ABSTRACT
BACKGROUND: In subjects with a high prevalence of metabolic risk abnormalities, the preferred replacement for saturated fat is unresolved. OBJECTIVE: The objective was to study whether carbohydrate or monounsaturated fat is a preferred replacement for saturated fat. DESIGN: Fifty-two men and 33 women, selected to have any combination of HDL cholesterol < or = 30th percentile, triacylglycerol > or = 70th percentile, or insulin > or = 70th percentile, were enrolled in a 3-period, 7-wk randomized crossover study. The subjects consumed an average American diet (AAD; 36% of energy from fat) and 2 additional diets in which 7% of energy from saturated fat was replaced with either carbohydrate (CHO diet) or monounsaturated fatty acids (MUFA diet). RESULTS: Relative to the AAD, LDL cholesterol was lower with both the CHO (-7.0%) and MUFA (-6.3%) diets, whereas the difference in HDL cholesterol was smaller during the MUFA diet (-4.3%) than during the CHO diet (-7.2%). Plasma triacylglycerols tended to be lower with the MUFA diet, but were significantly higher with the CHO diet. Although dietary lipid responses varied on the basis of baseline lipid profiles, the response to diet did not differ between subjects with or without the metabolic syndrome or with or without insulin resistance. Postprandial triacylglycerol concentrations did not differ significantly between the diets. Lipoprotein(a) concentrations increased with both the CHO (20%) and MUFA (11%) diets relative to the AAD. CONCLUSIONS: In the study population, who were at increased risk of coronary artery disease, MUFA provided a greater reduction in risk as a replacement for saturated fat than did carbohydrate.
Subject(s)
Dietary Carbohydrates/administration & dosage , Dietary Fats, Unsaturated/administration & dosage , Dietary Fats/administration & dosage , Adult , Apolipoprotein A-I/blood , Apolipoproteins B/blood , Blood Glucose/metabolism , Cholesterol/blood , Cross-Over Studies , Dietary Carbohydrates/metabolism , Dietary Fats/metabolism , Dietary Fats, Unsaturated/metabolism , Double-Blind Method , Female , Humans , Insulin/blood , Lipoprotein(a)/blood , Male , Middle Aged , Postprandial Period , Triglycerides/blood , Uric Acid/bloodABSTRACT
We investigated the effects of atorvastatin on the lipid and the apoA-I-containing HDL subpopulation profiles in 86 patients with established coronary heart disease (CHD). The entire drug treatment period lasted 12 weeks (4-week periods of 20 then 40, then 80 mg/day). Each dose of atorvastatin treatment resulted in significant reductions in plasma total-C, LDL-C, and triglyceride (TG), and non-significant increases in HDL-C levels compared with placebo treatment. ApoA-I levels did not change significantly during any of the treatment periods. Despite the modest increase of HDL-C (6%, 7%, 5%) and no change in apoA-I levels, the distribution of the apoA-I-containing HDL subpopulations changed significantly during each treatment period. There were significant increases in the concentrations of the large LpA-I alpha-1 (24%, 39%, 26%) and pre alpha-1 (51%, 61%, 63%) subpopulations at the expense of the small lipoprotein LpA-I:A-II alpha-3 subpopulations which decreased on all doses, and the decreases were significant on the 40 and 80 mg/day doses (6%, 5%). Atorvastatin influences the lipid-related risk for CHD in two ways: first, it significantly decreases LDL-C and TG levels while increasing HDL-C, and second, it significantly shifts the HDL subpopulation profile of CHD patients toward that observed in subjects without CHD.
Subject(s)
Anticholesteremic Agents/administration & dosage , Apolipoprotein A-I/blood , Coronary Disease/drug therapy , Heptanoic Acids/administration & dosage , Lipoproteins, HDL/blood , Pyrroles/administration & dosage , Adult , Aged , Atorvastatin , Coronary Disease/blood , Coronary Disease/enzymology , Cross-Over Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Lipids/blood , Lipoproteins, HDL/classification , Male , Middle AgedABSTRACT
We compared the effects of five different statins (atorvastatin, simvastatin, pravastatin, lovastatin, and fluvastatin) on the lipid, lipoprotein, and apolipoprotein (apo) A-I-containing high-density lipoprotein (HDL) subpopulation profiles of 86 coronary heart disease (CHD) patients. Patients with established CHD, and low density lipoprotein (LDL) cholesterol (C)>130 mg/dl, and triglyceride (TG)<400 mg/dl, were treated with atorvastatin 20, 40, and 80 mg/day and one of the other four statins at 20, 40, and when available 80 mg/day in increasing doses (4 weeks of each dose) in a randomized crossover fashion. There was an 8-week placebo controlled washout period between different drug treatments. All five statins on each dose resulted in significant reductions in total- and LDL-C compared to placebo treatment. There were also decreases in plasma TG and increases in HDL-C and apoA-I concentrations, but not all treatments changed these parameters significantly. Each statin except fluvastatin improved the HDL subpopulation profile by increasing the concentrations of the large, cholesterol-rich, LpA-I alpha-1 and prealpha-1 HDL subpopulations. CHD patients have significantly lower concentration of the large, LpA-I alpha-1 HDL particles compared to controls. Our data indicate that statins which are the most effective in lowering LDL-C and TG are also the most effective agents in modifying the HDL subpopulation profile in CHD patients towards the patterns found in healthy individuals. The order of efficacy of statins in increasing alpha-1 HDL subpopulation was: atorvastatin, simvastatin, pravastatin, lovastatin and fluvastatin.
