Sex-based differences in the impact of baseline plasma uricemia on long-term mortality risk following acute coronary syndrome: a 26-year follow-up study

Abstract Introduction The impact of plasma uricemia levels on long-term mortality following Acute Coronary Syndrome (ACS) remains uncertain, particularly in relation to sex differences. Aim This study aims to evaluate the association between uricemia levels during ACS and very long-term all-cause mortality risk. Additionally, it explores potential sex-related differences in this association. Methods We analyzed 571 unselected patients hospitalized in the Intensive Care Units of three hospitals and discharged alive. Survival analysis was performed using Cox regression models, considering uricemia as a continuous variable. A formal interaction between uricemia and sex was tested. Statistical analyses were conducted using STATA 18.0 (StataCorp LLC, TX, USA). Results The mean patient age was 66.2±1.9 years, with females comprising 30% of the cohort. Baseline uricemia levels averaged 5.7±1.8 mg/dL (5.8±1.8 in males vs. 5.4±1.9 in females; t=2.2; p=0.02). Over a 26-year follow-up (7,091 person-years), 483 patients (85%) died. In univariable analysis, baseline uricemia was significantly associated with all-cause mortality (HR=1.08; 95% CI=1.04-1.12; z=3.7; p0.0001). This association remained robust in multivariable analysis, adjusting for age, sex, Killip class, total cholesterol, diabetes mellitus, and uricemia (HR=1.07; 95% CI=1.02-1.11; z=2.9; p=0.003). A significant interaction between uricemia and sex was observed in the fully adjusted model (HR=1.12; 95% CI=1.01-1.23; z=2.2; p=0.02). In females, elevated uricemia was strongly associated with increased mortality risk (HR=1.17; 95% CI=1.07-1.28; z=3.4; p=0.001), while no significant association was found in males. These findings were consistent for uricemia levels measured on both the first and seventh days of hospitalization. Conclusion This study suggests that elevated plasma uricemia levels during ACS are associated with a greater long-term mortality risk in females compared to males. These findings underscore the importance of incorporating sex-specific considerations into risk stratification and management strategies following ACS.