Oxidative stress reflected by increased F2-isoprostanes is associated with increasing urinary 11-dehydro thromboxane B2 levels in patients with coronary artery disease.
Peter McCullough M.D.
McCullough, P. A., A. Vasudevan, L. R. Lopez, C. Swift, M. Peterson, J. Bennett-Firmin, R. Schiffmann and T. Bottiglieri (2016). “Oxidative stress reflected by increased f2-isoprostanes is associated with increasing urinary 11-dehydro thromboxane b2 levels in patients with coronary artery disease.” Thromb Res 148: 85-88.
Acetylsalicylic acid (ASA, aspirin) is widely prescribed as an aid in primary and secondary prevention of coronary artery disease (CAD) as it inhibits > 95% of platelet cyclooxygenase-1 (COX-1) activity, reducing the production of thromboxane A2 (TxA2) . However, the non-platelet inflammatory COX-2 pathway remains active minimally affected by ASA. Based on the clinical development of complications or on laboratory tests, an inadequate response to ASA has been referred to as “aspirin resistance”  which is associated with increased risk of adverse outcomes . Oxidative stress has been recently recognized as a relevant underlying mechanism to explain incomplete ASA response. Along with the enzymatic pathways (COX-1; COX-2), there is a non-enzymatic arachidonic acid pathway that produces F2-isoprostanes by oxidative stress damage which can directly activate platelets by stimulating platelet thromboxane prostanoid receptors (TPR)  and is not affected by ASA . 8-isoprostaglandin-F2α (8-isoPGF2α) is considered a reliable laboratory biomarker of in vivo oxidative stress and a reliable noninvasive measurement of lipid peroxidation . We investigated the association of oxidative stress (urinary 8-isoPGF2α) and the adequacy of inhibition of COX-1 (urinary 11-dehydro thromboxane B2 [11dhTxB2]).