title: Measures of oxidative stress in heterozygous familial hypercholesterolaemia.
abstract: Familial hypercholesterolaemia (FH) may be associated with increased oxidative stress which may contribute to atherogenesis. Plasma lipid hydroperoxides (ROOHs), 8-epi PGF(2alpha) and alpha-tocopherol were measured in normal subjects and in newly referred heterozygous FH patients and used as indices of oxidative stress. ROOH levels were higher (+16%), albeit non-significantly, in FH patients than in controls subjects (4.4+/-0.3 vs. 3.8+/-0.3 micromol/l; n=51 and 40, respectively). 8-epi PGF(2alpha) levels were significantly greater (+56%) in the FH patients than in controls (0.43+/-0.06 vs. 0.27+/-0.05 nmol/l; P<0.05; n=14 and 16, respectively). FH patients with vascular disease had significantly higher (+32%) levels of ROOH compared with patients without vascular disease (4.9+/-0.40 vs. 3.7+/-0.33 micromol/l; P<0.05; n=27 and 24, respectively). Similarly, 8-epi PGF(2alpha) concentrations were higher (+100%) in the FH patients with vascular disease than in those without it (0.6+/-0.08 vs. 0.3+/-0.10 nmol/l; P<0.05; n=6 and 8, respectively). Absolute alpha-tocopherol levels in FH patients were similar to those in controls (21.0+/-0.70 vs. 23.8+/-1.30 micromol/l). When alpha-tocopherol levels were expressed relative to cholesterol, however, the concentrations were found to be significantly lower (-43%) in FH patients than in controls (2.9+/-0.10 vs. 5.1+/-0.40 micromol/mmol, P<0.0005). There were no differences in absolute or cholesterol standardised alpha-tocopherol levels in patients with and without vascular disease. These data suggest that oxidative stress is increased in FH-patients and is particularly pronounced in those patients with vascular disease. It is possible that increased oxidative stress may precede the development of vascular disease.
authors.affiliation: Division of Medicine, Department of Medicine, Royal Free and University College Medical School, The Middlesex Hospital, Mortimer Street, W1N 8AA, London, UK. rmhajnz@ucl.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Nourooz-Zadeh
authors.forename: C C
authors.initials: CC
authors.lastname: Smith
authors.forename: D J
authors.initials: DJ
authors.lastname: Betteridge
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000175:diagnosis* / Q000209:etiology*; D015415:Biomarkers / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D015237:Dinoprost / Q000097:blood*; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications*; D008054:Lipid Peroxides / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014810:Vitamin E / Q000097:blood*
chemical_list: D015415:Biomarkers; D008054:Lipid Peroxides; D014810:Vitamin E; D015237:Dinoprost