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      Effects of Atorvastatin on Lipid Profile and Non-Traditional Cardiovascular Risk Factors in Diabetic Patients on Hemodialysis

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          Background/Aims: Dyslipidemia and non-traditional cardiovascular (CV) risk factors, such as lipoprotein(a) (Lp(a)), homocysteine, oxidative stress and inflammation, are important determinants in the increased CV risk of hemodialysis (HD) patients. The aim of our study was to evaluate the effects of atorvastatin on these parameters in one of the groups with the highest CV risk: diabetic patients with end-stage renal disease under HD therapy. Methods: Twenty maintenance HD diabetic patients (mean age 64 ± 10 years, mean time on HD 25 ± 11 months) with low-density lipoprotein cholesterol (LDL-C) >2.59 mmol/l received atorvastatin (10 mg/day) for 4 months. Lipid profile, including total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoproteins A1 and B (Apo-A and Apo-B), and the non-traditional risk factors Lp(a), homocysteine, autoantibodies against oxidized LDL-C (anti-LDLox), total antioxidant status (TAS), and high sensitive C-reactive protein (hs-CRP), were measured at baseline and at the end of the study. Safety was assessed by clinical and laboratory (liver and muscle enzymes) monitoring once a month. Results: Mean percent reductions for TC, LDL-C and TG were 18.5% (p < 0.001), 22% (p < 0.001) and 19% (p < 0.01), respectively. The ratios of TC/HDL-C and LDL-C/HDL-C decreased after treatment (p < 0.05), whereas the ratios of LDL-C/Apo-B (p < 0.01) and Apo-A/Apo-B (p < 0.001) increased. No significant changes were observed in HDL-C. Concerning the non-traditional risk factors, levels of homocysteine, Lp(a), anti-LDLox and TAS did not change significantly. However, hs-CRP decreased from 5.4 (range 0.9–67.8) to 2.3 mg/l (range 0.4–21) (p < 0.01), whereas a concomitant increase in serum albumin was observed (from 38 ± 2 to 40 ± 1.7 g/l, p < 0.01). At baseline, hs-CRP was inversely associated with HDL-C and Apo-A, and directly related to Lp(a). The change in hs-CRP was inversely associated with the change of HDL-C, whereas a direct correlation was found with the change of TG. Conclusions: Atorvastatin administration to diabetic patients on HD is associated with improvement of lipid profile and reduction of hs-CRP. These effects may be critical for the reduction of CV risk and mortality in HD population.

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          Most cited references 13

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          The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis.

          Among patients with end-stage renal disease who are treated with hemodialysis, solute clearance during dialysis and nutritional adequacy are determinants of mortality. We determined the effects of reductions in blood urea nitrogen concentrations during dialysis and changes in serum albumin concentrations, as an indicator of nutritional status, on mortality in a large group of patients treated with hemodialysis. We analyzed retrospectively the demographic characteristics, mortality rate, duration of hemodialysis, serum albumin concentration, and urea reduction ratio (defined as the percent reduction in blood urea nitrogen concentration during a single dialysis treatment) in 13,473 patients treated from October 1, 1990, through March 31, 1991. The risk of death was determined as a function of the urea reduction ratio and serum albumin concentration. As compared with patients with urea reduction ratios of 65 to 69 percent, patients with values below 60 percent had a higher risk of death during follow-up (odds ratio, 1.28 for urea reduction ratios of 55 to 59 percent and 1.39 for ratios below 55 percent). Fifty-five percent of the patients had urea reduction ratios below 60 percent. The duration of dialysis was not predictive of mortality. The serum albumin concentration was a more powerful (21 times greater) predictor of death than the urea reduction ratio, and 60 percent of the patients had serum albumin concentrations predictive of an increased risk of death (values below 4.0 g per deciliter). The odds ratio for death was 1.48 for serum albumin concentrations of 3.5 to 3.9 g per deciliter and 3.13 for concentrations of 3.0 to 3.4 g per deciliter. Diabetic patients had lower serum albumin concentrations and urea reduction ratios than nondiabetic patients. Low urea reduction ratios during dialysis are associated with increased odds ratios for death. These risks are worsened by inadequate nutrition.
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            Factors predicting malnutrition in hemodialysis patients: a cross-sectional study.

            Signs of protein-energy malnutrition are common in maintenance hemodialysis (HD) patients and are associated with increased morbidity and mortality. To evaluate the nutritional status and relationship between various parameters used for assessing malnutrition, we performed a cross-sectional study in 128 unselected patients treated with hemodialysis (HD) thrice weekly for at least two weeks. Global nutritional status was evaluated by the subjective global nutritional assessment (SGNA). Body weight, skinfold thicknesses converted into % body fat mass (BFM), mid-arm muscle circumference, hand-grip strength and several laboratory values, including serum albumin (SA1b), plasma insulin-like growth factor I (p-IGF-I), serum C-reactive protein (SCRP) and plasma free amino acids, were recorded. Dose of dialysis and protein equivalence of nitrogen appearance (nPNA) were evaluated by urea kinetic modeling. The patients were subdivided into three groups based on SGNA: group I, normal nutritional status (36%); group II, mild malnutrition (51%); and group III, moderate or (in 2 cases) severe malnutrition (13%). Clinical factors associated with malnutrition were: high age, presence of cardiovascular disease and diabetes mellitus. nPNA and Kt/V(urea) were similar in the three groups. However, when normalized to desirable body wt, both were lower in groups II and III than in group I. Anthropometric factors associated with malnutrition were low body wt, skinfold thickness, mid-arm muscle circumference (MAMC), and handgrip strength. Biochemical factors associated with malnutrition were low serum levels of albumin and creatinine and low plasma levels of insulin-like growth factor 1 (IGF-1) and branched-chain amino acids (isoleucine, leucine and valine). The serum albumin (SAlb) level was not only a predictor of nutritional status, but was independently influenced by age, sex and SCRP. Plasma IGF-1 levels also reflected the presence and severity of malnutrition and appeared to be more closely associated than SAlb with anthropometric and biochemical indices of somatic protein mass. Elevated SCRP (> 20 mg/liter), which mainly reflected the presence of infection/inflammation and was associated with hypoalbuminemia, was more common in malnourished patients than in patients with normal nutritional status, and also more common in elderly than in younger patients. Plasma amino acid levels, with the possible exception of the branched-chain amino acids (isoleucine, leucine, valine), seem to be poor predictors of nutritional status in hemodialysis patients.
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              Low-density lipoprotein subclass patterns and risk of myocardial infarction.

              The association of low-density lipoprotein (LDL) subclass patterns with coronary heart disease was investigated in a case-control study of nonfatal myocardial infarction. Subclasses of LDL were analyzed by gradient gel electrophoresis of plasma samples from 109 cases and 121 controls. The LDL subclass pattern characterized by a preponderance of small, dense LDL particles was significantly associated with a threefold increased risk of myocardial infarction, independent of age, sex, and relative weight. Plasma levels of high-density lipoprotein cholesterol were decreased, and levels of triglyceride, very low-density lipoproteins, and intermediate-density lipoproteins were increased in subjects with this LDL subclass pattern. Multivariate logistic regression analyses showed that both high-density lipoprotein cholesterol and triglyceride levels contributed to the risk associated with the small, dense LDL subclass pattern. Thus, the metabolic trait responsible for this LDL subclass pattern results in a set of interrelated lipoprotein changes that lead to increased risk of coronary heart disease.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                December 2003
                17 November 2004
                : 95
                : 4
                : c128-c135
                Departments of aNephrology and bBiochemistry, and cResearch Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Tenerife, Spain
                74838 Nephron Clin Pract 2003;95:c128–c135
                © 2003 S. Karger AG, Basel

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                Figures: 2, Tables: 2, References: 49, Pages: 1
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