Published Online
on February 2, 2004

A more recent version of this article appeared on February 24, 2004

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Submitted on September 24, 2003
Revised on November 7, 2003
Accepted on November 18, 2003

Urinary 8-iso-Prostaglandin F₂ as a Risk Marker in Patients With Coronary Heart Disease. A Matched Case-Control Study

Edzard Schwedhelm PhD^*, Asja Bartling MD, Henrike Lenzen MD, Dimitrios Tsikas PhD, Renke Maas MD, Jens Brümmer MD, Frank-Mathias Gutzki Ing Chem, Jürgen Berger PhD, Jürgen C. Frölich MD, FRSM, and Rainer H. Böger MD

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.

^* To whom correspondence should be addressed. E-mail: schwedhelm{at}uke.uni-hamburg.de.

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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