Association of Nitrotyrosine Levels With Cardiovascular Disease and Modulation by Statin Therapy

CONTEXT Formation of nitric oxide–derived oxidants may serve as a mechanism linking inflammation to development of atherosclerosis. Nitrotyrosine, a specific marker for protein modification by nitric oxide–derived oxidants, is enriched in human atherosclerotic lesions and low-density lipoprotein (LDL) recovered from human atheroma. OBJECTIVES To determine whether systemic levels of nitrotyrosine are associated with the prevalence of coronary artery disease (CAD) and are modulated by hydroxymethylglutaryl coenzyme-A reductase inhibitor (statin) therapy. DESIGN, SETTING, AND PATIENTS A case-control and interventional study at 2 urban tertiary-care referral centers; recruitment for each was from June 1, 2001, until January 1, 2002. For the case-control study, 100 case-patients with established CAD and 108 patients with no clinically evident CAD were recruited consecutively. In the interventional study, participants aged 21 years or older with hypercholesterolemia (LDL cholesterol ≥130 mg/dL [≥3.5 mmol/L]) underwent nutrition and exercise counseling. Those whose levels did not decrease with 6 to 8 weeks were enrolled in the study (n = 35). For 12 weeks, they received 10 mg/d of oral atorvastatin therapy. MAIN OUTCOME MEASURES In the case-control study, the association between systemic levels of protein-bound nitrotyrosine, CAD risk, and presence of CAD. In the interventional study, the change in nitrotyrosine, lipoprotein, and C-reactive protein (CRP) levels. RESULTS Nitrotyrosine levels were significantly higher among patients with CAD (median 9.1 µmol/mol [interquartile range, 4.8-13.8 µmol/mol] tyrosine vs 5.2 µmol/mol [interquartile range, 2.2-8.4 µmol/mol]; P