Impact of metabolic abnormalities on the association between normal-range urinary albumin-to-creatinine ratio and cardiovascular mortality: evidence from the NHANES 1999-2018.

Background: The urinary albumin to creatinine ratio (UACR) is associated with adverse cardiovascular outcomes, even when within the normal range. However, the potential modification of this effect by metabolic abnormalities remains unclear. This study explored whether metabolic abnormalities modify the association between normal-range UACR and cardiovascular mortality.

Methods: This cohort study included 27,298 U.S. adults from the National Health and Nutrition Examination Survey 1999-2018, with mortality follow-up through December 31, 2019. Normal UACR (< 30 mg/g) was considered. Metabolic abnormalities were categorized into three groups based on the number of metabolic abnormality components: metabolic health (0 components), pre-metabolic syndrome (Pre-MetS, 1-2 components), and metabolic syndrome (MetS, 3-5 components). Multivariable Cox proportional hazards regression was used to estimate the association between normal UACR and cardiovascular mortality, stratified by metabolic abnormality groups.

Results: Over a median follow-up of 9.67 years, 764 cardiovascular deaths occurred. In the fully adjusted model, higher normal UACR was associated with an increased risk of cardiovascular death in metabolically abnormal individuals, but not in metabolically healthy individuals. When UACR was divided into tertiles, the highest tertile was associated with a 60% and 79% higher risk of cardiovascular mortality in the Pre-MetS and MetS groups, respectively, compared with the lowest tertile (Pre-MetS: HR, 1.60 [95% CI: 1.19-2.15]; MetS: HR, 1.79 [95% CI: 1.34-2.41]).

Conclusion: A higher normal UACR was associated with an increased risk of cardiovascular death in metabolically abnormal individuals, underscoring the need for early renal risk management in this population.