.147; p = 0.025], peripheral artery disease (OR 1.709; 95% CI, 1.039-2.812; p = 0.035), and deep vein thrombosis (OR 1.002; 95% CI, 1.000-1.004; p = 0.025). In the further analysis, similar causal associations were obtained from weighted median analysis and MR-Egger analysis with lower precision. No notable heterogeneities and horizontal pleiotropies were observed (p > 0.05). Conclusions/Interpretation: Our findings first provide direct evidence that genetic predisposition of anti-cytomegalovirus IgG levels increases the risk of coronary artery disease, peripheral artery disease, and deep vein thrombosis.

Time-varying spillovers among pilot carbon emission trading markets in China.

Clarifying the time-varying spillovers among pilot carbon emission permit trading markets in China is an important foundation for building the national carbon emission trading market. We calculate the dynamic spillover of carbon price return among the pilot carbon emission permit trading markets in China with the time-varying connectedness approach. The dataset is constructed from transaction data from seven pilot carbon markets in China during the period of June 23, 2014, to December 31, 2020. The quantitative analysis suggests that (i) Beijing and Chongqing carbon emission trading markets are the main spillover markets of carbon price returns, with strong pricing power, while the Guangdong and Tianjin markets are the main receivers of the price return spillover in other pilot carbon emission trading markets. (ii) The spillover effect among China's carbon markets has a strong policy orientation. The improvement and development of the carbon market driven by macroeconomic regulation and control policies can effectively improve the spillover ability of the carbon market, and the market trading activity, namely the volatility of the carbon price return rate, can amplify the spillover ability of the carbon market in the short term. (iii) There exist three types of price return spillover among China's pilot carbon emission trading markets, including central divergence, one-way chain transmission, and circular spillover. Along with the improvement of market operation efficiency, the central divergent type of spillover shifts to the pattern of circular spillover. It is necessary for the government to improve market efficiency and ensure the coordinated development of China's pilot carbon emission trading market and national carbon emission trading market.

The Characteristics, Long-Term Outcomes, Risk Factors, and Antithrombotic Therapy in Chinese Patients With Atrial Fibrillation and Bioprosthetic Valves.

Introduction: There were few data about the clinical profiles and long-term outcomes in Chinese patients with atrial fibrillation (AF) and bioprosthetic valves. Methods: The retrospective study enrolled 903 patients with bioprosthetic valve replacement at our hospital and discharged with a diagnosis of AF from January 2010 to December 2018. Results: The median age was 65.6 (61.9-69.1) years, and 548 (60.7%) patients were women. During a follow-up period of 3.84 (2.64-5.51) years, 68 (1.8 per 100 person-years) patients died, 81 (2.1 per 100 person-years) patients developed thromboembolism, and 23 (0.6 per 100 person-years) patients experienced major bleeding. The CHA2DS2-VASc score, as a categorical variable (low, moderate, or high risk), predicted the risk of thromboembolism with the C-statistic of 0.6 (95% CI: 0.511-0.689, p = 0.046). The incidence of the CHA2DS2-VASc score increment was 11.6 per 100 person-years, and the annual reclassification rate of stroke risk (from a low or moderate group to a higher group) was 12.7%. The current proportion of oral anticoagulants was 52.3, 59, and 63.2%, respectively, in the low, moderate, and high stroke risk groups. Age (OR: 1.04, 95% CI: 1.01-1.06, p = 0.01), left atrial size (OR: 1.05, 95% CI: 1.03-1.08, p < 0.001), and rheumatic heart disease (OR: 1.49, 95% CI: 1.05-2.10, p = 0.025) were positively associated with the use of oral anticoagulants. The history of chronic kidney disease (OR: 0.20, 95% CI: 0.05-0.76, p = 0.018), prior surgical ablation (OR: 0.33, 95% CI: 0.24-0.47, p < 0.001), and antiplatelet agent use (OR: 0.08, 95% CI: 0.05-0.13, p < 0.001) were inversely related to the use of oral anticoagulants. Higher admission estimated glomerular filtration rate (HR: 0.515, 95% CI: 0.311-0.853, p = 0.01), left ventricular ejection fraction (HR: 0.961, 95% CI: 0.931-0.992, p = 0.014), concomitant surgical ablation (HR: 0.348, 95% CI: 0.171-0.711, p = 0.004), and rheumatic heart disease history (HR: 0.515, 95% CI: 0.311-0.853, p = 0.01) were associated with a lower risk of death. Surgical ablation (HR: 0.263, 95% CI: 0.133-0.519, p < 0.001) and oral anticoagulants (HR: 0.587, 95% CI: 0.375-0.918, p = 0.019) were related to a lower risk of thromboembolism. Conclusion: Chinese patients with AF and bioprosthetic valve(s) were relatively young and had a high prevalence of rheumatic heart disease with few comorbidities. The percentage of mitral bioprosthetic valve replacement was high. The proportion of concomitant surgical ablation or surgical left atrial appendage occlusion or exclusion was relatively low. The thromboembolic events were the major long-term adverse events. The anticoagulation therapy was underused in patients at moderate or high stroke risk. The CHA2DS2-VASc score was verified to be used for predicting stroke risk in this population. The stroke risk dynamically changed; it needed to be reestimated once the risk factor changed.

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.

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.

The use of intravenous amiodarone in patients with atrial fibrillation and Wolff-Parkinson-White syndrome.

BACKGROUND: It was reported that intravenous amiodarone might induce ventricular fibrillation for acute treatment in patients with atrial fibrillation (AF) and Wolff-Parkinson-White (WPW) syndrome. No study was done to assess its application comprehensively in this population. METHODS: This study was a retrospective analysis and undertaken by reviewing medical records and electronic databases to search for patients admitted with tachycardia resulting from WPW syndrome and AF, who have intravenously administrated amiodarone at the emergency department from January 2008 to June 2018. RESULTS: Thirty patients were involved in this study, of which 27 were males. The mean age of the patients was 47.8 ± 17.0 years. The mean systolic blood pressure and diastolic blood pressure were 111.9 ± 18.3 mmHg and 76.1 ± 14.6 mmHg, respectively. The mean heart rate was 171 (150-189) beats per minute. Half of the patients (53.3%) had no comorbidities, and only one had prior syncope. Nearly 17 patients (56.7%) started with a loading dose of 150 mg. No ventricular acceleration or VF developed. The incidence of hypotension was 3.3% (1/30). Eighteen patients (60.0%) restored to sinus rhythm by amiodarone with the conversion time of 486.0 (229.0-1278.0) minutes. CONCLUSIONS: Intravenous amiodarone might be an alternative for acute treatment of AF and WPW syndrome in patients characterized by stable hemodynamics, relatively low admission heart rate, few comorbidities, elder age, and no prior syncope. The loading dosage of 150 mg appeared to be preferred, and the maintenance period was better to less than 12 hours. Monitoring and electrolyte correction were also necessary. It is essential to keep a defibrillator nearby during pharmacologic cardioversion.

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.

Gender-specific association between body mass index and all-cause mortality in patients with atrial fibrillation.

BACKGROUND: Elevated body mass index (BMI) is related with reduced mortality in various cardiovascular diseases. HYPOTHESIS: Gender-specific association between BMI and mortality exists in atrial fibrillation (AF). METHODS: In this multicenter observational study with a mean follow-up of 1 year, a total of 1991 AF patients were enrolled and divided into two groups based on the gender. The primary endpoint was all-cause mortality while the secondary endpoints were defined as cardiovascular mortality, stroke, and major adverse events during 1-year follow-up. Cox regression was performed to identify the association between BMI and clinical outcomes according to gender. RESULTS: Female patients with AF tended to be older (P = .027) and thinner (P < .001) than male patients with AF. They were more likely to have heart failure, hyperthyroidism, and valvular AF (all P < .05), but less likely to have coronary artery disease and prior myocardial infarction (all P < .01). Multivariate analysis revealed that overweight (HR(95%CI): 0.55(0.41-0.75), P < .001) and obese patients (HR(95%CI): 0.56(0.34-0.94), P = .028) were associated with significant lower all-cause mortality compared with normal weight patients for the entire cohort. Similar association between elevated BMI and reduced all-cause mortality were only identified in female patients with AF (overweight vs normal weight: HR(95%CI): 0.43(0.27-0.70); obesity vs normal weight: HR(95%CI): 0.46(0.22-0.97)), but not in male patients with AF. CONCLUSION: This study indicates that overweight and obesity were related with improved survival in patients with AF. The association between elevated BMI and reduced mortality was dependent on gender, which was only significant in female patients, rather than male patients.

Effects of angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker on one-year outcomes of patients with atrial fibrillation: insights from a multicenter registry study in China.

OBJECTIVE: To evaluate the effect of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) therapy on the prognosis of patients with atrial fibrillation (AF). METHODS: A total of 1, 991 AF patients from the AF registry were divided into two groups according to whether they were treated with ACEI/ARB at recruitment. Baseline characteristics were carefully collected and analyzed. Logistic regression was utilized to identify the predictors of ACEI/ARB therapy. The primary endpoint was all-cause mortality, while the secondary endpoints included cardiovascular mortality, stroke and major adverse events (MAEs) during the one-year follow-up period. Univariable and multivariable Cox regression were performed to identify the association between ACEI/ARB therapy and the one-year outcomes. RESULTS: In total, 759 AF patients (38.1%) were treated with ACEI/ARB. Compared with AF patients without ACEI/ARB therapy, patients treated with ACEI/ARB tended to be older and had a higher rate of permanent AF, hypertension, diabetes mellitus, heart failure (HF), left ventricular ejection fraction (LVEF) < 40%, coronary artery disease (CAD), prior myocardial infarction (MI), left ventricular hypertrophy, tobacco use and concomitant medications (all P < 0.05). Hypertension, HF, LVEF < 40%, CAD, prior MI and tobacco use were determined to be predictors of ACEI/ARB treatment. Multivariable analysis showed that ACEI/ARB therapy was associated with a significantly lower risk of one-year all-cause mortality [hazard ratio (HR) (95% CI): 0.682 (0.527-0.882), P = 0.003], cardiovascular mortality [HR (95% CI): 0.713 (0.514-0.988), P = 0.042] and MAEs [HR (95% CI): 0.698 (0.568-0.859), P = 0.001]. The association between ACEI/ARB therapy and reduced mortality was consistent in the subgroup analysis. CONCLUSIONS: In patients with AF, ACEI/ARB was related to significantly reduced one-year all-cause mortality, cardiovascular mortality and MAEs despite the high burden of cardiovascular comorbidities.

The association between plasma big endothelin-1 levels at admission and long-term outcomes in patients with atrial fibrillation.

BACKGROUND AND AIMS: The prognostic role of big endothelin-1 (ET-1) in atrial fibrillation (AF) is unclear. We aimed to assess its predictive value in patients with AF. METHODS: A total of 716 AF patients were enrolled and divided into two groups based on the optimal cut-off value of big ET-1 in predicting all-cause mortality. The primary outcomes were all-cause mortality and major adverse events (MAEs). Cox regression analysis and net reclassification improvement (NRI) analysis were performed to assess the predictive value of big ET-1 on outcomes. RESULTS: With the optimal cut-off value of 0.55 pmol/L, 326 patients were classified into the high big ET-1 levels group. Cardiac dysfunction and left atrial dilation were factors related to high big ET-1 levels. During a median follow-up of 3 years, patients with big ET-1 ≥ 0.55 pmol/L had notably higher risk of all-cause death (44.8% vs. 11.5%, p < 0.001), MAEs (51.8% vs. 17.4%, p < 0.001), cardiovascular death, major bleeding, and tended to have higher thromboembolic risk. After adjusting for confounding factors, high big ET-1 level was an independent predictor of all-cause mortality (hazard ratio (HR) 2.11, 95% confidence interval (CI) 1.46-3.05; p < 0.001), MAEs (HR 2.05, 95% CI 1.50-2.80; p = 0.001), and cardiovascular death (HR 2.44, 95% CI 1.52-3.93; p < 0.001). NRI analysis showed that big ET-1 allowed a significant improvement of 0.32 in the accuracy of predicting the risk of both all-cause mortality and MAEs. CONCLUSIONS: Elevated big ET-1 levels is an independent predictor of long-term all-cause mortality, MAEs, and cardiovascular death in patients with AF.

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.