Influence of simvastatin on aspects of thrombogenesis in CAPD patients.
BACKGROUND
Patients on continuous ambulatory peritoneal dialysis (CAPD) are prone to dyslipidemia and have a high risk of cardiovascular death. Statins show beneficial effects on serum lipids and thrombogenesis in various groups of patients, but prospective studies have so far not been performed on CAPD patients.


OBJECTIVE
To determine the effects of 6 months' treatment with simvastatin on platelet function and some hemostatic parameters, markers of endothelial cell injury, in 14 CAPD patients with hypercholesterolemia.


METHODS
Simvastatin was given in a dose of 10 mg at bedtime. Commercially available kits were used for all determinations.


RESULTS
Cholesterol and low density lipoprotein fell significantly as early as after 1 month of the therapy (p < 0.001). Platelet aggregation in whole blood and platelet-rich plasma was transiently decreased by simvastatin therapy. The fibrinolytic activity index increased significantly after 6 months of simvastatin administration (p < 0.05), reaching values observed in the control group, whereas euglobulin clot lysis time, which was also significantly shortened after 6 months (p < 0.05), did not reach values obtained in healthy volunteers. Vascular cell adhesion molecule, thrombomodulin, and protein Z decreased significantly after 3 months of the therapy (p < 0.05, p < 0.05, and p < 0.01, respectively), whereas intercellular adhesion molecule decreased after 6 months (p < 0.05). Vascular endothelial growth factor and its receptor, protein Z, total tissue factor pathway inhibitor (TFPI),TFPI/Xa complexes, and thrombin activatable fibrinolysis inhibitor concentration and activity fell significantly after 6 months of treatment with simvastatin (all p < 0.05). Tissue plasminogen activator concentration increased after 1 month (p < 0.01 after 1 month, p < 0.05 after 3 and 6 months), whereas total homocysteine fell after 6 months of simvastatin therapy (p < 0.05). Truncated TFPI decreased significantly as early as after 1 month of therapy (p < 0.05 after 1 month, p < 0.01 after 3 and 6 months).


CONCLUSIONS
Simvastatin is an effective hypolipemic agent in CAPD patients. It favorably affects platelet aggregation and the extrinsic coagulation pathway, improves fibrinolysis, and ameliorates endothelial dysfunction. Simvastatin might reduce the risk of thrombotic complications in CAPD patients.
Malyszko
Jolanta
J
Nephrology and Department of Internal Medicine, Medical University, Bialystok, Poland. jolmal@poczta.onet.pl
Malyszko
Jacek S
JS
Hryszko
Tomasz
T
Mysliwiec
Michal
M
D000328:Adult; D004334:Drug Administration Schedule; D042783:Endothelial Cells / Q000187:drug effects; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy; D007676:Kidney Failure, Chronic / Q000628:therapy; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D011446:Prospective Studies; D019821:Simvastatin / Q000008:administration & dosage*; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin