High levels of urinary F2-isoprostanes predict cardiovascular mortality in postmenopausal women

Background: F2-isoprostanes are prostaglandin-like compounds formed via arachidonic acid oxidation during oxidative stress. Objective: To study the relation between urinary concentrations of 8-iso-prostaglandin F2α (8-iso PGF2α) and mortality due to cardiovascular disease (CVD) in a nested case-cohort design. Methods: Follow-up duration of this prospective study among postmenopausal women was 18 years. Cases included 141 women who died of coronary heart disease and 109 women who died of stroke, whereas controls were a random cohort sample of 142 women. The concentration of 8-iso PGF2α was determined with liquid chromatography/tandem mass spectrometry in urine samples collected at baseline. Results: Smokers had 34.8% higher urinary 8-iso PGF2α concentrations than nonsmokers (P < 0.001). High levels of urinary 8-iso PGF2α were associated with increased incidence of fatal CVD. Women who were in the highest quartile of urinary 8-iso PGF2α levels had, independently of age, an odds ratio of 1.8 (95% confidence interval, 1.1-3.1, P < 0.05) for CVD mortality. Further adjustment by systolic blood pressure, history of CVD, diabetes, smoking, and body mass index did not attenuate this association. Conclusion: Women with high levels of urinary 8-iso PGF2α had an 80% increased risk of dying of coronary heart disease or stroke, supporting involvement of oxidative stress in the pathophysiology of cardiovascular disease.