High-dose atorvastatin therapy is required for significant improvement of endothelial function in heterozygous...

This study evaluated endothelial dysfunction (ED) by measuring flow-mediated vasodilation (FMD) and for six months documented changes in ED, LDL-C levels and serum concentrations of inflammatory markers with high- and low-dose atorvastatin therapy. In 23 heterozygous familial hypercholesterolaemic (FH) patients, FMD, LDL-C and inflammatory markers (sVCAM-1, sICAM-1, E-selectin and highly sensitive C-reactive protein) were measured at baseline (untreated) and on atorvastatin 20 and 80 mg/day. In untreated patients, FMD was significantly reduced (mean +/- SD = 3.09 +/- 0.91%) compared with 10 normocholesterolaemic controls (8.71 +/- 2.41%; p < 0.01). FMD improved non-significantly with atorvastatin 20 mg/day (5.60 +/- 1.17%), but showed a significant improvement (8.54 +/- 1.11%; p < 0.01) with atorvastatin 80 mg/day. LDL-C decreased markedly (-42.4%; p < 0.0001) on 20 mg/day and decreased further (-48.6%; p < 0.05) on 80 mg/day. FMD improvement, however, did not correlate with LDL-C reduction. No significant changes occurred in any inflammatory markers. We concluded that ED was present in untreated FH patients and improved significantly on high-dose atorvastatin. There was no correlation between the changes in FMD and LDL-C, suggesting either a LDLC-independent effect on ED, or that a marked reduction in LDL-C is required to normalise ED in FH.