Effect of Moderate and High-Dose Simvastatin on Asymmetric Dimethylarginine-Homocysteine Metabolic Pathways in Patients with Newly Detected Severe Hypercholesterolemia

The assumption that statin therapy can decrease asymmetric dimethylarginine through lowering low-density lipoprotein cholesterol levels seems logical and yet arises some controversy. The aim of the present study is to compare the effects of moderate (40 mg) to high (80 mg) simvastatin doses on asymmetric dimethylarginine and total homocysteine levels in patients with newly detected severe hypercholesterolemia (after target LDL-C levels, ≤2.6 mmol/L, are reached). 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 homocysteine-by a high-performance liquid chromatographic method. There was a statistically significant decrease in total cholesterol, triglycerides, low-density lipoprotein cholesterol, and apolipoprotein-B levels as well as in the apolipoprotein-B/apolipoprotein-A1 index after a 1-month therapy with 40 mg simvastatin (P <0.001). Asymmetric dimethylarginine and total homocysteine levels were also decreased but the difference did not reach statistical significance (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-A1, and apolipoprotein-B). Asymmetric dimethylarginine and total homocysteine levels were lowered significantly with 80 mg simvastatin (P <0.001; P= 0.038). In conclusion, optimizing the target values of low-density lipoprotein cholesterol, a moderate dose (40 mg) of simvastatin has no effect on asymmetric dimethylarginine and total homocysteine in contrast to a high dose (80 mg) after target LDL-C levels are reached (≤2.6 mmol/L) in patients with newly detected severe hypercholesterolemia.