P-104: The effect of rosuvastatin on endothelial function in patients with moderate hypercholesterolaemia

Hypercholesterolaemia increases cardiovascular risk, and endothelial function is impaired even before the development of frank atherosclerosis. Some statins have been shown to reverse this impairment within weeks. We hypothesised that markers of endothelial function would improve after 9 weeks of treatment with rosuvastatin, a new and potent statin. 30 subjects (27 male) with fasting low-density lipoprotein cholesterol (LDL-C) ≥3.5mmol/L were randomised to daily rosuvastatin 10mg, 80mg, or placebo for 9 weeks. Assessments were conducted at weeks 0, 2 and 9. Endothelium-dependent vasodilator function and basal nitric oxide tone were assessed by measuring forearm blood flow responses to Substance P, sodium nitroprusside, and acetylcholine, and L-mono-N-methyl-arginine respectively. Arterial stiffness (measured by pulse wave analysis) and pulse wave velocity were assessed at each visit. Plasma markers of endothelial function were measured: von Willebrand factor (vWF), high-sensitivity C-reactive protein, endothelin-1 (weeks 0, 2 and 9) and tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) activity and antigen levels (weeks 0 and 9). Fasting lipids were measured at each visit. LDL-C was significantly reduced by rosuvastatin, by 48% (10mg) and 56% (80mg), at 9 weeks. High density lipoprotein cholesterol (HDL-C) was increased by 10% (10mg) and 12% (80mg). PAI-1 antigen net release was significantly lower for rosuvastatin 80mg (but not for rosuvastatin 10mg) than placebo (p