Patients with familial hyperlipoproteinaemia (HLP) are at high risk for the premature development of atherosclerosis. This study was designed to investigate the effect of long-term treatment (8 months) with the HMG-CoA-reductase inhibitor SYN (20-40 mg/day) on platelet reactivity and PGIo receptors in 12 HLP patients (B) as compared with 11 untreated HLP patients (A) and 11 healthy subjects (C). Treatment with SYN reduced the plasma cholesterol to 234 ± 12 mg/dl as compared to 307 ± 21 (A) and 195 ± 14 mg/dl (C), respectively. Collagen (0.6 pg/ml) induced platelet thromboxane (TXB2) formation was 50±6 ng/ml in group A and significantly reduced to 32 ± 3 (B) which was not different from the 28±3 ng/ml in group C. Similar results were obtained by measuring pTatelet ATP secretion and aggregation. SYN treatment significantly improved the reduced number of PGI2 receptors (determined according to Schillinger & Prior, 1980) and normalized the iloprost (ILO, 30 nM) induced cAMP stimulation in platelet-rich plasma while the kg remained unchanged:These data demonstrate that SYN-treatment of HLP patients at doses that reduce plasma cholesterol by about 25% results in sig-ficant improvement of platelet function. This includes both normalization of platelet hyperreactivity against proaggregatory agents as well as platelet hyporeactivity aganist PGI2. The last effect might involve an increase of the (reduced) number of PGI2 receptors in HLP type IIa.
Effect of long-term HMG-CoA-reductase inhibitor therapy on large artery endothelial function and distensibility after kidney transplantation
