Degenerative mitral valve disease (DMVD) [1, 2] is characterized by degenerative changes in the connective tissue of the mitral valve with age, such as fibrotic degeneration and calcium deposition, resulting in mitral valve dysfunction causing hemodynamic changes. Mitral valve calcification, regurgitation, and stenosis can be secondary to abnormal heart load function, arrhythmias, heart failure, etc. Degenerative mitral valve disease lacks obvious clinical symptoms in theearly stages. Nevertheless, once combined with moderate-severe valve stenosis, incomplete closure, atrial fibrillation, or heart failure, it brings significant challenges for treatment, poor prognosis, and significantly shortened life expectancy [3, 4]. It has been calculated that the number of DMVD patients worldwide was approximately 24.23 million in 2019, and these prevalence numbers are expected to increase further. Moreover, the development of mitral valve disease is closely related to socioeconomic and cultural levels, with degenerative disease being the most common cause of DMVD in developed Western countries [5]. In contrast, mitral valve disease due to rheumatic pathology is more common in low-income countries [6]. With the rapid economic development of countries, the increasing aging of the population, and the rising incidence of chronic heart diseases, degenerative lesions will replace rheumatic lesions and gradually become the leading cause of mitral valve lesions [7]. For global health systems, this imposes an enormous public health burden and a noticeable increase in the consumption of social health resources and costs. Therefore, global DMVD prevention and control is quite critical. However, no studies have updated the epidemiological changes of DMVD since 2019, and the 2017 epidemiological studies did not deeply penetrate the effect of different regions, countries, age, and sexes [8].

This study relies on data from the Global Study of Diseases, Injuries, and Risk Factors 2019 (GBD2019) to provide a standardized and detailed analysis of the burden of DMVD [9]. Evaluating the trends of DMVD at the global, regional and national levels can help individual countries develop effective management strategies, rational allocation of medical resources to improve the outcomes of DMVD, and enhance patients’ quality of life.

This study provides a detailed analysis of four epidemiological indicators of global DMVD, namely incidence, prevalence, deaths, and DALYs from 1990–2019, based on GBD 2019 data. The study shows that the burden of DMVD is gradually increasing globally. Over the past 30 years, the incidences increased by 57.16%, the prevalence increased by 70.41%, the deaths increased by 54.55%, and the DALYs increased by 41.05%. In 2019, the number of new cases of DMVD was 1.064 million, the prevalence was about 24.229 million, the deaths were about 0.034 million, and the DALYs were about 0.883 million. It is comforting to note that the ASRs for all outcomes are exhibiting a decline, indicating a reduction in the real incidence of DMVD when adjusted for age demographics. With the aging of the global population, there is an increase in the absolute cases of DMVD. However, this increase may not be apparent in the ASR, possibly due to shifts in demographic patterns, enhancements in healthcare, and heightened awareness of health among the population. Based on the BAPC model predictions, the total incidence of DMVD during 2030 in females will be 0.72 million with an ASIR of 15.59 per 100,000, and in males, 0.51 million with an ASIR of 11.75 per 100,000 and a total incidence of 1.23 million with an ASIR of 14.03 per 100,000. The growing burden on public health necessitates considering factors such as population dynamics, the quality of health services, the efficacy of preventive measures, and socio-economic influences when analyzing disease burden and devising public health strategies.

Observing global patterns in DMVD epidemiology reveals that the prevalence rate of DMVD is progressively decreasing in the majority of high-income countries, serving as a model for other nations. However, it is concerning that the prevalence of DMVD is rapidly rising across Asia. This trend could be associated with the region’s swift economic growth in recent years, the significant aging of the population in most Asian countries, and the shift in the cause of valve disease from rheumatic factors to degenerative diseases among the elderly [8, 16]. In addition, due to the gradual westernization of the Asian diet and the increasing incidence of coronary heart disease [17], non-rheumatic ischemic mitral regurgitation disease will gradually increase with the increase of coronary heart disease [18]. It will be diagnosed as DMVD on ultrasound, leading to a gradual increase in the prevalence of DMVD. When pinpointed to countries, both in terms of the number of prevalence and ASPR, countries with a greater burden of DMVD have significant aging populations, most notably Japan, Italy, and the United States, with high numbers of prevalence and ASPR. The study also found an interesting phenomenon that countries in the Middle East have incredibly high growth rates in terms of prevalence. Unlike other countries with aging populations, aging in the Middle East is not severe [19, 20]. The dramatic increase in prevalence in the Middle East can be attributed to the high economic development in recent years, which has led to a significant increase in the availability of medical resources and a significant increase in the detection of DMVD. In addition, the population in the Middle East is changing its diet to one high in fat, sugar, salt and cholesterol, and the prevalence of hypertension and diabetes is gradually increasing [21]. At the same time, degenerative mitral valve disease is closely related to diabetes, hypertension, and coronary heart disease [18], all of which contribute to the rapid increase in the prevalence of DMVD in the Middle East. We can therefore target increased healthcare spending on diseases such as coronary heart disease, diabetes, and hypertension, combined with some of the more advanced public health approaches in terms of prevention and treatment policies in European countries.

There are also significant sex and age differences in the disease burden of DMVD. The rate of prevalence, deaths, and DLAYs of DMVD gradually increased with increasing age. However, the incidence decreases progressively after 65 years, which has not been observed in the past. This could be because co-morbidities with common risk factors for DMVD lead patients to seek medical care before age 65, the incidence of which gradually decreases after age 65. The severe burden of DMVD is concentrated in groups after age 55, and aging is a crucial factor in constituting DMVD. With aging, the tissues of the mitral valve gradually harden and lose their elasticity, becoming susceptible to long-term cardiac stress, leading to the development of DMVD. Studies show that the declining metabolic rate in the elderly may lead to glucose and lipid metabolic disorders, which may increase the risk of mitral valve disease, and hypertension is a significant risk factor for DMVD [22]. As population aging progresses, the number of people with hypertension will also increase, thus increasing the risk of developing DMVD [23]. The overall burden is significantly higher for females compared to males at almost all ages in 2019, with this difference being particularly pronounced in the postmenopausal period. Moreover, in various SDI regions, females also bear a higher burden. Some studies suggest that estrogen changes may lead to changes in the cardiovascular system, including decreased protection of vascular endothelial cells, decreased oxidoreductase activity, and increased inflammation [24], which may lead to thinning and stiffening of the mitral valve, thereby increasing the risk of DMVD in females [25]. Studies have found that the physiology of the heart is different in females and males. The mitral valve in females is usually smaller than in males and is more susceptible to stress, resulting in degenerative changes such as calcification, stiffening, and loss of elasticity [26]. In addition, researchers have found that episodes of autoimmune disease are associated with mitral valve disease and that females are more likely than males to develop autoimmune diseases such as systemic lupus erythematosus, which can cause heart valve damage [27, 28]. However, these burdens are reflected in the number of diseases and the considerable sex inequalities in surgical treatment. The males dominate surgical treatment [29]. Notably, the threshold values indicating the size of the heart requiring surgery were established primarily using the male population [30]. At the same time, fewer females met the recommended surgical criteria for ventricular enlargement in mitral valve disease. Furthermore, economic circumstances partially underpin this issue, as the diminished quality of life and lowered productivity in females with DMVD may exacerbate the income disparity between males and females. This widening gap could lead to decreased access to healthcare, which might explain the rise in female mortality and DALYs associated with DMVD. Consequently, future research should concentrate on exploring sex-specific traits in clinical presentations and outcomes among patients who receive suitable interventions, aiming to eradicate sex inequalities in this context.

The impact of DMVD differs among areas characterized by diverse levels of economic and social development. According to the study, all regions experienced an increase in the burden of DMVD, though the extent of this increase varied. Still, overall deaths and DALYs showed a decreasing trend in high and high-middle SDI regions and were lower in low SDI regions than in high SDI regions. This may be related to the comparative adequacy of medical resources and services in developed regions, the generally higher level of education and health insurance coverage of people, and the more developed infrastructure [7]. In further analysis of the relationship between ASIR, ASDR, EAPC, and HDI, during 1990–2019, EAPC of ASDR was significantly negatively correlated with baseline ASDR, while EAPC of ASIR with was positively correlated with baseline ASIR (45/100,000). For countries with high ASR in 1990, DMVD was more likely to decrease, and possible explanations for this result are: (1) the higher the baseline ASR, the more significant the change in EAPC, (2) countries with high ASR are better able to prioritize DMVD as a high priority for disease prevention programs. In observing the relationship between ASIR, ASDR, EAPC, and HDI, ASIR tended to increase gradually with increasing HDI. In countries with a higher HDI, there was a rise in the ASIR of DMVD. Concurrently, the EAPC of the ASDR was notably lower in regions with high HDI compared to middle and low HDI countries. Moreover, regions with a higher HDI observed a decrease in the ASDR of DMVD. This is consistent with the phenomena we observed in the high and high-middle SDI regions, which, side-by-side, corroborates our study. Regarding DALYs, aging is the most impactful driver in high and high-middle SDI regions. According to the trend of DALYs, it can be observed that epidemiological changes play a driving role in low, low-middle and middle SDI regions, which is an unfavorable phenomenon. Conversely, epidemiological changes negatively affected high and high-middle SDI regions, suggesting they have made some progress in combating DMVD. Studies on disease severity have shown that DMVD is a significantly higher threat to human health in less economically developed regions than in developed regions, which is a severe problem. Consequently, it is imperative for national and regional health departments to proactively explore health and DMVD management strategies that are tailored to their respective economic and health circumstances.

DMVD remains a significant public health problem that cannot be ignored, despite a decreasing trend in the ASR of global incidence, prevalence, deaths and DALYs from 1990 to 2019. However, we note an adverse development trend in countries with low SDI and seriously aging societies, and sex inequality is particularly prominent. This indicates the need to reposition current prevention and treatment strategies, with some national health administrations developing corresponding strategies for preventing an increase in DMVD based on local health, education, economic conditions, sex differences, and age differences.

DMVD, Non-rheumatic degenerative mitral valve disease; GBD2019, Global Burden of Disease, Injury, and Risk Factor Study 2019; UI, uncertainty interval; SDI, Socio-Demographic Index; DALYs, disability-adjusted life years; ASR, age-standardized rate; ASDR, age-standardized DALYs rate; ASIR, age-standardized incidence rate; ASPR, age-standardized prevalence rates; ICD, International Classification of Diseases; EAPC, estimated annual percentage change; CI, confidence interval; BAPC, Bayesian Age-Period-Cohort; HDI, Human development index.

All data were obtained from the open public database: Global Health Data Exchange (GHDx) query tool (http://ghdx.healthdata.org/gbd-results-tool).

CMW, SJY, and WR conceived, designed, and planned the study. CMW, MLS, and HC acquired GL, and PL interpreted the results. CMW and SJY drafted the manuscript. WR, CMW, HC, GL, MLS, PL and SJY contributed to the critical revision of the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Ethics approval was exempted by the Ethics Committee of Southwest Medical University because the GBD is a publicly available database, and all participants’ data were anonymous.

Thank you for the cooperation of the authors.

This study was supported by projects from Sichuan Administration of traditional Chinese Medicine (Number: 2020HJZX004, 2023MS379, 2021ZD05), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (Number: ZYYCXTD-C-202207), and Innovation Team of Sichuan Provincial Administration of Traditional Chinese Medicine (Number: 2022C007).

The authors declare no conflict of interest.