Global, regional, and national burden of non-rheumatic calcific aortic valve disease from 1990 to 2021, with projections of incidence to 2050: a systematic analysis of the global burden of disease study 2021 and Mendelian randomization analysis

Background Non-rheumatic calcific aortic valve disease (NRCAVD) is a growing global health concern; however, comprehensive insights into its burden remain limited. This study aimed to analyse the global burden, trends, and determinants of NRCAVD from 1990 to 2021 and to project future trends. Methods Data from the Global Burden of Disease 2021 were used to calculate age-standardized rates of prevalence, incidence, mortality, and disability-adjusted life-years (DALYs). Decomposition analysis, two-sample Mendelian randomization (MR), and the autoregressive integrated moving average (ARIMA) model were applied to explore the influencing factors, causal associations, and future projections. Results The prevalence and incidence of NRCAVD increased globally between 1990 and 2021, with higher burdens in Western Europe and North America. Mortality and DALY rates decreased despite rising absolute numbers. The burden varied according to socio-demographic index (SDI), sex, and age. Aging and population growth drove the increase in DALYs, while body mass index was identified as a causal risk factor. Projections suggest an increasing prevalence in males and stable mortality rates by 2050. Conclusion NRCAVD burden has grown and exhibits diverse trends. Targeted interventions, particularly for high-risk groups, are required to mitigate future disease effects.