Sex differences in the association between plasma branched-chain amino acids and risk of ischemic stroke: A nested case-control study from China

Objectives: The aim of this study was to investigate the prospective associations between plasma branched-chain amino acids (BCAAs) and the risk of ischemic stroke in men and women. Methods: We conducted a nested case-control study within a community-based cohort in China. The cohort consisted of 15,926 participants in 2013-2018. A total of 321 ischemic stroke cases were identified during the follow up and individually matched with 321 controls by date of birth (+/- 1 year) and sex. Females accounted for 55.8% (n = 358, 179 cases vs 179 controls) of the study population. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between plasma BCAAs and ischemic stroke risk by conditional logistic regression. Results: Elevated plasma isoleucine was associated with a higher risk of ischemic stroke in women. The OR for the highest compared to the lowest quartile was 2.22 (95% CI: 1.11-4.44, P trend = 0.005) after adjustment for body mass index, education attainment, smoking, hypertension, renal function, menopause and physical activity. A similar association was found for total BCAAs (adjusted OR = 2.03, 95% CI: 1.05-3.95, P trend = 0.04). In contrast, no significant association of plasma BCAAs with ischemic stroke risk was observed in men. Conclusions: Plasma isoleucine and total BCAAs were significantly associated with ischemic stroke risk in women, but not in men, highlighting sex differences in BCAAs metabolism and stroke pathogenesis.