Ischaemic heart disease remains the leading cause of death worldwide, with myocardial infarction accounting for a substantial proportion of this burden. Although physical activity is widely promoted as a cornerstone of cardiovascular prevention, the scale of heart disease mortality attributable to low physical activity at a global level has been less clearly defined. A new study combining Global Burden of Disease (GBD) data with genetic analysis now offers a comprehensive view of how inactivity contributes to myocardial infarction risk worldwide.
Using data spanning more than three decades, the researchers examined trends in ischaemic heart disease mortality attributable to low physical activity between 1990 and 2021, alongside a Mendelian randomization analysis to explore whether physical activity has a causal effect on myocardial infarction risk.
Rising Mortality Attributable to Inactivity
Analysis of GBD 2021 data revealed a concerning upward trend in the global age-standardized death rate for ischaemic heart disease linked to low physical activity. Between 1990 and 2021, mortality attributable to insufficient activity increased steadily, with an estimated annual percentage change of 0.70%. This suggests that, despite growing awareness of the benefits of exercise, physical inactivity continues to make a significant and increasing contribution to cardiovascular mortality worldwide.
These findings highlight the persistent gap between public health recommendations and real-world behaviour, particularly in the context of ageing populations, urbanisation, and increasingly sedentary lifestyles.
Genetic Evidence Supports a Protective Role
To strengthen causal inference, the researchers complemented epidemiological trends with Mendelian randomization analysis using genome-wide association study data. Physical activity was defined broadly, encompassing exercise undertaken in the preceding four weeks, such as swimming, cycling, fitness activities, and recreational sports.
The genetic analysis demonstrated an inverse association between physical activity and myocardial infarction risk. Individuals genetically predisposed to higher levels of physical activity had a substantially lower risk of myocardial infarction, with an odds ratio of 0.17. This finding supports the hypothesis that physical activity itself, rather than confounding lifestyle factors, plays a protective role in reducing heart attack risk.
However, the authors noted significant heterogeneity among the genetic instruments used, suggesting some instability in the effect estimates. This underscores the complexity of capturing physical activity through genetic proxies and the need for more refined tools in future research.
Implications for Cardiovascular Prevention
Together, these findings reinforce physical inactivity as a major and growing contributor to the global burden of ischaemic heart disease. At the same time, genetic evidence lends support to the protective role of physical activity against myocardial infarction. The authors conclude that strengthening global strategies to promote physical activity remains essential, while calling for larger genetic studies to further clarify the causal relationship and inform more targeted prevention efforts.
Reference
Guo Y et al. Physical activity and myocardial infarction risk: insights from the global burden of disease study 1990–2021 and Mendelian randomization analysis. BMC Cardiovasc Disord. 2025;DOI: 10.1186/s12872-025-05453-6.
