A 12-week, prospective, open-label analysis of the effect of rosuvastatin on triglyceride-rich lipoprotein metabolism in patients with primary dyslipidemia (Journal article)

Kostapanos, M. S./ Milionis, H. J./ Filippatos, T. D./ Nakou, E. S./ Bairaktari, E. T./ Tselepis, A. D./ Elisaf, M. S.


BACKGROUND: Although the effect of statins on lowering low-density lipoprotein cholesterol (LDL-C) has been extensively studied, their hypotriglyceridemic capacity is not fully understood. OBJECTIVE: The present study examined clinical and laboratory factors potentially associated with the triglyceride (TG)-lowering effect of rosuvastatin. METHODS: Eligible patients had primary dyslipidemia and a moderate risk of heart disease. Patients were prescribed rosuvastatin 10 mg/d in an open-label fashion and kept 3-day food diaries. Laboratory measurements, performed at baseline and 12 weeks, included serum lipid parameters (total cholesterol [TC], TGs, LDL-C, high-density lipoprotein cholesterol [HDL-C], and apolipoprotein [apo] levels), non-lipid metabolic variables (including carbohydrate metabolism parameters and renal, liver, and thyroid function tests), and LDL-subfraction profile (by high-resolution 3% polyacrylamide gel electrophoresis). Tolerability was assessed at each visit. RESULTS: Participants were 75 hyperlipidemic patients (39 men and 36 women; mean age, 51.7 years). At 12 weeks, TC levels were reduced by 35.1% (P < 0.001), TGs by 15.2% (P < 0.001), LDL-C by 48.5% (P < 0.001), apoE by 35.4% (P < 0.001), and apoE by 17.3% (P < 0.001) from baseline, whereas HDL-C and apoA1 levels were not significantly changed. Stepwise linear regression analysis showed that baseline TG levels were most significantly correlated (R(2) = 42.0%; P < 0.001) with the TG-lowering effect of rosuvastatin, followed by the reduction in apoCIII levels (R(2) = 13.6%; P < 0.01). Rosuvastatin use was associated with a reduction in cholesterol mass of both large LDL particles (mean [SD], from 150.5 [36.6] to 90.5 [24.3] mg/dL; P < 0.001) and small, dense LDL (sdLDL) particles (from 11.5 [8.4] to 6.6 [4.5] mg/dL; P < 0.001). Rosuvastatin had no effect on cholesterol distribution of the LDL subfractions (mean [SD], large particles, from 90.8% [7.0%] to 91.8% [5.1%]; sdLDL, from 7.1% [4.7%] to 7.5% [4.8%]) or the mean LDL particle size (from 26.5 [4.2] to 26.6 [4.0] rim). A significant increase in mean LDL particle size after rosuvastatin treatment (mean [SD], from 26.4 [0.4] to 26.9 [0.4] rim; P = 0.02) was observed only in patients with baseline TG levels > or =120 mg/dL. No serious adverse events requiring study treatment discontinuation were reported. One patient who presented with headache and 2 patients who presented with fatigue quickly recovered without discontinuing rosuvastatin treatment. A posttreatment elevation in aminotransferase levels <3-fold the upper limit of normal (ULN) was recorded in 5 (6.7%) patients, and 2 (2.7%) patients experienced elevated creatine kinase concentrations <5-fold ULN. CONCLUSION: Baseline TG levels were the most important independent variable associated with the TG-lowering effect of rosuvastatin.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Apolipoproteins/blood,Blood Glucose,Diet,Dyslipidemias/*drug therapy,Female,Fluorobenzenes/adverse effects/*therapeutic use,Humans,Hypolipidemic Agents/adverse effects/*therapeutic use,Insulin/metabolism,Lipoproteins/blood/*metabolism,Male,Middle Aged,Patient Compliance,Prospective Studies,Pyrimidines/adverse effects/*therapeutic use,Sulfonamides/adverse effects/*therapeutic use,Triglycerides/blood/*metabolism
URI: http://olympias.lib.uoi.gr/jspui/handle/123456789/24406
ISSN: 0149-2918
Link: http://www.ncbi.nlm.nih.gov/pubmed/17825691
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