Supplementary Material for: Trends and potential risk factors of lower extremity peripheral arterial disease: results from the Global Burden of Disease Study 2021

Background: Lower extremity peripheral arterial disease (LEPAD), causing reduced limb blood flow and significant morbidity, is a major global health concern. Understanding its burden and attributable risk factors is crucial for public health planning. Aim: To quantify the global, regional, and national burden of LEPAD and disability-adjusted life-years (DALYs) lost attributable to key risk factors from 1990 to 2021. Design & Methods: This analysis utilized data from the Global Burden of Disease Study 2021. It employed multi-source data and advanced statistical modeling to estimate LEPAD prevalence, incidence, mortality, DALYs, and risk factor attribution across 204 countries and territories. Results: In 2021, there were 113.7 million LEPAD survivors and 10.0 million new cases globally, with females comprising 67.0% of prevalent cases. LEPAD caused 67,000 deaths and 1.5 million DALYs. Six key risk factors accounted for most attributable DALYs: high fasting plasma glucose (36.06%), kidney dysfunction (28.64%), smoking (25.04%), hypertension (21.72%), lead exposure (15.05%), and high body-mass index (BMI, 8.75%). Low- and middle-income countries bore a disproportionate burden (68.8% of incident cases, 60.9% of DALYs). While global incidence and mortality modestly declined since 1990, increases occurred in lower-middle and low Socio-Demographic Index regions. Conclusions: LEPAD imposes a substantial global burden, disproportionately affecting females and populations in low-resource settings. Modifiable metabolic (glucose, kidney function, BMI, hypertension) and behavioral (smoking) risks dominate. Targeted interventions, especially in high-burden regions experiencing increasing trends, are urgently needed to mitigate LEPAD-related morbidity and mortality. Future research should focus on effective interventions and healthcare access barriers.