[The physiopathology and pharmacological approach to multiple metabolic and blood coagulation syndromes, the characteristics of atherogenesis].
Isolated vascular risk factors (e.g. hypercholesterolemia, hypertension, etc) are not commonly found in high risk patients. In fact, more often, constellations of risk factors are detected, giving rise to a so-called polymetabolic syndrome. Among the associated factors, insulin-resistance with altered carbohydrate tolerance, hypertriglyceridemia, hypertension and reduced HDL-cholesterol levels are most often described. Recent epidemiological studies underline the possible genetic basis of this syndrome, as shown in the highly consanguineous Utah population. The major determinant of the syndrome seems to be insulin-resistance. Development of hypertension within this syndrome may be linked to hyperinsulinemia, with increased intracellular Ca++ and/or obesity. The reduction of HDL-cholesterol may be secondary to the hypertriglyceridemia, again secondary to hyperstimulation, most likely from hyperinsulinemia. In the polymetabolic syndrome frequent alterations in the hemocoagulative system, mainly hyperfibrinogenemia/reduction of fibrinolysis, are recognized. Recently a circulating antagonist of fibrinolysis, PAI-1 has been described: PAI-1 levels are significantly correlated to those of plasma triglycerides. Regulation of fibrinogenemia is, instead, more complex and may only be partly linked to an increase of circulating lipids/lipoproteins. Development and stabilization of the syndrome, with the consequent vascular alterations, may be effectively prevented or treated by diet, and also by specific drugs. The choice is addressed to drugs reducing insulin-resistance and/or plasma triglycerides, possibly also raising HDL-cholesterol and reducing fibrinogen; among the possible options, bezafibrate seems to exert the largest number of effects.
Sirtori
C R
CR
Istituto di Scienze Farmacologiche, Università degli Studi, Milano.
D001161:Arteriosclerosis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D001777:Blood Coagulation / Q000187:drug effects; D001778:Blood Coagulation Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D008659:Metabolic Diseases / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D013577:Syndrome
Fisiopatologia e approccio farmacologico alle sindromi polimetabolica ed emocoagulativa, caratteristiche dell'aterogenesi.