Prothrombotic markers in familial combined hyperlipidemia: Evidence of endothelial cell activation and relation to metabolic syndrome

• Published in: Atherosclerosis Vol. 175; no. 2; pp. 345 - 351
• Main Authors: Georgieva, Anna M, Cate, Hugo Ten, Keulen, Eric T.P, van Oerle, René, Govers-Riemslag, José W.P, Hamulyák, Karly, van der Kallen, Carla J.H, Van Greevenbroek, Marleen M.J, de Bruin, Tjerk W.A
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.08.2004; Elsevier
• Subjects: Adult; Antithrombin III; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood Coagulation Factors - metabolism; Blood vessels and receptors; Cardiology. Vascular system; Case-Control Studies; Coronary artery disease; Cross-Sectional Studies; Female; Fibrin Fibrinogen Degradation Products - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Hyperlipidemia, Familial Combined - blood; Hyperlipoproteinemia; IMT; Lipoproteins - blood; Male; Medical sciences; Metabolic syndrome; Middle Aged; PAI-1; Peptide Hydrolases - blood; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Thrombomodulin - blood; Triglycerides - blood; Vertebrates: cardiovascular system; von Willebrand Factor; WHR; vWF; sTF; sd LDL-cholesterol; TAT; HDL-cholesterol; CAD; Apo B; Hyperlipoproteinemia; Metabolic syndrome; sTM; Coronary artery disease; TC; LDL-cholesterol; IMT; TG; PAI-1; von Willebrand Factor; F XIIa; t-PA; Endocrinopathy; Endothelial cell; Metabolic diseases; Cardiovascular disease; Lipids; Lipoprotein; Coronary heart disease; Thrombosis; Vascular disease; X Syndrome; Atherosclerosis; Metabolic activation; Hyperlipemia; Dyslipemia; Willebrand factor
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2004.04.006

Background: Familial combined hyperlipidemia (FCHL) is characterized by a varied expression of hypertriglyceridemia and hypercholesterolemia within a family, and a high risk of premature coronary artery disease. The present study evaluated a number of potential prothrombotic markers in familial combined hyperlipidemia, and studied their relationship to the hypercholesterolemic (Fredrickson type IIa) and hypertriglyceridemic (IIb and IV) phenotypes. Methods and results: Selected prothrombotic markers were studied in 68 subjects: 34 hyperlipidemic subjects with familial combined hyperlipidemia and 34 controls. FCHL patients exhibited significantly higher Thrombin–Antithrombin complex (TAT), activated coagulation factor XII (F XIIa), von Willebrand Factor (vWF), Plasminogen Activator Inhibitor-1 (PAI-1) and tissue derived Plasminogen Activator (t-PA) values in comparison to controls. Within the subgroup of familial combined hyperlipidemia subjects, elevated PAI-1 activity and soluble Thrombomodulin levels were particularly associated with features of the metabolic syndrome, including hyperinsulinemia, hypertriglyceridemia and predominance of small dense low density lipoprotein (LDL). Conclusions: A general pattern of activated blood coagulation and endothelial activation is present in all hyperlipidemic subjects studied, independent of metabolic phenotype. In those familial combined hyperlipidemia subjects with features of the metabolic syndrome, impaired fibrinolysis can provide an additional cardiovascular risk factor.