Plasma predictors of ischemic complications of atherosclerosis: open issues

In western countries, acute myocardial infarction is the commonest cause of morbidity and mortality [19]. An occlusive coronary thrombus on an ulcerated atherosclerotic plaque in the coronary arteries is the etiological event in more than 90% of patients with Q-wave myocardial infarction [38]. The underlying abnormality in non-Q-wave myocardial infarction is often a ruptured atherosclerotic plaque, which acts as a nidus for the deposition and activation of platelets. In this case, thrombosis occurs, but may not be totally occlusive, or an early spontaneous recanalization may occur. On the other hand, some clinical trials showed that a prolonged treatment with antiplatelet drugs significantly reduces the recurrence of coronary ischemia. Thus, atherosclerosis is a necessary condition for myocardial infarction, but it is not sufficient in that it usually needs the occurrence of thrombosis. However, only 25-30% of these thrombotic events are prevented by the administration of antiplatelets drugs. In recent years, epidemiological studies identified some hemostatic parameters whose abnormalities may help predict the risk of ischemic events: fibrinogen [14], plasminogen activator inhibitor-1 (PAI-1) [3], lipoprotein(a) [46], anticardiolipin antibodies (ACA) and lupus anticoagulant (LA) [10], leukocyte count [34], blood viscosity [34]. Some of these, such as fibronogen and PAI-1 are acute-phase proteins. It is known that personal conditions or environmental factors, such as excess weight, diabetes mellitus, arterial hypertension, cigarette smoking etc, are associated with a high risk of atherosclerosis and myocardial infarction [29] and are known to affect plasma levels of some acute-phase proteins. Thus, the question is whether these hemostatic variables may help predict thrombosis in individuals. Furthermore, in addition to personal and environmental factors, genetic variations can affect plasma levels of some of these variables. Thus, an additional question is to establish the extent to which abnormalities of these variables is just the epiphenomenon of as yet unknown events in atherosclerosis.