Fibrinolytic parameters and insulin resistance in young survivors myocardial infarction with heterozygous familial hypercholesterolemia

A characteristic feature of patients with heterozygous familial hypercholes terolemia (FH) is the premature occurrence of coronary artery disease becau se of elevated LDL cholesterol levels. Hyperinsulinemia and insulin resista nce, important characteristics of the cardiovascular dysmetabolic syndrome (CDS), were found to be associated with coronary artery disease in FH subje cts, as in the general population. We investigated whether hypofibrinolysis , as part of CDS, is independently associated with symptomatic coronary art ery disease in these high -risk patients. Clinical examination (body mass index, waist circumference, blood pressure) and blood analysis (plasma tissue plasminogen activator (t-PA) antigen, pl asminogen activator inhibitor (PAI-1) antigen and activity, fibrinogen, ser um lipids and lipoproteins, fasting glucose and insulin) were carried out i n 39 male patients with heterozygous FH (aged 46.6+/-8.8 years). Insulin re sistance was calculated using the homeostasis model assessment (HOMA) mathe matical model. Thirteen of the patients had suffered a myocardial infarctio n (MI) 5 to 8 years ago (aged 47.8 +/- 6.1 years) and 26 were free of coron ary artery disease (aged 45.9 +/- 9.9 years). There was no difference in to tal and LDL cholesterol between the two groups. Patients with previous myoc ardial infarction had significantly higher levels of insulin, insulin resis tance, triglycerides, t-PA antigen, PAI-1 antigen and activity, and signifi cantly lower values of HDL cholesterol. Other widely recognised risk factor s for coronary artery disease, such as smoking, systolic and diastolic bloo d pressure, obesity and age, did not differ significantly between the group s. In the logistic regression model, PAI-1 antigen, as a marker of hypofibr inolysis, emerged as an independent risk factor for the occurrence of myoca rdial infarction (odds ratio 1.55; p = 0.02). In summary our results suggest that the impairment of fibrinolytic activity resulting from elevated levels of PAI-1 antigen and activity and t-PA anti gen is an independent variable in CDS associated with the premature occurre nce of myocardial infarction in male patients with FH.