Albuminuria in assessing the risk of cardiovascular events and bleeding in patients with coronary and peripheral artery disease

Aim. To assess the significance of albuminuria in predicting prognosis-determining events (cardiovascular (CVEs) and hemorrhagic events) in patients with multifocal atherosclerosis, including in comparison with the generally accepted endothelial dysfunction laboratory marker — von Willebrand factor (VWF).

Material and methods. The study included participants of the single-center prospective registry REGATA-1 with coronary and peripheral artery disease. The albumin-to-creatinine ratio in a single morning urine sample and plasma VWF activity were determined. The primary endpoint was the sum of following prognosis-determining events: myocardial infarction, unstable angina, stroke, transient ischemic attack, peripheral artery disease, amputation, major/clinically significant bleeding (BARC 2-5).

Results. A total of 148 patients were included (median age 66 [65; 67] years, 79,1% men). An increase in the urine albumin level (at least mild, >10 mg/g) was detected in 71,3% of patients.

Median follow-up duration was 17 [15; 20] months; 7 CVEs and 18 BARC 2-3 bleedings were registered. ROC analysis revealed the albuminuria cutoff point of 10,6 mg/g, values above which are associated with an increase in the rate of prognosis-determining events. These events were registered in 4,5% of patients with albuminuria <10,6 mg/g and in 21,9% of patients with higher values (p_log-rank=0,007).

According to multivariate analysis, the odds ratio (OR) was 5,5 (95% confidence interval (CI) 1,23-24,72), p=0,026. When analyzing secondary endpoints, a trend towards an increase in the risk of CVEs (p=0,065) and hemorrhagic events (p=0,05) was noted. In this cohort, no association was demonstrated between the glomerular filtration rate and the risk of prognosis-determining events.

The cutoff point for VWF was 157%. The incidence of prognosis-determining events was significantly higher in individuals with elevated VWF (23,0% vs 10,8%, p=0,048). In multivariate analysis, VWF lost its significance (OR 2,18; 95% CI 0,84-5,65; p=0,11). In 31,2% of patients, there was a simultaneous increase in albuminuria and VWF, and in this subgroup every third person had prognosis-determining events; in multivariate analysis, the OR was 3,53 (95% CI 1,31-9,49), p=0,012. The combined marker is associated with an increased risk of hemorrhagic events (p=0,006) and CVEs (p=0,027).

Conclusion. In patients with multifocal atherosclerosis, albuminuria >10,6 mg/g is an independent (including from the estimated glomerular filtration rate) predictor of CVEs and hemorrhagic events. The most unfavorable prognosis is in patients with a combination of albuminuria >10,6 mg/g and EF >157%.

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