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06-04-2010 | Cardiometabolic | Article

Endothelial dysfunction marker affect varies by statin dose


Free abstract

MedWire News: The pleiotropic effect of statins on markers of endothelial dysfunction may vary according to dose in patients with newly diagnosed severe hypercholesterolemia, a study suggests.

A moderate, 40 g/day dose of simvastatin did not significantly affect plasma levels of asymmetric dimethylarginine (ADMA) and total homocysteine after target low-density lipoprotein (LDL) cholesterol levels had been reached.

However, high-dose simvastatin at 80 mg/day improved levels of both endothelial dysfunction markers.

The Bulgarian research team says: “This study provides further evidence to support the hypothesis that the pleiotropic effects of statins regarding the markers of endothelium dysfunction - ADMA and total homocysteine - are different when these drugs are given in a moderate and in a high dose.”

Lyudmila Vladimirova-Kitova and colleagues from the University of Plovdiv studied 120 adults with newly detected severe hypercholesterolemia, who had total cholesterol levels of at least 7.5 mmol/l (290.0 mg/dl) and LDL cholesterol levels of at least 4.9 mmol/l (189.5 mg/dl).

After a month of receiving 40 mg/day simvastatin, there was a statistically significant decrease in total cholesterol, triglycerides, LDL cholesterol, and both apolipoprotein (apo)-B levels and the apo-B/apo-A1 index.

ADMA and total homocysteine levels also decreased, but the difference did not reach statistical significance.

Statin therapy was discontinued for a month, after which 66 patients received 40 mg/day simvastatin while 48 patients received the 80 mg/day dose.

Results showed that high-dose simvastatin treatment resulted in a significant decrease in ADMA and total homocysteine levels among the 40 patients who achieved target LDL cholesterol levels of 2.6 mmol/l (100.5 mg/dl) or less.

Reporting in the journal Cardiovascular Therapeutics, the researchers say: “The higher simvastatin dose, according to our results may be preferred in hypercholesterolemic patients with high baseline levels of ADMA and total homocysteine as a really therapeutic decision for clinical practice at this stage.”

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Anita Wilkinson