摘要

第一部分 中国及各省份先天性心脏病疾病负担研究

背景

自2005年以来，先天性心脏病（Congenital heart disease，CHD）已成为我国最常见的出生缺陷。随着诊断和治疗水平的显著进步，CHD患者数量持续增加，在全球CHD疾病负担中占据重要比例。然而，目前缺乏我国连续时间段内CHD疾病负担的详细数据，省级层面的数据尤其匮乏。在本研究中，我们旨在通过评估我国各省份CHD的发病率、患病率、死亡率、伤残调整寿命年（Disability-adjusted life year，DALY），并结合反映区域发展的健康相关指标，探讨我国及各省级单位的CHD疾病负担。

方法

由于我国省级层面的全球疾病负担（Global Burden of Disease，GBD）相关数据未公开，反应CHD疾病负担的相关指标，如发病率、患病率、死亡率和DALY等，均从中国疾病预防控制中心慢性非传染性疾病预防控制中心获取。反映区域发展的健康相关指标则来自国家卫生健康委员会发布的《卫生统计年鉴》，这些指标包括经济不平等状况、医疗卫生财政支出、医疗设施条件、个人教育水平、医疗服务提供者的负担、产前诊断率以及医疗保险覆盖率等。本研究通过广义线性回归模型来探究所获取的指标与CHD疾病负担之间的关系，并采用贝叶斯年龄-队列-时期（Bayesian age-period-cohort，BAPC）模型来预测我国CHD未来的疾病负担情况。

结果

CHD已成为我国≤20岁人群的第二大死因。2019年，CHD估计导致25312人死亡（95% 不确定区间 [Uncertain interval，UI]：21314-30078），相较于1990年（99568 人死亡，95% UI：77975-135785）下降了74.6%（95% UI：-83.5至-63.8）。江苏（下降80.3%）、河南（下降81.9%）、湖北（下降82.3%）、内蒙古（下降81.0%）、四川（下降84.5%）、陕西（下降81.4%）、辽宁（下降81.9%）和黑龙江（下降81.8%）等地在死亡率方面有显著改善。从1990年到2019年，年龄标准化的DALY率大幅下降（64.7%，95% UI：48.7-77.6）。在过去三十年里，西藏的DALY率最高（1990年：每10万人中1713年，95% UI：488-3337；2019年：每10万人800年，95% UI：351-1334），而北京（1990年：每10万人295年，95% UI：227-378；2019年：每10万人121年，95% UI：95-166）和广东（1990年：每10万人262年，95% UI：197-437；2019年：每10万人117年，95% UI：83-183）的CHD疾病负担相对较轻。国内生产总值中医疗卫生财政支出的比例、医院偿债能力、床位数量、平均受教育年限、个人医疗支出、卫生工作者工作量和产前诊断率与死亡率的变化相关。高等教育普及率与患病率的变化相关。从1990年到2019年，成年CHD患者已成为主要患病群体。根据BAPC模型预测，到2042年，我国CHD死亡率预计将持续下降（-77.9%，95% 置信区间 [Confidence interval，CI]：-91.6至-46.6），而患病率则预计无显著变化。

结论

本研究首次描绘了1990年至2019年我国省级层面的CHD疾病负担情况，填补了我国CHD流行病学研究的空白。此外，结合从《卫生统计年鉴》中获取的指标，本研究揭示了当前CHD管理中存在的不足，并为未来调整方向提供潜在可行建议，包括进一步提升围产期诊断水平，让基层医生了解CHD的治疗效果和患者术后生活质量；倡导精准且有效的首次畸形矫正手术；并将先天性心脏病视为一种终身慢性病来管理。

关键词：先天性心脏病、疾病负担、医疗保健、政策建议

第二部分 中国先天性心脏病患者外科矫治住院经济负担：

一项源自国家心血管病中心的研究

背景

关于先天性心脏病（Congenital heart disease，CHD）的经济数据较为稀缺，过往研究多源自发达国家，发展中国家的CHD患者治疗经济负担研究较少，而了解该患者群体治疗经济负担有助于相关卫生政策的进一步调整。因此，本研究旨在从医院视角探究CHD外科矫治的住院费用以及相关医疗政策的潜在改进方向。

方法

本研究使用中国CHD外科数据库，对2018年5月至2020年12月于国家心血管病中心的CHD外科住院患者相关治疗费用进行分析。总住院费用划分为11个项目（药品、影像检查、耗材、手术、医疗护理、实验室检验、治疗、检查、医疗服务、住宿及其他等），并依据胸外科医师协会-欧洲心胸外科协会（Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery，STAT）分级、年份、不同年龄组以及CHD复杂程度展开进一步亚组分析。为更清晰地描述CHD患者外科住院经济负担，我们通过国家统计局获取经济数据（国内生产总值[Gross domestic product，GDP]、人均GDP、人均可支配收入以及2020年人民币兑美元年均汇率等）。此外，我们还运用广义线性模型探究影响费用的潜在因素。

结果

所有数值均以2020年人民币（¥）为单位呈现。本研究共纳入6568例CHD外科住院病例。总住院花费中位数为64,900元（约合9,409美元，四分位间距[Interquartile range，IQR]：35,819元），其中STAT 1级患者支出最低，为57,014元（约合8,266美元，IQR：16,774元），STAT 5级患者支出最高，为194,862元（约合28,251美元，IQR：130,010元）。2018-2020年期间的费用中位数分别为62,014元（约合8,991美元，IQR：32,628元）、64,846元（约合9,401美元，IQR：34,469元）和67,867元（约合9,839美元，IQR：41,496元）。就年龄而言，≤1月年龄组的费用中位数最高，为144,380 元（约合20,932美元，IQR：92,584元）。年龄、STAT分级、急诊手术、遗传综合征、延迟关胸、机械通气时间以及并发症等因素，均对住院费用有显著影响。

结论

本研究首次详细阐述了我国CHD患者外科住院费用，揭示其造成的经济负担。研究结果显示，我国在CHD治疗方面已取得显著进展，但该疾病仍给家庭和社会带来沉重的经济负担。此外，2018年至2020年期间，住院费用呈上升趋势，且新生儿群体被视为外科治疗经济负担最高的人群。

关键词：先天性心脏病、经济负担、医疗健康、政策建议

第三部分 极端温度暴露对先天性心脏病患者死亡率的影响：

一项基于人群的全国性病例交叉研究

背景

先天性心脏病（Congenital heart disease，CHD）与非适宜温度之间的关联尚未得到充分研究，本研究旨在探究极端温度暴露（即寒潮或热浪）对CHD死亡率的影响。

方法

我们回顾性分析了中国死因监测数据集，提取了2013年至2021年间主要死因为CHD的死亡记录。温度和空气污染物数据分别来自ERA5-Land再分析数据集和中国高分辨率高质量近地表空气污染物数据库。本研究采用两阶段病例交叉研究设计，并开展了敏感性分析和亚组分析，以检验研究结果的稳健性并确定易感人群。

结果

本研究共纳入32,168例CHD死亡病例，结果显示寒潮暴露与CHD死亡率之间存在显著关联，而热浪暴露的影响则较轻。在全国范围内，比值比（Odd ratio, OR）介于1.05（95% 置信区间：1.00-1.10）至1.15（1.03-1.29）之间，在非季风区域影响更为显著，最高可达1.67（1.20-2.32）。在全国范围内，每1000例CHD死亡病例中有4.09例归因于寒潮暴露，在非季风区域则为每1000例CHD死亡中有13.30例归因于寒潮暴露。使用体感温度进行分析以及在模型中纳入空气污染物进行调整后进行敏感性分析，均证实了主要研究结果的稳健性。本研究还确定女性和儿童CHD患者为对寒潮暴露的易感人群。

结论

本研究首次证实了寒潮暴露对CHD死亡率具有显著影响，这种影响在非季风区域以及女性和儿童群体中尤为明显。这些研究结果或许提示医疗专业人员应建议CHD患者避免在暴露于寒潮环境中，同时也为卫生保健政策的调整提供了潜在参考依据。

Abstract

Part 1. National and Subnational Burden of Congenital Heart Disease in China

Background

Congenital heart disease (CHD) has become the foremost birth defect in China since 2005. However, there is scarce data to delineate the burden in a consecutive period, not to mention at the provincial level of China. In this study, we aimed at investigating the national and regional burden of CHD in China, by assessing incidence, prevalence, mortality, disability-adjusted life year (DALY) and health-related metrics reflecting regional development.

Methods

CHD-related estimates, including incidence, prevalence, mortality and DALY, were obtained from the Chinese Center for Disease Control and Prevention due to the publicly unavailable of provincial level data of Global Burden of Disease (GBD) study in China. Health-related metrics were retrieved from the healthcare statistics yearbook released by the National Health Commission of China, including economic inequity, healthcare fiscal expenditure, healthcare facility condition, personal education level, healthcare provider’s burden, prenatal diagnosis rate and health insurance coverage. A generalized linear regression model was utilized to investigate the relationship between retrieved metrics and CHD burden, and a Bayesian age-period-cohort (BAPC) model was adopted to project the future burden of CHD in China.

Results

CHD has notably become the second leading cause of death in the young generation (≦ 20-year-old), and it was attributable to an estimated 25312 deaths in 2019 (95% UI, 21314 to 30078), with a 74.6% decline (95% UI, -83.5 to -63.8) from 1990 (99568 [95% UI, 77975 to 135785]). Great improvements in CHD mortality were observed in Jiangsu (80.3% decline), Henan (81.9% decline), Hubei (82.3% decline), Inner Mongolia (81.0% decline), Sichuan (84.5% decline), Shaanxi (81.4% decline), Liaoning (81.9% decline) and Heilongjiang (81.8% decline). From 1990 to 2019, a huge decrease (64.7%, [95%UI, 48.7 to 77.6]) was obtained in the age-standardized DALY rate. In the past three decades, Tibet had the highest DALY rate (1990: 1713 per 100,000 individuals, 95% UI [488 to 3337]; 2019: 800 per 100,000 individuals, 95% UI [351 to 1334]), while Beijing (1990: 295 per 100,000 individuals, 95% UI [227 to 378]; 2019: 121 per 100,000 individuals, 95% UI [95 to 166]) as well as Guangdong (1990: 262 per 100,000 individuals, 95% UI [197 to 437]; 2019: 117 per 100,000 individuals, 95% UI [83 to 183]) exhibited superior performance. For mortality, the proportion of healthcare fiscal expenditure in the gross domestic product, hospital liability, bed number, average education duration, personal healthcare expenditure, health workers’ workload and prenatal diagnosis were associated with the change in mortality. For prevalence, higher education percentage was an extra factor. Adult CHD patients have become the prominent population from 1990 to 2019. According to the BAPC model, the CHD mortality rate is expected to consistently decrease until 2042 (-77.9%, 95% CI [-91.6 to -46.6]), while there is no significant change in prevalence projection.

Conclusion

This study, for the first time, delineates the CHD burden at the provincial level from 1990 to 2019 and fulfils the gap in the epidemiology of CHD in China. Additionally, combined with the metrics retrieved from the healthcare statistics yearbooks, it unveils the shortage in current CHD management and hints at several future perspectives: further improve perinatal diagnosis and familiar primary care doctors with CHD treatment outcomes and quality of life; advocate delicate first-time correction of anomalies; recognize CHD as a life-long chronic disease.

Key words: Congenital heart disease; Disease burden; Healthcare; Policy suggestion

Part 2. Economic Burden of Congenital Heart Surgery in China: Results From the National Center for Cardiovascular Diseases

Background

Economic data on congenital heart disease (CHD) are scarce. Most previous studies were from the developed countries, and there has been little research on the economic burden of treating CHD patients in developing countries. However, understanding the economic burden of treatment for this population is instructive to the health policies adjustment. Therefore, from a hospital perspective, this study aimed to explore the inpatient costs of congenital heart surgery, subsequent economic burden, and potential improvement directions of related medical policies.

Methods

Data from the Chinese Database for Congenital Heart Surgery (CDCHS) were employed to conduct an analysis of the inpatient costs associated with congenital heart surgery ranging from May 2018 to December 2020. The overall expenditure was categorized into 11 categories, namely medications, imaging, consumable items, surgery, medical cares, laboratory tests, therapy, examinations, medical services, accommodations, and others. Subgroup analyses were carried out with the following variables: Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT), different years, various age groups, and the complexity of CHD. To further depict the economic burden, economic data including the gross domestic product (GDP), GDP per capita, per capita disposable income, and the average annual exchange rate of the Chinese Yuan against the US dollar in 2020, were obtained from the National Bureau of Statistics of China. Moreover, a generalized linear model was utilized to explore the potential factors influencing these costs.

Results

All values were presented in 2020 Chinese Yuan (¥). A total of 6,568 hospitalizations were included in this study. The median of the overall total expenditure was ¥64,900 (≈ 9,409 US Dollars [USD], with an interquartile range [IQR] of ¥35,819). The expenditure was lowest in the STAT 1, which was ¥57,014 (≈ 8,266 USD, IQR: ¥16,774), and reached the highest in the STAT 5, reaching ¥194,862 (≈ 28,251 USD, IQR: ¥130,010). During the period from 2018 to 2020, the median costs were ¥62,014 (≈ 8,991 USD, IQR: ¥32,628) in 2018, ¥64,846 (≈ 9,401 USD, IQR: ¥34,469) in 2019, and ¥67,867 (≈ 9,839 USD, IQR: ¥41,496) in 2020. In terms of age, the group of patients aged ≤1 month had the highest median cost, which was ¥144,380 (≈ 20,932 USD, IQR: ¥92,584). Age, STAT category, emergent operation, genetic syndrome, sternal closure delay, mechanical ventilation time, and complications had a significant impact on the inpatient costs.

Conclusion

This study represented the first detailed elucidation of the economic burden associated with congenital heart surgery in China. The findings indicated that, although remarkable progress has been made in the treatment of CHD, it continued to impose a substantial economic burden on both families and society. Moreover, an upward trend in inpatient costs was found from 2018 to 2020. Neonates emerged as the most challenging subgroup to manage with the highest economic burden.

Key words: Congenital heart disease; Economic burden; Healthcare; Policy suggestion

Part 3. Impact of Extreme Temperature Exposure on Congenital Heart Disease Mortality: a Population-Based Nationwide Case-crossover Study

Background

The exploration of the relationship between the mortality of congenital heart disease (CHD) and non-optimal temperatures has been relatively scarce. In this study, our objective was to assess the impact of extreme temperatures on the mortality of CHD.

Methods

We retrospectively review the National Mortality Surveillance System of China and extracted death records primarily due to CHD spanning from 2013 to 2021. Data on temperature and air pollutants were sourced from the ERA5-Land reanalysis dataset and the ChinaHighAirPollutants database. To conduct the research, we employed a two-stage case-crossover study design. Additionally, sensitivity analyses and subgroup analyses were carried out. The former was aimed at validating the reliability of our findings, while the latter was intended to identify the population groups more susceptible to relevant factors.

Results

A total of 32,168 CHD deaths were enrolled into the study. The results indicated a substantial link between cold extremes and CHD mortality, whereas heat had little impact on the mortality. Nationwide, the odds ratio (OR) ranged between 1.05 (95% confidence interval [CI]: 1.00-1.10) and 1.15 (95% CI: 1.03-1.29). This effect was more prominent in non-monsoon regions, where the OR reached up to 1.67 (95% CI: 1.20-2.32). On a national scale, cold extremes were responsible for an attributable fraction of 4.09 per 1000 CHD deaths. In non-monsoon regions, it rose to 13.30 per 1000 CHD deaths. In the sensitivity analyses, which utilized apparent temperature and adjusted for air pollutants in the model, affirmed the reliability of the primary findings. Furthermore, female and pediatric CHD patients were recognized as the subgroups particularly vulnerable to cold extremes.

Conclusion

This nationwide study is the first to reveal the impact of cold extremes on CHD mortality, especially in non-monsoon regions and among female and pediatric CHD patients. These results implied that healthcare providers should suggest CHD patients to be cautious when it comes to cold extremes. Moreover, they offer valuable perspectives for the adjustment of healthcare policies to the improvement of CHD management.