Abstract

Background: Postmenopausal hormone therapy has been shown to increase stroke risk. It is unclear whether high exposure to pytoestrogens, such as soy isoflavones, may confer the same risk of stroke. Objective: To examine associations of urinary isoflavonoids, which reflect isoflavones intake, absorption, and metabolism, with risk of ischemic stroke in postmenopausal Chinese women. Design: A nested case-control study. Method: We identified 1438 incident cases of ischemic stroke druing 1997-2010 and individually matched them to 1438 controls on age, date and time of sample collection, time since last meal, and recent use of antibiotics. All subjects were postmenopausal women who had never used hormone therapy and had no history of CVD or cancer at baseline. Seven isoflavonoids were measured by LC-MS and standardized by urinary creatinine. Results: We found no significant difference between case-control pairs in mean levels of total or individual urinary isoflavonoids, including 3 parent compounds (daidzein, genistein, and glycitein) and 4 metabolites derived from intestinal bacteria (dihydrogenistein, dihydrodaidzein, O-desmethylangolensin, and equol). Multivariate analyses revealed that women in the highest quintile of equol concentration had a lower risk of ischemic stroke (OR=0.77, 95%CI=0.60-0.98). Analyses stratified by equol producing status showed a significant inverse association between isoflavone bacterial metabolites and stroke risk in equol producers (31.8% of the study population, OR=0.40 across extreme quartiles, 95%CI=0.18-0.87, Ptrend=0.002), but no association in equol non-producers. Conclusion: Overall, this large prospective study suggests that urinary isoflavonoids are not associated with risk of ischemic stroke in postmenopausal Chinese women. High level of bacteria-derived metabolites of isoflavones, however, was associated with a reduced risk in equol producers, suggesting a possible interaction between gut microbiome and soy foods in the pathogenesis of ischemic stroke.

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