Abstract
BACKGROUND: Urinary albumin excretion is an established marker of cardiovascular (CV) risk in people with type 2 diabetes mellitus (T2DM). However, its prognostic significance within the normoalbuminuric range (< 30 mg/g) remains uncertain, particularly regarding sex-specific differences. This study examined whether urinary albumin-to-creatinine ratio (UACR; KDIGO A1 range) is associated with coronary artery disease (CAD) severity and 6-year major adverse cardiovascular events (MACE) in women and in men with T2DM and preserved kidney function (eGFR > 60 mL/min/1.73 m², UACR < 30 mg/g), treating sex differences as a co-primary objective. METHODS: We conducted a retrospective cohort study involving adults with T2DM who underwent diagnostic coronary angiography. Baseline associations between log-transformed UACR, CAD severity, CV risk factors, and inflammatory markers were evaluated using multivariable linear regression. MACE (defined as non-fatal myocardial infarction or unstable angina requiring urgent revascularization, stroke, or CV death) were recorded during 6-year of follow-up. Cox proportional hazards models, adjusted for age, sex, hypertension, smoking, BMI, lipid profile, hs-CRP, and ACEI/ARB use, were used to assess UACR-MACE associations. RESULTS: We included 420 adults (180 women, 42.9%) with a mean of age 65.3 ± 10.7 years and a median UACR 7.56 mg/g (IQR 4.12-15.5). Significant CAD was present in 310 participants (73.8%), and 78 experienced MACE during follow-up (35.5%). Higher UACR was independently associated with greater coronary stenosis (adjusted R² = 0.090, p < 0.001). Kaplan-Meier analysis showed a significantly higher incidence of MACE in the highest UACR tertile (log-rank p = 0.039). In multivariable Cox models adjusted for age, sex, hypertension, smoking, lipid profile, hs-CRP, SSI, and ACEI/ARB use, higher log-UACR independently predicted MACE (adjusted HR 1.67, 95% CI 1.35-2.10; p < 0.01). In sex-stratified Cox models, higher log-UACR predicted MACE in both sexes and remained independently associated in multivariable analyses (adjusted HR 1.67, 95% CI 1.35-2.10; p < 0.01). Associations were directionally stronger in women, who showed higher cumulative event rates across UACR tertiles, although the formal UACR × sex interaction did not reach statistical significance. CONCLUSIONS: Within the normoalbuminuric range, UACR is associated with greater CAD burden and higher 6-year MACE risk, with sex-specific differences. These findings suggest potential sex-related variation in the prognostic value of high-normal albuminuria, particularly among women, warranting validation in larger and more diverse cohorts.