title: Plasma ceruloplasmin, a regulator of nitric oxide activity, and incident cardiovascular risk in patients with CKD.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: David J
authors: DJ
authors: Kennedy
authors: Yiying
authors: Y
authors: Fan
authors: Yuping
authors: Y
authors: Wu
authors: Michael
authors: M
authors: Pepoy
authors: Stanley L
authors: SL
authors: Hazen
authors: W H Wilson
authors: WH
authors: Tang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D002570:Ceruloplasmin / Q000032:analysis*; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009820:Ohio / Q000453:epidemiology; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000503:physiopathology; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D002570:Ceruloplasmin