铜蓝蛋白和急性期蛋白水平与慢性透析患者的心血管疾病相关。

Ceruloplasmin and acute phase protein levels are associated with cardiovascular disease in chronic dialysis patients.

作者信息

Panichi Vincenzo, Taccola Daniele, Rizza Giovanni Manca, Consani Cristina, Migliori Massimiliano, Filippi Cristina, Paoletti Sabrina, Sidoti Antonino, Borracelli Donella, Panicucci Erica, Giovannini Luca

机构信息

Dipartimento Medicina Interna, Sezione di Nefrologia, Università di Pisa, Pisa, Italy.

出版信息

J Nephrol. 2004 Sep-Oct;17(5):715-20.

PMID:15593040

Abstract

BACKGROUND

The most frequent cause of death in hemodialysis (HD) patients is cardiovascular disease (CVD), and chronic inflammation has been identified as an epidemiologically important risk factor for CVD. Elevated levels of minor acute phase reactants, such as ceruloplasmin (Cp) and transferrin, have been related to an increased cardiovascular risk in the general population, but little information is available regarding dialysis patients. We investigated the correlation between Cp and copper concentration (Cu) with major acute phase reactants such as C-reactive protein (CRP) and interleukin-6 (IL-6) in a population of chronic dialytic patients. Furthermore, we evaluated the relationship between long-lasting acute phase proteins such as Cp and nutritional markers.

PATIENTS AND METHODS

CRP (Berhing Diagnostic, high sensitivity modified nephelometric technique, detection limit 0.1 mcg/mL), IL-6 (EIA, RD Systems), serum albumin, prealbumin, Cp (Berhing, nephelometric assay), copper (mass spectrometry, Varian) and standard laboratory routine analysis were determined in 75 stable chronic dialysis patients (age 60 +/- 16 yrs; dialytic age 65 +/- 50 months ) starting a midweek dialytic session.

RESULTS

Thirty-seven patients (49%) had clinical signs of cerebrovascular, cardiovascular or peripheral vascular disease. Fifty-one patients (67%) showed biochemical inflammation markers as suggested by elevated CRP levels (mean 12.4 mg/L, SD 11.5) and IL-6 (mean 21.3 pg/mL, SD 19.7) with a positive correlation (r=0.65; p<0.001) between CRP and IL-6. CRP and IL-6 also related negatively to nutritional markers such as albumin and prealbumin (r=-0.42; p<0.01). Cp related significantly to CRP (r=0.4; p<0.001) and IL-6 (r=0.41; p<0.001), and as expected to copper (r=0.96; p<0.001), but not with serum albumin and prealbumin. In a multivariate logistic regression analysis, age (p<0.001), dialytic age (p>0.01), IL-6 (p=0.04) and Cp (p=0.02) were the strongest risk factors for cardio-vascular disease (CVD).

CONCLUSION

These data suggest that serum Cp could be useful in monitoring the ""chronic inflamed"" patient and support the suggestion that elevated metalloprotein levels are associated with an increased cardiovascular risk in a population of stable dialysis patients.

摘要

背景

血液透析（HD）患者最常见的死亡原因是心血管疾病（CVD），慢性炎症已被确定为CVD在流行病学上的重要危险因素。在普通人群中，诸如铜蓝蛋白（Cp）和转铁蛋白等次要急性期反应物水平升高与心血管风险增加有关，但关于透析患者的相关信息却很少。我们调查了慢性透析患者群体中Cp和铜浓度（Cu）与主要急性期反应物如C反应蛋白（CRP）和白细胞介素-6（IL-6）之间的相关性。此外，我们评估了诸如Cp等持久急性期蛋白与营养指标之间的关系。

患者与方法

在75例开始进行周中透析治疗的稳定慢性透析患者（年龄60±16岁；透析龄65±50个月）中测定了CRP（贝林诊断公司，高灵敏度改良散射比浊法，检测限0.1 mcg/mL）、IL-6（酶免疫分析，RD系统公司）、血清白蛋白、前白蛋白、Cp（贝林公司，散射比浊法测定）、铜（质谱分析法，瓦里安公司）以及标准实验室常规分析指标。

结果

37例患者（49%）有脑血管、心血管或外周血管疾病的临床体征。51例患者（67%）表现出生物化学炎症标志物升高，如CRP水平升高（平均12.4 mg/L，标准差11.5）和IL-6升高（平均21.3 pg/mL，标准差19.7），CRP与IL-6呈正相关（r = 0.65；p < 0.001）。CRP和IL-6也与白蛋白和前白蛋白等营养指标呈负相关（r = -0.42；p < 0.01）。Cp与CRP（r = 0.4；p < 0.001）和IL-6（r = 0.41；p < 0.001）显著相关，并且如预期的那样与铜相关（r = 0.96；p < 0.001），但与血清白蛋白和前白蛋白无关。在多因素逻辑回归分析中，年龄（p < 0.001）、透析龄（p > 0.01）、IL-6（p = 0.04）和Cp（p = 0.02）是心血管疾病（CVD）的最强危险因素。