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.
- myocardial infarction
- percutaneous coronary intervention
- delivery of health care
- outcome assessment
- health care
Data availability statement
No data are available. The data underlying this article cannot be shared publicly due to the privacy of individuals who participated in the study.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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- myocardial infarction
- percutaneous coronary intervention
- delivery of health care
- outcome assessment
- health care
What is already known about this subject?
Access to acute cardiovascular care improved and health services capacity increased in China between 2001 and 2011.
What does this study add?
This most recent nationally representative study of ST segment elevation myocardial infarction in China found the use of acute reperfusion increased between 2011 and 2015, but no significant improvement occurred in outcomes.
How might this impact on clinical practice?
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.
Over the past two decades in China access to acute cardiovascular care has improved and health services capacity has increased. Insurance reform began in 2003 and achieved the goal of minimum universal coverage by 2011.1 This period was also marked by an increasing burden of acute cardiovascular events and a focus on effective in-hospital management strategies. In response, several guideline updates for acute myocardial infarction (AMI) care were released during this period.2 3
Dynamic changes also occurred in the epidemiology and quality of care for ST segment elevation myocardial infarction (STEMI) hospitalisations in China between 2001 and 2011.4 Although a previous study found marked improvements in use of primary percutaneous coronary intervention (pPCI) as well as adjunctive STEMI therapies, the overall reperfusion rate and patient outcomes had not changed.4
The focus of healthcare reform in China has evolved from increasing access to care and expanding capacity to improving efficiency and quality of acute cardiovascular care.5 In this latest iteration of the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Retrospective AMI Study, we report data from 2015 to evaluate changes in patient characteristics, presentations, use of guideline-based therapies and outcomes. Our focus is to determine whether the improvements in quality of care observed from 2001 to 2011 have continued and whether outcomes changed, and to identify areas for improvement.
Accordingly, our aims were to assess national changes among patients presenting with STEMI in 2011 and 2015 in (1) patient characteristics (demographic, cardiovascular risk factors, medical history, clinical characteristics), (2) in-hospital management (use of recommended treatments, procedures and diagnostic tests, and inappropriate use of non-evidence-based treatments), and (3) patient outcomes (in-hospital and 7-day mortality and complications).
Data source and study design
The design of the China PEACE-Retrospective AMI Study had been previously described.6 In addition to a nationally representative sample of patients admitted for AMI in China during 2011, which was created in the China PEACE-Retrospective AMI Study, we also included a more recent sample of patients admitted in 2015 from the same nationally representative hospital cohort, using the same random sampling process (online supplemental methods).
In the first stage, we created a sample of hospitals that are representative of hospitals in China, excluding military hospitals, prison hospitals, specialised hospitals without a division for cardiovascular disease and hospitals for traditional Chinese medicine. We stratified the sample by five economic geographical regions (online supplemental methods). In the second stage, using systematic random sampling procedures we selected patients with AMI from the local hospital database of each sampled hospital (online supplemental methods). Discharges with AMI were identified according to the International Classification of Diseases-Clinical Modification codes, including versions 9 (410.xx) and 10 (I21.xx), when available, or through principal diagnosis terms noted at discharge. Data were collected by central abstraction of medical charts with use of standardised data definitions. At each sampling stage, data quality was monitored by random auditing of 5% of the medical records, with overall variable accuracy exceeding 98%. A waiver of patients’ written consent was approved since it was not feasible to approach patients hospitalised several years ago in a retrospective study. All collaborating hospitals accepted the central ethics approval except for five hospitals, which obtained local approval from internal ethics committees (online supplemental methods).
Only patients with a definite discharge diagnosis of STEMI were included in the study sample. The diagnosis of STEMI was determined by the combination of clinical discharge diagnosis terms and ECG results and validated by review of ECGs from randomly selected records by a cardiologist not involved in data abstraction. We treated left bundle branch block as a STEMI equivalent.
We excluded all patients whose STEMI occurred during the course of the hospitalisation because STEMI during hospitalisation could be considered one severe and rare complication of other clinical conditions (ie, coronary artery bypass graft and trauma), so the treatment could be very different, making it difficult to measure quality of care. For the analysis of treatments, procedures and tests, we excluded patients who had transferred in from other hospitals or who had a length of stay of 24 hours or shorter. For the analysis of in-hospital outcomes, we excluded patients who were transferred in from another hospital because we sought to characterise patients admitted directly to the hospital. We also excluded patients who were transferred out because their admissions were truncated. We further excluded patients who were discharged alive within 24 hours because they may have left against medical advice and there was very little time for treatment.
Variables included patient-level characteristics (age, sex, cardiovascular risk factors, medical history and clinical characteristics at admission), defined as documentation on the admission notes, discharge diagnosis or positive laboratory test results (total cholesterol >5.18 mmol/L or low-density lipoprotein ≥3.37 mmol/L, or high-density lipoprotein <1.04 mmol/L in men or <1.30 mmol/L in women).
We assessed use of treatments recommended by the 2010 China National Guideline for STEMI,2 which were consistent with those recommended by the guidelines in the USA.7 These treatments included reperfusion therapy, aspirin within 24 hours of admission, clopidogrel or ticagrelor within 24 hours of admission, β blockers within 24 hours of admission, ACE inhibitors or angiotensin receptor blockers during hospital admission, and statins during hospital admission. We excluded patients with documented contraindications (online supplemental methods).2 We also assessed use of magnesium sulfate (a treatment with no documented survival benefits in the setting of STEMI),8 traditional Chinese medicine, other procedures and tests. We included the seven main categories of traditional Chinese medicine used for coronary heart disease (online supplemental methods). We did not include some care processes (eg, door-to-balloon time and counselling for smoking cessation) due to inadequate documentation on the medical records.
We compared patients’ in-hospital outcomes with three measures: death, death or withdrawal from treatment due to terminal status at discharge (referred to as treatment withdrawal), and composite complications (including death, treatment withdrawal, reinfarction, cardiogenic shock, ischaemic stroke or congestive heart failure, defined in online supplemental methods). Treatment withdrawal is common in China due to reluctance of many patients to die in the hospital. The Chinese Government uses in-hospital death or treatment withdrawal as a quality measure for hospitals.9 Cardiologists in the coordinating study centre adjudicated the clinical status of patients who withdrew from treatment using medical records.
We examined patient characteristics, treatments, tests, procedures and crude rates of outcomes across different study years using the χ2 test for categorical variables and the Mann-Whitney test for continuous variables. We used percentages with 95% CI to describe categorical variables and median with IQR to describe continuous variables. We used multiple imputation for missing age values. To estimate nationally representative numbers of hospitalisations for 2011 and 2015, we applied sampling weights proportional to the inverse sampling fraction of hospitals within each stratum and the sampling fraction of patients within each hospital.
We did multilevel logistic regressions accounting for clustering of patients within hospitals. We included year 2015 as key explanatory variable, while adjusting for patients’ demographics (age and sex), risk factors or medical history (hypertension, diabetes, current smoker, previous myocardial infarction, previous coronary heart disease and previous stroke), and clinical characteristics at admission (chest discomfort, cardiac arrest, acute stroke, heart rate and systolic blood pressure). The dependent variables were in-hospital death, in-hospital death or treatment withdrawal, and in-hospital composite complications. We transformed continuous variables (eg, age, heart rate and systolic blood pressure) into categorical variables according to clinically meaningful cut-off values. We report OR and 95% CI from the multilevel logistic regression related to the year indicators. In view of the small decrease in length of hospital stay over time, a sensitivity analysis was performed using 7-day outcomes using the same approach as for in-hospital outcomes. We also repeat outcome analyses using a sample of patients that includes patients transferred in from other facilities.
All comparisons were two-sided, with statistical significance defined as p<0.05. Statistical analysis was done with SAS V.9.2 software and R V.3.0.2.
Patient and public involvement
This research was done without patient or public involvement.
Demographical and clinical characteristics
During 2011 and 2015, we identified 21 167 patients with AMI, including 15 807 patients with STEMI, in 166 hospitals in China (figure 1A, online supplemental figure S1). The absolute number of STEMI hospitalisations increased in our sample from 7696 in 2011 to 8111 in 2015 (figure 1A). Applying sample weighting showed the number of patients hospitalised with STEMI increased from 0.21 million in 2011 to 0.38 million in 2015 (figure 1B). In our sample, the proportion of patients with STEMI among all patients with AMI decreased 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; online supplemental table S1). Between 2011 and 2015, the median age of patients and the proportion of women did not change (table 1). In 2015, the median age was 65 years (IQR 55–74) and 28.5% of patients were women (table 1).
Among patients with STEMI, the prevalence of diabetes and dyslipidaemia increased (p<0.001), the prevalence of smoking decreased (p<0.05), and the prevalence of hypertension did not change (p=0.1; table 1). In 2015, 51.7% of patients had hypertension, 22.4% had diabetes, 79.5% had dyslipidaemia and 35.2% were current smokers (table 1). The proportion of patients with a medical history of myocardial infarction decreased from 10.6% in 2011 to 7% in 2015, while a medical history of coronary heart disease and percutaneous coronary intervention became more prevalent (p<0.01; table 1).
Between 2011 and 2015, the median time between symptom onset and hospital admission increased from 12 hours (IQR 3–72) to 24 hours (IQR 4–96) (p<0.0001; table 1). In 2015, 56.9% (95% CI 55.7 to 58) of patients had a long prehospital delay, defined as >12 hours between symptom onset and admission (online supplemental table S2). The prevalence of left bundle branch block on admission decreased, while the prevalence of cardiogenic shock, acute stroke and tachycardia (defined as heart rate >110 beats per minute) increased (p<0.05; table 1). The median Mini-Global Registry of Acute Coronary Events scores did not change significantly between 2011 and 2015 (table 1).
Among all patients with STEMI, the rate of reperfusion eligibility decreased from 49.3% (95% CI 48.1 to 50.5) in 2011 to 42.2% (95% CI 41.1 to 43.4) in 2015 (p<0.0001; online supplemental table S3). Among ineligible patients, ineligibility was principally driven by increased prevalence of long prehospital delay (online supplemental table S4).
Use of treatments, procedures and diagnostic tests
After exclusion of 630 patients transferred in from other facilities and 1416 patients with length of stay ≤24 hours, 13 761 patients with STEMI were included in the analysis of treatments, procedures and tests (online supplemental figure S1).
Use of troponin tests increased from 63.1% (95% CI 62 to 64.3) in 2011 to 80.0% (95% CI 79.1 to 80.9) in 2015 (p<0.0001; table 2). Use of other cardiac enzyme tests decreased between 2001 and 2015 (p<0.0001; table 2). Use of echocardiography increased from 63.1% (95% CI 61.9 to 64.2) in 2011 to 72.1% (95% CI 71 to 73.1) in 2015 (p<0.0001; table 2).
Among patients eligible for reperfusion, the proportion receiving reperfusion therapies increased from 54.0% (95% CI 52.3 to 55.7) in 2011 to 59.7% (95% CI 57.9 to 61.4) in 2015, in which use of pPCI increased from 21.1% (95% CI 19.7 to 22.5) to 33.7% (95% CI 32.1 to 35.4) and use of fibrinolytic therapy decreased from 32.9% (95% CI 31.3 to 34.5) to 25.9% (95% CI 24.4 to 27.5) (p<0.01; table 2). Meanwhile, the prehospital delay of patients who received reperfusion therapy was longer in 2015 than in 2011 (3 hours (IQR 2–6) vs 3 hours (IQR 2–5), p<0.0001).
Use of statins and use of clopidogrel or ticagrelor increased between 2011 and 2015 (p<0.0001; table 2). Use of ACE inhibitors or angiotensin receptor blockers decreased (p<0.0001; table 2). Use of magnesium sulfate increased (p<0.001) and use of traditional Chinese medicine did not significantly change (p=0.2; table 2). Use of coronary angiography during hospitalisation increased (p<0.0001; table 2).
In-hospital and 7-day outcomes
After exclusion of 630 patients transferred in from other facilities, 2281 patients transferred out to other facilities and 132 patients discharged alive within 24 hours, 12 764 patients with STEMI were included in the analysis of in-hospital and 7-day outcomes (6472 in year 2011 and 6292 in year 2015; online supplemental figure S1).
The median length of stay decreased from 11 days (IQR 7–15) to 10 days (IQR 7–13) (p<0.0001; online supplemental table S5). Crude rates of in-hospital death were unchanged between 2011 and 2015 (p=0.9; online supplemental table S5). Adjustment for patient demographic and clinical characteristics in the multilevel logistic regression model did not differ significantly between 2011 and 2015 with respect to death, treatment withdrawal or complications during hospitalisation (p>0.05; figure 2). Adjusted outcomes calculated with a 7-day timeframe showed similar results as the in-hospital analysis (figure 3). With the inclusion of 630 patients transferred in from other facilities, adjusted in-hospital outcomes and 7-day outcomes remained similar to the main analyses (online supplemental figures S2 and S3).
In this nationally representative retrospective study in China, our findings had implications for measuring and improving quality of care for STEMI. First, the number of AMI hospitalisations doubled from 2011 to 2015. Although the proportion of those with STEMI decreased, the total number of patients with STEMI nearly doubled. Second, among patients with STEMI, the proportion of patients eligible for reperfusion decreased, primarily due to an increase in prehospital delay. Third, among those eligible for reperfusion, while significantly more received guideline-recommended therapy, substantial room for improvement remained. Fourth, among those receiving reperfusion therapy, we observed a continued shift away from fibrinolytic therapy towards pPCI. Finally, patient in-hospital outcomes did not improve between 2011 and 2015.
Regarding epidemiology, we note that from 2011 to 2015, non-ST segment elevation myocardial infarction (NSTEMI) cases as a proportion of all AMI cases increased, continuing the trend observed between 2001 and 2011. As we have previously reported, this is likely due to both an increased use of sensitive biomarkers for myocardial injury in China,10 which would increase the diagnoses of NSTEMI,11 as well as a concomitant change in the Chinese population at risk of AMI.12 Despite increasing numbers of NSTEMI, the predominant AMI presentation in China continues to be STEMI, in contrast to high-income countries. This could be attributable to China’s comparatively higher rates of smoking and lower rates of use of preventive therapy (eg, aspirin, statins), which are factors more strongly associated with STEMI than NSTEMI.13–15 Similarly, this study found an increased proportion of patients with concomitant stroke in 2015, which might be explained by the unchanged or worsened prevalence of stroke-related risk factors, such as hypertension, diabetes and dyslipidaemia.16
We found processes of care improved, consistent with prior studies.17 18 For example, we found a notable increase in use of antiplatelet therapies, which may be attributable to the introduction of ticagrelor as a guideline-based medical therapy (GDMT) for AMI during the study period.19 However, obstacles remain, such as the persistent use of ineffective therapies such as magnesium sulfate, which had been shown to vary by hospital and physician characteristics in China.20 21 To improve the uptake of GDMT and other evidence-based processes in AMI care, a deeper understanding of the sources of practice variation is needed, many of which may be related to local and regional differences in resource allocation. Similarly, although the rate of cardiogenic shock increased over time, use of mechanical support devices such as intra-aortic balloon pump (IABP) decreased. This could be explained by a prior finding that in clinical practice in China, IABP is more often used as preventive implantation before pPCI and less often used for cardiogenic shock.22 Further, the Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock II (IABP-SHOCK II) trial results were published in 2012 and may have influenced clinical practice away from use of IABP for cardiogenic shock.23
Despite an increase in use of reperfusion therapies and guideline-based medications, we found no significant improvement in patient outcomes (in-hospital and 7-day mortality and complications) in 2015 compared with 2011. It is likely that there are multiple mechanisms for this finding. First, clinical outcomes may be confounded by variables not captured in this study. A prior study on geographical variation in China’s quality of care for STEMI reported a similar paradox. The western region, which had the best performance in processes of care, such as use of clopidogrel, ACE inhibitors/angiotensin receptor blockers and statins, had worse mortality than hospitals in the central region, which had worse performance on processes of care.24 However, second, we did find a decrease in the proportion of patients eligible for reperfusion on admission, with one of the drivers being increased prehospital delay, which may have masked the potential benefit of increased reperfusion rate among those eligible as observed at a cohort level. Further, we found that although marked shifts in acute reperfusion therapy occurred with a move from fibrinolysis to pPCI, among reperfused patients the time to reperfusion increased in 2015.
Prior studies vary in their reports of the prevalence of prehospital delay, with studies reporting from 8.6% to 34.1% of patients with STEMI in China present to the hospital >12 hours after symptom onset.25 26 Prehospital delay can be influenced by accessibility (eg, transportation or distance to hospitals), affordability and patient preferences, factors not captured by many quality of care studies including our study. Further, these three factors may vary across time and geography and interact with one another. For example, as transportation and affordability improve, some patients may choose to bypass local hospitals for more distant hospitals perceived to offer better care. Prior studies on patient choice have shown that for severe conditions, patients prefer large hospitals with advanced equipment and expert physicians.27–29 Regardless, this is a finding worthy of further indepth study, as timely reperfusion is key for optimal outcomes for STEMI. To reliably deliver good outcomes in time-bound STEMI care, a unified STEMI network is ideal with the involvement of physician societies, state governments, ambulance agencies and hospitals.
Our findings have important implications for practice and policy. Given the increasing number of STEMI hospitalisations, prevention of cardiovascular diseases remains a public health priority. To improve outcomes for patients with existing cardiovascular conditions, China has instituted several hospital-based initiatives, such as the establishment of national (and provincial) medical quality control centres to routinely measure the performance of local hospitals on major diseases, as well as healthcare alliance with vertical collaborations between hospitals of varied levels to facilitate dissemination of clinical knowledge and experiences.30 31 Efforts to improve reperfusion of eligible patients remain important. Prehospital delay in China is higher than in high-income countries.32–34 Studies have shown that 24% of Chinese patients with STEMI present without typical chest pain and often seek non-emergent medical care when no chest pain occurs, which delays definitive treatment.33 35 This highlights the need to increase population awareness of the symptoms of myocardial infarction, especially atypical symptoms, and the importance of seeking timely care STEMI care; such efforts require involvement of physician societies, state governments, ambulance agencies and hospitals.36 37 In general, exploration of a broader range of care processes, beyond hospital treatment, would enhance quality improvement efforts.
The present study has several limitations. First, as a fixed cohort of hospitals that was representative in 2011, the China PEACE network’s 2015 iteration may not reflect the national increase in hospitals treating STEMI between 2011 and 2015. Second, the quality of our data depends on the accuracy and completeness of prior documentation and abstraction. Nevertheless, the standardised procedures for abstraction of medical records ensure the reliability of our results in describing the treatments and outcomes. Third, changes in the clinical characteristics, care and outcomes are likely to have occurred between 2015 and the present. However, our data remain the most recently available data that are nationally representative. Fourth, some quality metrics of STEMI care, such as door-to-balloon, were missing since they were not routinely documented on the medical records.
In conclusion, our study identifies several changes in patient characteristics, treatment patterns and outcomes for STEMI in China from 2011 to 2015. The overall number of STEMI hospitalisations has increased substantially even though the proportion of STEMI continues to reduce. Prehospital delay renders a larger proportion of patients ineligible for reperfusion, highlighting an urgent need for improvement.38 39 Further, increasing reperfusion rates and use of pPCI have not translated to an improvement in mortality, which warrants further study. The health system of China can benefit from an integrated data repository which can enable real-time assessments of treatment patterns and outcomes to improve the quality of care.
Data availability statement
No data are available. The data underlying this article cannot be shared publicly due to the privacy of individuals who participated in the study.
Patient consent for publication
The central ethics committee at the China National Center for Cardiovascular Diseases approved the China PEACE-Retrospective AMI Study.
We appreciate the multiple contributions made by the study teams at the Fuwai Hospital National Clinical Research Center for Cardiovascular Diseases and the Yale New Haven Hospital Center for Outcomes Research and Evaluation in the realms of study design and operation, particularly the data collection efforts.
TZ and XL contributed equally.
Correction notice Since this article was first published online, the term infarction in the title has been corrected. It previously contained a typo.
Collaborators Aba Tibetan and Qiang Autonomous Prefecture People's Hospital, ShipingWeng, ShuyingXie; Affiliated Hospital of Guiyang Medical College, Lirong Wu, Jiulin Chen; Affiliated Hospital of Hainan Medical College, Tianfa Li, Jun Wang; Affiliated Zhongshan Hospital of Dalian University, Qin Yu, Xiaofei Li; Alxa League Central Hospital, Zhong Li, ShiguoHao, Yuzhen Zhang, Xuemei Wu; Baiquan County People's Hospital, Yachen Zhang, Zhifeng Liu; Biyang People's Hospital, Zhongxin Wang, HaoJia; Bortala Mongol Autonomous Prefecture People's Hospital, Bayin Bate, BadengQiqige; Changda Hospital Of Anshan, Xiang Jin, Ting Cai; Chengwu County People's Hospital, Fengqin Liu, Dayong Xu; Chenxi County People's Hospital, Xuejin He, Shui Yang; Chongren County People's Hospital, Chun Yuan, Jiping Wang; County People's Hospital of Jinning, LihuaGu, Lin Li, Shijiao Chen; Dalian Municipal Central Hospital, YongchaoZhi, Lili Sun; Dao County People's Hospital, Shengcheng Zhou, Lingjiao Jin; Daofu County People's Hospital, Yong Leng, Liangchuan Zhang, Tianyun Deng; Dingyuan County People's Hospital of Anhui Province, Yuanjin Wang, Wenhua Zhang, Xinmin Ma; Dongyang People's Hospital, Weimin Li, Liang Lu, Xuan Ge; Dulong and Nu Autonomous County People's Hospital of Gongshan, Xiaoping Wu, Yanming He; Dunhua City Hospital of Jilin Province, FanjuMeng, Jia Li; Fenghuang County People's Hospital, Dexi Liao, Guangyong Liu, Wen Qin; Fengshan County People’s Hospital, Wen Long, Xiangwen Chen; Fourth Hospital of Baotou City, Baohong Zhang, Yonghou Yin, Bin Tian; Fourth People's Hospital of Zigong City, Yong Yi, Chaoyong Wu; Fugu County People's Hospital of Shaanxi Province, Baoqi Liu, Zhihui Zhao, Haiming Li; Fujian Provincial Hospital, YansongGuo, Xinjing Chen; Fuling Center Hospital of Chongqing City, Liquan Xiang, Lin Ning; Gannan County People's Hospital, Mei Chen, Xin Jin, Guiling Li; General Hospital of the Yangtze River Shipping, Xiuqi Li, Xing’an Wu; Gongcheng Yao Autonomous County People's Hospital, Congjun Tan, Mingfang Feng, Meili Wang; Guangchang County People's Hospital, Liangfa Wen, Xiang Fu, QunxingXie; Guilin People's Hospital, Wei Zhang, Yanni Zhuang, Hua Lu;Guiping People's Hospital, Jiaqian Lu, Yu Huang; Haerbin 242 Hospital, Yin Zhou, Qiuling Hu; Haiyan People's Hospital, Chunhui Xiao, Xiaoli Hu; Heling Ge Er County People's Hospital, Yongshuan Wu, Qiuli Wang; Helong Municipal People's Hospital, Youlin Xu, Xuefei Yu; Henan Provincial People's Hospital, Chuanyu Gao, Jianhong Zhang, You Zhang; Heze Municipal Hospital, WentangNiu, Xiaolei Ma, Yong Wang; HGKY Group Company General Hospital, Xiaowen Pan, Yanlong Liu; Hua Xin HospitalFirst Hospital of Tsinghua University, Lifu Miao, Yanping Yin, Zhiying Zhang; Huairen People's Hospital, Shutang Feng; Huayin People's Hospital, Aiping Wang, Jiangli Zhang, Feipeng Li; Huaying People's Hospital, Hong Wang; Hunchun Hospital, Lijun Yu, Xinxin Zhao; Huizhou Municipal Central Hospital, Yuansheng Shen, Zhiming Li, Lizhen He; Hunan Province Mawangdui Hospital, ZhiyiRong, Wei Luo; Ji'an Municipal Central People's hospital, Xueqiao Wang; Jianghua Yao Autonomous County People's Hospital, Rongjun Wan, Jianglin Tang, Guanghan Wu; Jiangsu Haimen People's Hospital, Jie Wu, Bin Xu; Jiangxi Provincial People's Hospital, Qing Huang, Xiaohe Wu; Jiangzi County People's Hospital, Sang Ge, Pian Pu, PingcuoDuoji; Jilin Province People's Hospital, Hui Dai, Yuming Du, Wei Guo; Jilin Integrated Traditional Chinese & Western Medicine Hospital, Jilin Province, Jianping Shi; Jinghai County Hospital, Peihua Zhao, Jingsheng Sun; Jingxi County People's Hospital, Hongxiang Li, Wen Liang; Jingxing County Hospital, Zhiwen Dong, Zhenhai Zhao; Jingzhou Central Hospital, Xin Li, Qin Xu; Jiuquan City People’s Hospital, Yaofeng Yuan, Zhirong Li; Jixi People's Hospital of The Jixi Municipal People's Hospital Medical Group, Jinbo Gao; Jize County Hospital, Qiu’eGuo; Kangbao County People's Hospital, Ruiqing Zhao, Guangjun Song; Keshiketengqi Hospital of Chifeng City, Lize Wang, Haiyun Song; Lanping Bai and Pumi Autonomous County People's Hospital, Jinwen He, Jinming He; Laoting County Hospital, Keyong Shang, Changjiang Liu, Kuituan Xi; Liaoyang Central Hospital, Rihui Liu, Peng Guo; Liaoyuan Central Hospital, ChaoyangGuo, Xiangjun Liu, Rujun Zhao, Zeyong Yu; Lindian County Hospital, Wenzhou Li, Xudong Jing, Huanling Wang; Linxiang People's Hospital, Xiyuan Zhao, Chao Zhang, Long Chen; Liujiang County People's Hospital, Meifa Wei, Yan Liu, Shengde Chen; Longyan First Hospital, Kaihong Chen, Yong Fang, Ying Liao; Luancheng County Hospital, Junli Wang, Tianyu Liu, Suzhe Cheng; Lucheng People's Hospital, Yunke Zhou, XiaoxiaNiu, Huifang Cao; Luchuan County People's Hospital, Zebin Feng, Min Feng; Luxi County People's Hospital, FeilongDuan, Haiming Yi; Luyi County People's Hospital, Yuanxun Xu, AnranGuo; Macheng People's Hospital, Xianshun Zhou, HongzhuanCai, Peng Zheng; Mengcheng First People's Hospital, GaofengGuo; MenglianLahudaiwa autonomous counties People's Hospital, Xiang Li; Min County People's Hospital, MinwuBao, Yuhong Liu; Nanjing First Hospital, Shaoliang Chen, HaiboJia, Hongjuan Peng; Nan’an Hospital, Duanping Dai, Shaoxiong Hong; Nantong Third People's Hospital, Song Chen, Dongya Zhang, Ying Wang; Nanyang Central Hospital, Yudong Li, Jianbu Gao, Shouzhong Yang; Ningwu County People's Hospital, Junhu An; Peking University People's Hospital, Chenyang Shen, Yunfeng Liu; Peking University Shenzhen Hospital, Chun Wu, Huan Qu, Saiyong Chen; People's Hospital of Jingyu, Yuhui Lin, Dehai Jiao; People's Hospital of Yueqing City, Manhong Wang, Qiu Wang; Pianguan County People's Hospital, YingliangXue, Ruijun Zhang; Puding County People's Hospital, Cheng Yuan, Lei Wu; Qinghai Red Cross Hospital, Jianqing Zhang, Chunmei Wei, Yanmei Shen; Qinshui County People's Hospital, Hehua Zhang, Hongmei Pan, Yong Gao; Qinyang People's Hospital, Xiaowen Ma, Yanli Liang, Tianbiao Wang; Queshan County People's Hospital, Daguo Zhao; Quzhou People's Hospital, XiaomingTu, Zhenyan Gao; Rongjiang County People's Hospital, Fangning Wang, Qiang Yang; Rudong County People's Hospital, Xiaoping Kang, Jianbin Fang, Dongmei Liu; Ruyang County People's Hospital, Chengning Shen, Mengfei Li; Shangluo Central Hospital, Yingmin Guan, Wenfeng Wang, Ting Xiao; ShangqiuChangzheng People's Hospital, Qian Wang; Shaoyang County People's Hospital, Fengyun Jiang, Kaiyou Wu; Shengsi People's Hospital, Songguo Wang; Shenyang Weikang Hospital, Xujie Fu, Shu Zhang,Lifang Gao; ShougangShuicheng Iron & Steel (Group) Co·, Ltd. General Hospital, Min Zhang, Kai Fu, XiaojingDuan; Shuangshan Hospital Of Anshan, Rui Xiao, Ruixia Wu, Bin Li; Siziwang County People's Hospital, Hongtu Zhang, Yuerong Ma, Zhonghui Cao; SunanYugur Autonomous County People's Hospital, Zhansheng Ba, Wanhai Fu; Taizhou Hospital of Zhejiang Province, Jianjun Jiang, YafeiMi, Weiwei Zhou; The Affiliated Hospital of Beihua University, Feng Sun, Qi Zhang, Shiyu Zheng; The Fifth People's Hospital of Dalian, Jing Zhang, Yang Zhong; The First Affiliated Hospital of Hebei North University, Fangjiang Li, Xiaoyuan Wang; The First Affiliated Hospital of Henan University of Science & Technology, Pingshuan Dong, Laijing Du, Wei Liu; The First Affiliated Hospital Of Jia Mu Si University, Zhaofa He, Meihua Jin; The First Hospital of Fuzhou City, Ting Jiang, Zhuoyan Chen; The First Hospital of Xi’an, Manli Cheng, YuqiangJi; The First People's Hospital of Danzhou, Youhua Zhou, Jvyuan Li; The First People's Hospital of Guangzhou, Yizhi Pan, Jian Liu; The First People's Hospital of Guangyuan, Tianxun Wang, Ping Yang; The Fourth People's Hospital of Shangqiu Shi, Guiyu Huang, JianjunPan,QingliangCai,Qianying Wang; The General Hospital of Yongzhou, Hunan Province, MingliLv; The people's hospital of Wuchuan, Yuanming Yi, Xuelian Deng; The People's Hospital of Yuanling, Wenhua Chen, RongCai; The People's Hospital of Zhijiang City, Bing Zhang; The Second Affiliated Hospital of Harbin Medical University, Bo Yu, Yousheng Xu, Zhengqiu Wang; The Second Affiliated Hospital of Kunming Medical University, Jun Shu, Ge Zhang, Kai Li; The Second Central Hospital of Baoding City, Guang Ma, PuxiaSuo; The Second People's Hospital of Liaoyuan City, Aimin Zhang, Yongfen Kang; Tianjin Medical University General Hospital, Zheng Wan,Yuemin Sun, Bo Bian; Tibet Autonomous Region People's Hospital, Xuejun Hu, DawaCiren; Tongchuan Mining Bureau Central Hospital, GuojiongJia, Jieli Pan; Tongliang County People's Hospital, Guofu Li, Hongliang Zhang, Longliang Zhan; Tongliao City Horqin District First People's Hospital, Junping Fang, Xinli Yu; Ulanqab Central Hospital, Dacheng Wang, Dajun Liu, Xinhong Cao; Wencheng County People's Hospital, Yi Tian, HaishengZhu,Wanchuan Liu; Wuhai People's Hospital, Zhaohai Zhou, Lei Shi; Wuhu Second People's Hospital, Wuwang Fang, Manxin Chen; Wulate County People's Hospital, FuqinHan, JianyeFu, Yunmei Wang; Wuqiang County People's Hospital, Binglu Liu, YanliangZhang, Xiupin Yuan; Wuyishan Municipal Hospital, Qingfei Lin, Yun Chen; Xiangtan County People's Hospital, Yuliang Zhu, ZhiqiangCai; Xing County People's Hospital, Xingping Li, LirongAo; Xingshan County People's Hospital, Shubing Wu, Hui Zhang; Xinmi First People's Hospital, Fusheng Zhao, Guangming Yang; Xinshao County People's Hospital, Renfei Liu, Wenwei Ai; Xiuwu County People's Hospital, JianbaoChang,Haijie Zhao; Xuanhan County People's Hospital, Qijun Ran, Xuan Ma; Xupu County People's Hospital, Shijun Jiang, Xiaochun Shu; Yanggao County People's Hospital, Zhiru Peng, Yan Han; Yanqing County Hospital, Jianbin Wang, Li Yang; Ying County People's Hospital, Yu Shen, Xingcun Shang; Yitong Manchu Autonomous County First People's Hospital, Haifeng Wang; Yongxing County People's Hospital, Hongyan Li, Zhisong Liao, Yang Cao; Yuanzhou District People's Hospital of Guyuan City, Xiaoping Gao, MeiyingCai, Lining You; Yuncheng Central Hospital, Xuexin Li, Shuqin Li, Yingjia Li; Yunlong County People's Hospital, Jianxun Yang, Song Ai, Jianfei Ma; Yuyao People's Hospital, Lailin Deng; ZhangjiachuanHui Autonomous County First People's Hospital, Keyu Wang, Shitang Gao, Jian Guan; Zhouning County Hospital, Banghua He, Youyi Lu; Zhuoni County People's Hospital, Weirong Yang, Hong Li; Zhuozi County People's Hospital, Zhizhong Zhang, Xiaohong Chi; Zuoyun County People's Hospital, Ru Duan, Guangli Wang.
Contributors XL, FM, JL and HK designed the study. TZ, XL and HK conceived of this article. TZ and XL wrote the manuscript, with further contributions from YL and KM. XB, SH and YG completed all statistical analyses. All authors interpreted the data, contributed to critical revisions and approved the final version of the article. XL takes responsibility for the overall content as guarantor.
Funding This project was partly supported by the National Key Research and Development Program (2017YFC1310803, 2017YFC1310801) from the Ministry of Science and Technology of China and the 111 Project from the Ministry of Education of China (B16005).
Disclaimer The sponsors had no role in the conduct of the study; in the collection, management, analysis and interpretation of the data; or in the preparation or approval of the manuscript.
Competing interests JL reported receiving research grants, through Fuwai Hospital, from the People’s Republic of China for work to improve the management of hypertension and blood lipids and to improve care quality and patient outcomes of cardiovascular disease; receiving research agreements, through the National Center for Cardiovascular Diseases and Fuwai Hospital, from Amgen for a multicentre clinical trial assessing the efficacy and safety of omecamtiv mecarbil and for dyslipidaemic patient registration; receiving a research agreement, through Fuwai Hospital, from Sanofi for a multicentre clinical trial on the effects of sotagliflozin; receiving a research agreement, through Fuwai Hospital, with the University of Oxford for a multicentre clinical trial of empagliflozin; receiving a research agreement, through the National Center for Cardiovascular Diseases, from AstraZeneca for clinical research methods training, outside the submitted work; and receiving a research agreement, through the National Center for Cardiovascular Diseases, from Lilly for physician training, outside the submitted work. HK works under contract with the Centers for Medicare & Medicaid Services to support quality measurement programmes; was a recipient of a research grant, through Yale, from Medtronic and the US Food and Drug Administration to develop methods for postmarket surveillance of medical devices; was a recipient of a research grant with Medtronic and is the recipient of a research grant from Johnson & Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold & Porter law firm for work related to the Sanofi clopidogrel litigation, from the Martin/Baughman law firm for work related to the Cook IVC filter litigation, and from the Siegfried and Jensen law firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a participant/participant representative of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook and the Physician Advisory Board for Aetna; and is the founder of Hugo Health, a personal health information platform, and cofounder of Refactor Health, an enterprise healthcare AI-augmented data management company. FM has a contract with the American College of Cardiology as the Chief Scientific Advisor for the NCDR and has received travel expenses from the Fuwai Hospital. YL is supported by the National Heart, Lung, and Blood Institute (K12HL138037) and was a recipient of a research agreement, through Yale, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion.
Provenance and peer review Not commissioned; externally peer reviewed.