Simvastatin and Asymmetric Dimethylarginine-Homocysteine Metabolic Pathways in Patients with Newly Detected Severe Hypercholesterolemia

Background: The idea that statin therapy decreases asymmetric dimethylarginine through lowering low-density lipoprotein cholesterol levels seems logic. However, controversy exists in the literature concerning this issue. This study compares the effect of moderate (40 mg) to high (80 mg) simvastatin doses on asymmetric dimethylarginine levels in patients with newly detected severe hypercholesterolemia (after targeted LDL levels of <= 2.6 mmol/L are reached). Methods: The study included 120 adult patients with newly detected severe hypercholesterolemia (total cholesterol >= 7.5 mmol/L and low-density lipoprotein cholesterol >= 4.9 mmol/L). Asymmetric dimethylarginine levels were determined by enzyme-linked immunosorbent assay, total homocystein by the high performance liquid chromatography method. Results: A statistically significant decrease exists in total cholesterol, triglycerides, low-density lipoprotein cholesterol and apolipoprotein-B levels as well as apolipoprotein-B/apolipoprotein-A(1) index following one month of 40 mg simvastatin therapy (P < 0.001). Asymmetric dimethylarginine and total homocystein levels were also decreased but the difference was not significant (p = 0.571; p = 0.569). A dose dependent effect was established comparing the influence of moderate (40 mg) to high (80 mg) simvastatin doses on the tested atherogenic biomarkers (lipid profile, apolipoprotein-A(1), apolipoprotein-B). Asymmetric dimethylarginine and total homocystein levels showed a statistically significant decrease with 80 mg simvastatin (p < 0.001; p = 0.038). In the group of 40 patients, who had reached LDL-cholesterol target levels on 80 mg simvastatin, a reduction in ADMA levels demonstrated a statistically significant correlation with the reduction of LDL-cholesterol (r(xy) = 0.355; p <0.01) and of Apo-B (r(xy) = 0.508; p < 0.001). The backward selection process selected percent ApoB-change as the most important statistically significant factor related to percent ADMA-change (F = 21.127; p = 0.001; R-2 = 0.265). Conclusions: Optimizing the target values of low-density lipoprotein cholesterol to the moderate dose (40 mg) of simvastatin has no effect on asymmetric dimethylarginine and total homocysteine in contrast to high dose (80 mg) after targeted LDL of <= 2.6 mmol/L levels are reached in patients with newly detected severe hypercholesterolemia. (Clin. Lab. 2010;56:291-302)