Impact of Conventional Stroke Risk Factors on Early- and Late-Onset Ischemic Stroke: A Mendelian Randomization Study

• DOI: 10.1161/strokeaha.124.048015
• Publication Date: 2025-02-24T19:00:31Z
• Authors: Kevin T.K. Nguyen; Huichun Xu; Brady J. Gaynor; Patrick F. McArdle; Timothy D. O’Connor; James A. Perry; Bradford B. Worrall; Rainer Malik; Giorgio B. Boncor...; Sally N. Adebamowo; Ramin Zand; John W. Cole; Steven J. Kittner; Braxton D. Mitchell
• Keywords: Mendelian Randomization; Stroke

BACKGROUND: Stroke incidence is decreasing in older ages but increasing young adults. These divergent trends are at least partially attributable not only to diverging stroke risk factors may also be due differences the impact of different ages. To address this latter possibility, we used Mendelian randomization assess association between early-onset ischemic ([EOS]; onset 18–59 years) and late-onset ([LOS]; ≥60 years). METHODS: We identified genetic variants from GWAS Catalog for use as instrumental variables proxy conventional then estimated effects these on younger individuals UK Biobank. estimates estimate causal EOS (n=6728 cases) LOS (n=9272) cases SiGN (Stroke Genetic Network) EOSC (Early-Onset Consortium). Lastly, compared odds ratios LOS, stratified by TOAST (Trial ORG 10172 Acute Treatment) subtypes, determine if could attributed subtype distributions. RESULTS: was associated with higher levels body mass index, blood pressure, type 2 diabetes, lower HDL (high-density lipoprotein) cholesterol (all P ≤0.002), whereas systolic pressure ( =0.0001). The effect index significantly stronger than (odds ratio, 1.26 versus 1.03; =0.008). After subtype-stratified analysis, difference sizes diminished no longer significant. CONCLUSIONS: results support a relationship LOS. Interventions that target traits reduce risk.