Abstract
INTRODUCTION: Ischemic heart disease (IHD), particularly myocardial infarction (MI), ranks as a leading cause of death globally. While studies have associated physical activity (PA) with a decreased risk of MI, the extent of the global IHD burden attributable to LPA and the impact of PA on MI remain uncertain. METHODS: This study accessed data from the Global Burden of Disease (GBD) 2021 and employed Mendelian randomization (MR) to evaluate these relationships. We analyzed the global age-standardized death rate (ASDR) for IHD attributable to LPA from 1990 to 2021. Additionally, we utilized the MR analysis to assess the relationship between PA and MI, using relevant data from GWAS databases. Within this framework, PA is defined based on the types of PA in the last 4 weeks, including other exercises such as swimming, cycling, keep fit, and bowling. RESULTS: From 1990 to 2021, the global ASDR for IHD attributable to LPA exhibited an upward trend (estimated annual percentage change [EAPC] = 0.70, 95% CI: 0.61 to 0.79). The MR analysis revealed an inverse association between PA and MI (IVW method: OR = 0.17, 95% CI: 0.04 to 0.68, P = 0.01). However, significant heterogeneity was observed among the instrumental variables (Cochran’s Q = 18.25, P = 0.01), indicating potential instability in the effect estimates. CONCLUSIONS: This study highlights that LPA contributes significantly to the global burden of IHD, with an increasing trend in related mortality from 1990 to 2021. From a genetic perspective, MR analysis indicates that PA reduce the risk of MI, though further research using larger sample sizes and more robust genetic tools is required to definitively establish this relationship. Globally, promoting PA is essential for reducing the burden of disease and enhancing cardiovascular health. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-025-05453-6.