Lipid and apolipoprotein levels and distribution in patients with hypertriglyceridemia: Effect of triglyceride reductions with atorvastatin

Atorvastatin is a new hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) r eductase inhibitor that has been demonstrated to be efficacious in reducing both triglyceride (TG) and cholesterol (CHOL) levels in humans. Twenty-sev en (N = 27) patients with primary hypertriglyceridemia (TG > 350 mg/dL) wer e studied before and after 4 weeks on atorvastatin treatment at a dosage of either 20 (n = 16) or 80 (n = 11) mg/d. The present report examines change s in the plasma levels of several apolipoproteins, including apolipoprotein C-ll (apoC-II), apoC-III, and apoE, after atorvastatin. Dose-dependent red uctions in both CHOL (20.3% v 43.1%) and TG (26.5% v 45.8%) for the low and high dose, respectively, have been reported in these individuals. In addit ion to the reductions in apoB commonly associated with the use of HMG-CoA r eductase inhibitors, significant reductions in apoE (37% and 49%), apoC-II (28% and 42%), and apoC-III(18% and 30%) were observed with this agent at t he 20- and 80-mg/d dosage, respectively. Using fast protein liquid chromato graphy (FPLC) to fractionate whole plasma according to particle size, the e ffect of atorvastatin on lipid and apolipoprotein distribution in 20 lipopr otein fractions was also determined. Our results indicate that after 4 week s on atorvastatin, (1) there was a 5-fold increase in the CHOL content as a ssessed by the CHOL/apoB ratio for 13 subfractions from very-low-density li poprotein (VLDL) to small low-density lipoprotein (LDL); (2) there was a st atistically significant reduction in the percentage of plasma apoB associat ed with VLDL-sized particles (30.5% v 26.8%); (3) there was a preferential reduction in plasma apoE from non-apoB-containing lipoproteins with treatme nt; (4) the losses of apoC-II and apoC-III, on the other hand, were compara ble for all lipoprotein fractions; and (5) the fraction of plasma TG associ ated with HDL was increased after treatment. These changes in lipids and ap olipoproteins did not depend on the dose of atorvastatin. There was, on the other hand, a dose-dependent reduction in cholesteryl ester transfer prote in (CETP) activity, defined as the percentage of H-3-cholesteryl oleate tra nsferred from high-density lipoprotein (HDL) to LDL. CETP activity was redu ced by 10.3% and 26.4% with the low and high dose of atorvastatin. Together , these composition data would be consistent with a net reduction in the nu mber of TO-rich lipoproteins that may be explained by (1) a reduction in VL DL synthesis, (2) a preferential removal of VLDL without conversion to LDL, and (3) a preferential accelerated removal of a subpopulation of LDL. Copy right (C) 2000 by W.B. Saunders Company.