title: A 12-week, prospective, open-label analysis of the effect of rosuvastatin on triglyceride-rich lipoprotein metabolism in patients with primary dyslipidemia.
abstract: 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.
  
  
  CONCLUSIONS
  Baseline TG levels were the most important independent variable associated with the TG-lowering effect of rosuvastatin.
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kostapanos
authors.forename: Haralampos J
authors.initials: HJ
authors.lastname: Milionis
authors.forename: Theodosios D
authors.initials: TD
authors.lastname: Filippatos
authors.forename: Eleni S
authors.initials: ES
authors.lastname: Nakou
authors.forename: Eleni T
authors.initials: ET
authors.lastname: Bairaktari
authors.forename: Alexandros D
authors.initials: AD
authors.lastname: Tselepis
authors.forename: Moses S
authors.initials: MS
authors.lastname: Elisaf
mesh_terms: D001053:Apolipoproteins / Q000097:blood; D001786:Blood Glucose; D004032:Diet; D050171:Dyslipidemias / Q000188:drug therapy*; D005260:Female; D005464:Fluorobenzenes / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011446:Prospective Studies; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*