title: Systemic elevations of free radical oxidation products of arachidonic acid are associated with angiographic evidence of coronary artery disease.
abstract: Oxidant stress is widely believed to participate in cardiovascular disease pathogenesis. However, progress in defining appropriate systemic antioxidant targeted therapies has been hindered by uncertainty in defining clinically relevant systemic oxidant stress measures. In a case control study, 50 subjects with CAD (>50% stenosis in one or more major coronary vessels) and 54 without CAD (<30% stenosis in all major coronary vessels) were tested. Plasma was isolated and stored under conditions designed to prevent artificial lipid peroxidation. Systemic levels of multiple (n=9) specific fatty acid oxidation products including individual hydroxyoctadecadienoic acids (HODEs), hydroxyeicosatetraenoic acids (HETEs), and F(2)-isoprostanes were simultaneously measured by high-performance liquid chromatography (HPLC) with on-line tandem mass spectrometry, along with traditional risk factors and C-reactive protein (CRP) levels. Of the markers monitored, only 9-HETE and F(2)-isoprostanes, both products of free radical-mediated arachidonic acid oxidation, were significantly elevated in patients with angiographically defined CAD (9-HETE, 8.7 +/- 4 vs 6.8 +/- 4 micromol/mol arachidonate, P = 0.011; and F(2)-isoprostanes, 9.4 +/- 5 vs 6.2 +/- 3 micromol/mol arachidonate, P < 0.001). In multivariable analyses with simultaneous adjustment for Framingham risk score and C-reactive protein, 9-HETE (4th quartile OR = 4.8, 95% CI=1.3 to 17.1; P = 0.016) and F(2)-isoprostanes (4th quartile OR=9.7, 95% CI=2.56 to 36.9; P < 0.001) remained strong and independent predictors of CAD risk. Systemic levels of 9-HETE and F(2)-isoprostanes are independently associated with angiographic evidence of CAD and appear superior to other specific oxidation products of arachidonic and linoleic acids as predictors of the presence of angiographically evident coronary artery disease.
authors.affiliation: Department of Cell Biology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
authors.forename: Mehdi H
authors.initials: MH
authors.lastname: Shishehbor
authors.forename: Renliang
authors.initials: R
authors.lastname: Zhang
authors.forename: Hector
authors.initials: H
authors.lastname: Medina
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Brennan
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Brennan
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ellis
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
mesh_terms: D016718:Arachidonic Acid / Q000737:chemistry*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D028441:F2-Isoprostanes / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D011379:Prognosis
chemical_list: D028441:F2-Isoprostanes; D005227:Fatty Acids; D005609:Free Radicals; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; D002097:C-Reactive Protein