Fibrinolytic parameters and insulin resistance in young survivors of myocardial infarction with heterozygous familial hypercholesterolemia.
A characteristic feature of patients with heterozygous familial hypercholesterolemia (FH) is the premature occurrence of coronary artery disease because of elevated LDL cholesterol levels. Hyperinsulinemia and insulin resistance, important characteristics of the cardiovascular dysmetabolic syndrome (CDS), were found to be associated with coronary artery disease in FH subjects, as in the general population. We investigated whether hypofibrinolysis, as part of CDS, is independently associated with symptomatic coronary artery 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, plasminogen activator inhibitor (PAI-1) antigen and activity, fibrinogen, serum lipids and lipoproteins, fasting glucose and insulin) were carried out in 39 male patients with heterozygous FH (aged 46.6 +/- 8.8 years). Insulin resistance was calculated using the homeostasis model assessment (HOMA) mathematical model. Thirteen of the patients had suffered a myocardial infarction (MI) 5 to 8 years ago (aged 47.8 +/- 6.1 years) and 26 were free of coronary artery disease (aged 45.9 +/- 9.9 years). There was no difference in total and LDL cholesterol between the two groups. Patients with previous myocardial infarction had significantly higher levels of insulin, insulin resistance, triglycerides, t-PA antigen, PAI-1 antigen and activity, and significantly lower values of HDL cholesterol. Other widely recognised risk factors for coronary artery disease, such as smoking, systolic and diastolic blood pressure, obesity and age, did not differ significantly between the groups. In the logistic regression model, PAI-1 antigen, as a marker of hypofibrinolysis, emerged as an independent risk factor for the occurrence of myocardial 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 antigen is an independent variable in CDS associated with the premature occurrence of myocardial infarction in male patients with FH.
Department of Angiology, Hospital of Internal Medicine, University Clinical Centre, Ljubljana, Slovenia.
M
M
Sebestjen
B
B
Zegura
B
B
Guzic-Salobir
I
I
Keber
D000328:Adult; D000367:Age Factors; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005342:Fibrinolysis; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications* / Q000235:genetics*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012307:Risk Factors; D012737:Sex Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D010959:Tissue Plasminogen Activator