Background and aims: Early atherosclerosis is characterized by reduced large artery distensibility, paralleled by an increased peroxynitrite formation and nitration of tyrosine in proteins. The aim of the present study was to investigate the short-term effect of cholesterol lowering with rosuvastatin on 3-nitrotyrosine (3-NT), a marker of peroxynitrite-mediated oxidative stress, and on arterial stiffness.
Methods and results: 71 outpatients with primary hypercholesterolemia were recruited for this randomized open-label intervention study; 35 patients were assigned to 4-week rosuvastatin therapy (10mg daily) with a low-fat diet, and 36 patients to a low-fat diet only. Within the cohort of 71 hypercholesterolemic patients, there was a significant correlation between cholesterol levels, 3-NT and aortic pulse wave velocity (aPWV), that is a reliable measure of aortic stiffness. Among those patients who received rosuvastatin, significant reductions in plasma cholesterol, 3-NT and aPWV were observed. Reductions in both aPWV and 3-NT levels correlated significantly with the decrease in plasma cholesterol. Reduction of plasma cholesterol was the only independent predictor for reduced arterial stiffness following rosuvastatin therapy.
Conclusion: Cholesterol reduction achieved following short-term rosuvastatin therapy is associated with a decrease in peroxynitrite-mediated oxidative stress and an improvement in large artery distensibility; reduction in arterial stiffness is directly attributable to rosuvastatin-induced cholesterol lowering and not to reduction of plasma 3-NT levels.