Urinary 8-iso-prostaglandin F2α as a risk marker in patients with coronary heart disease -: A matched case-control study

Background - Oxidative stress is involved in the pathophysiology of atherosclerosis, diabetes mellitus, hypertension, obesity, and cigarette smoking, all of these being risk factors for coronary heart disease (CHD). We tested the hypothesis that risk factors of CHD are associated with abundant systemic oxidative stress. Methods and Results - We conducted a case-control study with 93 CHD patients and 93 control subjects frequency-matched by age and sex. Urinary excretion of the F-2-isoprostane 8-iso-prostaglandin (PG) F-2alpha and its major urinary metabolite, 2,3-dinor-5,6-dihydro-8-iso-PGF(2alpha), were measured by gas chromatography - tandem mass spectrometry. Body mass index, systolic blood pressure, and C-reactive protein were elevated in CHD patients ( P < 0.01). Urinary 8-iso-PGF(2α) and 2,3-dinor-5,6-dihydro-8-iso-PGF(2α) also differed, from 77 (interquartile range, 61 - 101) to 139 ( 93 - 231) pmol/mmol creatinine and from 120 (91 - 151) to 193 (140 - 275) pmol/mmol in control subjects and case subjects, respectively (P < 0.001). 8-iso-PGF(2alpha) and its metabolite were highly correlated (Spearman's rho = 0.664, P < 0.001). HDL cholesterol was diminished in CHD patients ( P < 0.001). All of these characteristics predicted CHD in univariate analysis. In a multivariate model, the odds ratios were increased only for 8-iso-PGF(2alpha) (greater than or equal to131 pmol/mmol, P < 0.001) and C-reactive protein (>3 mg/ L, P < 0.01), ie, by 30.8 (95% CI, 7.7 - 124) and 7.2 (1.9 - 27.6), respectively. 8-iso-PGF(2α) was found to be a novel marker in addition to known risk factors of CHD, ie, diabetes mellitus, hypercholesterolemia, hypertension, and smoking. Urinary excretion of 8-iso-PGF(2α) correlated with the number of risk factors for all subjects ( P < 0.001 for trend). Conclusions - 8-iso-PGF(2alpha) is a sensitive and independent risk marker of CHD.