title: Urinary 8-iso-prostaglandin F2alpha as a risk marker in patients with coronary heart disease: a matched case-control study.
abstract: 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.
authors.affiliation: Clinical Pharmacology Unit, Institute of Experimental and Clinical Pharmacology, University Hospital Hamburg-Eppendorf, Germany. schwedhelm@uke.uni-hamburg.de
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.forename: Asja
authors.initials: A
authors.lastname: Bartling
authors.forename: Henrike
authors.initials: H
authors.lastname: Lenzen
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsikas
authors.forename: Renke
authors.initials: R
authors.lastname: Maas
authors.forename: Jens
authors.initials: J
authors.lastname: Brümmer
authors.forename: Frank-Mathias
authors.initials: FM
authors.lastname: Gutzki
authors.forename: Jürgen
authors.initials: J
authors.lastname: Berger
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Frölich
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
mesh_terms: 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
chemical_list: 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