Activated platelets in patients with severe hypertriglyceridemia: effects of triglyceride-lowering therapy.
Hypertriglyceridemia, a risk factor for cardiovascular disease, has been associated with hypercoagulability, but whether platelet activation is implicated is unknown. This study was designed to compare the in vivo platelet activation status between patients with severe hypertriglyceridemia and age- and sex-matched control subjects, and to evaluate the effects of triglyceride-lowering therapy. Sixteen patients with primary hypertriglyceridemia were included in a double-blind, placebo-controlled cross-over trial with 400 mg bezafibrate once daily. Platelet activation was analysed by double label flow cytometry, using monoclonal antibodies against GP53, P-selectin, and platelet-bound fibrinogen. Surface expression of the lysosomal membrane protein GP53 was significantly higher in the hypertriglyceridemic patients at baseline as compared to the group of age- and sex-matched controls (16.3+/-4.8% vs. 8.9+/-3.4%, respectively, P<0.001). No differences in the expression of P-selectin and fibrinogen binding were observed. In response to bezafibrate therapy, the expression of GP53 in the patient group decreased from 16.3+/-4.8% to 13.1+/-4.1% (P=0.018). The expression of P-selectin and fibrinogen binding was not affected by bezafibrate therapy. In conclusion, patients with hypertriglyceridemia have an increased in vivo platelet activation status, which can be improved by bezafibrate therapy.
de Man
F H
FH
Department of Cardiology, C5-P, Leiden University Medical Centre, P. O. Box 9600, 2300 RC, Leiden, The Netherlands. a.van_der_laarse@lumc.nl
Nieuwland
R
R
van der Laarse
A
A
Romijn
F
F
Smelt
A H
AH
Gevers Leuven
J A
JA
Sturk
A
A
D015703:Antigens, CD / Q000032:analysis; D001629:Bezafibrate / Q000627:therapeutic use*; D001792:Blood Platelets / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000032:analysis; D015539:Platelet Activation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D060149:Tetraspanin 30; D014280:Triglycerides / Q000097:blood*
D015703:Antigens, CD; C554586:CD63 protein, human; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D014280:Triglycerides; C030104:lipoprotein cholesterol; D005340:Fibrinogen; D002784:Cholesterol; D001629:Bezafibrate