Sex-specific associations of low-level urinary albumin-creatinine ratio with mortality and adverse cardiac events in older adults

Abstract Albuminuria is traditionally defined using fixed urinary albumin–creatinine ratio (UACR) thresholds, although cardiovascular disease (CVD) risk has been reported to increase continuously across the UACR spectrum. Whether these associations are present in healthy older adults and differ by sex remains unclear. We examined sex-specific associations between low-level UACR, mortality, and cardiovascular outcomes in older adults with preserved kidney function. From the ASPirin in Reducing Events in the Elderly (ASPREE) study, we included 5396 males and 6305 females aged ≥ 70 years with baseline UACR and eGFR ≥ 60 mL/min/1.73 m 2 ). Sex-stratified Cox models examined associations between UACR quintiles (Q) and mortality, CVD, major adverse cardiovascular events (MACE), and stroke, using Q1 as reference. Over a median follow-up of 8.3–8.6 years, increasing UACR was associated with progressively higher risk of all-cause mortality in both sexes, despite most values being below the guideline thresholds. Mortality risk reached statistical significance for males from Q4 (HR 1.45; 95% CI 1.18–1.77) and females from Q2 (HR 1.33; 95% CI 1.04–1.71). Males also had a statistically significant increase in CVD from Q4 (HR 1.32; 95% CI 1.03–1.70) and MACE and stroke in Q5 (HR 1.61; 95% CI 1.25–2.07 and HR 1.96; 95%CI 1.38–1.78). Despite an increasing trend in females, adverse cardiovascular outcomes did not reach significance. UACR levels below guideline thresholds were associated with all-cause mortality in both sexes, with increased cardiovascular disease predominately observed in men. These findings support a continuous relationship between UACR and risk and suggest that even low-level albuminuria may have prognostic significance in healthy older adults.