(Circulation. 1997;96:69-75.)
© 1997 American Heart Association, Inc.
Articles |
Diabetes Mellitus, Hypercholesterolemia, and Hypertension but Not Vascular Disease Per Se Are Associated With Persistent Platelet Activation In Vivo
Evidence Derived From the Study of Peripheral Arterial Disease
From the Departments of Medicine (G.D., C.G.) and Pharmacology (C.P.), University of Chieti "G. D'Annunzio"; the Institute of Internal and Vascular Medicine (P.G., R.V., G.G.N.), University of Perugia; Department of Medicine (F.V., S.B.), University of Rome; the Research Center of Vascular Diseases (M.C.), University of Milan; and Department of Pharmacology (G.C.), Catholic University of Rome, Italy.
Correspondence to Prof Carlo Patrono, Cattedra di Farmacologia I, Università degli Studi "G. D'Annunzio," Via dei Vestini, 31, 66013 Chieti, Italy. E-mail cpatrono{at}unich.it
Background Previous studies relating increased thromboxane (TX) biosynthesis to cardiovascular risk factors do not answer the question whether platelet activation is merely a consequence of more prevalent atherosclerotic lesions or reflects the influence of metabolic and hemodynamic disturbances on platelet biochemistry and function.
Methods and Results We examined 64 patients with large-vessel peripheral arterial disease and 64 age- and sex-matched control subjects. TXA2 biosynthesis was investigated in relation to cardiovascular risk factors by repeated measurements of the urinary excretion of its major enzymatic metabolite, 11-dehydro-TXB2, by radioimmunoassay. Urinary 11-dehydro-TXB2 was significantly (P=.0001) higher in patients with peripheral arterial disease (57±26 ng/h) than in control subjects (26±7 ng/h). Seventy percent of patients had metabolite excretion >2 SD above the normal mean. However, 11-dehydro-TXB2 excretion was enhanced only in association with cardiovascular risk factors. Multivariate analysis showed that diabetes, hypercholesterolemia, and hypertension were independently related to 11-dehydro-TXB2 excretion. During a median follow-up of 48 months, 8 patients experienced major vascular events. These patients had significantly (P=.001) higher 11-dehydro-TXB2 excretion at baseline than patients who remained event free.
Conclusions The occurrence of large-vessel peripheral arterial disease per se is not a trigger of platelet activation in vivo. Rather, the rate of TXA2 biosynthesis appears to reflect the influence of coexisting disorders such as diabetes mellitus, hypercholesterolemia, and hypertension on platelet biochemistry and function. Enhanced TXA2 biosynthesis may represent a common link between such diverse risk factors and the thrombotic complications of peripheral arterial disease.
Key Words: peripheral vascular disease • thromboxane • diabetes mellitus • hypercholesterolemia • hypertension
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