Published online before print February 2, 2004, doi: 10.1161/01.CIR.0000116761.93647.30
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(Circulation. 2004;109:843-848.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Urinary 8-iso-Prostaglandin F2
as a Risk Marker in Patients With Coronary Heart Disease
A Matched Case-Control Study
From the Clinical Pharmacology Unit, Institute of Experimental and Clinical Pharmacology (E.S., R.M., R.H.B.), Institute of Clinical Chemistry (J. Brümmer), and Institute of Mathematics and Data Processing in Medicine (J. Berger), University Hospital Hamburg-Eppendorf, and the Institute of Clinical Pharmacology (A.B., H.L., D.T., F.-M.G., J.C.F.), Hannover Medical School, Germany.
Correspondence to Dr rer nat Edzard Schwedhelm, Institut für Experimentelle und Klinische Pharmakologie, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, D-20246 Hamburg, Germany. E-mail schwedhelm{at}uke.uni-hamburg.de
Received September 24, 2003; revision received November 7, 2003; accepted November 18, 2003.
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 F2-isoprostane 8-iso-prostaglandin (PG) F2
and its major urinary metabolite, 2,3-dinor-5,6-dihydro-8-iso-PGF2, 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-PGF2 and 2,3-dinor-5,6-dihydro-8-iso-PGF2 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-PGF2 and its metabolite were highly correlated (Spearman’s 
=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-PGF2 (
131 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-PGF2 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-PGF2 correlated with the number of risk factors for all subjects (P<0.001 for trend).
Conclusions— 8-iso-PGF2 is a sensitive and independent risk marker of CHD.
Key Words: prostaglandins • coronary disease • C-reactive protein • isoprostanes • risk factors
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