<b>Global Burden, Socio-demographic Index Correlations, and Mendelian Randomization Analysis of Risk Factors in Ischemic Heart Disease: A Comprehensive Study Based on GBD 2021 Data</b><b></b>

Objective Based on GBD 2021 data, to analyze the global trends in the burden of ischemic heart disease (IHD) from 1990 to 2021, its association with the Socio-demographic Index (SDI), and to evaluate the causal effects of risk factors. Methods IHD epidemiology and risk factor data from 204 countries and territories globally were extracted. Age-standardized rates (ASR) and average annual percentage change (AAPC) were calculated. Joinpoint regression, Mendelian randomization (MR), and ARIMA models were employed for trend analysis, causal inference, and prediction. Results Globally, the age-standardized incidence, mortality, and DALY rates of IHD declined (AAPC: -0.379, -1.200, and -1.083, respectively), while the prevalence rate slightly increased (AAPC: 0.040).North Africa, the Middle East, and Central Asia had the heaviest burden, while low-middle SDI regions had the highest incidence and prevalence rates.MR showed that smoking, high BMI, high waist-to-hip ratio, and high triglycerides increase IHD risk, while LDL-C had a protective effect (OR=0.996, p=0.006).Predictions indicate that the disease burden among females will continue to worsen in the future. Conclusion The burden of IHD is closely associated with SDI, necessitating targeted prevention and control strategies for low-middle SDI regions and addressing gender disparities.