Urinary 11-dehydro-thromboxane B2 levels are associated with vascular inflammation and prognosis in atherosclerotic cardiovascular disease

Abstract

Cyclooxygenase-derived thromboxane (TxA2) and prostacyclin (PGI2) regulate atherogenesis in preclinical models. However, the relationship between TxA2 and PGI2 biosynthesis, vascular inflammation, and atherosclerotic cardiovascular disease (ASCVD) progression in humans remains unclear. The association between stable urine metabolites of thromboxane (TxA2-M) and prostacyclin (PGI2-M), circulating levels of cellular adhesion molecules (CAMs: E-selectin, P-selectin), chemokines and C-reactive protein, and the incidence of major adverse cardiovascular events (MACE) were evaluated in 120 patients with stable ASCVD on aspirin therapy. Urinary TxA2-M levels were significantly correlated with circulating P-selectin (r=0.319, p<0.001) and E-selectin (r=0.245, p=0.007) levels, and associated with higher risk of MACE (p=0.043). In contrast, PGI2-M levels were not significantly associated with CAM levels or MACE. These results provide insight into the contribution of TxA2 biosynthesis to ASCVD progression in humans, and suggest that patients with elevated TxA2-M levels may be predisposed to advanced platelet and endothelial activation and higher risk of adverse cardiovascular outcomes.