Amplified and distinctive genotoxicity of titanium dioxide nanoparticles in transformed yeast reporters with human cytochrome P450 (CYP) genes.

Titanium dioxide nanoparticles (nTiO2) have been considered a possible carcinogen to humans, but most existing studies have overlooked the role of human enzymes in assessing the genotoxicity of nTiO2. Here, a toxicogenomics-based in vitro genotoxicity assay using a GFP-fused yeast reporter library was employed to elucidate the genotoxic potential and mechanisms of nTiO2. Moreover, two new GFP-fused yeast reporter libraries containing either human CYP1A1 or CYP1A2 genes were constructed by transformation to investigate the potential modulation of nTiO2 genotoxicity in the presence of human CYP enzymes. This study found a lack of appreciable nTiO2 genotoxicity as indicated by the yeast reporter library in the absence of CYP expression but a significantly elevated indication of genotoxicity in either CYP1A1- or CYP1A2-expressing yeast. The intracellular reactive oxygen species (ROS) measurement indicated significantly higher ROS in yeast expressing either enzyme. The detected mitochondrial DNA damage suggested mitochondria as one of the target sites for oxidative damage by nTiO2 in the presence of either one of the CYP enzymes. The results thus indicated that the genotoxicity of nTiO2 was enhanced by human CYP1A1 or CYP1A2 enzyme and was associated with elevated oxidative stress, which suggested that the similar mechanisms could occur in human cells.

Healthy lifestyle, statin, and mortality in people with high CVD risk: A nationwide population-based cohort study.

Objective: To examine the joint association of healthy lifestyles and statin use with all-cause and cardiovascular mortality in high-risk individuals, and evaluate the survival benefits by life expectancy. Methods: During 2015-2021, participants aged 35-75 years were recruited by the China Health Evaluation And risk Reduction through nationwide Teamwork. Based on number of healthy lifestyles related to smoking, alcohol drinking, physical activity, and diet, we categorized them into: very healthy (3-4), healthy (2), and unhealthy (0-1). Statin use was determined by self-report taking statin in last two weeks. Results: Among the 265,209 included participants at high risk, 6979 deaths were observed, including 3236 CVD deaths during a median 3.6 years of follow-up. Individuals taking statin and with a very healthy lifestyle had the lowest risk of all-cause (HR: 0.70; 95 %CI: 0.57-0.87) and cardiovascular mortality (0.56; 0.40-0.79), compared with statin non-users with an unhealthy lifestyle. High-risk participants taking statin and with a very healthy lifestyle had the highest years of life gained (5.90 years at 35-year-old [4.14-7.67; P < 0.001]) compared with statin non-users with an unhealthy lifestyle among high-risk people. And their life expectancy was comparable with those without high risk but with a very healthy lifestyle (4.49 vs. 4.68 years). Conclusion: The combination of preventive medication and multiple healthy lifestyles was associated with lower risk of all-cause and cardiovascular mortality and largest survival benefits. Integrated strategy to improve long-term health for high-risk people was urgently needed.

Relationship between daytime napping and cardiovascular disease: A two-sample mendelian randomization study.

OBJECTIVE: Daytime napping has been reported to have a potential association with an increased risk of cardiovascular diseases (CVDs) in several cohort studies, but the causal effects are unclear. In this study, we aimed to investigate the relationship between daytime napping and CVDs, as well as to validate causality in this relationship by Mendelian randomization (MR). METHODS: A two-sample MR method was used to evaluate the causal effect of daytime napping on CVDs. The exposure of daytime napping was extracted from publicly available genome-wide association studies (GWASs) in the UK Biobank, and the outcomes of 14 CVDs were obtained from the FinnGen consortium. A total of 49 single-nucleotide polymorphisms (SNPs) were used as the instrumental variables. The effect estimates were calculated by using the inverse-variance weighted method. RESULTS: The MR analyses showed that genetically predicted daytime napping was associated with an increased risk of five CVDs, including heart failure (odds ratio (OR): 1.71, 95% CI: 1.19-2.44, p = 0.003), hypertension (OR: 1.51, 95% CI: 1.05-2.16, p = 0.026), atrial fibrillation (OR: 1.71, 95% CI: 1.02-2.88, p = 0.042), cardiac arrythmias (OR: 1.47, 95% CI: 1.47, 95% CI: 1.01-2.13, p = 0.042) and coronary atherosclerosis (OR: 1.77, 95% CI: 1.17-2.68, p = 0.006). No significant influence was observed for other CVDs. CONCLUSION: This two-sample MR analysis suggested that daytime napping was causally associated with an increased risk of heart failure, hypertension, atrial fibrillation, cardiac arrythmias and coronary atherosclerosis.

Sociodemographic Factors, Leisure-Time Physical Activity and Mortality.

INTRODUCTION: Exploring sociodemographic effect modification is important to provide evidence for developing targeted recommendations and reducing health inequalities. This study evaluated how sociodemographic factors including age, sex, race/ethnicity and socioeconomic status (SES) modify the association between leisure-time physical activity (LTPA) and all-cause and major cause-specific mortality. METHODS: The study sample included 471,992 people from the 1997-2018 National Health Interview Survey (NHIS) and 41,830 people from the 1999-2018 National Health and Nutrition Examination Survey (NHANES). Data were analyzed in December 2022. Mortality data from the National Death Index were available to December 31, 2019. Sufficient LTPA was defined as at least 150 minutes of moderate and/or vigorous intensity per week. RESULTS: There were 46,289 deaths in NHIS participants and 4,617 deaths in NHANES participants during a mean follow-up of 10 years. Individuals with sufficient LTPA had lower risk of all-cause (NHIS: hazard ratio, 0.74, 95% CI: [0.74-0.74]; NHANES: 0.73 [0.68-0.79]) and cardiovascular mortality (NHIS: 0.75 [0.75-0.75]; NHANES: 0.80 [0.69-0.93]) compared with inactive participants. The subgroup analysis showed significant interactions between LTPA and all sociodemographic factors. Associations between LTPA and mortality were weaker among younger individuals, males, Hispanic adults or those of low SES, respectively. CONCLUSIONS: Sociodemographic factors significantly modified the associations between LTPA and mortality. The health benefits of sufficient LTPA were smaller in younger individuals, males, Hispanic adults or those of low SES. These findings can help identify target populations for promotion of physical activity to reduce health inequalities and the development of physical activity guidelines.

Prognostic value of Growth differentiation factors 15 in Acute heart failure patients with preserved ejection fraction.

AIMS: There is an increasing proportion of hospitalized heart failure (HF) patients classified as HF with preserved ejection fraction (HFpEF) around the world. Growth differentiation factor 15 (GDF-15) is a promising biomarker in HFpEF prognostication; however, the majority of the existing data has been derived from the research on undifferentiated HF, whereas the studies focusing on HFpEF are still limited. This study aimed to determine the prognostic power of GDF-15 in the hospitalized patients with HFpEF in a Chinese cohort. METHODS AND RESULTS: We analysed the levels of serum GDF-15 in 380 patients hospitalized for acute onset of HFpEF measured by heart ultrasound at admission in a prospective cohort. The associations of GDF-15 with 1 year risk of all-cause death and 1 year HF readmission were assessed by the Cox proportional hazards model. Area under the receiver operating characteristic curves was used to compare predictive accuracy. GDF-15 was strongly correlated with 1 year HF readmission and 1 year all-cause death, with event rates of 24.8%, 40.0%, and 50.0% for 1 year HF readmission (P < 0.001), respectively, and with 11.2%, 13.6%, and 24.6% for 1 year all-cause death (P = 0.004) in the corresponding tertile, respectively. In the multivariate linear regression model, GDF-15 had a significantly negative correlation with haemoglobin (P = 0.01) and a positive correlation with creatinine (P = 0.01), alanine transaminase (P = 0.001), and therapy of aldosterone antagonist (P = 0.018). The univariate Cox regression model of GDF-15 showed that c-statistic was 0.632 for 1 year HF readmission and 0.644 for 1 year all-cause death, which were superior to the N-terminal pro-brain natriuretic peptide (NT-proBNP) model with c-statistics of 0.595 and 0.610, respectively. In the multivariable Cox regression model, GDF-15 tertiles independently predicted 1 year HF readmission (hazard ratio 2.25, 95% confidence interval: 1.43-3.54, P < 0.001) after adjusting for baseline Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) risk score, history of HF, NT-proBNP, and high-sensitivity cardiac troponin T. Compared with the model including all the adjusted variables, the model with the addition of GDF-15 improved predictive power, with c-statistic increasing from 0.643 to 0.657 for 1 year HF readmission and from 0.638 to 0.660 for 1 year all-cause death. CONCLUSIONS: In hospitalized patients with HFpEF, GDF-15 measured within 48 h of admission is a strong independent biomarker for 1 year HF readmission and even better than NT-proBNP. GDF-15 combined with the traditional indicators provided incremental prognostic value in this population.

Primary care institutional characteristics associated with hypertension awareness, treatment, and control in the China PEACE-Million Persons Project and primary health-care survey: a cross-sectional study.

BACKGROUND: Since 2010, China has made vast financial investments and policy changes to the primary care system. We aimed to assess how hypertension awareness, treatment, and control might be used to assess quality of primary care systems, which reflect the outcomes of public health services and medical care. METHODS: We used The China Patient-centred Evaluative Assessment of Cardiac Events Million Persons Project, a government-funded public health project that focuses on cardiovascular disease risk in China. We linked primary care institution characteristics that were captured in the survey between 2016 and 2017 to the participant-level data gathered in baseline visits between 2014 and 2021. Participants were included if they had hypertension and lived in the towns or streets that took part in the primary care survey. Participants were excluded if they had missing data for blood pressure measurement, history of hypertension, sex, or age. Primary care institutions were excluded if the catchment area had fewer than 100 participants with hypertension. Hypertension awareness was defined as the proportion of participants with hypertension who self-reported a hypertension diagnosis. Hypertension treatment was defined as the proportion of participants who currently use antihypertensive medications among those who were aware. Hypertension control was defined as the proportion of participants with an average systolic blood pressure less than 140 mm Hg and an average diastolic blood pressure less than 90 mm Hg over two readings among those who were treated during the study. All patients were included in the analysis. This trial was registered at ClinicalTrials.gov, NCT02536456. FINDINGS: Between Sept 15, 2014, and March 16, 2021, we assessed 503 township-level primary care institutions for eligibility. 70 institutions were excluded as they could not be linked with individual data or because their catchment area had fewer than 100 participants with hypertension. We analysed 433 township-level primary care institutions across all 31 provinces of mainland China, including 660 565 individuals with hypertension in their catchment areas. Across townships, age-sex standardised hypertension awareness varied from 8·2% to 81·0%, treatment varied from 2·6% to 96·5%, and control proportions varied from 0% to 62·4%. Hypertension awareness, treatment, and control were significantly associated with the following institutional characteristics: government funding through balance allocation (ie, institutions have their human resources funded by local government, but need to be self-supporting in other aspects; awareness odds ratio 0·88, 95% CI 0·78-0·99; p=0·027), having financial problems that interrupted routine service delivery (awareness 0·81, 0·72-0·92; p=0·0007, control 0·84; 0·75-0·94, p=0·0034), setting performance-based bonus (treatment 1·39, 1·07-1·80; p=0·013), basic salary defined by number of patient visits (control 0·85, 0·76-0·95; p=0·0053), using electronic referrals (treatment 1·41, 1·14-1·73; p=0·0012, control 1·17; 1·03-1·33, p=0·014), implementing family physician contract services (awareness 1·13, 1·00-1·28; p=0·045, control 1·30; 1·15-1·46, p<0·0001), and proportion of physicians who are formally licensed (awareness per 10% increase 1·04, 1·01-1·08; p=0·019, treatment 1·08; 1·02-1·14, p=0·0077; control per 10% increase 1·07, 1·03-1·10; p=0·0006). INTERPRETATION: The role of primary care role in hypertension management might benefit from new strategies that promote best practices in institutional financing, performance appraisal, service delivery, and information technology. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Science, and the National High Level Hospital Clinical Research Funding. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Prevalence, treatment, and attributed mortality of elevated blood pressure among a nationwide population-based cohort of stroke survivors in China.

Background: Elevated blood pressure (BP) is associated with substantial morbidity and mortality in stroke survivors. China has the highest prevalence of stroke survivors and accounts for one-third of stroke-related deaths worldwide. We aimed to describe the prevalence and treatment of elevated BP across age, sex, and region, and assess the mortality attributable to elevated BP among stroke survivors in China. Materials and methods: Based on 3,820,651 participants aged 35-75 years from all 31 provinces in mainland China recruited from September 2014 to September 2020, we assessed the prevalence and treatment of elevated BP (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) among those with self-reported stroke and stratified by age group, sex, and geographic region. We estimated the age- and sex-specific population attributable fractions of death from elevated BP. Results: Among 91,406 stroke survivors, the mean (SD) age was 62 (8) years, and 49.0% were male. The median interquartile range (IQR) stroke duration was 4 (2, 7) years. The prevalence of elevated BP was 61.3% overall, and increased with age (from 47.5% aged 35-44 years to 64.6% aged 65-75 years). The increment of prevalence was larger in female patients than male patients. Elevated BP was more prevalent in northeast (66.8%) and less in south (54.3%) China. Treatment rate among patients with elevated BP was 38.1%, and rates were low across all age groups, sexes, and regions. Elevated BP accounted for 33 and 21% of cardiovascular and all-cause mortality among stroke survivors, respectively. The proportion exceeded 50% for cardiovascular mortality among patients aged 35-54 years. Conclusion: In this nationwide cohort of stroke survivors from China, elevated BP and its non-treatment were highly prevalent across all age groups, sexes, and regions. Elevated BP accounted for nearly one-third cardiovascular mortality in stroke survivors, and particularly higher in young and middle-aged patients. National strategies targeting elevated BP are warranted to address the high stroke burden in China.

Impact of Non-cardiac Comorbidities on Long-Term Clinical Outcomes and Health Status After Acute Heart Failure in China.

Background: Individual non-cardiac comorbidities are prevalent in HF; however, few studies reported how the aggregate burden of non-cardiac comorbidities affects long-term outcomes, and it is unknown whether this burden is associated with changes in health status. Aims: To assess the association of the overall burden of non-cardiac comorbidities with clinical outcomes and quality of life (QoL) in patients hospitalized for heart failure (HF). Methods: We prospectively enrolled patients hospitalized for HF from 52 hospitals in China. Eight key non-cardiac comorbidities [diabetes, chronic renal disease, chronic obstructive pulmonary disease (COPD), anemia, stroke, cancer, peripheral arterial disease (PAD), and liver cirrhosis] were included, and patients were categorized into four groups: none, one, two, and three or more comorbidities. We fitted Cox proportional hazards models to assess the burden of comorbidities on 1-year death and rehospitalization. Results: Of the 4,866 patients, 25.3% had no non-cardiac comorbidity, 32.2% had one, 22.9% had two, and 19.6% had three or more in China. Compared with those without non-cardiac comorbidities, patients with three or more comorbidities had higher risks of 1-year all-cause death [heart rate, HR 1.89; 95% confidence interval (CI) 1.48-2.39] and all-rehospitalization (HR 1.35; 95%CI 1.15-1.58) after adjustment. Although all patients with HF experienced a longitudinal improvement in QoL in the 180 days after discharge, those with three or more non-cardiac comorbidities had an unadjusted 11.4 (95%CI -13.4 to -9.4) lower Kansas City Cardiomyopathy Questionnaire (KCCQ) scores than patients without comorbidities. This difference decreased to -6.4 (95%CI -8.6 to -4.2) after adjustment for covariates. Conclusion: Among patients hospitalized with HF in this study, a higher burden of non-cardiac comorbidities was significantly associated with worse health-related QoL (HRQoL), increased risks of death, and rehospitalization post-discharge. The findings highlight the need to address the management of comorbidities effectively in standardized HF care.

Systolic Blood Pressure and 1-Year Clinical Outcomes in Patients Hospitalized for Heart Failure.

Background: High systolic blood pressure (SBP) is an important risk factor for the progression of heart failure (HF); however, the association between SBP and prognosis among patients with established HF was uncertain. This study aimed to investigate the association between SBP and long-term clinical outcomes in patients hospitalized for HF. Methods: This study prospectively enrolled adult patients hospitalized for HF in 52 hospitals from 20 provinces in China. SBPs were measured in a stable condition judged by clinicians during hospitalization before discharge according to the standard research protocol. The primary outcomes included 1-year all-cause death and HF readmission. The multivariable Cox proportional hazards regression models were fitted to examine the association between SBP and clinical outcomes. Restricted cubic splines were used to examine the non-linear associations. Results: The 4,564 patients had a mean age of 65.3 ± 13.5 years and 37.9% were female. The average SBP was 123.2 ± 19.0 mmHg. One-year all-cause death and HF readmission were 16.9 and 32.7%, respectively. After adjustment, patients with SBP < 110 mmHg had a higher risk of all-cause death compared with those with SBP of 130-139 mmHg (HR 1.71; 95% CI: 1.32-2.20). Patients with SBP < 110 mmHg (HR 1.36; 95% CI: 1.14-1.64) and SBP ≥ 150 mmHg (HR 1.26; 95% CI: 1.01-1.58) had a higher risk of HF readmission, and the association between SBP and HF readmission followed a J-curve relationship with the nadir SBP around 130 mmHg. These associations were consistent regardless of age, sex, left ventricular ejection fraction, hypertension, coronary heart disease, and medications for HF. Conclusion: In patients hospitalized for HF, lower SBP in a stable phase during hospitalization portends an increased risk of 1-year death, and a J-curve association has been observed between SBP and 1-year HF readmission. These associations were consistent among clinically important subgroups.

Discharge heart rate and 1-year clinical outcomes in heart failure patients with atrial fibrillation.

BACKGROUND: The association between heart rate and 1-year clinical outcomes in heart failure (HF) patients with atrial fibrillation (AF), and whether this association depends on left ventricular ejection fraction (LVEF), are unclear. We investigated the relationship between discharge heart rate and 1-year clinical outcomes after discharge among hospitalized HF patients with AF, and further explored this association that differ by LVEF level. METHODS: In this analysis, we enrolled 1760 hospitalized HF patients with AF from the China Patient-centered Evaluative Assessment of Cardiac Events Prospective Heart Failure study from August 2016 to May 2018. Patients were categorized into three groups with low (<65 beats per minute [bpm]), moderate (65-85 bpm), and high (≥86 bpm) heart rate measured at discharge. Cox proportional hazard models were employed to explore the association between heart rate and 1-year primary outcome, which was defined as a composite outcome of all-cause death and HF rehospitalization. RESULTS: Among 1760 patients, 723 (41.1%) were women, the median age was 69 (interquartile range [IQR]: 60-77) years, median discharge heart rate was 75 (IQR: 69-84) bpm, and 934 (53.1%) had an LVEF <50%. During 1-year follow-up, a total of 792 (45.0%) individuals died or had at least one HF hospitalization. After adjusting for demographic characteristics, smoking status, medical history, anthropometric characteristics, and medications used at discharge, the groups with low (hazard ratio [HR]: 1.32, 95% confidence interval [CI]: 1.05-1.68, P = 0.020) and high (HR: 1.34, 95% CI: 1.07-1.67, P = 0.009) heart rate were associated with a higher risk of 1-year primary outcome compared with the moderate group. A significant interaction between discharge heart rate and LVEF for the primary outcome was observed (P for interaction was 0.045). Among the patients with LVEF ≥50%, only those with high heart rate were associated with a higher risk of primary outcome compared with the group with moderate heart rate (HR: 1.38, 95% CI: 1.01-1.89, P = 0.046), whereas there was no difference between the groups with low and moderate heart rate. Among the patients with LVEF <50%, only those with low heart rate were associated with a higher risk of primary outcome compared with the group with moderate heart rate (HR: 1.46, 95% CI: 1.09-1.96, P = 0.012), whereas there was no difference between the groups with high and moderate heart rate. CONCLUSIONS: Among the overall HF patients with AF, both low (<65 bpm) and high (≥86 bpm) heart rates were associated with poorer outcomes as compared with moderate (65-85 bpm) heart rate. Among patients with LVEF ≥50%, only a high heart rate was associated with higher risk; while among those with LVEF <50%, only a low heart rate was associated with higher risk as compared with the group with moderate heart rate. TRAIL REGISTRATION: Clinicaltrials.gov; NCT02878811.

ß-blocker and 1-year outcomes among patients hospitalized for heart failure with mid-range ejection fraction.

AIMS: The beneficial effect of ß-blocker on heart failure with reduced ejection fraction is well established. However, its effect on the 1-year outcome of heart failure with mid-range ejection fraction (HFmrEF) remains unclear. METHODS AND RESULTS: We analysed the data of the patients with left ventricular ejection fraction (LVEF) between 40% and 49% in China Patient-centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (China PEACE 5p-HF Study), in which patients hospitalized for heart failure from 52 Chinese hospitals were recruited from 2016 to 2018. Two primary outcomes were all-cause death and all-cause hospitalization. The associations between ß-blocker use at discharge and outcomes were assessed by inverse probability of treatment weighting (IPTW)-weighted Cox regression analyses. To assess consistency, IPTW adjusting medications analyses, multivariable analyses and dose-effect analyses were performed. A total of 1035 HFmrEF patients were included in the analysis. The mean age was 65.5 ± 12.7 years and 377 (36.4%) were female. The median (interquartile range) of LVEF was 44% (42-47%). Six hundred and sixty-one (63.8%) were treated with ß-blocker. Patients using ß-blocker were younger with better cardiac function, and more likely to use renin-angiotensin system inhibitor and mineralocorticoid receptor antagonist. During the 1-year follow-up, death occurred in 84 (12.7%) treated and 85 (22.7%) untreated patients (P < 0.0001); all-cause hospitalization occurred in 298 (45.1%) treated and 188 (50.3%) untreated patients (P = 0.04). After IPTW-weighted adjustment, ß-blocker use was significantly associated with lower risk of all-cause death [hazard ratio (HR): 0.70; 95% confidence interval (CI): 0.51-0.96, P = 0.03], but not with lower all-cause hospitalization (HR, 0.92, 95% CI, 0.76-1.10, P = 0.36). Consistency analyses showed consistent favourable effect of ß-blocker on all-cause death, but not on all-cause hospitalization. CONCLUSIONS: Among patients with HFmrEF, ß-blocker use was associated with lower risk of all-cause death, but not with lower risk of all-cause hospitalization.

Prognostic Value of Multiple Circulating Biomarkers for 2-Year Death in Acute Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a major global public health burden and lacks effective risk stratification. We aimed to assess a multi-biomarker model in improving risk prediction in HFpEF. Methods: We analyzed 18 biomarkers from the main pathophysiological domains of HF in 380 patients hospitalized for HFpEF from a prospective cohort. The association between these biomarkers and 2-year risk of all-cause death was assessed by Cox proportional hazards model. Support vector machine (SVM), a supervised machine learning method, was used to develop a prediction model of 2-year all-cause and cardiovascular death using a combination of 18 biomarkers and clinical indicators. The improvement of this model was evaluated by c-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: The median age of patients was 71-years, and 50.5% were female. Multiple biomarkers independently predicted the 2-year risk of death in Cox regression model, including N-terminal pro B-type brain-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-TnT), growth differentiation factor-15 (GDF-15), tumor necrosis factor-α (TNFα), endoglin, and 3 biomarkers of extracellular matrix turnover [tissue inhibitor of metalloproteinases (TIMP)-1, matrix metalloproteinase (MMP)-2, and MMP-9) (FDR < 0.05). The SVM model effectively predicted the 2-year risk of all-cause death in patients with acute HFpEF in training set (AUC 0.834, 95% CI: 0.771-0.895) and validation set (AUC 0.798, 95% CI: 0.719-0.877). The NRI and IDI indicated that the SVM model significantly improved patient classification compared to the reference model in both sets (p < 0.05). Conclusions: Multiple circulating biomarkers coupled with an appropriate machine-learning method could effectively predict the risk of long-term mortality in patients with acute HFpEF. It is a promising strategy for improving risk stratification in HFpEF.

Characteristics, interventions and outcomes of patients with valvular heart disease hospitalised in China: a cross-sectional study.

OBJECTIVES: Little is known about contemporary characteristics and management of valvular heart disease (VHD) in China. This study aimed to examine the clinical characteristics, aetiology and type of VHD, interventions and in-hospital outcomes of patients with VHD hospitalised in China. METHODS: We used a two-stage random sampling design to create a nationally representative sample of patients with VHD hospitalised in 2015 in China and included adult patients with mild, moderate or severe VHD. We abstracted data from medical records, including echocardiogram reports, on patient characteristics, aetiology, type and severity of VHD, interventions and in-hospital outcomes. We weighted our findings to estimate nationally representative hospitalisations. We performed multivariable logistic regression analysis to identify factors associated with valve intervention. RESULTS: In 2015, 38 841 patients with VHD were hospitalised in 188 randomly sampled hospitals, representing 662 384 inpatients with VHD in China. We sampled 9363 patients, mean age 68.7 years (95% CI 42.2 to 95.2) and 46.8% (95% CI 45.8% to 47.8%) male, with an echocardiogram. Degenerative origin was the predominant aetiology overall (33.3%, 95% CI 32.3% to 34.3%), while rheumatic origin was the most frequent aetiology among patients with VHD as the primary diagnosis (37.4%, 95% CI 35.9% to 38.8%). Rheumatic origin was also the most common aetiology among patients with moderate or severe VHD (27.3%, 95% CI 25.6% to 29.0% and 33.6%, 95% CI 31.9% to 35.2%, respectively). The most common VHD was mitral regurgitation (79.1%, 95% CI 78.2% to 79.9%), followed by tricuspid regurgitation (77.4%, 95% CI 76.5% to 78.2%). Among patients with a primary diagnosis of severe VHD who were admitted to facilities capable of valve intervention, 35.6% (95% CI 33.1% to 38.1%) underwent valve intervention during the hospitalisation. The likelihood of intervention decreased significantly among patients with higher operative risk. CONCLUSIONS: Among patients with VHD hospitalised in China, the predominant aetiology was degenerative in origin; among patients with moderate or severe VHD, rheumatic origin was the most common aetiology. Targeted strategies and policies should be promoted to address degenerative VHD. Patients with severe VHD may be undertreated, particularly those with high operative risk.

Beta-blockers and 1-year clinical outcomes in hospitalized heart failure patients with atrial fibrillation.

OBJECTIVE: To assess the association between beta-blockers and 1-year clinical outcomes in heart failure (HF) patients with atrial fibrillation (AF), and further explore this association that differs by left ventricular ejection fraction (LVEF) level. METHODS: We enrolled hospitalized HF patients with AF from China Patient-centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study. COX proportional hazard regression models were employed to calculate hazard ratio of beta-blockers. The primary outcome was all-cause death. RESULTS: Among 1762 HF patients with AF (756 women [41.4%]), 1041 (56%) received beta-blockers at discharge and 1272 (72.2%) had an LVEF > 40%. During one year follow up, all-cause death occurred in 305 (17.3%), cardiovascular death occurred in 203 patients (11.5%), and rehospitalizations for HF occurred in 622 patients (35.2%). After adjusting for demographic characteristics, social economic status, smoking status, medical history, anthropometric characteristics, and medications used at discharge, the use of beta-blockers at discharge was not associated with all-cause death [hazard ratio (HR): 0.86; 95% Confidence Interval (CI): 0.65-1.12; P = 0.256], cardiovascular death (HR: 0.76, 95% CI: 0.52-1.11; P = 0.160), or the composite outcome of all-cause death and HF rehospitalization (HR: 0.97, 95% CI: 0.82-1.14; P = 0.687) in the entire cohort. There were no significant interactions between use of beta-blockers at discharge and LVEF with respect to all-cause death, cardiovascular death, or composite outcome. In the adjusted models, the use of beta-blockers at discharge was not associated with all-cause death, cardiovascular death, or composite outcome across the different levels of LVEF: reduced (< 40%), mid-range (40%-49%), or preserved LVEF (≥ 50%). CONCLUSION: Among HF patients with AF, the use of beta-blockers at discharge was not associated with 1-year clinical outcomes, regardless of LVEF.

Changes in ST segment elevation myocardial infarction hospitalisations in China from 2011 to 2015.

OBJECTIVE: Access to acute cardiovascular care has improved and health services capacity has increased over the past decades. We assessed national changes in (1) patient characteristics, (2) in-hospital management and (3) patient outcomes among patients presenting with ST segment elevation myocardial infarction (STEMI) in 2011-2015 in China. METHODS: In a nationally representative sample of hospitals in China, we created two random cohorts of patients in 2011 and 2015 separately. We weighted our findings to estimate nationally representative numbers and assessed changes from 2011 to 2015. Data were abstracted from medical charts centrally using standardised definitions. RESULTS: While the proportion of patients with STEMI among all patients with acute myocardial infarction decreased over time from 82.5% (95% CI 81.7 to 83.3) in 2011 to 68.5% (95% CI 67.7 to 69.3) in 2015 (p<0.0001), the weighted national estimate of patients with STEMI increased from 210 000 to 380 000. The rate of reperfusion eligibility among patients with STEMI decreased from 49.3% (95% CI 48.1 to 50.5) to 42.2% (95% CI 41.1 to 43.4) in 2015 (p<0.0001); ineligibility was principally driven by larger proportions with prehospital delay exceeding 12 hours (67.4%-76.7%, p<0.0001). Among eligible patients, the proportion receiving reperfusion therapies increased from 54% (95% CI 52.3 to 55.7) to 59.7% (95% CI 57.9 to 61.4) (p<0.0001). Crude and risk-adjusted rates of in-hospital death did not differ significantly between 2011 and 2015. CONCLUSIONS: In this most recent nationally representative study of STEMI in China, the use of acute reperfusion increased, but no significant improvement occurred in outcomes. There is a need to continue efforts to prevent cardiovascular diseases, to monitor changes in in-hospital treatments and outcomes, and to reduce prehospital delay.

Health Status Predicts Short- and Long-Term Risk of Composite Clinical Outcomes in Acute Heart Failure.

OBJECTIVES: This study aims to examine the association between the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 score and the 30-day and 1-year rates of composite events of cardiovascular death and heart failure (HF) rehospitalization in patients with acute HF. BACKGROUND: Few studies reported the prognostic effects of KCCQ in acute HF. METHODS: This study prospectively enrolled adult patients hospitalized for HF from 52 hospitals in China and collected the KCCQ-12 score within 48 hour of index admission. The study used multivariable Cox regression to examine the association between KCCQ-12 score and 30-day and 1-year composite events and was further stratified by new-onset HF and acutely decompensated chronic heart failure (ADCHF). Subgroup analyses were performed to explore the potential heterogeneity. The study evaluated the incremental prognostic value of KCCQ-12 score over N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and established risk scores by C-statistics, net reclassification improvement, and integrated discrimination improvement. RESULTS: Among 4,898 patients, 29.4% had new-onset HF. After adjustment, each 10-point decrease in the KCCQ-12 score was associated with a 13% increase in 30-day risk and a 7% increase in 1-year risk. The associations were consistent regardless of new-onset HF or ADCHF, age, sex, left ventricular ejection fraction, New York Heart Association functional class, NT-proBNP level, comorbidities, and renal function. Adding KCCQ-12 score to NT-proBNP and established risk scores significantly improved prognostic capabilities measured by C-statistics, net reclassification improvement, and integrated discrimination improvement. CONCLUSIONS: In acute HF, a poor KCCQ-12 score predicted short- and long-term risks of cardiovascular death and HF rehospitalization. KCCQ-12 could serve as a convenient tool for rapid initial risk stratification and provide additional prognostic value over NT-proBNP and established risk scores.

Development and validation of a risk prediction model for in-hospital major cardiovascular events in patients hospitalised for acute myocardial infarction.

OBJECTIVES: Patients admitted to hospital with acute myocardial infarction (AMI) have considerable variability in in-hospital risks, resulting in higher demands on healthcare resources. Simple risk-assessment tools are important for the identification of patients with higher risk to inform clinical decisions. However, few risk assessment tools have been built that are suitable for populations with AMI in China. We aim to develop and validate a risk prediction model, and further build a risk scoring system. DESIGN: Data from a nationally representative retrospective study was used to develop the model. Patients from a prospective study and another nationally representative retrospective study were both used for external validation. SETTING: 161 nationally representative hospitals, and 53 and 157 other hospitals were involved in the above three studies, respectively. PARTICIPANTS: 8010 patients hospitalised for AMI were included as development sample, and 4485 and 11 223 other patients were included as validation samples in their corresponding studies. PRIMARY AND SECONDARY OUTCOME MEASURES: The in-hospital major adverse cardiovascular events (MACE) was defined as death from any cause, recurrent AMI, or ischaemic stroke. RESULTS: The proportion of in-hospital MACE was 11.7%, 8.8% and 11.4% among the development sample and two external-validation samples, respectively. Nine predictors (ie, age, sex, left ventricular ejection fraction, Killip class, systolic blood pressure, creatinine, white blood cell count, heart rate and blood glucose) were independently associated with in-hospital MACE. The model performed well on both discrimination and calibration capability, with areas under the Receiver Operating Characteristic Curve (ROC) curve of 0.85, 0.74 and 0.80, and calibration slopes of 0.98, 0.84 and 0.97 in the development sample and two external validation samples, respectively. A point-based risk scoring system was built with good discrimination and reclassification ability. CONCLUSIONS: A prediction model using readily available clinical parameters was developed and externally validated to estimate risks of in-hospital MACE among patients with AMI, thereby better informing decision-making in improving clinical care.

Are medical record front page data suitable for risk adjustment in hospital performance measurement? Development and validation of a risk model of in-hospital mortality after acute myocardial infarction.

OBJECTIVES: To develop a model of in-hospital mortality using medical record front page (MRFP) data and assess its validity in case-mix standardisation by comparison with a model developed using the complete medical record data. DESIGN: A nationally representative retrospective study. SETTING: Representative hospitals in China, covering 161 hospitals in modelling cohort and 156 hospitals in validation cohort. PARTICIPANTS: Representative patients admitted for acute myocardial infarction. 8370 patients in modelling cohort and 9704 patients in validation cohort. PRIMARY OUTCOME MEASURES: In-hospital mortality, which was defined explicitly as death that occurred during hospitalisation, and the hospital-level risk standardised mortality rate (RSMR). RESULTS: A total of 14 variables were included in the model predicting in-hospital mortality based on MRFP data, with the area under receiver operating characteristic curve of 0.78 among modelling cohort and 0.79 among validation cohort. The median of absolute difference between the hospital RSMR predicted by hierarchical generalised linear models established based on MRFP data and complete medical record data, which was built as 'reference model', was 0.08% (10th and 90th percentiles: -1.8% and 1.6%). In the regression model comparing the RSMR between two models, the slope and intercept of the regression equation is 0.90 and 0.007 in modelling cohort, while 0.85 and 0.010 in validation cohort, which indicated that the evaluation capability from two models were very similar. CONCLUSIONS: The models based on MRFP data showed good discrimination and calibration capability, as well as similar risk prediction effect in comparison with the model based on complete medical record data, which proved that MRFP data could be suitable for risk adjustment in hospital performance measurement.

Association between use of Qingfei Paidu Tang and mortality in hospitalized patients with COVID-19: A national retrospective registry study.

BACKGROUND: Qingfei Paidu Tang (QPT), a formula of traditional Chinese medicine, which was suggested to be able to ease symptoms in patients with Coronavirus Disease 2019 (COVID-19), has been recommended by clinical guidelines and widely used to treat COVID-19 in China. However, whether it decreases mortality remains unknown. PURPOSE: We aimed to explore the association between QPT use and in-hospital mortality among patients hospitalized for COVID-19. STUDY DESIGN: A retrospective study based on a real-world database was conducted. METHODS: We identified patients consecutively hospitalized with COVID-19 in 15 hospitals from a national retrospective registry in China, from January through May 2020. Data on patients' characteristics, treatments, and outcomes were extracted from the electronic medical records. The association of QPT use with COVID-19 related mortality was evaluated using Cox proportional hazards models based on propensity score analysis. RESULTS: Of the 8939 patients included, 28.7% received QPT. The COVID-19 related mortality was 1.2% (95% confidence interval [CI] 0.8% to 1.7%) among the patients receiving QPT and 4.8% (95% CI 4.3% to 5.3%) among those not receiving QPT. After adjustment for patient characteristics and concomitant treatments, QPT use was associated with a relative reduction of 50% in-hospital COVID-19 related mortality (hazard ratio, 0.50; 95% CI, 0.37 to 0.66 p < 0.001). This association was consistent across subgroups by sex and age. Meanwhile, the incidences of acute liver injury (8.9% [95% CI, 7.8% to 10.1%] vs. 9.9% [95% CI, 9.2% to 10.7%]; odds ratio, 0.96 [95% CI, 0.81% to 1.14%], p = 0.658) and acute kidney injury (1.6% [95% CI, 1.2% to 2.2%] vs. 3.0% [95% CI, 2.6% to 3.5%]; odds ratio, 0.85 [95% CI, 0.62 to 1.17], p = 0.318) were comparable between patients receiving QPT and those not receiving QPT. The major study limitations included that the study was an observational study based on real-world data rather than a randomized control trial, and the quality of data could be affected by the accuracy and completeness of medical records. CONCLUSIONS: QPT was associated with a substantially lower risk of in-hospital mortality, without extra risk of acute liver injury or acute kidney injury among patients hospitalized with COVID-19.

Use of angiotensin receptor blocker is associated with improved 1 year mortality in heart failure with mid-range ejection fraction.

AIMS: Current evidence about the effect of angiotensin receptor blocker (ARB) on the outcome of heart failure with mid-range ejection fraction (HFmrEF) is lacking. We aim to assess the association between use of ARB and 1 year all-cause mortality after hospitalization for HFmrEF. METHODS AND RESULTS: We analysed the data of patients with ejection fraction of 40-49% in China Patient-centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study; 4907 patients hospitalized for heart failure from 52 Chinese hospitals were enrolled from August 2016 to May 2018. Use of ARB was determined by prescriptions at discharge. Patients who died during hospitalization or were using angiotensin-converting enzyme inhibitors at discharge were excluded. The association between the use of ARB and outcome was assessed using stabilized inverse probability of treatment weighting-adjusted Kaplan-Meier and Cox regression analyses. A total of 701 patients with HFmrEF were included for analysis. The mean age was 66.4 ± 12.8 years, and 267 (38.1%) were female. Of them, 244 were treated (34.8%) with ARB. During the 1 year follow-up period, patients treated with ARB had lower all-cause mortality compared with untreated patients (11.5% vs. 21.9%, P = 0.0005). Inverse probability of treatment weighting-adjusted Cox regression analysis showed that use of ARB was associated with significantly reduced all-cause mortality (adjusted hazard ratio 0.44, 95% confidence interval 0.28-0.69, P = 0.0004). CONCLUSIONS: Among patients hospitalized for HFmrEF, the use of ARB was associated with lower 1 year mortality after discharge.