Correlates of endothelial function and their relationship with inflammation in patients with familial hypercholesterolaemia.
Atherosclerosis is characterized by a low-grade systemic inflammatory response and endothelial dysfunction. The aim of the present study was to investigate a possible relationship between systemic markers of inflammation, serum markers of endothelial activation and endothelium-dependent vasodilatation in a group of high-risk patients, and to evaluate the effects of intervention with high doses of simvastatin on these parameters. In patients with heterozygous familial hypercholesterolaemia, without atherosclerotic events, flow-mediated vasodilatation (FMD) of the brachial artery was measured after a wash-out period for lipid-lowering drugs (baseline) and after 6 weeks of treatment with simvastatin 80 mg daily. Levels of C-reactive protein (CRP), soluble intercellular cell-adhesion molecule (s-ICAM) and soluble E-selectin (s-E-selectin) were determined at baseline and again after 6 weeks and 12 months of therapy. A total of 35 subjects participated in the study (mean age 42 years; 60% male). When divided into tertiles according to FMD (<3.9%, 3.9-9.0% and >9.0%), no differences in levels of CRP, s-ICAM-1 and/or s-E-selectin were detected between the groups. Moreover, no changes in FMD, levels of CRP or levels of s-ICAM-1 and/or s-E-selectin were found during treatment with simvastatin. We conclude that endothelial function, as reflected by FMD, does not seem to be related to markers of inflammation in familial hypercholesterolaemia subjects at high risk of, but without clinically overt signs of, atherosclerosis. Moreover, aggressive lipid-lowering therapy with simvastatin does not result in improved endothelial function or in a reduction of markers of inflammation in these patients.
van Haelst
Paul L
PL
Department of Cardiology, University Hospital Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands. P.L.van.Haelst@thorax.azg.nl
van Doormaal
Jasper J
JJ
Asselbergs
Folkert W
FW
van Roon
Arie M
AM
Veeger
Nic J G M
NJ
Henneman
Maureen M
MM
Smit
Andries J
AJ
Tervaert
Jan Willem Cohen
JW
May
Johan F
JF
Gans
Rijk O B
RO
D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000627:therapeutic use; D019821:Simvastatin / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography; D014664:Vasodilation; D014665:Vasodilator Agents / Q000627:therapeutic use
D000924:Anticholesteremic Agents; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019040:E-Selectin; D014280:Triglycerides; D014665:Vasodilator Agents; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D002784:Cholesterol; D019821:Simvastatin; D005996:Nitroglycerin