Burden of Non-Rheumatic Calcific Aortic Valve Disease in China from 1990 to 2021 and Projections to 2031: Insights from the Global Burden of Disease 2021

Burden of Non-Rheumatic Calcific Aortic Valve Disease in China from 1990 to 2021 and Projections to 2031: Insights from the Global Burden of Disease 2021 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Burden of Non-Rheumatic Calcific Aortic Valve Disease in China from 1990 to 2021 and Projections to 2031: Insights from the Global Burden of Disease 2021 WeiHua shi, JingChang Zhang, Zhitao Xie, YiSheng zheng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7350266/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Non-rheumatic calcific aortic valve disease(nrCAVD) is one of the causes of cardiovascular disease-related deaths and poses a significant challenge to healthcare. Understanding the burden of non-rheumatic calcific aortic valve disease is crucial for health policy formulation and healthcare resource allocation. This study aims to assess the burden, trends, and inequalities of non-rheumatic calcific aortic valve disease in China and predict future trends. Methods Data on non-rheumatic calcific aortic valve disease-related Deaths, disability-adjusted life years (DALYs), age-standardized Deaths rate (ASMR), age-standardized incidence rate (ASIR), and their average annual percentage change (AAPC) were obtained from the The Global Burden of Disease (GBD) 2021 database. Subsequently, the burden of non-rheumatic calcific aortic valve disease in 204 countries, including China, from 1990 to 2021 was analyzed, stratified by gender and Socio-demographic Index (SDI), and further projected to 2031. Results The number of cases of prevalence, incidence, Deaths, and DALYs of nrCAVD in China continued to increase from 1990 to 2021, with men having higher numbers than women in most indicators. Among all age groups, the number of cases was significantly higher in people aged 55 and above, especially in the 65–74 age group. The ASIRand age-standardized prevalence rate (ASPR) showed an upward trend, while the age-standardized Deaths rate (ASMR) and DALY rate showed a stable or downward trend. The incidence rate was positively correlated with SDI. The ASIR in China is expected to continue to rise in the next 10 years, and the ASMR in women will continue to decline. Conclusion The burden of nrCAVD in China continued to increase from 1990 to 2021, which is a health problem that cannot be ignored, and showed significant age and gender differences. In the next 10 years, the burden of nrCAVD in China will continue to increase. Effective and targeted strategies are needed to prevent and manage nrCAVD in this population to reduce the overall burden. Non-rheumatic calcific aortic valve disease (nrCAVD) disease burden Incidence Prevalence The Global Burden of Disease (GBD) Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Non-rheumatic calcific aortic valve disease (nrCAVD) is a common heart valve disease characterized by progressive calcification of the valve leaflets, leading to aortic valve remodeling and stenosis, and causing hemodynamic disorders. It is associated with increased morbidity and Deaths [ 1 , 2 ] , and there is no available drug treatment. With the aging of the population and changes in lifestyle, its impact on population health is increasingly prominent. In the past few decades, with the rapid global economic and social development, the overall disease burden of non-communicable diseases has continued to rise. As an important part of the burden of non-communicable diseases, the prevalence of nrCAVD has shown a significant upward trend, and it has significant Deaths and morbidity risks in the global population [ 3 – 5 ] . In a subsequent analysis of a multicenter randomized controlled trial, aortic valve calcification was observed in approximately 14% of 1769 participants aged 50–70 years [ 6 ] . In addition, a meta-analysis found that the prevalence of aortic sclerosis ranged from 9% in studies with a mean age of 54 years to 42% in studies with a mean age of 81 years [ 7 ] . These data highlight the high incidence of nrCAVD in the aging population. Although Simon Yadgir et al. and Chengzhi Yang et al. reported the global general changes in non-rheumatic valve diseases from 1990 to 2017 and from 1990 to 2021, respectively [ 8 , 9 ] , up to now, the burden of nrCAVD in China has not been reported. Understanding the changing trend of the disease burden of nrCAVD in China is of great significance for formulating effective prevention and control strategies. The GBD study provides a rich data resource for a comprehensive assessment of the disease burden [ 10 ] . This study uses GBD 2021 data to systematically analyze the disease burden of nrCAVD in China from 1990 to 2021 and predict the trend in the next 10 years, in order to provide reference for relevant health decisions. Methods 1.1 Data sources We used the latest data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021), with non-rheumatic calcific aortic valve disease in China as the research object. Data on incidence, prevalence, Deaths, and DALYs by age group and gender were extracted to comprehensively assess the disease burden. The GBD database uses UI instead of precise statistical values. Therefore, statistical significance cannot be directly calculated when comparing values (numbers, ratios, or percentages). P < 0.05 indicates a statistical difference [10] . 1.2 Socio-demographic Index (SDI) SDI is a comprehensive indicator that combines education level (≥15 years old), per capita income, and fertility rate of women under 25 years old to evaluate social and economic development. The SDI ranges from 0 (minimum development) to 1 (maximum development). A higher value indicates better socio-economic and health status [11] . According to the SDI quintiles, 204 countries and regions are divided into five groups: low SDI, low-middle SDI, middle SDI, high-middle SDI, and high SDI. 1.3 Study indicators and analysis methods When analyzing the global disease burden attributed to nrCAVD, the study considered indicators such as incidence, DALY, age-standardized rate (ASR), and percentage change(PC). From 1990 to 2021, we used the regression model to study the time trend of the burden in China, expressed as the AAPC. The 95% uncertainty interval (UI) is defined by the 2.5th and 97.5th percentiles. We also predicted the burden of nrCAVD from 2022 to 2031. Calculations, mapping, and data cleaning were completed using R software (version 4.5.0). Results 2.1 Burden of nrCAVD in China The burden of nrCAVD in China, measured by the number of cases, continued to increase from 1990 to 2021, including prevalence, incidence, Deaths, and DALYs. In these indicators, the number of men was usually more than that of women. However, the Deaths rate of women was significantly higher than that of men. The total number of incident cases in men increased from 28,056 (95% UI: 23,075, 33,630) in 1990 to 86,026 (95% UI: 66,966, 108,719) in 2021. For women, it increased from 38,402 (95% UI: 31,869, 46,135) in 1990 to 88,489 (95% UI: 70,123, 109,407) in 2021 (Table 1). However, in the past nearly 30 years, the disability-adjusted life years and Deaths rates of both men and women showed a gradually decreasing trend, while the incidence and prevalence rates of both men and women showed an upward trend (Table 2). 2.2 Number of nrCAVD cases by age group From 1990 to 2021, the number of cases of nrCAVD in various age groups in China, including prevalence, incidence, Deaths, and DALYs is shown in Figure 1. In these indicators, the number of men in incidence, Deaths, and DALYs was usually more than that of women in all age groups under 90 years old. The number of women in the age group after 90 years old was more than that of men, but in terms of prevalence, the number of women after 85 years old was more than that of men. In terms of prevalence, the number of men and women aged 55-80 years old increased significantly, especially in the 65-74 age group. In terms of incidence, the number of women aged 55-79 years old increased significantly, especially in the 65-69 age group: 5,863 in men and 4,766 in women. In terms of Deaths, the Deaths rates of both men and women increased significantly between 65-89 years old, but there was no age-related upward trend. DALYs also indicated that the number of people in the 65-84 age group was the largest, especially in the 70-74 age group (Figure 1D). 2.3 Age-standardized incidence/prevalence rates in China A comparative analysis of the incidence and prevalence rates of nrCAVD in China by age group and gender from 1990 to 2021 (Figure 2). In all age groups, the prevalence of nrCAVD in both men and women increased significantly, with the most obvious changes observed in the elderly population. Especially after 50 years old, the prevalence of both men and women showed a straight upward trend (Figure 2A). The incidence rate also basically showed an upward trend. In the 70-74 age group, the incidence rates of nrCAVD in both men and women in China reached the first peak, then the incidence rate in women in the 75-79 age group decreased slightly, and the incidence rate in men in the 75-84 age group decreased slightly, but continued to rise gradually after 85 years old (Figure 2B). Figure 3 (A/B) also shows the age-standardized prevalence/incidence rates in China. It can be seen from the figure that the number of nrCAVD cases and the prevalence/incidence rates increased year by year from 1990 to 2021, and the prevalence/incidence rates of male patients were higher than those of female patients from 1990 to 2021. 2.4 Trends of nrCAVD from 1990 to 2021 Trends of nrCAVD from 1990 to 2021 was showed in Fig4.In China, from 1990 to 2021, the curve of ASPR of nrCAVD fluctuated greatly and showed an upward trend, indicating that the ASPR of nrCAVD in China increased year by year from 1990 to 2021. The age-standardized incidence rate (ASIR) showed an upward trend although with small fluctuations. The DALYs showed a downward trend after 2000. The ASMR basically fluctuated little, indicating that the Deaths rate was basically stable from 1990 to 2021. 2.5 Socio-demographic Index The correlation between the incidence rate of nrCAVD and the Socio-demographic Index (SDI) is shown in Figure 5. It can be seen from Figure 5 that the incidence rate of the disease was positively correlated with SDI (p < 0.001, r = 0.854) and showed an upward trend from 1990 to 2021, which indicates that social and economic development affects the incidence rate of nrCAVD. China is approximately in the range of SDI 0.6-0.75, belonging to a high-middle SDI country, which suggests that with the social development in China, the incidence rate of nrCAVD is also increasing year by year, and it may be necessary to strengthen health intervention in the future. 2.6 Prediction for China in the next 10 years The predicted prevalence and incidence rates of nrCAVD in Chinese men and women by 2031 are shown in Figure 6. The overall ASIR of nrCAVD in China will maintain a relatively stable upward trend; and no significant difference was observed between genders. In the next 10 years, the ASIR of both men and women is expected to show an upward trend (Figures 6A and B). In the next 10 years, significant differences were observed between genders in the ASMR. The ASMR of men will remain basically stable, while the ASMR of women will continue to decline (Figures 6C and D). Discussion Based on the GBD 2021 database, this study systematically analyzed the changing trend of the disease burden of nrCAVD in China from 1990 to 2021 and predicted its development trend in the next 10 years. The results reveal the significant characteristics, gender and age differences, and social demographic influencing factors of the burden of nrCAVD in China, providing important scientific basis for formulating targeted prevention and control strategies. Multiple driving factors for the overall burden change of nrCAVD The results show that the number of cases of prevalence, incidence, Deaths, and DALYs of nrCAVD in China continued to increase from 1990 to 2021, which is consistent with the background of the rising burden of global non-communicable diseases [12, 13] . Population aging is the primary driving factor. With the extension of life expectancy in China, the proportion of the elderly population aged 65 and above is gradually increasing. As a typical age-related disease, the high incidence of nrCAVD in the elderly directly leads to the expansion of the case base. The progress of medical diagnostic technology also plays an important role. In the past 30 years, the popularization of imaging technologies such as computed tomography and cardiac ultrasound has significantly improved the detection rate of nrCAVD, especially with the improvement of diagnostic capabilities in primary medical institutions, many asymptomatic or mild patients can be identified early, which to a certain extent explains the upward trend of incidence and prevalence rates [14-16] . It is worth noting that while the number of cases increases, the ASMR of both men and women is basically stable, and the DALYs shows a gradually decreasing trend, which reflects the progress of cardiovascular medical services in China. In the past 20 years, China has made significant progress in the standardized diagnosis and treatment of cardiovascular diseases such as coronary heart disease and heart failure, and the management of heart valve diseases has also benefited, including optimizing drug treatment regimens, improving the grasp of surgical indications, and enhancing the quality of postoperative rehabilitation. These factors have jointly reduced the Deaths risk and functional impairment of nrCAVD patients. Epidemiological Significance of Age and Gender Differences The age distribution characteristics identified in this study provide important targets for the precise prevention and control of nrCAVD. The number of cases in people aged 55 and above increased significantly, especially the 65-74 age group, which became the core population bearing the disease burden. This is closely related to the pathophysiological mechanism of aortic valve calcification. With the increase of age, aortic valve endothelial cell damage, lipid deposition and chronic inflammatory response gradually intensify [14] , leading to a linear upward trend in the prevalence rate of people over 50 years old. As the main consumer group of social medical resources, the high incidence and prevalence of people aged 65-74 suggest that this age group should be included in the scope of key screening and intervention . In addition, the analysis of gender differences reveals the complex epidemiological characteristics of nrCAVD. Compared with women, men have always faced a heavier burden in the past 30 years [17] . Men have more cases in incidence, Deaths and DALYs in all age groups, which may be attributed to the complex interaction of biological, behavioral and social factors. Men are more likely to engage in high-risk behaviors, such as excessive drinking and bad eating habits, and are less likely to seek preventive health care or adopt early risk management strategies. In addition, social norms often discourage men from expressing emotions or managing stress effectively, leading to maladaptive coping mechanisms, such as hostility and substance use, thus exacerbating cardiovascular risks [18] . Public Health Enlightenment Related to Socio-Demographic Index The finding that the incidence of nrCAVD is positively correlated with SDI (p < 0.001, r = 0.854) has important policy significance. With the social and economic development of China, the accompanying lifestyle changes (such as increased intake of high-fat/sodium diet and reduced physical activity) have led to the increase in the prevalence of metabolic risk factors such as obesity and hypertension. These factors indirectly increase the risk of nrCAVD by promoting the process of vascular calcification. At the same time, areas with high SDI have more abundant medical resources and stronger diagnostic capabilities, which may also amplify the statistical differences in incidence [19] . This positive correlation challenges the traditional cognition that "social and economic development will inevitably improve health outcomes", suggesting that we need to be alert to the "developmental growth" of non-communicable disease burden during the economic transition period. With the advancement of China's urbanization process, residents' dietary structure has changed from the traditional high-fiber diet to high-fat and high-protein diet, and the working mode has changed from manual labor to sedentary office work. These changes occur simultaneously with the improvement of SDI, forming a "risk factor cluster effect" for the incidence of nrCAVD. Therefore, cardiovascular health promotion strategies need to be incorporated into social and economic development plans, and measures such as optimizing dietary guidelines, building sports facilities and implementing workplace health management should be taken to offset the disease risks brought by the improvement of SDI. Prevention and Control Challenges and Responses to Future Trend Prediction The prediction result that ASIR will continue to rise in the next 10 years warns that the disease burden of nrCAVD will further increase. The inertia of population aging, the continuous exposure to metabolic risk factors, and the cumulative effect of diseases brought by the extension of life expectancy together constitute the driving force for the rise of incidence. This trend poses a double challenge to the medical system: on the one hand, it is necessary to expand the coverage of disease monitoring and intervention; on the other hand, it is necessary to improve the accessibility of advanced treatment technologies such as valve replacement/repair to meet the growing clinical needs. The gender-specific prediction results provide a direction for differentiated prevention and control. The contrast between the stable ASMR of men and the continuous decline of ASMR of women may be related to the fact that the accessibility of medical services for women has improved faster than that for men, suggesting that the gender-specific medical resource allocation strategy has achieved initial results. In the future, we should continue to strengthen the cardiovascular health management of women, especially elderly women, and pay attention to the Deaths control of male patients. We can improve the prognosis of male patients by strengthening smoking cessation intervention and optimizing comorbidity management. Limitations of the Study There are certain limitations in this study that need to be explained. Firstly, the study relies on data from the GBD 2021 database, and its disease classification and diagnostic criteria may have slight differences from China's clinical practice, which may affect the accuracy of the absolute values of the results. Secondly, GBD data uses statistical models to estimate uncertainty intervals, and cannot directly calculate the statistical significance of inter-group comparisons, which may limit the accuracy of some difference analyses. Finally, the future trend prediction is based on the deduction of historical data models, and does not include potential influencing factors such as public health emergencies or medical technological breakthroughs, so the actual changes may have deviations. Conclusion In conclusion, this study provides a comprehensive and effective analysis of the epidemiology of nrCAVD in China so far, and its results have important reference value for health policy formulation. In the future, it may be necessary to formulate multi-level nrCAVD prevention and control strategies. At the primary prevention level, it is necessary to carry out risk factor screening and lifestyle intervention for people over 55 years old; at the secondary prevention level, a precise diagnosis path based on age and gender should be established to improve the early detection rate; at the treatment level, it is necessary to optimize the layout of medical resources to ensure the accessibility of treatment in high-burden areas. By integrating public health policies with clinical practice, we hope to effectively curb the rising trend of nrCAVD burden in the next decade. Declarations Ethics approval and consent to participate: The data utilized in this study are publicly accessible from the Global Burden of Disease 2021 database, and no human tissues or samples were involved. Therefore, ethics approval and informed consent are not applicable. Consent for publication: Not applicable. Availability of data and materials: Publicly available data were analyzed in this study. The data can be accessed from the Global Burden of Disease (GBD) 2021 database: https://vizhub.healthdata.org/gbd-results/. Competing interests: The authors declare no competing interests. Funding: The authors did not receive support from any organization for the submitted work. Authors' contributions: Jingchang Zhang (ZJC): conception and design of the study; Weihua Shi (SWH) and Zhitao Xie (XZT): data analysis and figure generation; Yisheng Zheng (ZYS) and Weihua Shi (SWH): drafting the initial manuscript; Jingchang Zhang (ZJC): revising the manuscript and final approval. All authors read and approved the final version. Acknowledgments: We acknowledge the Global Burden of Diseases database for providing meaningful data. Authors' information: Not applicable. References Lindman B R, Clavel M A, Mathieu P, et al., Calcific aortic stenosis[J]. Nat Rev Dis Primers, 2016, 2: 16006. Peters A S, Duggan J P, Trachiotis G D, et al., Epidemiology of Valvular Heart Disease[J]. 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Shen M, Tastet L, Capoulade R, et al., Effect of bicuspid aortic valve phenotype on progression of aortic stenosis[J]. Eur Heart J Cardiovasc Imaging, 2020, 21(7): 727-734. Regitz-Zagrosek V, Gebhard C, Gender medicine: effects of sex and gender on cardiovascular disease manifestation and outcomes[J]. Nat Rev Cardiol, 2023, 20(4): 236-247. O'neil A, Scovelle A J, Milner A J, et al., Gender/Sex as a Social Determinant of Cardiovascular Risk[J]. Circulation, 2018, 137(8): 854-864. Chen H Y, Engert J C, Thanassoulis G, Risk factors for valvular calcification[J]. Curr Opin Endocrinol Diabetes Obes, 2019, 26(2): 96-102. Tables Table 1 and 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. 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02:26:55","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":77926,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7350266/v1/da1c49be207f293f6ba85658.html"},{"id":93541121,"identity":"6d634ceb-69cb-4e9b-8e98-33a4820d071a","added_by":"auto","created_at":"2025-10-15 02:26:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":335408,"visible":true,"origin":"","legend":"\u003cp\u003eBar charts of various age groups. A: Disability-adjusted life years (DALYs); B: Deaths; C: Incidence; D: Prevalence rate. The abscissa represents the year; the ordinate represents the age; blue represents men; red represents women.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7350266/v1/b725b91237d7d2f11bbd0940.png"},{"id":93541122,"identity":"206cacd4-4dd1-41cd-af64-ba78d7713742","added_by":"auto","created_at":"2025-10-15 02:26:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":142152,"visible":true,"origin":"","legend":"\u003cp\u003eLine charts of various age groups. A: Age-specific prevalence rate; B: Age-specific incidence rate. The abscissa represents the age group; the ordinate represents the age-standardized rate. Blue represents men; red represents women.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7350266/v1/37c8d67c8b07e72e09280fa1.png"},{"id":93539469,"identity":"424d41ab-2e9e-45be-896f-7a88ac9782a5","added_by":"auto","created_at":"2025-10-15 02:18:55","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":187675,"visible":true,"origin":"","legend":"\u003cp\u003eCombined dual-axis charts (bar charts/line charts). A: Age-standardized prevalence rate; B: Age-standardized incidence rate. Both the bar charts and line charts show that the number of nrCAVD cases and the prevalence/incidence rates increased year by year from 1990 to 2021, and the prevalence/incidence rates of male patients were higher than those of female patients from 1990 to 2021. The abscissa represents the year; the left ordinate represents the number of cases; the right ordinate represents the age-standardized prevalence/incidence rate. The bar chart represents the left ordinate,, the number of cases; the curve represents the right ordinate, the age-standardized prevalence/incidence rate. Blue represents men; red represents women.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7350266/v1/5e1e206b8ec4e59aa7b0fa5f.png"},{"id":93539473,"identity":"9ee1bff4-590e-4a96-b347-c9d8633077c5","added_by":"auto","created_at":"2025-10-15 02:18:55","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":617346,"visible":true,"origin":"","legend":"\u003cp\u003eTrend chart. The abscissa represents the year; the ordinate represents the age-standardized rate, including age-standardized incidence rate (ASIR), age-standardized Deaths rate (ASMR), age-standardized disability-adjusted life years (DALYs), and age-standardized prevalence rate (ASPR).\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7350266/v1/53fbb9c7dadf38303346702d.png"},{"id":93539466,"identity":"ab0f59ae-a745-4104-99e4-e3282e594129","added_by":"auto","created_at":"2025-10-15 02:18:55","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":200230,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation chart between the incidence rate of the disease and the Socio-demographic Index. The abscissa represents the Socio-demographic Index; the ordinate represents the age-standardized incidence rate. The points in the figure represent countries. (p \u0026lt; 0.001, r = 0.854 \u0026gt; 0) indicates that the incidence rate of the disease is positively correlated with the Socio-demographic Index.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7350266/v1/62a5274dee04596b45404017.png"},{"id":93539484,"identity":"9973a8c3-b94f-4906-a9b1-98d07782bfd2","added_by":"auto","created_at":"2025-10-15 02:18:55","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":173946,"visible":true,"origin":"","legend":"\u003cp\u003ePrediction chart of nrCAVD in China in the next decade. A/B: Age-standardized incidence rate (ASIR); C/D: Age-standardized Deaths rate (ASMR).\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-7350266/v1/0b4a4b7e2308af2094828751.png"},{"id":96452807,"identity":"9da63469-1260-48b2-8874-8a06c9a778c1","added_by":"auto","created_at":"2025-11-21 09:46:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2268021,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7350266/v1/26d43fe5-9238-48b6-b28e-656da7398ceb.pdf"},{"id":93539460,"identity":"635117a6-d9c3-43d8-9539-7b6bccaa6d11","added_by":"auto","created_at":"2025-10-15 02:18:54","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19632,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7350266/v1/988b6e1fe47af4c6d13eea35.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Burden of Non-Rheumatic Calcific Aortic Valve Disease in China from 1990 to 2021 and Projections to 2031: Insights from the Global Burden of Disease 2021","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNon-rheumatic calcific aortic valve disease (nrCAVD) is a common heart valve disease characterized by progressive calcification of the valve leaflets, leading to aortic valve remodeling and stenosis, and causing hemodynamic disorders. It is associated with increased morbidity and Deaths \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e, and there is no available drug treatment. With the aging of the population and changes in lifestyle, its impact on population health is increasingly prominent. In the past few decades, with the rapid global economic and social development, the overall disease burden of non-communicable diseases has continued to rise. As an important part of the burden of non-communicable diseases, the prevalence of nrCAVD has shown a significant upward trend, and it has significant Deaths and morbidity risks in the global population\u003csup\u003e[\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn a subsequent analysis of a multicenter randomized controlled trial, aortic valve calcification was observed in approximately 14% of 1769 participants aged 50\u0026ndash;70 years \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. In addition, a meta-analysis found that the prevalence of aortic sclerosis ranged from 9% in studies with a mean age of 54 years to 42% in studies with a mean age of 81 years\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. These data highlight the high incidence of nrCAVD in the aging population.\u003c/p\u003e\u003cp\u003eAlthough Simon Yadgir et al. and Chengzhi Yang et al. reported the global general changes in non-rheumatic valve diseases from 1990 to 2017 and from 1990 to 2021, respectively\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e, up to now, the burden of nrCAVD in China has not been reported. Understanding the changing trend of the disease burden of nrCAVD in China is of great significance for formulating effective prevention and control strategies.\u003c/p\u003e\u003cp\u003eThe GBD study provides a rich data resource for a comprehensive assessment of the disease burden\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. This study uses GBD 2021 data to systematically analyze the disease burden of nrCAVD in China from 1990 to 2021 and predict the trend in the next 10 years, in order to provide reference for relevant health decisions.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e1.1 Data sources\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe used the latest data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021), with non-rheumatic calcific aortic valve disease in China as the research object. Data on incidence, prevalence, Deaths, and DALYs by age group and gender were extracted to comprehensively assess the disease burden. The GBD database uses UI instead of precise statistical values. Therefore, statistical significance cannot be directly calculated when comparing values (numbers, ratios, or percentages). P \u0026lt; 0.05 indicates a statistical difference \u003csup\u003e[10]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.2 Socio-demographic Index (SDI)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSDI is a comprehensive indicator that combines education level (\u0026ge;15 years old), per capita income, and fertility rate of women under 25 years old to evaluate social and economic development. The SDI ranges from 0 (minimum development) to 1 (maximum development). A higher value indicates better socio-economic and health status\u003csup\u003e[11]\u003c/sup\u003e. According to the SDI quintiles, 204 countries and regions are divided into five groups: low SDI, low-middle SDI, middle SDI, high-middle SDI, and high SDI.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.3 Study indicators and analysis methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhen analyzing the global disease burden attributed to nrCAVD, the study considered indicators such as incidence, DALY, age-standardized rate (ASR), and percentage change(PC). From 1990 to 2021, we used the regression model to study the time trend of the burden in China, expressed as the AAPC. The 95% uncertainty interval (UI) is defined by the 2.5th and 97.5th percentiles. We also predicted the burden of nrCAVD from 2022 to 2031. Calculations, mapping, and data cleaning were completed using R software (version 4.5.0).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e2.1 Burden of nrCAVD in China\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe burden of nrCAVD in China, measured by the number of cases, continued to increase from 1990 to 2021, including prevalence, incidence, Deaths, and DALYs. In these indicators, the number of men was usually more than that of women. However, the Deaths rate of women was significantly higher than that of men. The total number of incident cases in men increased from 28,056 (95% UI: 23,075, 33,630) in 1990 to 86,026 (95% UI: 66,966, 108,719) in 2021. For women, it increased from 38,402 (95% UI: 31,869, 46,135) in 1990 to 88,489 (95% UI: 70,123, 109,407) in 2021 (Table 1). However, in the past nearly 30 years, the disability-adjusted life years and Deaths rates of both men and women showed a gradually decreasing trend, while the incidence and prevalence rates of both men and women showed an upward trend (Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2 Number of nrCAVD cases by age group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom 1990 to 2021, the number of cases of nrCAVD in various age groups in China, including prevalence, incidence, Deaths, and DALYs is shown in Figure 1. In these indicators, the number of men in incidence, Deaths, and DALYs was usually more than that of women in all age groups under 90 years old. The number of women in the age group after 90 years old was more than that of men, but in terms of prevalence, the number of women after 85 years old was more than that of men. In terms of prevalence, the number of men and women aged 55-80 years old increased significantly, especially in the 65-74 age group. In terms of incidence, the number of women aged 55-79 years old increased significantly, especially in the 65-69 age group: 5,863 in men and 4,766 in women. In terms of Deaths, the Deaths rates of both men and women increased significantly between 65-89 years old, but there was no age-related upward trend. DALYs also indicated that the number of people in the 65-84 age group was the largest, especially in the 70-74 age group (Figure 1D).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Age-standardized incidence/prevalence rates in China\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA comparative analysis of the incidence and prevalence rates of nrCAVD in China by age group and gender from 1990 to 2021 (Figure 2). In all age groups, the prevalence of nrCAVD in both men and women increased significantly, with the most obvious changes observed in the elderly population. Especially after 50 years old, the prevalence of both men and women showed a straight upward trend (Figure 2A). The incidence rate also basically showed an upward trend. In the 70-74 age group, the incidence rates of nrCAVD in both men and women in China reached the first peak, then the incidence rate in women in the 75-79 age group decreased slightly, and the incidence rate in men in the 75-84 age group decreased slightly, but continued to rise gradually after 85 years old (Figure 2B). Figure 3 (A/B) also shows the age-standardized prevalence/incidence rates in China. It can be seen from the figure that the number of nrCAVD cases and the prevalence/incidence rates increased year by year from 1990 to 2021, and the prevalence/incidence rates of male patients were higher than those of female patients from 1990 to 2021.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4 Trends of nrCAVD from 1990 to 2021\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTrends of nrCAVD from 1990 to 2021 was showed in Fig4.In China, from 1990 to 2021, the curve of ASPR of nrCAVD fluctuated greatly and showed an upward trend, indicating that the ASPR of nrCAVD in China increased year by year from 1990 to 2021. The age-standardized incidence rate (ASIR) showed an upward trend although with small fluctuations. The DALYs showed a downward trend after 2000. The ASMR basically fluctuated little, indicating that the Deaths rate was basically stable from 1990 to 2021.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.5 Socio-demographic Index\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe correlation between the incidence rate of nrCAVD and the Socio-demographic Index (SDI) is shown in Figure 5. It can be seen from Figure 5 that the incidence rate of the disease was positively correlated with SDI (p \u0026lt; 0.001, r = 0.854) and showed an upward trend from 1990 to 2021, which indicates that social and economic development affects the incidence rate of nrCAVD. China is approximately in the range of SDI 0.6-0.75, belonging to a high-middle SDI country, which suggests that with the social development in China, the incidence rate of nrCAVD is also increasing year by year, and it may be necessary to strengthen health intervention in the future.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.6 Prediction for China in the next 10 years\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe predicted prevalence and incidence rates of nrCAVD in Chinese men and women by 2031 are shown in Figure 6. The overall ASIR of nrCAVD in China will maintain a relatively stable upward trend; and no significant difference was observed between genders. In the next 10 years, the ASIR of both men and women is expected to show an upward trend (Figures 6A and B). In the next 10 years, significant differences were observed between genders in the ASMR. The ASMR of men will remain basically stable, while the ASMR of women will continue to decline (Figures 6C and D).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBased on the GBD 2021 database, this study systematically analyzed the changing trend of the disease burden of nrCAVD in China from 1990 to 2021 and predicted its development trend in the next 10 years. The results reveal the significant characteristics, gender and age differences, and social demographic influencing factors of the burden of nrCAVD in China, providing important scientific basis for formulating targeted prevention and control strategies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMultiple driving factors for the overall burden change of nrCAVD\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results show that the number of cases of prevalence, incidence, Deaths, and DALYs of nrCAVD in China continued to increase from 1990 to 2021, which is consistent with the background of the rising burden of global non-communicable diseases\u003csup\u003e[12, 13]\u003c/sup\u003e. Population aging is the primary driving factor. With the extension of life expectancy in China, the proportion of the elderly population aged 65 and above is gradually increasing. As a typical age-related disease, the high incidence of nrCAVD in the elderly directly leads to the expansion of the case base. The progress of medical diagnostic technology also plays an important role. In the past 30 years, the popularization of imaging technologies such as computed tomography and cardiac ultrasound has significantly improved the detection rate of nrCAVD, especially with the improvement of diagnostic capabilities in primary medical institutions, many asymptomatic or mild patients can be identified early, which to a certain extent explains the upward trend of incidence and prevalence rates \u003csup\u003e[14-16]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIt is worth noting that while the number of cases increases, the ASMR of both men and women is basically stable, and the DALYs shows a gradually decreasing trend, which reflects the progress of cardiovascular medical services in China. In the past 20 years, China has made significant progress in the standardized diagnosis and treatment of cardiovascular diseases such as coronary heart disease and heart failure, and the management of heart valve diseases has also benefited, including optimizing drug treatment regimens, improving the grasp of surgical indications, and enhancing the quality of postoperative rehabilitation. These factors have jointly reduced the Deaths risk and functional impairment of nrCAVD patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEpidemiological Significance of Age and Gender Differences \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe age distribution characteristics identified in this study provide important targets for the precise prevention and control of nrCAVD. The number of cases in people aged 55 and above increased significantly, especially the 65-74 age group, which became the core population bearing the disease burden. This is closely related to the pathophysiological mechanism of aortic valve calcification. With the increase of age, aortic valve endothelial cell damage, lipid deposition and chronic inflammatory response gradually intensify\u003csup\u003e[14]\u003c/sup\u003e, leading to a linear upward trend in the prevalence rate of people over 50 years old. As the main consumer group of social medical resources, the high incidence and prevalence of people aged 65-74 suggest that this age group should be included in the scope of key screening and intervention . \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn addition, the analysis of gender differences reveals the complex epidemiological characteristics of nrCAVD. Compared with women, men have always faced a heavier burden in the past 30 years\u003csup\u003e[17]\u003c/sup\u003e. Men have more cases in incidence, Deaths and DALYs in all age groups, which may be attributed to the complex interaction of biological, behavioral and social factors. Men are more likely to engage in high-risk behaviors, such as excessive drinking and bad eating habits, and are less likely to seek preventive health care or adopt early risk management strategies. In addition, social norms often discourage men from expressing emotions or managing stress effectively, leading to maladaptive coping mechanisms, such as hostility and substance use, thus exacerbating cardiovascular risks\u003csup\u003e[18]\u003c/sup\u003e. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublic Health Enlightenment Related to Socio-Demographic Index \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe finding that the incidence of nrCAVD is positively correlated with SDI (p \u0026lt; 0.001, r = 0.854) has important policy significance. With the social and economic development of China, the accompanying lifestyle changes (such as increased intake of high-fat/sodium diet and reduced physical activity) have led to the increase in the prevalence of metabolic risk factors such as obesity and hypertension. These factors indirectly increase the risk of nrCAVD by promoting the process of vascular calcification. At the same time, areas with high SDI have more abundant medical resources and stronger diagnostic capabilities, which may also amplify the statistical differences in incidence\u003csup\u003e[19]\u003c/sup\u003e. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis positive correlation challenges the traditional cognition that \u0026quot;social and economic development will inevitably improve health outcomes\u0026quot;, suggesting that we need to be alert to the \u0026quot;developmental growth\u0026quot; of non-communicable disease burden during the economic transition period. With the advancement of China\u0026apos;s urbanization process, residents\u0026apos; dietary structure has changed from the traditional high-fiber diet to high-fat and high-protein diet, and the working mode has changed from manual labor to sedentary office work. These changes occur simultaneously with the improvement of SDI, forming a \u0026quot;risk factor cluster effect\u0026quot; for the incidence of nrCAVD. Therefore, cardiovascular health promotion strategies need to be incorporated into social and economic development plans, and measures such as optimizing dietary guidelines, building sports facilities and implementing workplace health management should be taken to offset the disease risks brought by the improvement of SDI. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrevention and Control Challenges and Responses to Future Trend Prediction \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe prediction result that ASIR will continue to rise in the next 10 years warns that the disease burden of nrCAVD will further increase. The inertia of population aging, the continuous exposure to metabolic risk factors, and the cumulative effect of diseases brought by the extension of life expectancy together constitute the driving force for the rise of incidence. This trend poses a double challenge to the medical system: on the one hand, it is necessary to expand the coverage of disease monitoring and intervention; on the other hand, it is necessary to improve the accessibility of advanced treatment technologies such as valve replacement/repair to meet the growing clinical needs. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe gender-specific prediction results provide a direction for differentiated prevention and control. The contrast between the stable ASMR of men and the continuous decline of ASMR of women may be related to the fact that the accessibility of medical services for women has improved faster than that for men, suggesting that the gender-specific medical resource allocation strategy has achieved initial results. In the future, we should continue to strengthen the cardiovascular health management of women, especially elderly women, and pay attention to the Deaths control of male patients. We can improve the prognosis of male patients by strengthening smoking cessation intervention and optimizing comorbidity management. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations of the Study \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are certain limitations in this study that need to be explained. Firstly, the study relies on data from the GBD 2021 database, and its disease classification and diagnostic criteria may have slight differences from China\u0026apos;s clinical practice, which may affect the accuracy of the absolute values of the results. Secondly, GBD data uses statistical models to estimate uncertainty intervals, and cannot directly calculate the statistical significance of inter-group comparisons, which may limit the accuracy of some difference analyses. Finally, the future trend prediction is based on the deduction of historical data models, and does not include potential influencing factors such as public health emergencies or medical technological breakthroughs, so the actual changes may have deviations. \u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this study provides a comprehensive and effective analysis of the epidemiology of nrCAVD in China so far, and its results have important reference value for health policy formulation. In the future, it may be necessary to formulate multi-level nrCAVD prevention and control strategies. At the primary prevention level, it is necessary to carry out risk factor screening and lifestyle intervention for people over 55 years old; at the secondary prevention level, a precise diagnosis path based on age and gender should be established to improve the early detection rate; at the treatment level, it is necessary to optimize the layout of medical resources to ensure the accessibility of treatment in high-burden areas. By integrating public health policies with clinical practice, we hope to effectively curb the rising trend of nrCAVD burden in the next decade.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate:\u003c/p\u003e\n\u003cp\u003eThe data utilized in this study are publicly accessible from the Global Burden of Disease 2021 database, and no human tissues or samples were involved. Therefore, ethics approval and informed consent are not applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent for publication:\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials:\u003c/p\u003e\n\u003cp\u003ePublicly available data were analyzed in this study. The data can be accessed from the Global Burden of Disease (GBD) 2021 database: https://vizhub.healthdata.org/gbd-results/.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCompeting interests:\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFunding:\u003c/p\u003e\n\u003cp\u003eThe authors did not receive support from any organization for the submitted work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions:\u003c/p\u003e\n\u003cp\u003eJingchang Zhang (ZJC): conception and design of the study; Weihua Shi (SWH) and Zhitao Xie (XZT): data analysis and figure generation; Yisheng Zheng (ZYS) and Weihua Shi (SWH): drafting the initial manuscript; Jingchang Zhang (ZJC): revising the manuscript and final approval. All authors read and approved the final version.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAcknowledgments:\u003c/p\u003e\n\u003cp\u003eWe acknowledge the Global Burden of Diseases database for providing meaningful data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; information:\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLindman B R, Clavel M A, Mathieu P, et al., Calcific aortic stenosis[J]. Nat Rev Dis Primers, 2016, 2: 16006.\u003c/li\u003e\n\u003cli\u003ePeters A S, Duggan J P, Trachiotis G D, et al., Epidemiology of Valvular Heart Disease[J]. Surg Clin North Am, 2022, 102(3): 517-528.\u003c/li\u003e\n\u003cli\u003eGlobal burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019[J]. Lancet, 2020, 396(10258): 1204-1222.\u003c/li\u003e\n\u003cli\u003eArabloo J, Omidi N, Rezapour A, et al., The burden of nonrheumatic valvular heart diseases in Iran between 1990 and 2017: Results from the global burden of disease study 2017[J]. Int J Cardiol Heart Vasc, 2022, 39: 100956.\u003c/li\u003e\n\u003cli\u003eNejad M, Ahmadi N, Mohammadi E, et al., Global and regional burden and quality of care of non-rheumatic valvular heart diseases: a systematic analysis of Global Burden of Disease 1990-2017[J]. Int J Qual Health Care, 2022, 34(2).\u003c/li\u003e\n\u003cli\u003eWilliams M C, Massera D, Moss A J, et al., Prevalence and clinical implications of valvular calcification on coronary computed tomography angiography[J]. Eur Heart J Cardiovasc Imaging, 2021, 22(3): 262-270.\u003c/li\u003e\n\u003cli\u003eCoffey S, Cox B, Williams M J, The prevalence, incidence, progression, and risks of aortic valve sclerosis: a systematic review and meta-analysis[J]. J Am Coll Cardiol, 2014, 63(25 Pt A): 2852-2861.\u003c/li\u003e\n\u003cli\u003eYadgir S, Johnson C O, Aboyans V, et al., Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017[J]. Circulation, 2020, 141(21): 1670-1680.\u003c/li\u003e\n\u003cli\u003eYang C, Xu H, Jia R, et al., Global Burden and Improvement Gap of Non-Rheumatic Calcific Aortic Valve Disease: 1990-2019 Findings from Global Burden of Disease Study 2019[J]. J Clin Med, 2022, 11(22).\u003c/li\u003e\n\u003cli\u003eGlobal incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021[J]. Lancet, 2024, 403(10440): 2133-2161.\u003c/li\u003e\n\u003cli\u003eTian C, Zhang X, Tang H, et al., Disease burden of aortic aneurysm from 1990 to 2021 with a forecast to 2045: insights from the global burden of disease 2021[J]. BMC Public Health, 2025, 25(1): 1829.\u003c/li\u003e\n\u003cli\u003eKong X, Wang M, Jiang Y, Global burden of atrial fibrillation attributable to high body mass index from 1990 to 2021: findings from the Global Burden of Disease Study 2021[J]. BMC Cardiovasc Disord, 2024, 24(1): 542.\u003c/li\u003e\n\u003cli\u003eXu S, Liu Z, Tang M, et al., Burden, risk factors, and projections of ischemic heart disease in China (1990-2021): findings from the 2021 GBD study[J]. Front Cardiovasc Med, 2025, 12: 1549147.\u003c/li\u003e\n\u003cli\u003eLindman B R, Sukul D, Dweck M R, et al., Evaluating Medical Therapy for Calcific Aortic Stenosis: JACC State-of-the-Art Review[J]. J Am Coll Cardiol, 2021, 78(23): 2354-2376.\u003c/li\u003e\n\u003cli\u003eDoris M K, Jenkins W, Robson P, et al., Computed tomography aortic valve calcium scoring for the assessment of aortic stenosis progression[J]. Heart, 2020, 106(24): 1906-1913.\u003c/li\u003e\n\u003cli\u003eShen M, Tastet L, Capoulade R, et al., Effect of bicuspid aortic valve phenotype on progression of aortic stenosis[J]. Eur Heart J Cardiovasc Imaging, 2020, 21(7): 727-734.\u003c/li\u003e\n\u003cli\u003eRegitz-Zagrosek V, Gebhard C, Gender medicine: effects of sex and gender on cardiovascular disease manifestation and outcomes[J]. Nat Rev Cardiol, 2023, 20(4): 236-247.\u003c/li\u003e\n\u003cli\u003eO\u0026apos;neil A, Scovelle A J, Milner A J, et al., Gender/Sex as a Social Determinant of Cardiovascular Risk[J]. Circulation, 2018, 137(8): 854-864.\u003c/li\u003e\n\u003cli\u003eChen H Y, Engert J C, Thanassoulis G, Risk factors for valvular calcification[J]. Curr Opin Endocrinol Diabetes Obes, 2019, 26(2): 96-102. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Non-rheumatic calcific aortic valve disease (nrCAVD), disease burden, Incidence, Prevalence, The Global Burden of Disease (GBD)","lastPublishedDoi":"10.21203/rs.3.rs-7350266/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7350266/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eNon-rheumatic calcific aortic valve disease(nrCAVD) is one of the causes of cardiovascular disease-related deaths and poses a significant challenge to healthcare. Understanding the burden of non-rheumatic calcific aortic valve disease is crucial for health policy formulation and healthcare resource allocation. This study aims to assess the burden, trends, and inequalities of non-rheumatic calcific aortic valve disease in China and predict future trends.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eData on non-rheumatic calcific aortic valve disease-related Deaths, disability-adjusted life years (DALYs), age-standardized Deaths rate (ASMR), age-standardized incidence rate (ASIR), and their average annual percentage change (AAPC) were obtained from the The Global Burden of Disease (GBD) 2021 database. Subsequently, the burden of non-rheumatic calcific aortic valve disease in 204 countries, including China, from 1990 to 2021 was analyzed, stratified by gender and Socio-demographic Index (SDI), and further projected to 2031.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe number of cases of prevalence, incidence, Deaths, and DALYs of nrCAVD in China continued to increase from 1990 to 2021, with men having higher numbers than women in most indicators. Among all age groups, the number of cases was significantly higher in people aged 55 and above, especially in the 65\u0026ndash;74 age group. The ASIRand age-standardized prevalence rate (ASPR) showed an upward trend, while the age-standardized Deaths rate (ASMR) and DALY rate showed a stable or downward trend. The incidence rate was positively correlated with SDI. The ASIR in China is expected to continue to rise in the next 10 years, and the ASMR in women will continue to decline.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThe burden of nrCAVD in China continued to increase from 1990 to 2021, which is a health problem that cannot be ignored, and showed significant age and gender differences. In the next 10 years, the burden of nrCAVD in China will continue to increase. Effective and targeted strategies are needed to prevent and manage nrCAVD in this population to reduce the overall burden.\u003c/p\u003e","manuscriptTitle":"Burden of Non-Rheumatic Calcific Aortic Valve Disease in China from 1990 to 2021 and Projections to 2031: Insights from the Global Burden of Disease 2021","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-15 02:18:50","doi":"10.21203/rs.3.rs-7350266/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"67e93ac3-3ad8-48db-87c0-06ae066a93c0","owner":[],"postedDate":"October 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-19T13:53:57+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-15 02:18:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7350266","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7350266","identity":"rs-7350266","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}