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


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.
Georgieva
Anna M
AM
Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Academic Hospital Maastricht and University of Maastricht, AZ Maastricht, The Netherlands.
Cate
Hugo Ten
HT
Keulen
Eric T P
ET
van Oerle
René
R
Govers-Riemslag
José W P
JW
Hamulyák
Karly
K
van der Kallen
Carla J H
CJ
Van Greevenbroek
Marleen M J
MM
De Bruin
Tjerk W A
TW
D000328:Adult; D000990:Antithrombin III; D001779:Blood Coagulation Factors / Q000378:metabolism*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood; D018180:Thrombomodulin / Q000097:blood; D014280:Triglycerides / Q000097:blood
D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; D008074:Lipoproteins; D018180:Thrombomodulin; D014280:Triglycerides; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D000990:Antithrombin III; D010447:Peptide Hydrolases