key: cord-0734361-9bdvnezq
authors: Lu, Jiapeng; Yang, Yang; Cui, Jianlan; Xu, Wei; Wu, Chaoqun; Li, Jing; Li, Xi
title: Alcohol use disorder and its association with quality of life and mortality in Chinese male adults: a population-based cohort study
date: 2022-04-19
journal: BMC Public Health
DOI: 10.1186/s12889-022-13146-4
sha: a10975e8202c7e0943e7f2d98a51869bc8333ce7
doc_id: 734361
cord_uid: 9bdvnezq

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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-13146-4.

Alcohol use caused 108 million (9%) disability adjusted life years (DALY) globally, of which one sixth were directly related to alcohol use disorder (AUD) [1] . AUD is one of the most prevalent mental disorders affecting nearly 10% of the general population worldwide [2, 3] . Understanding the population distribution and health effects of AUD is necessary for developing intervention strategies for reducing the related disease burden.

A systematic review including 38 studies published before 2010 has reported that the prevalence of AUD in China was 10.1% in men and 0.1% in women, but the quality of included studies was generally low and the between-study heterogeneity was very large (I 2 > 99%) [4] . Other prior studies also evaluated the burden of alcohol abuse or problem drinking in some regions of China, and identified the potential risk factors of alcohol abuse, such as middle age, male gender and low education level; however, these findings were constrained by small sample sizes and incomplete regional coverage [5] [6] [7] . Despite the increasing alcohol consumption and growing proportion of heavy drinking in China [8, 9] , national epidemiological evidence on AUD is still limited. Previous studies have revealed that male drinkers with AUD or problem drinking had about a two-fold higher risk of all-cause mortality, but the specific associations of AUD with cause-specific mortality, such as mortality from cardiovascular diseases, cancer and injuries, were not reported [6, 10, 11] . Another study found that males with problem drinking had poorer self-reported health and were more likely to have symptoms of depression and anxiety, while little is known about how quality of life was compromised in male with AUD [6] .

Accordingly, we aimed to demonstrate the distribution of AUD in men and its variations across population subgroups in China, identify potential sociodemographic and health-related characteristics associated with AUD, and assess the associations of AUD with quality of life and all-cause and cause-specific mortality.

The China PEACE Million Persons Project is a government-funded public health project across China. The details of the project design have been described previously [12] . Briefly, from September 2014 through November 2019, 254 county-level regions in all 31 provinces in mainland China were selected as study sites to provide diversity in geographic distribution, population structure (ethnicity distribution), and exposure to risk factors and disease patterns. Although the study sites were not randomly selected, the selection had considered population size, population stability, and local capacity to support the project. Local residents aged 35 to 75 years, who were currently registered in the community's Hukou (a record officially identifying area residents), or had lived in the community for at least 6 of the prior 12 months, were invited and recruited in this project. The overall response rate was about 30%. Enrolled participants with serial project ID number ended with 1, 3, 5, or 7, who were chosen for detailed lifestyle survey as a representative sample of the entire project cohort, were included in the study analyses. We excluded female participants as the rate of alcohol drinking among them was very low (approximately 5.9%). The central ethics committee at the China National Center for Cardiovascular Diseases approved this project. All enrolled participants provided written informed consent.

For each participant, standardized in-person interviews were conducted by trained personnel to collect information on socio-demographic status (education, annual household income, health insurance and marital status), lifestyle (tobacco smoking, alcohol drinking, diet and physical activity), medical history and quality of life. Blood pressure, height, and weight were measured using the unified protocols and devices.

The presence of AUD was evaluated by the alcohol use disorders identification test (AUDIT) score [13] . Each of the 10 questions in the AUDIT has a set of responses, which has a score ranging from 0 to 4. The response scores of all 10 questions were added up to get the total score for each participant. The presence of AUD was defined as the total AUDIT score equal to or greater than 8 according to the recommendation by the World Health Organization (WHO) [13] . Current drinker was defined based on Question 1, as drinking at least once every month during the past 12 months [14] . The AUDIT has three conceptual domains including hazardous alcohol use, presence of dependence symptoms and harmful alcohol use. A score of 1 or more on Question 2 or Question 3 indicates consumption at a hazardous level. Points scored above 0 on questions 4-6 (especially weekly or daily symptoms) imply the presence or incipience of alcohol dependence symptoms. Points scored on questions 7-10 indicate that harmful alcohol use has already occurred. The AUDIT has been validated in Chinese population, which has high validity (0.93-0.95) and high reliability (0.95-0.99) [15] . And it has high sensitivity (0.877-1.000) and specificity (0.881-0.900) for identifying participants with AUD.

The three-level EuroQol five-dimension (EQ-5D-3L) instrument was used to assess the quality of life (QOL) [16] . For each participant, an index score from the EQ-5D-3L instrument was calculated based on the time trade-off method for Chinese population [17] . The highest index score was 0.961 as the optimal QOL, indicating no health-related reduction of QOL. A lower index score indicated a lower QOL.

Further, we ascertained the vital status and causes of death of each enrolled participant through China's Centre for Disease Prevention and Control's National Mortality Surveillance System and Vital Registration, with annual active confirmation from local residential, medical, health insurance and administrative records. We used the International Classification of Diseases (ICD)-10 to code the mortality records. All-cause mortality and mortality from CVD (ICD-10: I00-I99), cancer (ICD10: C00-C97) and injuries (ICD10: L55-L55.9, L56.3, L56.8-L56.9, L58-L58.9, U00-U03, V00-V86.9, V87.2-V87.3, V88.2-V88.3, V90-V98.8, W00-W46.2, W49-W62.9, W64-W70.9, W73-W75.9, W77-W81.9, W83-W94.9, W97.9, W99-X06.9, X08-X39.9, X46-X48.9, X50-X54.9, X57-X58.9, X60-X64.9, X66-Y08.9, Y35-Y84.9, Y87.0-Y87.1, Y88-Y88.3, Y89.0-Y89.1) were analyzed.

Patient characteristics were summarized using proportion for categorical variables and mean ± standard deviation or median (interquartile range) as appropriate for continuous variables. Continuous variables were compared using the Student's t test or Mann-Whitney U test according to data distribution, and categorical variables using the chi-square test. Standardized mean differences (SMD) were calculated to compare patient characteristics between current drinkers and non-drinkers, and between drinkers with and without AUD. When the absolute value of the SMD was < 0.2, the between-group difference was thought to be small [18] . The 95% confidence intervals (CI) for prevalence rates were calculated using the Clopper-Pearson method [19] . To quantify the variability in rates of AUD among the study sites, we calculated the median odds ratio (MOR) by fitting a multivariable mixed model with random effects at the study site level.

We fitted multivariable mixed models with study site as random effects and a logit link function to assess the associations of demographic, socioeconomic and healthrelated factors with AUD in the study population. The four dependent variables were whether the male drinkers had AUD, hazardous alcohol use, dependence symptoms, and harmful alcohol use. The individual characteristics included in the model were age, urbanity, education level, annual household income, marital status, smoking, obesity, and diagnosed CVD, hypertension, and diabetes.

We assessed the association of AUD with quality of life and mortality in all male drinkers and in subgroups stratified by age group and geographical region. A multivariable mixed models with study sites as random effects and a logit link function were fitted to assess the associations of AUD with quality of life (optimal QOL vs. non-optimal QOL) adjusted for age, geographic regions, education level, annual household income, marital status, medical insurance, smoking, history of hypertension, history of diabetes and BMI groups. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% CIs for the AUD with all-cause mortality. Competing risk models were used to calculate HRs and 95% CIs for the AUD with cause-specific mortality. All models were adjusted by age, education, annual household income, current smoking and BMI. As the mortality data were available up to 31 December 2019, we censored the follow-up at this date or the date of death, whichever occurred first. P < 0.05 was considered statistically significant. All analyses were conducted with SAS 9.4 (SAS Institute Inc., Cary, North Carolina).

Among the 367 120 men included, the average age was 56.6 ± 10.1 years. Overall, about three fifths of them were living in rural areas, 19% had an annual household income over 50 000 Yuan RMB, 26% had a high school education or above, 98% had social health insurance, and 95% were currently in marriage (Table 1) . Meanwhile, nearly half of these men were current smokers, one quarter with low physical activity, and one sixth obese. Regarding the medical comorbidities, 25% of them had diagnosed hypertension, 7.6% diagnosed diabetes, 4.0% prior coronary health disease or stroke, 0.2% chronic kidney disease, and 0.1% cancers (Table 1) .

A total of 152 514 (41.5%) men in the study cohort were current drinkers, and their average age was 55.7 ± 9.8 years. The socioeconomic profiles, risk factors and medical histories of current drinkers were similar to those of non-drinkers ( Table 1) .

The prevalence of AUD was showed in Table 2 . The crude rate of AUD in the study population was 10.7% (39 163, 95%CI: 10.6%-10.8%). After age-standardization according to the 2010 population census of China, the rate of AUD was 11.4% (95%CI: 11.3%-11.5%). Across the 247 study sites with at least 200 men per site, the age-standardized AUD rates ranged from 0.2% to 35.1%, with a median of 9.8% and an MOR of 2.2 (95%CI: 2.0-2.3). Among the male drinkers, the crude rate of AUD was 25.6% (95%CI: 25.4%-25.8%). After age-standardization according to the 2010 population census of China, the rate of AUD was 26.1% (95%CI: 25.9%-26.4%). Across the 220 study sites with at least 200 male drinkers per site, the proportion of male drinkers with AUD ranged from 3.3% to 57.7% across study sites, with a median of 23.1% and an MOR of 1.8 (95%CI: 1.7-1.9).

Among male drinkers, 42.8% of them had hazardous alcohol use, followed by 40.3% having harmful alcohol use and 8.1% with dependence symptoms. After 

It was found that male drinkers who were aged 45-54 years, currently smoking, obese, with a higher education level, with diagnosed hypertension, and without diagnosed CVD had a higher rate of AUD (all P < 0.05) ( Table 3 ). In the multivariable models, these correlations remained statistically significant. Regarding different conceptual domains of AUD, for hazardous alcohol use, dependence symptoms and harmful alcohol use, the associated factors including age, education, smoking, obesity and diagnosed hypertension were generally similar with the overall AUD (Table 4) . For dependence symptoms, the males living in rural areas had a higher rate of dependence symptoms than those in urban areas (OR: 1.27, 95%CI: 1.06-1.52).

During the follow-up with a median duration of 2.4 years (IQR: 1.2-3.6 years), there were 1639 (1.12%) deaths occurring among male drinkers, including 575 (0.39%) deaths from CVD, 639 (0.43%) from cancer, and 163 (0.11%) from injuries. All-cause and causespecific mortality rates were both higher in male drinkers with AUD compared with those without AUD. After adjusting covariates in the Cox regression model, male drinkers with AUD had a 20% higher risk for all-cause mortality compared with those without AUD (HR: 1.20, 95% CI: 1.08-1.35, P < 0.001). Regarding the specific causes of death, male drinkers with AUD had a 30% higher risk for mortality from cancer (HR: 1.29, 95% CI: 1.08-1.54, P = 0.004) compared with those without AUD; while no significant association was found for mortality from CVD (HR: 1.18, 95% CI: 0.97-1.43, P = 0.09) or injuries (HR: 1.25, 95%CI: 0.89-1.76, P = 0.19) (Fig. 1) . Subgroup analyses showed that the AUD was significantly associated with higher risk for all-cause mortality in the central (HR: 1.55, 95% CI: 1.20-2.01) and western (HR: 1.37, 95% CI: 1.07-1.76) regions, but not in eastern region (Additional file 1). And AUD was significantly associated with higher risk for cancer mortality in the central region (HR: 1.85, 95% CI: 1.21-2.81), but not in other regions.

Based on the index score from EQ-5D-3L instrument, male drinkers with AUD had a slightly lower QOL compared with those without AUD (mean ± SD: 0.95 ± 0.04 for participants without AUD and 0.94 ± 0.05 for participants with AUD, P < 0.001). The crude rates of men with optimal QOL were 81.8% in those with AUD and 88.2% in those without AUD (OR: 0.65, 95% CI: 0.63-0.67, P < 0.001). After adjusting for individual characteristics, multivariable mixed models identified that 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). In addition, hazardous alcohol use (OR: 0.76, 95% CI: 0.74-0.79, P < 0.001), dependence symptoms (OR: 0.55, 95% CI: 0.52-0.58, P < 0.001), and harmful alcohol use (OR: 0.55, 95% CI: 0.54-0.57, P < 0.001) were significantly associated with optimal QOL. Subgroup analyses showed that the associations of AUD and its three domains with QOL were significant in all age groups, and the magnitude of the associations was larger in those who were younger (Fig. 2 ). Significant associations of AUD and its three domains with QOL were also identified in all geographical regions (Additional file 1).

In this national population-based study, we found that around one fourth of male drinkers (i.e., nearly one ninth of male adults) in China had AUD based on AUDIT score. Male drinkers who were aged 45-54 years, currently smoking, obese, with a higher education level, with diagnosed hypertension, or without diagnosed CVD had higher rates of AUD. The presence of AUD was associated with lower QOL as well as higher risk of all-cause mortality and cancer-specific mortality. This study adds to the existing literature in several ways. First, to our knowledge, this is the first time that a validated screening tool has been used to estimate the prevalence of AUD in China at the national level. The rate of AUD was consistent with the findings from a systematic review in China (10.1% in male) using heterogeneous tools [4] and a population-based study on problem drinking (8% of male and 24% of male drinkers) [6] . The overall rate of AUD in China was lower than that in the United States. A national survey in the US reported that about 18% of male adults had AUD [20] . In our study, male drinkers aged 45-54 had the highest rate of AUD, which could be due to the highest prevalence of regular drinking and alcohol consumption in this age group [21] . Inconsistent with the previous study [6] , we found male drinkers with a higher education level had a slightly higher rate of AUD. This could be explained by the more rapid increase in prevalence of alcohol drinking and higher percentage of heavier drinkers among Chinese men with a higher education level in the past decade [8] . Moreover, this study recruited participants with diverse sociodemographic characteristics, who came from 55% of the prefecture-level cities scattered over all 31 provinces of mainland China. It is the first time a 20-fold difference in the prevalence of AUD at county level was reported, which awaits further studies to explore the potential causes of alcohol problems in different regions of China. Second, we described the prevalence of the three conceptual domains of AUD including hazardous alcohol use, presence of dependence symptoms and harmful alcohol use, and examined their associated individual characteristics. Compared with the presence of dependence symptoms, hazardous alcohol use and harmful alcohol use were more common in Chinese male drinkers, which was consistent with previous studies [22, 23] . Multivariable mixed models found that the individual characteristics associated with the three domains were largely similar with those of the overall AUD; meanwhile, living in rural areas was one of the most significant factors that were associated with a higher prevalence of dependence symptoms. A previous Chinese study with a regional representative sample also reported that rural residents were more likely to have alcohol dependence compared to urban residents [23] . The higher prevalence of dependence symptoms in rural areas was attributed to their higher level of alcohol consumption.

Thirdly, we explored the association of the presence of AUD with health outcomes including mortality and health-related QOL among male drinkers. Previous studies had reported an increasing risk of all-cause mortality with AUD or problem drinking [6, 10, 24] . Our study further revealed an even stronger association of AUD with cancer-specific mortality. The evidence of association of AUD with overall health status is limited, except for some mental disorders, such as anxiety and depression [6, 20, 25] . In our study, we investigated the relationship between AUD and health-related QOL, and observed that male drinkers with AUD were less likely to have optimal QOL compared with those without AUD. Further studies that could generate more detailed knowledge on the influence of AUD on different dimensions of QOL, such as functional and psychologic states, are needed. Moreover, we found that the impacts of AUD on QOL were stronger in younger population. Given the higher rate of AUD in younger group, more targeted and stronger strategies for middle age male drinkers should be considered to prevent AUD and the consequent health-related harms.

The findings based on our analyses have notable policy implications. Alcohol use was estimated to account for 2.84 million deaths annually, with an increase of 10% during the past decade [1] . In China, alcohol consumption per capita increased from 4.1 L in 2005 to 7.2 L in 2016, and the prevalence of heavy episodic drinking reached 53% among male drinkers [26] . Consequently, the prevalence of AUD and its health harm are likely to increase in the future. Health education and counselling for alcohol drinkers, which could effectively reduce alcohol consumption, should therefore be provided in primary care settings in order to prevent cardiovascular diseases and cancer [27] .

Behavioral interventions for alcohol drinkers should also be included in the scopes of service in primary health care institutions. Secondly, although there are Fig. 1 Association of AUD with all-cause and cause-specific mortality among male drinkers. AUD Alcohol use disorder, HR Hazard ratio, CI Confidence interval tertiary psychiatric hospitals with addiction units for the treatment of patients with AUD in several mega cities in China [28] , the accessibility to the treatment by psychiatric specialists is yet to improve in most areas across the country.

The findings should be explained considering several limitations. First of all, the AUDIT is a screening tool, not a clinical diagnosis tool; thus, participants with AUD defined in this study were not clinically diagnosed. However, the AUDIT is an efficient tool for early detecting patients experiencing alcohol abuse and dependence in the primary care settings and understanding the burden of AUD in the general population [15] . Second, the QOL findings were derived from cross-sectional data. Third, Fig. 2 Association of AUD and its three domains with quality of life among male drinkers. AUD Alcohol use disorder, OR Odds ratio, CI Confidence interval the participants were followed up for a short period. The limited number of events may result in reduced statistical power to detect significant impact of AUD on mortality, especially on cause-specific mortality. Lastly, the study sample is not a nationally or regionally random sample, which would limit the representativeness of the rate of AUD observed in this study. Nevertheless, the association between AUD and health-related outcomes could still be generalizable to the general population.

In conclusion, our results showed that one in nine middle-aged men had AUD in China. Male drinkers with AUD were associated with lower QOL and higher risks of all-cause mortality and cancer-specific mortality. National strategies for reducing alcohol consumption and improving health education for alcohol drinkers in primary care settings are imperative to prevent and control alcohol-related harms.

AUD or problem drinking was associated with some health-related measures, such as anxiety and depression.

Male drinkers with AUD or problem drinking had higher risk for all-cause mortality.

Male drinkers with AUD were less likely to have optimal quality of life compared with those without AUD.

AUD was prospectively associated with a 20% higher risk for all-cause mortality and 30% higher risk for mortality from cancer.

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study

Global Burden of Disease and the Impact of Mental and Addictive Disorders

The epidemiology of alcohol use disorders cross-nationally: Findings from the World Mental Health Surveys

Prevalence of alcohol use disorders in mainland China: a systematic review

Epidemiology of alcohol abuse and dependence in rural chinese men

Problem drinking, wellbeing and mortality risk in Chinese men: findings from the China Kadoorie Biobank

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Patterns and trends of alcohol consumption in rural and urban areas of China: findings from the China Kadoorie Biobank

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Alcohol use disorders and mortality: a systematic review and meta-analysis

Alcohol Use Disorders Identification Test (AUDIT) and mortality risk: a systematic review and meta-analysis

Protocol for the China PEACE (Patient-centered Evaluative Assessment of Cardiac Events) Million Persons Project pilot

The Alcohol Use Disorders Identification Test: Guidelines for Use in Primary Care

Analysis of the alcohol drinking behavior and influencing factors among emerging adults and young adults: a cross-sectional study in Wuhan, China

The Chinese translations of Alcohol Use Disorders Identification Test (AUDIT) in China: a systematic review

Variation in Chinese population health related quality of life: results from a EuroQol study in Beijing, China. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research

Statistical Power Analysis for the Behavioral Sciences

The Use of Confidence or Fiducial Limits Illustrated in the Case of the Binomial

Epidemiology of DSM-5 Alcohol Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions III

Alcohol consumption in 0.5 million people from 10 diverse regions of China: prevalence, patterns and socio-demographic and health-related correlates

Associations of cohort and socio-demographic correlates with transitions from alcohol use to disorders and remission in metropolitan China

Prevalence, treatment, and associated disability of mental disorders in four provinces in China during 2001-05: an epidemiological survey

Alcohol Use Disorder and Mortality Across the Lifespan: A Longitudinal Cohort and Co-relative Analysis

Anxiety and alcohol use disorders: comorbidity and treatment considerations

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Effectiveness of brief alcohol interventions in primary care populations

Satisfaction of psychiatric inpatients in China: clinical and institutional correlates in a national sample

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We appreciate the multiple contributions made by study teams at the National Center for Cardiovascular Diseases, and the local sites in the collaborative network in the realms of study design and operations, particularly data collection by Shuang Hu, Hao Dai, Hui Zhong and Binbin Jin. 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. No other disclosures were reported.

The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s12889-022-13146-4. Table 1 Authors' contributions XL and JLi conceived the China PEACE Million Persons Project and take responsibility for its all aspects. JLu conceived this article. JLu wrote the manuscript, with further contributions from YY, JC, WX, CW, JLi and XL. JLu completed all the statistical analysis. All authors interpreted data, contributed to critical revisions, and read and approved the final version of the article.

This project was supported by the CAMS Innovation Fund for Medical Science (2021-1-I2M-011), the National Key Research and Development Program (2017YFC1310801, 2017YFC1310803) from the Ministry of Science and Technology of China, the Ministry of Finance of China and National Health Commission of China. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or the decision to submit the manuscript for publication.

The datasets generated and/or analysed during the current study are not publicly available due to that the China PEACE Million Persons Project is a national program, and as the government policy stipulates, it is not permissible for the researchers to make the raw data publicly available at this time. And currently, it is not yet possible for other researchers to apply for the access.

The central ethics committee at the China National Center for Cardiovascular Disease approved this project. All enrolled participants provided written informed consent. And all methods were performed in accordance with the Declaration of Helsinki.

Not applicable.

Dr. Jing Li reported receiving research grants, through Fuwai Hospital, from Chinese government and Chinese Academy of Medical Sciences for work to improve the management of hypertension and blood lipids and to improve patient outcomes of cardiovascular disease and COVID-19; receiving research agreements, through the National Center for Cardiovascular Diseases and Fuwai Hospital, from Amgen for a multicenter clinical trial assessing the efficacy and safety of omecamtiv mecarbil and for dyslipidemic patient registration; receiving a research agreement, through Fuwai Hospital, from Sanofi for a multicenter clinical trial on the effects of sotagliflozin; receiving a research agreement, through Fuwai Hospital, with the University of Oxford for a multicenter clinical trial of empagliflozin; receiving a research agreement, through the National Center for Cardiovascular Diseases, from