Plasma phospholipid transfer protein activity in patients with low HDL andcardiovascular disease treated with simvastatin and niacin

Plasma phospholipid transfer protein (PLTP) is an important modulator of hi gh-density lipoprotein (HDL) metabolism, regulating its particle size, comp osition, and mass. In patients with low HDL and cardiovascular disease (CVD ), plasma PLTP activity is positively correlated with the concentration of HDL particles containing apo A-I but not apo A-II (Lp(A-1)). We recently co mpleted a study to determine the effect of simvastatin and niacin (S-N) the rapy on disease progression/regression in these patients, and found that th is therapy selectively increased Lp(A-I). To determine if PLTP was also inc reased with this drug therapy, we measured the PLTP activity in the plasma of 30 of these patients obtained at baseline and after 12 months of therapy , and compared the changes to a similar group of 31 patients who received p lacebo for the drugs. No significant increase in PLTP activity was observed in either group of patients. However, changes in apo A-I and A-II between these two time points were correlated with the corresponding change in PLTP activity. The correlation coefficients were r = 0.57 (P = 0.001) and r = 0 .43 (P = 0.02) for apo A-I, and r = 0.54 (P = 0.002) and r = 0.41 (P = 0.02 ) for apo A-II in the placebo and S-N group, respectively. At baseline, PLT P activity correlated positively with the percent of plasma apo A-I associa ted with Lp(A-I) (r = 0.38, P = 0.04) and the amounts of apo A-I in these p articles (r = 0.43, P = 0.02). These relationships persisted in patients wh o took placebo for 12 months (r = 0.46, P = 0.009 and r = 0.37, P = 0.04, r espectively), but was attenuated in those treated with S-N. These data indi cate that S-N-induced increase in Lp(A-1) was PLTP-independent. It also con firms our previous observation that an interrelationship exists between PLT P and apo-specific DL particle subclasses in CVD patients with low HDL, and that this relationship is altered by drug intervention. (C) 2001 Elsevier Science B.V. All rights reserved.