Measures of oxidative stress in heterozygous familial hypercholesterolaemia

Familial hypercholesterolaemia (FH) may be associated with increased oxidative stress which may contribute to atherogenesis. Plasma lipid hydroperoxides (ROOHs), 8-epi PGF2α and α-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 μmol/l; n=51 and 40, respectively). 8-epi PGF2α 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 μmol/l; P<0.05; n=27 and 24, respectively). Similarly, 8-epi PGF2α 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 α-tocopherol levels in FH patients were similar to those in controls (21.0±0.70 vs. 23.8±1.30 μmol/l). When α-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 μmol/mmol, P<0.0005). There were no differences in absolute or cholesterol standardised α-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.