This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bröijersen, A. Articles by Hjemdahl, P. Search for Related Content PubMed PubMed Citation Articles by Bröijersen, A. Articles by Hjemdahl, P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:511-516.)
© 1996 American Heart Association, Inc.

Articles

Gemfibrozil Treatment of Combined Hyperlipoproteinemia

No Improvement of Fibrinolysis Despite Marked Reduction of Plasma Triglyceride Levels

Anders Bröijersen; Mats Eriksson; Björn Wiman; Bo Angelin; Paul Hjemdahl

From the Departments of Clinical Pharmacology (A.B., P.H.) and Clinical Chemistry (B.W.), Karolinska Hospital, Stockholm, and the Metabolism Unit (M.E., B.A.), Department of Medicine, Karolinska Institute at Huddinge University Hospital, Stockholm, Sweden.

Correspondence to Anders Bröijersen, Department of Clinical Pharmacology, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail broij@mb.ks.se.

Abstract Hypertriglyceridemia is linked to impaired fibrinolytic function, and lipid-lowering treatment with fibric acid derivatives could hypothetically improve fibrinolysis in this condition. We therefore conducted a double-blind, placebo-controlled, crossover study of gemfibrozil treatment on fibrinolytic function in 21 men with combined hyperlipoproteinemia. Measurements were performed at rest and during mental stress and after venous occlusion. The patients had clearly disturbed fibrinolytic function, with elevated plasminogen activator inhibitor–1 (PAI-1) activity at rest (25 U/mL; reference, <15 U/mL). Gemfibrozil reduced plasma total and VLDL cholesterol as well as all triglyceride fractions, whereas HDL cholesterol increased (P<.001 for all). Total triglyceride levels were reduced by 57±4% (from 5.3 to 2.1 mmol/L). Fasting serum insulin levels were not altered by gemfibrozil treatment. Plasma levels of PAI-1 activity and tissue-type plasminogen activator (TPA) activity or antigen were unaffected by gemfibrozil treatment both at rest and during the provocations. The levels of D-dimer, plasmin/antiplasmin complex, and fibrinogen were also uninfluenced by gemfibrozil treatment. Mental stress elevated plasma TPA (P=.0036) and lowered PAI-1 (P=.0012) activity during placebo but not gemfibrozil treatment (P=.28 and P=.17, respectively), but treatment effects did not differ by ANOVA on values (ie, stress minus rest). Venous occlusion reduced PAI-1 activity, whereas TPA and plasmin/antiplasmin complex increased during both treatments. Thus, gemfibrozil treatment did not improve fibrinolysis or lower fibrinogen levels in men with combined hyperlipoproteinemia despite marked reduction of plasma triglyceride levels. It seems unlikely that improved fibrinolysis explains the primary preventive effect of gemfibrozil.

Key Words: hyperlipoproteinemia • gemfibrozil • fibrinolysis • plasminogen activator inhibitor • tissue-type plasminogen activator

This article has been cited by other articles:

				L. Nilsson, T. Takemura, P. Eriksson, and A. Hamsten Effects of Fibrate Compounds on Expression of Plasminogen Activator Inhibitor-1 by Cultured Endothelial Cells Arterioscler Thromb Vasc Biol, June 1, 1999; 19(6): 1577 - 1581. [Abstract] [Full Text] [PDF]

				L. Nilsson, M. Gåfvels, L. Musakka, K. Ensler, D. K. Strickland, B. Angelin, A. Hamsten, and P. Eriksson VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor J. Lipid Res., May 1, 1999; 40(5): 913 - 919. [Abstract] [Full Text]

				J. Arts, M. Kockx, H. M.G. Princen, and T. Kooistra Studies on the Mechanism of Fibrate-Inhibited Expression of Plasminogen Activator Inhibitor-1 in Cultured Hepatocytes From Cynomolgus Monkey Arterioscler Thromb Vasc Biol, January 1, 1997; 17(1): 26 - 32. [Abstract] [Full Text]