Urinary 8-iso-prostaglandin F2alpha 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.


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) F2alpha and its major urinary metabolite, 2,3-dinor-5,6-dihydro-8-iso-PGF2alpha, 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-PGF2alpha and 2,3-dinor-5,6-dihydro-8-iso-PGF2alpha 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-PGF2alpha 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-PGF2alpha (> or =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-PGF2alpha 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-PGF2alpha correlated with the number of risk factors for all subjects (P<0.001 for trend).


CONCLUSIONS
8-iso-PGF2alpha is a sensitive and independent risk marker of CHD.
Schwedhelm
Edzard
E
Clinical Pharmacology Unit, Institute of Experimental and Clinical Pharmacology, University Hospital Hamburg-Eppendorf, Germany. schwedhelm@uke.uni-hamburg.de
Bartling
Asja
A
Lenzen
Henrike
H
Tsikas
Dimitrios
D
Maas
Renke
R
Brümmer
Jens
J
Gutzki
Frank-Mathias
FM
Berger
Jürgen
J
Frölich
Jürgen C
JC
Böger
Rainer H
RH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D015897:Comorbidity; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology / Q000652:urine*; D003920:Diabetes Mellitus / Q000453:epidemiology; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000652:urine*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005858:Germany / Q000453:epidemiology; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D018384:Oxidative Stress; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012907:Smoking / Q000453:epidemiology
C411579:2,3-dinor-5,6-dihydro-8-iso-prostaglandin F2(alpha); D015415:Biomarkers; C075750:8-epi-prostaglandin F2alpha; D002097:C-Reactive Protein; D015237:Dinoprost