High-dose atorvastatin therapy is required for significant improvement of endothelial function in heterozygous familial hypercholesterolaemic patients.
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.
Brown
Susan L
SL
Carbohydrate and Lipid Metabolism Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg.
Raal
Frederick J
FJ
Panz
Vanessa R
VR
Stevens
Belinda A
BA
Veller
Martin G
MG
D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D018836:Inflammation Mediators / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D011758:Pyrroles / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
D000924:Anticholesteremic Agents; D019040:E-Selectin; D006538:Heptanoic Acids; D018836:Inflammation Mediators; D011758:Pyrroles; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D000069059:Atorvastatin