Urine albumin-to-creatinine ratio and risks of incident arterial thromboembolism and pulmonary embolism among adults—a prospective cohort study

Background: It is well-established that reduced kidney function and large amounts of proteinuria are associated with thrombotic and embolic events. However, the relationship between urine albumin-to-creatinine ratio (UACR) and the risk of incident arterial thromboembolism (ATE) and pulmonary embolism (PE) remains unclear. Objectives: This study aims to clarify the relationship between UACR and the incidence of ATE and PE. We sought to determine whether UACR is a risk factor for these events. Methods: A total of 419,282 participants from the UK Biobank with available UACR data were included in the analysis. Cox proportional hazards regression models and restricted cubic spline analyses were used to examine the relationship between UACR and the risk of ATE and PE. Results: Over an average follow-up period of 13.9 years (range, 12.7-15.0 years), we identified 1220 incident ATE cases and 6879 PE events. Compared with a UACR of < 3 mg/mmol, the multivariable-adjusted hazard ratios for UACR of 3 to 30 mg/mmol and UACR of > 30 mg/mmol were as follows: 1.36 (95% CI, 1.00-1.85) and 2.48 (95% CI, 1.14-5.42) for incident ATE; 0.95 (95% CI, 0.82-1.09) and 1.70 (95% CI, 1.11-2.61) for PE, respectively. These associations remained consistent across various sensitivity analyses designed to address potential confounding factors. The findings were also robust in joint analyses considering both UACR and estimated glomerular filtration rate creatinine-cystatin C equation or serum albumin levels. Conclusion: This large cohort study demonstrates that moderately or severely increased albuminuria is associated with an increased risk of incident ATE and PE in adults. These findings highlight the importance of early identification and management of albuminuria as a potential strategy for the prevention of arterial and pulmonary thromboembolic events.