Background-F-2 isoprostanes are stable, free radical-catalyzed products of
arachidonic acid that reflect lipid peroxidation in vivo.
Methods and Results-Specific assays were developed by use of mass spectrome
try for the F-2 isoprostanes iPF(2 alpha)-III and iPF(2 alpha)-VI and arach
idonic acid (AA). Urinary excretion of the 2 F-2 isoprostanes was significa
ntly increased in hypercholesterolemic patients, whereas substrate AA in ur
ine did not differ between the groups. iPF(2a)-III (pmol/mmol creatinine) w
as elevated (P<0.0005) in homozygous familial hypercholesterolemic (HFH) pa
tients (85+/-5.5; n=38) compared with age- and sex-matched normocholesterol
emic control subjects (58+/-4.2; n=38), as were levels of iPF(2 alpha)-VI (
281+/-22 versus 175+/-13; P<0.0005). Serum cholesterol correlated with urin
ary iPF(2 alpha)-III (r=0.41; P<0.02) and iPF(2 alpha)-VI (r=0.39; P<0.03)
in HFH patients. Urinary excretion of iPF(2 alpha)-III (81+/-10 versus 59+/
-4; P<0.05) and iPF(2 alpha)-VI(195+/-18 versus 149+/-20; P<0.05) was also
increased in moderately hypercholesterolemic subjects (n=24) compared with
their controls. Urinary excretion of iPF(2 alpha)-III and iPF(2 alpha)-VI w
as correlated (r=0.57; P<0.0001; n=106). LDL iPF(2 alpha)-III levels (ng/mg
arachidonate) were elevated (P<0.01) in HFH patients (0.32+/-0.08) compare
d with controls (0.09+/-0.02). The concentrations of iPF(2)-III in LDL and
urine were significantly correlated (r=0.42; P<0.05) in HFH patients.
Conclusions-Asymptomatic patients with moderate and severe hypercholesterol
emia have evidence of oxidant stress in vivo.