Effect of pravastatin on intermediate-density and low-density lipoproteins containing apolipoprotein CIII in patients with diabetes mellitus.
The apolipoprotein (apo) B lipoproteins, intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL) that contain apo-CIII are associated with coronary heart disease in patients with diabetes mellitus. Apo-CIII is prominent in diabetic dyslipidemia. We studied whether these apo-B lipoprotein types containing apo-CIII in diabetics are reduced by 1 year of pravastatin treatment. We randomly selected 45 age- and gender-matched placebo/pravastatin pairs from diabetic patients in the Cholesterol and Recurrent Events trial, a randomized, double-blinded trial of pravastatin 40 mg monotherapy. Very-low-density lipoproteins (VLDL) and IDL + LDL particles were subdivided based on the presence of apo-E and apo-CIII to yield 3 particle types: E+CIII+, E-CIII+, and E-CIII-. Compared with placebo, pravastatin reduced IDL + LDL apo-B concentrations for E+CIII+, E-CIII+, and E-CIII- by 42% (p = 0.02), 17% (p = 0.7), and 29% (p = 0.002), respectively, commensurate with IDL + LDL cholesterol concentration reductions in the particle types of 29% (p = 0.002), 25% (p = 0.2), and 36% (p <0.0001), respectively. These IDL + LDL CIII+ particles are rich in triglycerides and cholesterol and are likely to be remnant particles of VLDL. Thus, pravastatin reduced potentially atherogenic remnant particles, a prominent component of diabetic dyslipidemia associated with coronary events; these results may contribute to its demonstrated effectiveness in reducing coronary heart disease in diabetics.
Lee
Sung-Joon
SJ
School of Medicine, Stanford University, Stanford, California, USA.
Sacks
Frank M
FM
D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000097:blood / Q000187:drug effects*; D003327:Coronary Disease / Q000097:blood / Q000209:etiology* / Q000517:prevention & control; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects*; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D000924:Anticholesteremic Agents; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D017035:Pravastatin