EFFECTS OF 2 DIFFERENT HMG-COA REDUCTASE INHIBITORS ON THROMBOXANE PRODUCTION IN TYPE IIA HYPERCHOLESTEROLEMIA

Many studies have found that familial hypercholesterolemia, a hyperlip oproteinemia associated with premature atherosclerosis, is characteriz ed by enhanced platelet aggregation. This study was undertaken to meas ure the urinary excretion of the two main urinary thromboxane B2 (TXB2 ) metabolites (2,3-dinor-TXB2 and 11-dehydro-TXB2) in 20 patients affe cted by familial hypercholesterolemia treated for one month with 40 mg /day of pravastatin (10 patients) in comparison to 10 normocholesterol emic subjects. After a run-in period, the type II A patients showed to tal cholesterol levels (296 +/- 32 mg/dL) significantly higher (P < 0. 001) than those of control subjects (155 + 46 mg/dL). The urinary conc entrations of 11-dehydro-TXB2 and 2,3-dinor-TXB2 also significantly di ffered (P < 0.001) between control group (1,463 +/- 1,440 and 386 +/- 447 pg/mg urinary creatinine) and treated patients (3,536 +/- 2,112 an d 914 +/- 572 pg/mg urinary creatinine). At baseline there was a posit ive correlation between total cholesterol (TC) levels and urinary TXB2 metabolite concentrations (2,3-dinor-TXB2 r=0.61, P<0.02; H-dehydro-T XB2, r=48, P<0.05), but not between low-density-lipoprotein cholestero l (LDL-C) and the urinary compounds. At the end of a four-week treatme nt, TC and LDL-C had decreased significantly from the baseline levels, by 27% and 30% in the fluvastatin group (P < 0.01) and by 23% and 31% in the pravastatin group (P < 0.01), with no significant difference b etween the two groups. After the two treatments with HMG-CoA reductase inhibitors, there was no statistically significant reduction of the u rinary metabolite levels. In addition, the positive correlation seen a t baseline between TC and TXB2 metabolites was no longer present. In a ccord with previous studies, we found a significant correlation betwee n TC levels and TXB2 metabolites concentrations in type IIA hyperchole sterolemic patients. Although short-term treatment with two statins re duced TC levels, it did not change the thromboxane metabolite excretio n.