Indices of reverse cholesterol transport in subjects with metabolic syndrome after treatment with rosuvastatin.
OBJECTIVE
The effects of the statin, rosuvastatin on indices of reverse cholesterol transport were studied in a randomized, placebo-controlled, cross-over trial in 25 overweight subjects with defined metabolic syndrome.


RESULTS
Four weeks' treatment with 40 mg/day rosuvastatin significantly reduced levels of plasma cholesterol (44%), LDL cholesterol (60%) and triglyceride (38%). HDL cholesterol (mean [S.D.]) rose (0.97[0.17] to 1.05[0.17]mmol/L; P<0.05) and the LpA-I component of HDL from 39[7] to 45[9]mg/dL (P<0.05). LCAT activity fell (0.55[0.13] to 0.35[0.07]nmol/mL/h; P<0.05); CETP activity and mass fell from 89[13] to 80[11]nmol//L/h and from 1.66[0.57] to 1.28[0.41]mug/mL respectively, (P<0.05). Cholesterol efflux in vitro (to plasmas from THP-1 activated cells) fell from 7.1[1.8]% (placebo) to 6.2[1.7]% (rosuvastatin); P<0.05, but when plasmas depleted of apoB lipoproteins were studied, the difference in efflux was no longer statistically significant. During placebo efflux was paradoxically inversely correlated with HDL-C (P=0.016) and LpA-I (P=0.035) concentrations but these correlations were absent after rosuvastatin.


CONCLUSIONS
The data suggest possible HDL dysfunctionality in subjects with metabolic syndrome. The reduced capacity of plasmas following statin treatment to stimulate cholesterol efflux in vitro occurred in association with reduction in apoB lipoproteins and reduced activities of CETP and LCAT, and despite increased levels of HDL cholesterol.
Sviridov
Dmitri
D
Baker Heart Research Institute, Melbourne, Australia.
Hoang
Anh
A
Ooi
Esther
E
Watts
Gerald
G
Barrett
P H R
PH
Nestel
Paul
P
D000328:Adult; D053480:Cholesterol Ester Transfer Proteins / Q000187:drug effects*; D008076:Cholesterol, HDL / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D005464:Fluorobenzenes / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy*; D008875:Middle Aged; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*
C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D007862:Phosphatidylcholine-Sterol O-Acyltransferase