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Postprandial lipoprotein metabolism is impaired in hypertriglyceridemia. It is unknown how and to what extent atorvastatin affects postprandial lipoprotein metabolism in hypertriglyceridemic patients. We evaluated the effect of 4 weeks of atorvastatin therapy (10 mg/day) on postprandial lipoprotein metabolism in 10 hypertriglyceridemic patients (age, 40 ؎ 3 years; body mass index, 27 ؎ 1 kg/m 2 ; cholesterol, 5.74 ؎ 0.34 mmol/l; triglycerides, 3.90 ؎ 0.66 mmol/l; HDL-cholesterol, 0.85 ؎ 0.05 mmol/l; and LDL-cholesterol, 3.18 ؎ 0.23 mmol/l). Patients were randomized to be studied with or without atorvastatin therapy. Postprandial lipoprotein metabolism was evaluated with a standardized oral fat load. Plasma was obtained every 2 h for 14 h. Large triglyceride-rich lipoproteins (TRLs) (containing chylomicrons) and small TRLs (containing chylomicron remnants) were isolated by ultracentrifugation, and cholesterol, triglyceride, apolipoprotein B-100 (apoB-100), apoB-48, apoC-III, and retinyl-palmitate concentrations were determined. Atorvastatin significantly ( P Ͻ 0.01) decreased fasting cholesterol ( ؊ 27%), triglycerides ( ؊ 43%), LDL-cholesterol ( ؊ 28%), and apoB-100 ( ؊ 31%), and increased HDL-cholesterol ( ؉ 19%). Incremental area under the curve (AUC) significantly ( P Ͻ 0.05) decreased for large TRL-cholesterol, -triglycerides, and -retinyl-palmitate, while none of the small TRL parameters changed. These findings contrast with the results in normolipidemic subjects, in which atorvastatin decreased the AUC for chylomicron remnants (small TRLs) but not for chylomicrons (large TRLs).We conclude that atorvastatin improves postprandial lipoprotein metabolism in addition to decreasing fasting lipid levels in hypertriglyceridemia. Such changes would be expected to improve the atherogenic profile. Hypertriglyceridemia is a very common abnormality that confers a high atherogenic potential, particularly in the context of diabetes (1). To counter this, many hypertriglyceridemic diabetic patients are treated with HMG-CoA-reductase inhibitors, and recent studies support that diabetic patients benefit from such treatment (2, 3).Despite increasing evidence of the importance of lipidindependent effects (pleiotropic effects) of statins, much of the beneficial effect may be related to changes in lipid metabolism. The inhibition of HMG-CoA-reductase leads to an up-regulation of the LDL receptor, resulting in an increased catabolism of LDL particles and thus lower LDL-cholesterol concentration (4). However, lipoproteins other than LDL, including postprandial triglyceride-rich lipoproteins (TRLs), can also be internalized into hepatocytes via the LDL receptor pathway (5-7). It is likely, therefore, that statins have profound effects on postprandial lipoprotein metabolism, particularly in hypertriglyceridemic patients. Because the concentration of postprandial lipoproteins is an independent risk factor for cardiovascular disease (8-12), such changes in postprandial metabolism may be one of the mechanisms by which risk red...

Direct adsorption of lipoproteins (DALI) apheresis has been shown to reduce effectively low-density lipoprotein (LDL) cholesterol and lipoprotein (a) concentrations. However, the effects on nontraditional risk indicators such as hemorheology and LDL subtypes have not been investigated so far. Five patients (2 women, 3 men, age 53 ± 8 years) with coronary artery disease and severe LDL hypercholesterolemia regularly treated with other LDL apheresis devices entered the study and were then treated with DALI for the first time. Hemorheological and lipoprotein parameters were measured before and immediately after the initial DALI apheresis as well as before the fourth DALI apheresis. Compared to baseline (before the first DALI apheresis), the following parameters were significantly improved (p < 0.05) after the first DALI apheresis: LDL cholesterol (69 ± 28 versus 208 ± 82 mg/dl) and cholesterol in each LDL subfraction as well as plasma viscosity (1.23 ± 0.04 versus 1.37 ± 0.06 mPa), C-reactive protein, native blood viscosity, red cell aggregation, and red cell deformability. When parameters before the fourth DALI apheresis were compared to baseline, LDL cholesterol was still lower, and red cell deformability was still improved while cholesterol in each subfraction showed a statistical trend to lower concentrations (0.08 < p < 0.14).In conclusion, DALI apheresis not only reduces LDL cholesterol but also induced a significant reduction of cholesterol in all LDL subfractions and improved various hemorheological parameters. Key Words: Low-density lipoprotein apheresis-Low-density lipoprotein subtypes-Low-density lipoprotein subfractions-Viscosity-Red cell deformability.

This pilot study indicates that at comparable fasting glucose concentration and at comparable HbA1c value pioglitazone is superior to sulfonylureas concerning the improvement of diabetic dyslipoproteinemia. Whether this relates to indirect effects (improvement in insulin sensitivity) or direct effects (stimulation of PPARalpha) remains to be determined.

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