Department of Cellular and Molecular Medicine, Lerner Research Institute,, †Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, and, §Center for Cardiovascular Diagnostics and Prevention, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, ‡Department of Mathematics, Cleveland State University, Cleveland, Ohio.
Clin J Am Soc Nephrol. 2014 Mar;9(3):462-7. doi: 10.2215/CJN.07720713. Epub 2013 Dec 5.
Increased serum levels of the acute-phase reactant ceruloplasmin predict adverse clinical outcomes in the setting of acute coronary syndromes and heart failure, but their role in patients with CKD is unclear. This study investigated the relationship of ceruloplasmin with clinical outcomes in CKD, especially with regard to traditional cardiac biomarkers.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Serum ceruloplasmin levels in consecutive study participants with CKD (n=654; estimated GFR<60 ml/min per 1.73 m(2)) as well as a control group of non-CKD participants matched for age and sex (n=250) were measured. Study participants were enrolled during 2001-2006 from a population of patients presenting for elective diagnostic coronary angiography and prospectively followed for 3 years (median follow-up=1095 days) to determine incident major adverse cardiac events (defined as a composite of death, nonfatal myocardial infarction, and stroke).
Serum ceruloplasmin levels in CKD patients were elevated versus controls (median [interquartile range]; 25.5 [21.8-29.6] versus 22.7 [19.7-26.5] mg/dl; P<0.001) and associated with increased risk of future major adverse cardiac events (hazard ratio, 1.35; 95% confidence interval, 1.0 to 1.82; P=0.04). After adjusting for traditional risk factors, higher serum ceruloplasmin was still associated with higher risk of major adverse cardiac events at 3 years (hazard ratio, 1.61; 95% confidence interval, 1.15 to 2.25; P=0.01).
In CKD patients, increased serum ceruloplasmin, a regulator of nitric oxide activity, is associated with increased risk of long-term adverse cardiovascular events, even after multivariable model adjustment for traditional clinical and biologic risk factors.
急性反应物质铜蓝蛋白的血清水平升高可预测急性冠脉综合征和心力衰竭患者的不良临床结局，但在慢性肾脏病（CKD）患者中的作用尚不清楚。本研究旨在探讨铜蓝蛋白与 CKD 患者临床结局的关系，特别是与传统心脏生物标志物的关系。
设计、设置、参与者和测量：连续纳入 654 例 CKD 患者（估计肾小球滤过率<60ml/min/1.73m2）和 250 例年龄和性别匹配的非 CKD 患者（对照组）进行研究，测量其血清铜蓝蛋白水平。2001-2006 年期间，前瞻性地随访研究参与者 3 年（中位随访时间=1095 天），以确定主要不良心脏事件（定义为死亡、非致死性心肌梗死和卒中的复合终点）的发生情况。
与对照组相比，CKD 患者的血清铜蓝蛋白水平升高（中位数[四分位间距]；25.5[21.8-29.6] vs. 22.7[19.7-26.5]mg/dl；P<0.001），且未来发生主要不良心脏事件的风险增加（风险比，1.35；95%置信区间，1.0 至 1.82；P=0.04）。在调整了传统危险因素后，较高的血清铜蓝蛋白水平与 3 年后主要不良心脏事件的高风险仍相关（风险比，1.61；95%置信区间，1.15 至 2.25；P=0.01）。
在 CKD 患者中，作为一氧化氮活性调节剂的血清铜蓝蛋白升高与长期不良心血管事件的风险增加相关，即使在多变量模型中对传统临床和生物学危险因素进行了校正。
