NAD(P)H oxidase polymorphism (C242T) and high HDL cholesterol associate with recurrent coronary events in postinfarction patients.
We recently identified a subgroup of postinfarction patients at high-risk for recurrent coronary events defined by inflammation (high C-reactive protein) (CRP) and hypercholesterolemia. Within this subgroup, only elevated high-density lipoprotein cholesterol (HDL-C) from a set of metabolic, inflammatory and thrombogenic blood markers was associated with additional risk. To investigate the role of oxidative stress in this high-risk subgroup, we examined effects on risk of a polymorphism known to affect functional activity of NAD(P)H oxidase, an oxidative enzyme associated with generation of reactive oxygen species. The study population comprised non-diabetic patients of thrombogenic factors and recurrent coronary events (THROMBO) postinfarction study having complete blood marker and genotyping results (N=663) for C242T polymorphism of p22phox subunit (T allele associated with decreased activity). Cox multivariable regression, adjusted for significant clinical covariates, was used to assess within-subgroup risk associated with blood markers and polymorphism. In addition to elevated HDL-C (hazard ratio, 95% CI and p-value; 2.62, 1.05-6.55 and 0.039), significant independent risk was found for C242T (CC versus CT plus TT: 3.14, 1.34-7.35 and 0.0084). We conclude that oxidative stress plays a significant role in establishment of risk for recurrent coronary events in a high-risk subgroup of postinfarction patients defined by inflammation and hypercholesterolemia.
Corsetti
James P
JP
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Ryan
Dan
D
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Moss
Arthur J
AJ
Department of Medicine-Cardiology Unit, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Zareba
Wojciech
W
Department of Medicine-Cardiology Unit, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Sparks
Charles E
CE
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA. Electronic address: Charles_Sparks@urmc.rochester.edu.
D002097:C-Reactive Protein / Q000276:immunology; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000503:physiopathology*; D019255:NADPH Oxidases / Q000235:genetics*; D018384:Oxidative Stress / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012008:Recurrence
D008076:Cholesterol, HDL; D002097:C-Reactive Protein; D019255:NADPH Oxidases