Laboratory of Research on Lipoproteins and Atherosclerosis, Faculty of Sciences Ben M'sik, B.P. 7955, Sidi Othman, Casablanca, Morocco; Laboratory of Biochemistry, Pasteur Institute of Morocco, Casablanca, Morocco.
J Clin Lipidol. 2008 Feb;2(1):43-50. doi: 10.1016/j.jacl.2007.12.003. Epub 2008 Jan 4.
Hemodialysis patients are at high risk for atherosclerotic events. Enhanced oxidant stress, dyslipidemia, and inflammation may have a major role in this risk. In this work, we assessed lipoprotein status, total homocysteine, high-sensitivity C-reactive protein (hs-CRP), and paraoxonase activity in hemodialysis patients to determine the correlations among these parameters and to compare these values with those measured in normal control subjects.
We enrolled 109 end-stage renal disease patients on long-term hemodialysis and 100 age- and gender-matched healthy subjects. Total cholesterol, triglycerides, and high-density lipoprotein cholesterol levels were evaluated using colorimetric methods. Low-density lipoprotein (LDL) cholesterol was calculated according to the Friedewald formula. Serum levels of hs-CRP, apolipoproteins (Apo) AI, B, E, and lipoprotein(a) were measured by nephelometry. Lipoprotein particle (Lp) A-I and LpA-I:A-II were determined by immunoelectrophoresis. Total homocysteine levels were evaluated by the fluorescence polarization immunoassay method. Paraoxonase activity was determined using the paraoxon-like substrate.
Compared with controls, hemodialysis patients had more frequent atherogenic dyslipidemia, hyperhomocysteinemia, and elevated hs-CRP levels. These latter findings inversely correlate with ApoA-I and LpA-I:A-II and positively with ApoB, lipoprotein(a), and ApoB/ApoA-I ratio. Homocysteine levels correlated positively with age. Paraoxonase activity was decreased in hemodialysis patients, especially in elderly patients. This enzyme activity positively correlated with LpA-I:A-II, and inversely with hs-CRP, LDL-cholesterol, and ApoE levels.
The present study demonstrated an abnormal lipoprotein profile associated with increased hs-CRP and decreased paraoxonase activity in hemodialysis patients. Hence, inflammation, dyslipidemia, and increased oxidant stress linked to uremia may be contributors to increased cardiovascular risk in this population.
血液透析患者发生动脉粥样硬化事件的风险较高。增强的氧化应激、血脂异常和炎症可能在这种风险中起主要作用。在这项工作中，我们评估了血液透析患者的脂蛋白状态、总同型半胱氨酸、高敏 C 反应蛋白（hs-CRP）和对氧磷酶活性，以确定这些参数之间的相关性，并将这些值与正常对照组进行比较。
我们招募了 109 名长期血液透析的终末期肾病患者和 100 名年龄和性别匹配的健康对照者。使用比色法评估总胆固醇、甘油三酯和高密度脂蛋白胆固醇水平。根据 Friedewald 公式计算低密度脂蛋白（LDL）胆固醇。通过散射比浊法测量血清 hs-CRP、载脂蛋白（Apo）AI、B、E 和脂蛋白（a）水平。通过免疫电泳法测定脂蛋白颗粒（Lp）A-I 和 LpA-I:A-II。通过荧光偏振免疫测定法评估总同型半胱氨酸水平。使用对氧磷类似底物测定对氧磷酶活性。
与对照组相比，血液透析患者更频繁地发生致动脉粥样硬化血脂异常、高同型半胱氨酸血症和 hs-CRP 水平升高。这些发现与 ApoA-I 和 LpA-I:A-II 呈负相关，与 ApoB、脂蛋白（a）和 ApoB/ApoA-I 比值呈正相关。同型半胱氨酸水平与年龄呈正相关。血液透析患者的对氧磷酶活性降低，尤其是老年患者。这种酶活性与 LpA-I:A-II 呈正相关，与 hs-CRP、LDL 胆固醇和 ApoE 水平呈负相关。
本研究表明，血液透析患者存在异常的脂蛋白谱，伴有 hs-CRP 升高和对氧磷酶活性降低。因此，与尿毒症相关的炎症、血脂异常和氧化应激增加可能是导致该人群心血管风险增加的原因。
