AUTHOR=Tang LuYi , Yang BoWen , Li PeiWen , Chen YingQi , Liu Yi , Wang Ting , Ye Xiaohan TITLE=High systolic blood pressure and stroke: evidence from the NHANES 1999–2023 and global burden of disease 2021 JOURNAL=Experimental Biology and Medicine VOLUME=Volume 251 - 2026 YEAR=2026 URL=https://www.ebm-journal.org/journals/experimental-biology-and-medicine/articles/10.3389/ebm.2026.10868 DOI=10.3389/ebm.2026.10868 ISSN=1535-3699 ABSTRACT=High systolic blood pressure (HSBP) is a major modifiable risk factor for stroke, but trends in disease burden and causal associations related to HSBP in the United States require further investigation using multidimensional approaches. This study aims to elucidate this relationship by utilizing data from the Global Burden of Disease (GBD) database, the National Health and Nutrition Examination Survey (NHANES). This study integrated data from the GBD 2021 database and the NHANES. The GBD data provided macro-level estimates of stroke-related mortality and disability-adjusted life years (DALYs) attributable to various risk factors within the United States. By employing multivariable logistic regression models on individual-level NHANES data, the study assessed the association between HSBP history and stroke risk after adjusting for multiple confounding factors. GBD analysis revealed HSBP as the leading risk factor for U.S. stroke burden in 2021, with an increasing attributable burden since 2010, particularly among the elderly and women. NHANES analysis showed that HSBP significantly increased the risk of stroke (fully adjusted OR = 1.33, 95% CI: 1.17–1.51). Elevated SBP was additionally associated with increased all-cause mortality risk in stroke survivors (HR = 1.01). A novel U-shaped relationship emerged: stroke risk decreased below an SBP of 100 mmHg but increased sharply above this threshold. HSBP is the core driver and modifiable risk factor behind the persistently increasing stroke burden in the United States. The findings of this study highlight the critical importance of HSBP in stroke prevention and management.