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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Plasma ceruloplasmin, a regulator of nitric oxide activity, and incident cardiovascular risk in patients with CKD
David J Kennedy1, Yiying Fan, Yuping Wu
1Department 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.
Insights
Elevated ceruloplasmin in chronic kidney disease (CKD) patients predicts major adverse cardiac events. This acute-phase reactant is a significant risk factor for cardiovascular outcomes in CKD.
Area of Science:
- Nephrology
- Cardiology
- Biochemistry
Background:
- Elevated serum ceruloplasmin is linked to adverse outcomes in acute coronary syndromes and heart failure.
- The role of ceruloplasmin in patients with chronic kidney disease (CKD) remains unclear.
- Investigating ceruloplasmin's association with clinical outcomes in CKD is crucial.
Purpose of the Study:
- To investigate the relationship between serum ceruloplasmin levels and clinical outcomes in patients with CKD.
- To assess whether ceruloplasmin predicts major adverse cardiac events in CKD.
- To compare ceruloplasmin levels in CKD patients versus controls and evaluate its association with traditional cardiac biomarkers.
Main Methods:
- Serum ceruloplasmin levels were measured in 654 CKD patients (eGFR<60 ml/min/1.73 m²) and 250 controls.
- Participants were enrolled during elective diagnostic coronary angiography (2001-2006).
- Major adverse cardiac events (death, myocardial infarction, stroke) were prospectively followed for 3 years.
Main Results:
- CKD patients exhibited significantly higher serum ceruloplasmin levels compared to controls (P<0.001).
- Higher ceruloplasmin levels were associated with an increased risk of major adverse cardiac events (HR, 1.35; P=0.04).
- Even after adjusting for traditional risk factors, elevated ceruloplasmin remained a significant predictor of adverse cardiovascular events (HR, 1.61; P=0.01).
Conclusions:
- Increased serum ceruloplasmin is associated with a higher risk of long-term adverse cardiovascular events in CKD patients.
- Ceruloplasmin, a nitric oxide activity regulator, serves as a significant independent risk factor for cardiovascular events in CKD.
- These findings highlight ceruloplasmin's potential as a biomarker for cardiovascular risk stratification in CKD.
Background And Objectives:
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).
Results:
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).
Conclusion:
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.
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