EFFECT OF SIMVASTATIN ON SERUM-CHOLESTEROL AND PLATELET FREE CALCIUM IN NONOBESE, NONHYPERTENSIVE PATIENTS WITH HYPERLIPOPROTEINEMIA

The purpose of the present study was to analyze the relationship betwe en serum cholesterol and platelet free cytosolic calcium (PFCC) in non obese, nonhypertensive hypercholesterolemic patients submitted to a 12 -week course of simvastatin therapy. Twenty-four patients with type II hyperlipoproteinemia were treated with a placebo for 2 weeks, followe d by administration of simvastatin for 12 weeks (10-20 mg/day). The se rum lipids and baseline and vasopressin-stimulated (AVP 10(-7) M) PFCC were measured before and after 6 and 12 weeks of simvastatin therapy. Serum cholesterol and low-density lipoprotein (LDL) cholesterol respe ctively decreased by 22.5% and 29.5% at 6 weeks (P<0.01) and by 24% an d 33.5% at 12 weeks (P<0.01). PFCC was not increased in hyperlipidemic patients and did not change during simvastatin therapy. However, a si gnificant reduction in the AVP-stimulated PFCC was found during the hy pocholesterolemic treatment (329+/-24 nM at baseline and 226+/-20 nM a t week 12, P<0.01). Significant correlations were found between AVP-st imulated PFCC and total (r=0.34, n=66, P=0.04) or LDL cholesterol (r=0 .37, n=66, P=0.0017). These results suggest that circulating cholester ol does not correlate with PFCC in unstimulated platelets of nonobese, normotensive hypercholesterolemic patients. However, prolonged simvas tatin treatment normalizes platelet responsiveness to vasopressin. Thi s may lead to decreased platelet aggregability, an important process i n atherogenesis.