THROMBOXANE BIOSYNTHESIS, NEUTROPHIL AND COAGULATIVE ACTIVATION IN TYPE IIA HYPERCHOLESTEROLEMIA

Thromboxane (Tx) A(2) biosynthesis is enhanced in the majority of pati ents with type IIa hypercholesterolemia. Because blood clotting activa tion is an important component of the inflammatory response, involved in the initiation and progression of atherosclerotic plaques, we have investigated TxA(2) biosynthesis, neutrophil activation and thrombin g eneration in 24 patients with type IIa hypercholesterolemia. Urinary 1 1-dehydro-TxB(2), was significantly higher (p = 0.0001) in patients th an in 24 sex- and age marched healthy subjects. Similarly, prothrombin fragment 1+2 (F-1+2), thrombin-antithrombin III complexes and plasma elastase were significantly higher in patients than in controls. Urina ry 11-dehydro-TxB(2) excretion was correlated with plasma elastase (r = 0.758;p = 0.0001), and prothrombin fragment 1+2 (r = 0.804; p = 0.00 1). The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibit or simvastatin (20 mg/day for 2 months) significantly reduced choleste rol levels, urinary 11-dehydro-TxB(2) excretion, plasma elastase and p lasma F-1+2 in 8 patients. We conclude that type IIa hypercholesterole mia is associated with biochemical evidence of platelet, neutrophil an d blood clotting activation. The relationship between these events rem ains to be investigated.