title: Urinary biomarkers of oxidative and nitrosative stress and the risk for incident stroke: a nested case-control study from a community-based cohort.
abstract: BACKGROUND
  Oxidative and nitrosative stress has suggested to be involved in the pathophysiology of cardiovascular diseases, but has unclear relationship with the risk for incident stroke.
  
  
  METHODS
  In this nested case-control study, cases consisted of 131 participants who were free of stroke at screening and experienced incident stroke during the follow-up period. Controls were 1:1 frequency-matched for age and sex. Baseline levels of urinary creatinine-indexed biomarkers were measured using liquid chromatography-tandem mass spectrometry, including 8-iso-prostaglandin F₂α (8-iso-PGF₂α), 4-hydroxynonenal conjugate with mercapturic acid, 8-hydroxydeoxyguanosine and 8-nitroguanine.
  
  
  RESULTS
  The levels of urinary 8-iso-PGF₂α in stroke cases were higher than in controls [median (interquartile range), 1.13 (2.23-4.36) μg/g creatinine versus 0.71 (1.34-3.02) μg/g creatinine, p=0.004]. After adjusting cardiovascular risk factors, the association remained that higher level of urinary 8-iso-PGF₂α entailed the greater risk for incident stroke [per 1 standard deviation increase in log-transformed value, adjusted odds ratio, 1.40; 95% confidence interval (CI), 1.06-1.85; p=0.005] with a significant increasing trend across its quartiles (p for trend=0.016). After adding urinary 8-iso-PGF₂α, the prediction model not only improved discrimination between participants with or without incident stroke (integrated discrimination improvement, 0.025; 95% CI, 0.006-0.045; p=0.005), but enhanced stroke risk stratification (net reclassification improvement, 19.8%; 95% CI, 4.6-35.1%; p=0.011). In contrast, the relationships were non-significant among the other three biomarkers.
  
  
  CONCLUSIONS
  Our findings demonstrated that urinary 8-iso-PGF₂α could be an independent biomarker of oxidative stress for prediction of the risk for incident stroke.
authors: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan.
authors: Hung-Ju
authors: HJ
authors: Lin
authors: Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors: Shu-Ting
authors: ST
authors: Chen
authors: Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors: Hon-Yen
authors: HY
authors: Wu
authors: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan.
authors: Hsiu-Ching
authors: HC
authors: Hsu
authors: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan.
authors: Ming-Fong
authors: MF
authors: Chen
authors: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan.
authors: Yuan-Teh
authors: YT
authors: Lee
authors: Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors: Kuen-Yuh
authors: KY
authors: Wu
authors: Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan; Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address: klchien@ntu.edu.tw.
authors: Kuo-Liong
authors: KL
authors: Chien
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000447:Aldehydes / Q000652:urine; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000652:urine; D016022:Case-Control Studies; D002845:Chromatography / Q000379:methods; D003404:Creatinine / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000652:urine*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: C095838:8-nitroguanine; D000447:Aldehydes; D015415:Biomarkers; C075750:8-epi-prostaglandin F2alpha; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003404:Creatinine; D015237:Dinoprost; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal
keywords: 8-Iso-prostaglandin F(2α); Nested case–control study; Oxidative stress; Stroke; Urinary biomarkers