Global patterns and risk factors of early and late-onset ischemic stroke: a population-based analysis across 204 countries and territories

Li Li^1*Hongwei Liu^2,3Minheng Zhang⁴Haixia Fan⁵Miaomiao Hou⁶

• ¹Shanxi Provincial People's Hospital, Taiyuan, China
• ²Xuanwu Hospital of Capital Medical University, Beijing, China
• ³Taiyuan City Central Hospital, The Ninth Clinical Medical College of Shanxi Medical University, Taiyuan, China
• ⁴The First People's Hospital of Jinzhong, Jinzhong, China
• ⁵Fifth Hospital of Shanxi Medical University, Taiyuan, China
• ⁶Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Tongji Shanxi Hospital, Taiyuan, China

Background and purpose Globally, ischemic stroke remains a major cause of mortality and loss of disability-adjusted life years (DALYs). Notably, the incidence of ischemic stroke is decreasing among older adults but rising in younger populations. Historically, most studies have analyzed early-onset and late-onset ischemic stroke as separate entities, with limited attention to their potential overlap or shared spatial patterns. To address this research gap, we investigated the global co-occurrence patterns of these two stroke subtypes, mapped their spatial distributions, and identified the risk factors associated with each. Methods We analyzed data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, extracting incidence rates of early-and late-onset ischemic stroke, as well as exposure levels of 26 risk factors, across 204 countries and territories. We stratified the incidence distributions of the two stroke subtypes into quartiles to define their co-occurrence patterns, classifying regions into three categories: consistent incidence (of both subtypes), early-onset dominant, and late-onset dominant. To identify associations between risk factors and stroke subtypes, we used ensemble learning and negative binomial regression. We also estimated population attributable fractions (PAFs) to quantify the proportion of stroke burden attributable to each risk factor. Results Of the 204 regions evaluated, 104 had concordant incidence rates for the two stroke subtypes (i.e., similar quartile rankings for early-and late-onset stroke), while 52 were classified as early-onset dominant and 48 as late-onset dominant. For early-onset ischemic stroke, significant associated risk factors included elevated systolic blood pressure, active tobacco smoking, impaired kidney function, and high ambient temperature. For late-onset ischemic stroke, the key associated risk factors were elevated systolic blood pressure and secondhand smoke exposure. Collectively, these risk factors contributed to 18.26% of the global burden of early-onset ischemic stroke (PAF: 18.26%) and 16.99% of the global burden of late-onset ischemic stroke (PAF: 16.99%). Conclusions This study is the first to integrate analyses of global co-occurrence patterns of early-and late-onset ischemic stroke with their risk factors. The findings highlight the need for more rigorous research to validate causal links between these factors and each stroke subtype, thereby informing targeted prevention strategies across age groups.