Effect of pravastatin on plasma removal of a chylomicron-like emulsion in men with coronary artery disease.
The speed of the plasma removal of chylomicrons, the lipoproteins that carry dietary lipids absorbed in the intestine, may influence atherogenesis. Thus, the effects of a 30-day pravastatin or placebo treatment on the plasma kinetics of chylomicron-like emulsions were evaluated in 25 patients with coronary artery disease who were not hypertriglyceridemic in a randomized, single-blinded study. Eleven patients (53 +/- 4 years, 10 men) received pravastatin 40 mg/day and 14 received placebo (52 +/- 3 years, 13 men). Emulsions labeled with triolein ((3)H-TO) and cholesteryl oleate ((14)C-CO) to assess lipolysis and clearance of chylomicron and remnants, respectively, were injected intravenously in a bolus after a 12-hour fast. Blood samples were collected during 60 minutes to determine radio isotope decaying curves and fractional catabolic rates. Subjects were studied at baseline and after the treatment period. Compared with placebo (data expressed as mean +/- SEM), pravastatin treatment increased the (14)C-CO fractional catabolic rates (70 +/- 45% vs 18 +/- 10%, p = 0.01), reduced total cholesterol (-21 +/- 3% vs -3 +/- 2% p = 0.0001), low-density lipoprotein (LDL) cholesterol (-25 +/- 5% vs 4 +/- 6%, p = 0.0001), and apolipoprotein B levels (-22 +/- 3% vs -7 +/- 3% p = 0.01). (3)H-TO fractional catabolic rates, plasma triglycerides, very-low-density lipoprotein (VLDL) cholesterol and high-density lipoprotein (HDL) cholesterol variations did not differ between the groups. The fractional catabolic rate of (14)C-CO was inversely correlated with plasma apolipoprotein B levels (r = -0.7, p = 0.04). This suggests that besides reducing LDL cholesterol, pravastatin also increases chylomicron remnant clearance, with possible antiatherogenic implications.
Santos
R D
RD
Heart Institute (INCOR) of the Medical School Hospital, São Paulo, Brazil.
Sposito
A C
AC
Ventura
L I
LI
Cesar
L A
LA
Ramires
J A
JA
Maranhão
R C
RC
D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001055:Apolipoproteins B / Q000097:blood; D002914:Chylomicrons / Q000097:blood / Q000187:drug effects* / Q000493:pharmacokinetics; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005217:Fat Emulsions, Intravenous; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use*; D016037:Single-Blind Method
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D002914:Chylomicrons; D005217:Fat Emulsions, Intravenous; D008055:Lipids; D017035:Pravastatin