Pilot study examining the effect of cholesterol lowering on platelet nitric oxide responsiveness and arterial stiffness in subjects with isolated mild hypercholesterolaemia.

1. Hypercholesterolaemia has been associated with impaired endothelial function. However, there are no available data as to whether hypercholesterolaemia is also associated with platelet dysfunction. 2. In a group of asymptomatic adults with (n = 16) and without (n = 13) mild hypercholesterolaemia, we evaluated inhibition of platelet aggregation in response to the nitric oxide (NO) donor sodium nitroprusside (SNP), as well as the augmentation index (AIx), a parameter of arterial stiffness that is impaired in the presence of endothelial dysfunction. 3. Neither SNP response nor AIx varied significantly between normocholesterolaemic (NC) and hypercholesterolaemic (HC) subjects. 4. Three months treatment with pravastatin (40 mg/day) in HC subjects lowered mean (+/-SEM) total cholesterol levels from 6.6 +/- 0.2 to 5.5 +/- 0.2 mmol/L. Platelet response to SNP increased in platelet-rich plasma and tended to increase in whole blood. The AIx did not change significantly. However, falls in low-density lipoprotein (P = 0.03) and total cholesterol (P = 0.08) correlated with reductions in AIx in individual subjects. 5. These data provide evidence that moderate reduction of cholesterol levels may improve platelet responses to NO, whereas improvement in arterial stiffness may be detectable only with more extensive and/or a prolonged reduction in cholesterol levels.