PubMed · 12352021
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Barbara A Fielding, Keith N Frayn. 2002. Lipid metabolism.. https://doi.org/10.1097/00041433-200210000-00014
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To evaluate the potential dose effect of rosuvastatin on triglyceride (TG) levels in Japanese hypertriglyceridemic patients, we randomized 154 patients with TG levels of >or=200 and <800 mg/dL to 8 weeks of treatment with rosuvastatin 5, 10 or 20mg once daily; bezafibrate 200mg twice daily; or placebo. Compared with placebo, TG was reduced by 30.1% with rosuvastatin 5mg, 30.1% with 10mg and 32.3% with 20mg (all p<or=0.0001), with no evidence of a dose effect. Changes in TG were evident after 2 weeks of treatment and maintained thereafter. In a benchmark comparison, rosuvastatin across its dose range reduced TG by 29.1-31.1% from baseline versus 45.4% for bezafibrate. Compared with bezafibrate, rosuvastatin was superior with respect to changes in non-high-density lipoprotein cholesterol (non-HDL-C, -36.8 to -44.3% for rosuvastatin versus -2.0% for bezafibrate), low-density lipoprotein cholesterol (-31.9 to -41.0% versus +29.3%), total cholesterol (-27.1 to -33.3% versus +2.1%), although smaller improvements in HDL-C (12.4-16.7% versus 19.6%) were observed. Rosuvastatin also produced superior dose-related decreases in median high-sensitivity C-reactive protein (22.9-38.5%). Treatment was well tolerated in both rosuvastatin and bezafibrate patients, with clinically important increases in alanine aminotransferase being rare, no adverse effect on renal function being observed and no cases of myopathy or rhabdomyolysis being reported. The current study does not suggest a dose-related effect of rosuvastatin in lowering TG in hypertriglyceridemic Japanese patients, although dose-related improvements in other elements of the atherogenic lipid profile were observed.
Apolipoprotein M (apoM), a novel human apolipoprotein recently discovered, predominantly presents in high density lipoprotein (HDL) in plasma, exclusively expressed in liver and in kidney. The present data demonstrated apoM protects against atherosclerosis (AS) primarily via partaking in prebeta-HDL formation and promoting cholesterol efflux to HDL. However, this lipid-metabolism-associated pathway seems unlikely responsible for all atheroprotective effects of apoM. Notably, the human apoM gene is just located in the major histocompatibility complex class III region (MHC-III) on chromosome 6, many genes in this region are related to the immune and inflammatory response. Furthermore, apoM has been documented to link with some inflammatory factors including platelet activating factor (PAF) and leptin. These evidences indicate that apoM may be involved in inflammatory activities in vivo and the potential immuno- and inflam-reactive property of apoM may contribute to the anti-inflammatory function of HDL, as generally acknowledged as an important atheroprotective mechanism of HDL.
Cardiovascular risk increases with each decrement in renal function. Low-density lipoprotein (LDL) cholesterol levels are not associated with increased mortality, but high-density lipoprotein (HDL) levels are inversely associated with cardiovascular risk. Lipoprotein composition with increased abundance of small dense LDL and HDL and reduced levels of more buoyant isoforms is similar to what is found in states of insulin resistance and in the metabolic syndrome (MS). In both cases, high triglyceride levels are associated with reduced HDL levels. Chronic kidney disease (CKD) is itself associated with increasing insulin resistance as renal function fails. In both instances, decreased levels of apo A-I and apo A-II are a consequence of increased fractional catabolic rate (FCR), resulting from a predominance of small HDL particles. HDL maturation is impaired in CKD through decreased activity of lecithin:cholesterol acyltransferase (LCAT), and increased cholesterol ester transfer protein (CETP) activity in MS shuttles triglycerides back into HDL, thereby destabilizing it. Whether insulin resistance is entirely responsible for disorders of HDL metabolism in CKD, or whether the process is a result of unrelated pathophysiology, is currently unknown.