Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction: A Multicenter, Randomized, Double-Blind Trial.

BACKGROUND: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice. METHODS: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours. Before trial initiation, each center selected 1 of 3 PPA regimens (40 mg of enoxaparin once daily subcutaneously; 10 U·kg·h of unfractionated heparin intravenously, adjusted to maintain activated clotting time between 150 and 220 seconds; or 0.2 mg·kg·h of bivalirudin intravenously). The primary efficacy objective was to demonstrate superiority of PPA to reduce the primary efficacy end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, stent thrombosis (definite), or urgent revascularization (any vessel) within 30 days. The key secondary objective was to evaluate the effect of each specific anticoagulation regimen (enoxaparin, unfractionated heparin, or bivalirudin) on the primary efficacy end point. The primary safety end point was Bleeding Academic Research Consortium 3 to 5 bleeding at 30 days. RESULTS: Between January 10, 2019, and September 18, 2021, a total of 2989 patients were randomized. The primary efficacy end point occurred in 37 patients (2.5%) in both the PPA and placebo groups (hazard ratio, 1.00 [95% CI, 0.63 to 1.57]). The incidence of Bleeding Academic Research Consortium 3 to 5 bleeding did not differ between the PPA and placebo groups (8 [0.5%] vs 11 [0.7%] patients; hazard ratio, 0.74 [95% CI, 0.30 to 1.83]). CONCLUSIONS: Routine PPA after primary percutaneous coronary intervention was safe but did not reduce 30-day ischemic events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03664180.

Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial.

BACKGROUND: Uncertainty exists about whether lowering systolic blood pressure to less than 120 mm Hg is superior to that of less than 140 mm Hg, particularly in patients with diabetes and patients with previous stroke. METHODS: In this open-label, blinded-outcome, randomised controlled trial, participants with high cardiovascular risk were enrolled from 116 hospitals or communities in China. We used minimised randomisation to assign participants to intensive treatment targeting standard office systolic blood pressure of less than 120 mm Hg or standard treatment targeting less than 140 mm Hg. The primary outcome was a composite of myocardial infarction, revascularisation, hospitalisation for heart failure, stroke, or death from cardiovascular causes, assessed by the intention-to-treat principle. This trial was registered with ClinicalTrials.gov, NCT04030234. FINDINGS: Between Sept 17, 2019, and July 13, 2020, 11 255 participants (4359 with diabetes and 3022 with previous stroke) were assigned to intensive treatment (n=5624) or standard treatment (n=5631). Their mean age was 64·6 years (SD 7·1). The mean systolic blood pressure throughout the follow-up (except the first 3 months of titration) was 119·1 mm Hg (SD 11·1) in the intensive treatment group and 134·8 mm Hg (10·5) in the standard treatment group. During a median of 3·4 years of follow-up, the primary outcome event occurred in 547 (9·7%) participants in the intensive treatment group and 623 (11·1%) in the standard treatment group (hazard ratio [HR] 0·88, 95% CI 0·78-0·99; p=0·028). There was no heterogeneity of effects by diabetes status, duration of diabetes, or history of stroke. Serious adverse events of syncope occurred more frequently in the intensive treatment group (24 [0·4%] of 5624) than in standard treatment group (eight [0·1%] of 5631; HR 3·00, 95% CI 1·35-6·68). There was no significant between-group difference in the serious adverse events of hypotension, electrolyte abnormality, injurious fall, or acute kidney injury. INTERPRETATION: For hypertensive patients at high cardiovascular risk, regardless of the status of diabetes or history of stroke, the treatment strategy of targeting systolic blood pressure of less than 120 mm Hg, as compared with that of less than 140 mm Hg, prevents major vascular events, with minor excess risk. FUNDING: The Ministry of Science and Technology of China and Fuwai Hospital. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Design and rationale of the Comprehensive intelligent Hypertension managEment SyStem (CHESS) evaluation study: A cluster randomized controlled trial for hypertension management in primary care.

BACKGROUND: Hypertension management in China is suboptimal with high prevalence and low control rate due to various barriers, including lack of self-management awareness of patients and inadequate capacity of physicians. Digital therapeutic interventions including mobile health and computational device algorithms such as clinical decision support systems (CDSS) are scalable with the potential to improve blood pressure (BP) management and strengthen the healthcare system in resource-constrained areas, yet their effectiveness remains to be tested. The aim of this report is to describe the protocol of the Comprehensive intelligent Hypertension managEment SyStem (CHESS) evaluation study assessing the effect of a multifaceted hypertension management system for supporting patients and physicians on BP lowering in primary care settings. MATERIALS AND METHODS: The CHESS evaluation study is a parallel-group, cluster-randomized controlled trial conducted in primary care settings in China. Forty-one primary care sites from 3 counties of China are randomly assigned to either the usual care or the intervention group with the implementation of the CHESS system, more than 1,600 patients aged 35 to 80 years with uncontrolled hypertension and access to a smartphone by themselves or relatives are recruited into the study and followed up for 12 months. In the intervention group, participants receive patient-tailored reminders and alerts via messages or intelligent voice calls triggered by uploaded home blood pressure monitoring data and participants' characteristics, while physicians receive guideline-based prescription instructions according to updated individual data from each visit, and administrators receive auto-renewed feedback of hypertension management performance from the data analysis platform. The multiple components of the CHESS system can work synergistically and have undergone rigorous development and pilot evaluation using a theory-informed approach. The primary outcome is the mean change in 24-hour ambulatory systolic BP from baseline to 12 months. DISCUSSION: The CHESS trial will provide evidence and novel insight into the effectiveness and feasibility of an implementation strategy using a comprehensive digital BP management system for reducing hypertension burden in primary care settings. TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov, NCT05605418.

Development of a machine learning-based model for predicting individual responses to antihypertensive treatments.

BACKGROUND AND AIMS: Personalized antihypertensive drug selection is essential for optimizing hypertension management. The study aimed to develop a machine learning (ML) model to predict individual blood pressure (BP) responses to different antihypertensive medications. METHODS AND RESULTS: We used data from a pragmatic, cluster-randomized trial on hypertension management in China. Each patient's multiple visit records were included, and two consecutive visits were paired as the index and subsequent visits. The least absolute shrinkage and selection operator method was used to select index visit variables for predicting subsequent BP. The dataset was randomly divided into training and test sets in a 7:3 ratio. Model performance was evaluated using mean absolute error (MAE) and R-square in the test set. A total of 19,013 hypertension management visit records (6282 patients) were included. The mean age of the study population was 63.9 years, and 2657 (42.3%) were females. A total of 12 phenotypical features (age, sex, smoking within seven days, body mass index, waist circumference, index visit systolic BP, diastolic BP, heart rate, comorbidities of diabetes, dyslipidemia, coronary heart disease, and stroke), together with currently taking any prescribed antihypertensive medication regimens and visits time interval were selected to build the model. The Extreme Gradient Boost model performed best among all candidate algorithms, with an MAE of 8.57 mmHg and an R2 = 0.28 in the test set. CONCLUSION: The ML techniques exhibit significant potential for predicting individual responses to antihypertensive treatments, thereby aiding clinicians in achieving optimal BP control safely and efficiently. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03636334. Registered July 3, 2018, https://clinicaltrials.gov/study/NCT03636334.

Alcohol use disorder and its association with quality of life and mortality in Chinese male adults: a population-based cohort study.

AIMS: We aimed to demonstrate the distribution of alcohol use disorder (AUD) in China and assess its association with quality of life and mortality. METHODS: We studied 367 120 men aged 35-75 years from 31 provinces in the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project. At baseline, AUD was assessed by alcohol use disorders identification test score, and EQ-5D-3L questionnaire was used to measure the quality of life. Mortality data was collected via National Mortality Surveillance System and Vital Registration. Mixed models were fitted to assess the associations of AUD with quality of life, and Cox proportional hazard models were fitted for the associations with all-cause and cause-specific mortality. RESULTS: We identified 39 163 men with AUD, which accounted for 10.7% of male participants and 25.8% of male drinkers. In the multivariable analysis, male drinkers who were aged 45-54 years, with higher education level, currently smoking, obese, with diagnosed hypertension, and without diagnosed cardiovascular diseases had higher rates of AUD. Male drinkers with AUD were less likely to have optimal QOL compared with those without AUD (OR: 0.63, 95% CI: 0.61-0.65, P < 0.001). Moreover, among male drinkers, AUD was prospectively associated with a 20% higher risk for all-cause mortality and a 30% higher risk for mortality from cancer. CONCLUSIONS: In China one fourth of men who drank alcohol had AUD, which was associated with lower QOL and higher risk of all-cause mortality. National policies or strategies are urgently needed to control alcohol-related harms.

Quality of primary health care in China: challenges and recommendations.

China has substantially increased financial investment and introduced favourable policies for strengthening its primary health care system with core responsibilities in preventing and managing chronic diseases such as hypertension and emerging infectious diseases such as coronavirus disease 2019 (COVID-19). However, widespread gaps in the quality of primary health care still exist. In this Review, we aim to identify the causes for this poor quality, and provide policy recommendations. System challenges include: the suboptimal education and training of primary health-care practitioners, a fee-for-service payment system that incentivises testing and treatments over prevention, fragmentation of clinical care and public health service, and insufficient continuity of care throughout the entire health-care system. The following recommendations merit consideration: (1) enhancement of the quality of training for primary health-care physicians, (2) establishment of performance accountability to incentivise high-quality and high-value care; (3) integration of clinical care with the basic public health services, and (4) strengthening of the coordination between primary health-care institutions and hospitals. Additionally, China should consider modernising its primary health-care system through the establishment of a learning health system built on digital data and innovative technologies.

Healthy lifestyle behaviours and all-cause and cardiovascular mortality among 0.9 million Chinese adults.

BACKGROUND: Healthy lifestyle behaviours are effective means to reduce the burden of diseases. This study was aimed to fill the knowledge gaps on the distribution, associated factors, and potential health benefits on mortality of four healthy lifestyle behaviours in China. METHODS: During 2015-2019, participants aged 35-75 years from 31 provinces were recruited by the China PEACE Million Persons Project. Four healthy lifestyle behaviours were investigated in our study, including non-smoking, none or moderate alcohol use, sufficient leisure time physical activity (LTPA), and healthy diet. RESULTS: Among 903,499 participants, 74.1% were non-smokers, 96.0% had none or moderate alcohol use, 23.6% had sufficient LTPA, 11.1% had healthy diet, and only 2.8% had all the four healthy lifestyle behaviours. The adherence varied across seven regions; the highest median of county-level adherence to all the four healthy lifestyle behaviours was in North China (3.3%) while the lowest in the Southwest (0.8%) (p < 0.05). Participants who were female, elder, non-farmers, urban residents, with higher income or education, hypertensive or diabetic, or with a cardiovascular disease (CVD) history were more likely to adhere to all the four healthy lifestyle behaviours (p < 0.001). County-level per capital Gross Domestic Product (GDP) was positively associated with sufficient LTPA (p < 0.05 for both rural and urban areas) and healthy diet (p < 0.01 for urban areas), while negatively associated with none or moderate alcohol use (p < 0.01 for rural areas). Average annual temperature was negatively associated with none or moderate alcohol use (p < 0.05 for rural areas) and healthy diet (p < 0.001 for rural areas). Those adhering to all the four healthy lifestyle behaviours had lower risks of all-cause mortality (HR 0.64 [95% CI: 0.52, 0.79]) and cardiovascular mortality (HR 0.53 [0.37, 0.76]) after a median follow-up of 2.4 years. CONCLUSIONS: Adherence to healthy lifestyle behaviours in China was far from ideal. Targeted health promotion strategies were urgently needed.

Ligand-Mediated Photophysics Adjustability in Bis-tridentate Ir(III) Complexes and Their Application in Efficient Optical Limiting Materials.

A family of novel bis-tridentate Ir(III) complexes (Ir1-Ir5) incorporating both functional N∧C∧N-type ligands (L1-L5) and N∧N∧C-type ligand (L0) were synthesized attentively and characterized scientifically. The crystalline structures of Ir1, Ir3 and Ir4 were resoundingly confirmed by XRD. With the aid of experimental and theoretical methods, their photophysical properties at transient and steady states were scientifically investigated. The broadband charge-transfer absorption for these aforementioned Ir(III) complexes is up to 600 nm as shown in the UV-visible absorption spectrum. The emission lifetimes of their excited states are good. Between the visible and near-infrared regions, Ir1-Ir5 possessed powerful excited-state absorption. Hence, a remarkably robust reverse saturable absorption (RSA) process can occur once the complexes are irradiated by a 532 nm laser. The RSA effect follows the descending order: Ir3 > Ir5 > Ir4 ≈ Ir1 > Ir2. To sum up, modifying electron-donating units (-OCH3) and large π-conjugated units to the pyridyl N∧C∧N-type ligands is a systematic way to markedly raise the RSA effect. Therefore, these octahedral bis-tridentate Ir(III) complexes are potentially state-of-the-art optical limiting (OPL) materials.

Rationale and design of the RIGHT trial: A multicenter, randomized, double-blind, placebo-controlled trial of anticoagulation prolongation versus no anticoagulation after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

BACKGROUND: Current guidelines recommend anticoagulation therapy during primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI). However, whether anticoagulation should be continued after pPCI has not been well investigated. METHODS/DESIGN: The RIGHT trial is a prospective, multicenter, randomized, double-blind, placebo-controlled trial in STEMI patients treated with pPCI evaluating the prolongation of anticoagulation after the procedure. Patients are randomized in a 1:1 fashion to receive either prolonged anticoagulant or matching placebo (no anticoagulation) for at least 48 hours after the procedure. When randomized to anticoagulation prolongation, the patient is assigned to intravenous unfractionated heparin (UFH) or subcutaneous enoxaparin or intravenous bivalirudin (same drug and same regimen at each center). The primary efficacy endpoint is the composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, stent thrombosis (definite) or urgent revascularization (any vessel) at 30 days. The primary safety endpoint is major bleeding (BARC 3-5) at 30 days. Based on a superiority design and assuming a 35% relative risk reduction (from 7% to 4.5%), 2856 patients will be enrolled, accounting for a 5% drop-out rate (α = 0.05 and power = 80%). CONCLUSION: The RIGHT trial tests the hypothesis that post-procedural anticoagulation is superior to no anticoagulation in reducing ischemic events in STEMI patients undergoing pPCI.

DNA-Targeting RuII -Polypyridyl Complex with a Long-Lived Intraligand Excited State as a Potential Photodynamic Therapy Agent.

Subtle ligand modifications on RuII -polypyridyl complexes may result in different excited-state characteristics, which provides the opportunity to tune their photo-physicochemical properties and subsequently change their biological functions. Here, a DNA-targeting RuII -polypyridyl complex (named Ru1) with highly photosensitizing 3 IL (intraligand) excited state was designed based on a classical DNA-intercalator [Ru(bpy)2 (dppz)]⋅2 PF6 by incorporation of the dppz (dipyrido[3,2-a:2',3'-c]phenazine) ligand tethered with a pyrenyl group, which has four orders of magnitude higher potency than the model complex [Ru(bpy)2 (dppz)]⋅2 PF6 upon light irradiation. This study provides a facile strategy for the design of organelle-targeting RuII -polypyridyl complexes with dramatically improved photobiological activity.

Characteristics of High Cardiovascular Risk in 1.7 Million Chinese Adults.

Background: As cardiovascular risk increases in China, interest in strategies to mitigate it is growing. However, national information about the prevalence and treatment of high cardiovascular disease (CVD) risk is limited. Objective: To assess the prevalence and treatment of high CVD risk as well as variations in risk across population subgroups. Design: National project of CVD screening and management. Setting: 141 county-level regions in all 31 provinces of China. Participants: Local residents aged 35 to 75 years. Measurements: Rates of high CVD risk were assessed both in the overall study population and by age, sex, body mass index, geographic region, and socioeconomic status. Multivariable mixed models were fitted to assess the associations between individual characteristics and high CVD risk. Statin and aspirin use was evaluated among persons at high risk for CVD. Results: Among 1 680 126 participants, 9.5% (95% CI, 9.5% to 9.6%) had high risk for CVD. Mixed models identified persons who were of Han ethnicity, had medical insurance, were currently using alcohol, or were obese as more likely to be at high risk for CVD. Of those with high CVD risk, only 0.6% (CI, 0.5% to 0.6%) and 2.4% (CI, 2.3% to 2.5%) reported using statins and aspirin, respectively. Among persons with high CVD risk and hypertension, 31.8% were receiving antihypertensive medications. Limitation: Samples were not nationally representative. Conclusion: Of the 1.7 million participants, 1 in 10 had a high risk for CVD; among those at high risk, fewer than 3% were receiving statins or aspirin. An immense opportunity exists for risk mitigation in this substantial population. Primary Funding Source: Ministry of Finance and National Health Commission, China.

New-onset metabolic risk factors and the incidence of kidney stones: a prospective cohort study.

OBJECTIVE: To examine the association of kidney stones with new-onset hypertension, diabetes and obesity. PARTICIPANTS AND METHODS: This prospective cohort study included participants in the Qingdao Port Cardiovascular Health Study who were aged ≥18 years and had abdominal ultrasonography results in 2013 that were negative for kidney stones. Multivariable Cox regression models with time-dependent covariates were used to estimate the effects of new-onset hypertension, diabetes and obesity on the incidence of kidney stones. RESULTS: There were 9667 participants without kidney stones in 2013 (mean age 46.2 years; 75.6% men). During a mean (range) follow-up of 33.5 (6-42) months, 676 (7.0%) incident cases of kidney stones were identified. Kidney stones were more frequent among those who had new-onset of a metabolic factor vs those who did not (hypertension: 7.7 vs 6.0%; diabetes: 8.4 vs 6.6%; obesity: 7.4 vs 6.8%). Adjusted Cox models identified that increased risk of kidney stones was associated with new-onset hypertension (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.25-2.27), new-onset diabetes (HR 1.78, 95% CI 1.07-2.96), and new-onset obesity (HR 1.78, 95% CI 1.15-2.74). CONCLUSIONS: New-onset of hypertension, diabetes and obesity were all strongly associated with an increased risk of kidney stones in this prospective cohort study. Results suggest that a substantial proportion of kidney stones are potentially preventable by appropriate control of these metabolic risk factors.

Prevalence, awareness, treatment, and control of hypertension in China: data from 1·7 million adults in a population-based screening study (China PEACE Million Persons Project).

BACKGROUND: Hypertension is common in China and its prevalence is rising, yet it remains inadequately controlled. Few studies have the capacity to characterise the epidemiology and management of hypertension across many heterogeneous subgroups. We did a study of the prevalence, awareness, treatment, and control of hypertension in China and assessed their variations across many subpopulations. METHODS: We made use of data generated in the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project from Sept 15, 2014, to June 20, 2017, a population-based screening project that enrolled around 1·7 million community-dwelling adults aged 35-75 years from all 31 provinces in mainland China. In this population, we defined hypertension as systolic blood pressure of at least 140 mm Hg, or diastolic blood pressure of at least 90 mm Hg, or self-reported antihypertensive medication use in the previous 2 weeks. Hypertension awareness, treatment, and control were defined, respectively, among hypertensive adults as a self-reported diagnosis of hypertension, current use of antihypertensive medication, and blood pressure of less than 140/90 mm Hg. We assessed awareness, treatment, and control in 264 475 population subgroups-defined a priori by all possible combinations of 11 demographic and clinical factors (age [35-44, 45-54, 55-64, and 65-75 years], sex [men and women], geographical region [western, central, and eastern China], urbanity [urban vs rural], ethnic origin [Han and non-Han], occupation [farmer and non-farmer], annual household income [< ¥10 000, ¥10 000-50 000, and ≥¥50 000], education [primary school and below, middle school, high school, and college and above], previous cardiovascular events [yes or no], current smoker [yes or no], and diabetes [yes or no]), and their associations with individual and primary health-care site characteristics, using mixed models. FINDINGS: The sample contained 1 738 886 participants with a mean age of 55·6 years (SD 9·7), 59·5% of whom were women. 44·7% (95% CI 44·6-44·8) of the sample had hypertension, of whom 44·7% (44·6-44·8) were aware of their diagnosis, 30·1% (30·0-30·2) were taking prescribed antihypertensive medications, and 7·2% (7·1-7·2) had achieved control. The age-standardised and sex-standardised rates of hypertension prevalence, awareness, treatment, and control were 37·2% (37·1-37·3), 36·0% (35·8-36·2), 22·9% (22·7-23·0), and 5·7% (5·6-5·7), respectively. The most commonly used medication class was calcium-channel blockers (55·2%, 55·0-55·4). Among individuals whose hypertension was treated but not controlled, 81·5% (81·3-81·6) were using only one medication. The proportion of participants who were aware of their hypertension and were receiving treatment varied significantly across subpopulations; lower likelihoods of awareness and treatment were associated with male sex, younger age, lower income, and an absence of previous cardiovascular events, diabetes, obesity, or alcohol use (all p<0·01). By contrast, control rate was universally low across all subgroups (<30·0%). INTERPRETATION: Among Chinese adults aged 35-75 years, nearly half have hypertension, fewer than a third are being treated, and fewer than one in twelve are in control of their blood pressure. The low number of people in control is ubiquitous in all subgroups of the Chinese population and warrants broad-based, global strategy, such as greater efforts in prevention, as well as better screening and more effective and affordable treatment. FUNDING: Ministry of Finance and National Health and Family Planning Commission, China.

Availability, cost, and prescription patterns of antihypertensive medications in primary health care in China: a nationwide cross-sectional survey.

BACKGROUND: Around 200 million adults in China have hypertension, but few are treated or achieve adequate control of their blood pressure. Available and affordable medications are important for successfully controlling hypertension, but little is known about current patterns of access to, and use of, antihypertensive medications in Chinese primary health care. METHODS: We used data from a nationwide cross-sectional survey (the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project primary health care survey), which was undertaken between November, 2016 and May, 2017, to assess the availability, cost, and prescription patterns of 62 antihypertensive medications at primary health-care sites across 31 Chinese provinces. We surveyed 203 community health centres, 401 community health stations, 284 township health centres, and 2474 village clinics to assess variation in availability, cost, and prescription by economic region and type of site. We also assessed the use of high-value medications, defined as guideline-recommended and low-cost. We also examined the association of medication cost with availability and prescription patterns. FINDINGS: Our study sample included 3362 primary health-care sites and around 1 million people (613 638 people at 2758 rural sites and 478 393 people at 604 urban sites). Of the 3362 sites, 8·1% (95% CI 7·2-9·1) stocked no antihypertensive medications and 33·8% (32·2-35·4) stocked all four classes that were routinely used. Village clinics and sites in the western region of China had the lowest availability. Only 32·7% (32·2-33·3) of all sites stocked high-value medications, and few high-value medications were prescribed (11·2% [10·9-11·6] of all prescription records). High-cost medications were more likely to be prescribed than low-cost alternatives. INTERPRETATION: China has marked deficiencies in the availability, cost, and prescription of antihypertensive medications. High-value medications are not preferentially used. Future efforts to reduce the burden of hypertension, particularly through the work of primary health-care providers, will need to improve access to, and use of, antihypertensive medications, paying particular attention to those with high value. FUNDING: CAMS Innovation Fund for Medical Science, the Entrusted Project from the China National Development and Reform Commission, and the Major Public Health Service Project from the Ministry of Finance of China and National Health and Family Planning Commission of China.

The primary health-care system in China.

China has made remarkable progress in strengthening its primary health-care system. Nevertheless, the system still faces challenges in structural characteristics, incentives and policies, and quality of care, all of which diminish its preparedness to care for a fifth of the world's population, which is ageing and which has a growing prevalence of chronic non-communicable disease. These challenges include inadequate education and qualifications of its workforce, ageing and turnover of village doctors, fragmented health information technology systems, a paucity of digital data on everyday clinical practice, financial subsidies and incentives that do not encourage cost savings and good performance, insurance policies that hamper the efficiency of care delivery, an insufficient quality measurement and improvement system, and poor performance in the control of risk factors (such as hypertension and diabetes). As China deepens its health-care reform, it has the opportunity to build an integrated, cooperative primary health-care system, generating knowledge from practice that can support improvements, and bolstered by evidence-based performance indicators and incentives.

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.

Iron Metabolic Biomarkers and the Mortality Risk in the General Population: A Nationwide Population-Based Cohort Study.

Context: Iron is an essential element in the human body and plays a critical role in many physiological and cellular processes. However, the association between iron status and the risk of all-cause or cause-specific mortality has not been well-investigated. And it is unclear whether the association between iron metabolic biomarkers and the risk of mortality differs between people with and without diabetes mellitus (DM). Objective: This work aimed to investigate associations between iron metabolic biomarkers and all-cause and cause-specific mortality risk in the general population, and heterogeneities in the associations among population with and without DM.. Methods: A total of 29 166 adults from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999 to 2010 were included, with linkage to the National Death Index to December 31, 2019. Cox proportional-hazard models and Fine-Gray subdistribution hazard models were used to estimate associations between iron metabolic biomarkers and outcomes. Results: During a median follow-up of 18.83 years, 9378 deaths were observed, including 3420 cardiovascular disease (CVD) deaths and 1969 cancer deaths. A significant linear association between serum ferritin (SF) and all-cause mortality was observed among the overall population and those without DM. J-shaped associations between transferrin saturation (TSAT) and all-cause and CVD mortality were observed among all populations. In the overall population, compared to the first quartile (Q1) group, the adjusted hazard ratio (HR) (95% CI) for all-cause mortality was 1.07 (1.00-1.15), 1.05 (0.98-1.12), 1.13 (1.05-1.21) in Q2, Q3, and Q4 groups for SF, while the HR was 0.94 (0.88-0.99), 0.92 (0.86-0.97), and 0.93 (0.88-0.99) for TSAT. In individuals without DM, the adjusted HR of the Q4 of SF were 1.19 (1.03-1.37) for CVD mortality and 1.25 (1.05-1.48) for cancer mortality. In individuals with DM, the adjusted HRs of the Q4 of TSAT were 0.76 (0.62-0.93) for CVD mortality and 1.47 (1.07-2.03) for cancer mortality. Conclusion: Iron metabolism abnormalities increase mortality risk in the general population. The associations of iron status with mortality were significantly different between individuals with and without DM, which indicated tailored strategies for iron homeostasis are needed.

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.

Prognostic Value of a Multi-mRNA Signature for 1-Year All-Cause Death in Hospitalized Patients With Heart Failure With a Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction is a major global public health problem, while effective risk stratification tools are still lacking. We sought to construct a multi-mRNA signature to predict 1-year all-cause death. METHODS: We selected 30 patients with heart failure with preserved ejection fraction who died during 1-year follow-up and 30 who survived in the discovery set. One hundred seventy-one and 120 patients with heart failure with preserved ejection fraction were randomly selected as a test set and a validation set, respectively. We performed mRNA microarrays in all patients. RESULTS: We constructed a 5-mRNA signature for predicting 1-year all-cause death. The scores of the 5-mRNA signature were significantly associated with the 1-year risk of all-cause death in both the test set (hazard ratio, 2.72 [95% CI, 1.98-3.74]; P<0.001) and the validation set (hazard ratio, 3.95 [95% CI, 2.40-6.48]; P<0.001). Compared with a reference model, which included sex, ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) score, history of HF and NT-proBNP (N-terminal pro-B-type natriuretic peptide), the 5-mRNA signature had a better discrimination capability, with an increased area under the curve from 0.696 to 0.813 in the test set and from 0.712 to 0.848 in the validation set. A composite model integrating the 5-mRNA risk score and variables in the reference model demonstrated an excellent discrimination capability, with an area under the curve of 0.861 (95% CI, 0.784-0.939) in the test set and an area under the curve of 0.859 (95% CI, 0.755-0.963) in the validation set. The net reclassification improvement and integrated discrimination improvement indicated that the composite model significantly improved patient classification compared with the reference model in both sets (P<0.001). CONCLUSIONS: The 5-mRNA signature is a promising predictive tool for 1-year all-cause death and shows improved prognostic power over the established risk scores and NT-proBNP in patients with heart failure with preserved ejection fraction.