Sub-Optimal Response to ASA in Cardiovascular Ischemia Homocysteine-Related

Some epidemiological reports showed a significant association between the increased homocysteine serum levels (H-Hcy) and risk of ischemic cardiovascular disease (CVD). Acetyl-Salicylic Acid (ASA) is the drug commonly used to antagonize pro-thrombotic effect of Hcy. But, human and animal studies evidenced that ASA, given at habitual anti-ischemic dosage, may induce an incomplete inhibition of platelet (aspirin-resistance) in patients with CVD Hcy-related by several mechanisms. In these patients, doses higher than normal are requested to obtain an optimal ASA-response (aspirin-sensitivity). That happens because Hcy “per se” is a pro-aggregatory agent and acts as specific sensitizer of blood platelets with several mechanisms. On the contrary, its acetylated form (N-acetyl-homocysteine) obtained using high ASA doses, is able to reverse this effect restoring the platelets’ sensitivity. That happens with a still unknown mechanism.