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Correlates of endothelial function and their relationship with inflammation in patients with familial hypercholesterolaemia.

Abstract
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.
AuthorsPaul L van Haelst, Jasper J van Doormaal, Folkert W Asselbergs, Arie M van Roon, Nic J G M Veeger, Maureen M Henneman, Andries J Smit, Jan Willem Cohen Tervaert, Johan F May, Rijk O B Gans
JournalClinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 104 Issue 6 Pg. 627-32 (Jun 2003) ISSN: 0143-5221 [Print] England
PMID12558496 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticholesteremic Agents
  • Biomarkers
  • Cholesterol, HDL
  • Cholesterol, LDL
  • E-Selectin
  • Triglycerides
  • Vasodilator Agents
  • Intercellular Adhesion Molecule-1
  • C-Reactive Protein
  • Cholesterol
  • Simvastatin
  • Nitroglycerin
Topics
  • Adult
  • Anticholesteremic Agents (therapeutic use)
  • Biomarkers (blood)
  • Brachial Artery (diagnostic imaging, physiopathology)
  • C-Reactive Protein (analysis)
  • Cholesterol (blood)
  • Cholesterol, HDL (blood)
  • Cholesterol, LDL (blood)
  • E-Selectin (blood)
  • Endothelium, Vascular (physiopathology)
  • Enzyme-Linked Immunosorbent Assay (methods)
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperlipoproteinemia Type II (drug therapy, immunology, physiopathology)
  • Intercellular Adhesion Molecule-1 (blood)
  • Male
  • Middle Aged
  • Nitroglycerin (therapeutic use)
  • Simvastatin (therapeutic use)
  • Triglycerides (blood)
  • Ultrasonography
  • Vasodilation
  • Vasodilator Agents (therapeutic use)

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