Cardiovascular disease is a major cause of morbidity and mortality in patients with impaired renal function. Dyslipidemia has been established as a well-known traditional risk factor for cardiovascular disease (CVD) in the general population and it is well known that patients with chronic kidney disease (CKD) exhibit significant alterations in lipoprotein metabolism. In this review, the pathogenesis and treatment of CKD-induced dyslipidemia are discussed. Studies on lipid abnormalities in predialysis, hemodialysis and peritoneal dialysis patients are analyzed. In addition, the results of the studies that tested the effects of the hypolipidemic drugs on cardiovascular morbidity and mortality in patients with CKD are reported.

Abstract-Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A 2 that is primarily associated with low density lipoprotein (LDL). PAF-AH activity has also been found in high density lipoprotein (HDL), although it has recently been indicated that there is no PAF-AH protein in HDL. Plasma paraoxonase 1 (PON1) is an HDL-associated esterase, which also exhibits PAF-AH-like activity. The effect of atorvastatin (20 mg per day for 4 months) on PAF-AH and PON1 activities in patients with dyslipidemia of type IIA (nϭ55) or type IIB (nϭ21) was studied. In both patient groups, atorvastatin significantly reduced plasma PAF-AH activity because of the decrease in LDL plasma levels and the preferential decrease in PAF-AH activity on dense LDL subfractions (LDL-4 and LDL-5). Drug therapy did not affect HDL-associated PAF-AH activity or serum PON1 activities toward paraoxon and phenylacetate in either patient group. However, because of the reduction in LDL cholesterol levels, the ratios of HDL-associated PAF-AH and serum PON1 activities to LDL cholesterol levels were significantly increased after drug administration. The reduction of the LDL-associated PAF-AH activity and the elevation in the ratios of HDL-associated PAF-AH and PON1 activities to LDL plasma levels may represent a new dimension in the antiatherogenic effect of atorvastatin. Key Words: hyperlipidemia Ⅲ monocytes/macrophages Ⅲ platelet-activating factor acetylhydrolase Ⅲ paraoxonase Ⅲ atorvastatin P latelet-activating factor (PAF) is a potent lipid mediator involved in inflammatory diseases 1 as well as in atherogenesis. 2 In plasma, PAF is hydrolyzed and inactivated by PAF-acetylhydrolase (PAF-AH, EC 3.1.1.47), a Ca 2ϩ -independent phospholipase A 2 . 3 PAF-AH has a marked preference for phospholipids with short-chain moieties at the sn-2 position, and with the exception of PAF, PAF-AH can equally hydrolyze oxidized phospholipids containing a polyunsaturated fatty acyl residue at this position. 3 Plasma PAF-AH is complexed to lipoproteins 4,5 ; thus, it is also denoted as lipoprotein-associated phospholipase A 2 . 6 The role of this enzyme in inflammatory and atherosclerotic diseases remains to be established. Indeed, PAF-AH may represent a potent anti-inflammatory and antiatherogenic enzyme because it degrades PAF and proinflammatory oxidized phospholipids, molecules formed during the oxidation of LDL. 7 Consistent with the hypothesis that PAF-AH may exert a cardioprotective role are clinical studies showing that loss of plasma PAF-AH activity due to a G9943 T mutation in the PAF-AH gene may constitute a genetic determinant of atherosclerotic disease in the Japanese population. 8 In contrast to these findings, PAF-AH may exert proinflammatory and proatherogenic actions as a result of the hydrolysis of oxidized phospholipids, because bioactive oxidized free fatty acids 6 and lysophosphatidylcholine are generated. 9,10 A recent clinical study indicating that the mass of plasma PAF-AH could be a potential risk factor for coronary a...

Background:Recent clinical studies showed that lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is a predictor for incident atherosclerotic disease. We have previously shown that among the LDL subfractions, Lp-PLA 2 activity is preferentially associated with the atherogenic small, dense (sdLDL) particles in vitro. We investigated whether Lp-PLA 2 could be a marker of sdLDL in human plasma. Methods: One hundred and seventy-six individuals participated in the study. LDL subclass analysis was performed by polyacrylamide gel electrophoresis. Lp-PLA 2 activity and mass were determined in total plasma and in apolipoprotein B-depleted plasma (HDL-Lp-PLA 2 ). Non-HDL-Lp-PLA 2 activity and mass were calculated by subtracting the HDL-Lp-PLA 2 from total plasma Lp-PLA 2 . Results: On the basis of the LDL subclass analysis, participants were categorized into phenotype A and non-A (total cholesterol mass of the sdLDL subfractions <0.155 and >0.155 mmol/L, respectively). Unlike total plasma Lp-PLA 2 mass, total plasma Lp-PLA 2 activity and non-HDL-Lp-PLA 2 activity and mass were significantly higher in persons with phenotype non-A compared with persons with phenotype A, whereas HDLLp-PLA 2 activity and mass were lower in persons with phenotype non-A compared with phenotype A. Total plasma activity and non-HDL-Lp-PLA 2 activity and mass, but not Lp-PLA 2 mass, were correlated with sdLDL-cholesterol mass, proportion, and mean LDL

Type 2 diabetes mellitus and hypertension overlap in the population. In many subjects, development of diabetes mellitus is characterized by a relatively rapid increase in plasma glucose values. Whether a similar phenomenon occurs during the development of hypertension is not known. We analyzed the pattern of blood pressure (BP) changes during the development of hypertension in patients with or without diabetes mellitus using data from the MCDS (Mexico City Diabetes Study; a population-based study of diabetes mellitus in Hispanic whites) and in the FOS (Framingham Offspring Study, a community-based study in non-Hispanic whites) during a 7-year follow-up. Diabetes mellitus at baseline was a significant predictor of incident hypertension (in FOS, odds ratio, 3.14; 95% confidence interval, 2.17-4.54) independently of sex, age, body mass index, and familial diabetes mellitus. Conversely, hypertension at baseline was an independent predictor of incident diabetes mellitus (in FOS, odds ratio, 3.33; 95% CI, 2.50-4.44). In >60% of the converters, progression from normotension to hypertension was characterized by a steep increase in BP values, averaging 20 mm Hg for systolic BP within 3.5 years (in MCDS). In comparison with the nonconverters group, hypertension and diabetes mellitus converters shared a metabolic syndrome phenotype (hyperinsulinemia, higher body mass index, waist girth, BP, heart rate and pulse pressure, and dyslipidemia). Overall, results were similar in the 2 ethnic groups. We conclude that (1) development of hypertension and diabetes mellitus track each other over time, (2) transition from normotension to hypertension is characterized by a sharp increase in BP values, and (3) insulin resistance is one common feature of both prediabetes and prehypertension and an antecedent of progression to 2 respective disease states.