Elevated uric acid and impaired triglyceride metabolism predict mortality in women after ischemic stroke

Sex-specific differences in the impact of uric acid (UA) on ischemic stroke outcomes remain unclear. This study investigated the prognostic role of UA levels, focusing on sex-related differences and their underlying mechanisms. Between October 2018 and July 2019, we recruited acute ischemic stroke patients from the National University Hospital, Singapore, and age-matched healthy controls; stroke patients were followed for up to 80 months for all-cause mortality. UA levels were measured at baseline and, for a subset of participants, again at three months. Additional hormonal and stroke-related biomarkers were also analyzed, and proteomic analyses were undertaken to explore UA-related molecular pathways. A total of 765 ischemic stroke patients (mean age, 59.7 years; 28 % women) were followed for a median of 50 months. Elevated UA levels were strongly associated with reduced survival in women (log-rank p = 0.011) but not in men. Women in the highest quartile of UA (>370 μmol/l) showed a significantly increased risk of mortality (adjusted HR 9.56, 95 % CI 1.17-78.3). Comparative biomarker evaluation indicated rising NT-pro-brain natriuretic peptide (NT-proBNP) and triglycerides across UA quartiles in women (all p<0.05). Women who survived demonstrated higher UA levels at month 3 than non-survivors (p = 0.024). Proteomic analyses revealed significant alterations in triglyceride metabolism and catabolism pathways among women in the highest UA quartile. Subgroup analysis demonstrated that women with high UA but low triglyceride levels carried the greatest mortality risk (HR, 4.16; 95 % CI, 1.34-12.9). Elevated UA in women post-stroke signals a high mortality risk tied to disrupted triglyceride metabolism, positioning UA and triglyceride pathways as potential therapeutic targets.