Trends and disparities in risk factors of ischemic stroke among young and middle-aged adults (20-54 years) globally from 1990 to 2021: A population-based study.

This study aimed to analyze the global disease burden, temporal trends of ischemic stroke (IS) in adults aged 20 to 54 years (1990-2021), and temporal disparities in attributable risk factors. Using Global Burden of Disease 2021 data, we extracted estimates with 95% uncertainty intervals for IS prevalence, incidence, mortality, and disability-adjusted life years (DALYs) among adults aged 20 to 54 years. Trends were assessed globally and locally, stratified by sex and age subgroup. Age-period-cohort models estimated age, period, and cohort effects on prevalence and incidence, and population-attributable fractions were used to evaluate temporal changes in risk factor contributions. In 2021, adults aged 20 to 54 years had 16,301,644 prevalent IS cases and 1,324,743 incident cases worldwide, with rates of 432.46 and 35.14 per 100,000 population, respectively. IS caused 105,859 deaths and 6,967,488 DALYs, corresponding to mortality and DALY rates of 2.81 and 184.84 per 100,000 population. From 1990 to 2021, prevalence and incidence increased, whereas mortality and DALYs declined. Prevalence was higher among females, while incidence, mortality, and DALYs were higher among males. Marked heterogeneity was observed across socio-demographic index regions, Global Burden of Disease, Injuries, and Risk Factors Study regions, and countries. Greater burdens were concentrated in high-middle socio-demographic index regions, Eastern Europe, Central Asia, and parts of North Africa and the Middle East, while East Asia experienced the largest increase in incidence. Joinpoint regression showed fluctuating but overall increasing trends in prevalence and incidence, alongside sustained declines in mortality and DALY rates after the early 2000s. Age-period-cohort analysis indicated that the risks of IS prevalence and incidence increased with age, particularly after 35 years. Period effects peaked in 2017 to 2021, whereas cohort effects declined progressively from the 1942 to 1946 to the 1997 to 2001 birth cohorts. High low-density lipoprotein cholesterol, high systolic blood pressure, particulate matter pollution, smoking, and high body mass index were the leading contributors to IS-related DALYs. From 1990 to 2021, the population-attributable fractions of particulate matter pollution, smoking, and high-sodium diet decreased, whereas those of metabolic risks increased, particularly high systolic blood pressure and high body mass index. IS imposes a heavy global burden on young and middle-aged adults with an upward trend driven by metabolic, environmental, and lifestyle factors. Early screening and targeted risk management are critical.