Effects of atorvastatin on fasting and postprandial lipoprotein subclasses in coronary heart disease patients versus control subjects.
The effects of atorvastatin at 20, 40, and 80 mg/day on plasma lipoprotein subclasses were examined in a randomized, placebo-controlled fashion over 24 weeks in 103 patients in the fasting state who had coronary heart disease (CHD) with low-density lipoprotein (LDL) cholesterol levels >130 mg/dl. The effects of placebo and atorvastatin 40 mg/day were examined in 88 subjects with CHD in the fasting state and 4 hours after a meal rich in saturated fat and cholesterol. These findings were compared with results in 88 age- and gender-matched control subjects. Treatment at the 20, 40, and 80 mg/day dose levels resulted in LDL cholesterol reductions of 38%, 46%, and 52% (all p <0.0001), triglyceride reductions of 22%, 26%, and 30% (all p <0.0001), and high-density lipoprotein (HDL) cholesterol increases of 6%, 5%, and 3%, respectively (all p <0.05 at the 20- and 40-mg doses). The lowest total cholesterol/HDL cholesterol ratio was observed with the 80 mg/day dose of atorvastatin (p <0.0001 vs placebo). Remnant-like particle (RLP) cholesterol decreased 33%, 34%, and 32%, respectively (all p <0.0001). Lipoprotein(a) [Lp(a)] cholesterol decreased 9%, 16%, and 21% (all p <0.0001), although Lp(a) mass increased 9%, 8%, and 10%, respectively (all p <0.01). In the fed state, atorvastatin 40 mg/day normalized direct LDL cholesterol (29% below controls), triglycerides (8% above controls), and RLP cholesterol (10% below controls), with similar reductions in the fasting state. At this same dose level, atorvastatin treatment resulted in 39%, 35%, and 59% decreases in fasting triglyceride in large, medium, and small very LDLs, as well as 45%, 33%, and 47% reductions in cholesterol in large, medium, and small LDL, respectively, as assessed by nuclear magnetic resonance (all significant, p <0.05), normalizing these particles versus controls (77 cases vs 77 controls). Moreover, cholesterol in large HDL was increased 37% (p <0.001) by this treatment. Our data indicate that atorvastatin treatment normalizes levels of all classes of triglyceride-rich lipoproteins and LDL in both the fasting and fed states in patients with CHD compared with control subjects.
D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003327:Coronary Disease / Q000097:blood / Q000517:prevention & control*; D004041:Dietary Fats / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005215:Fasting / Q000097:blood*; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood / Q000187:drug effects; D008074:Lipoproteins / Q000097:blood / Q000145:classification / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004041:Dietary Fats; D006538:Heptanoic Acids; D017270:Lipoprotein(a); D008074:Lipoproteins; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin