David J Kennedy1, Yiying Fan, Yuping Wu, Michael Pepoy, Stanley L Hazen, W H Wilson Tang. 1. 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.
Abstract
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.
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.
Authors: W H Wilson Tang; Yuping Wu; Jaana Hartiala; Yiying Fan; Alexandre F R Stewart; Robert Roberts; Ruth McPherson; Paul L Fox; Hooman Allayee; Stanley L Hazen Journal: Arterioscler Thromb Vasc Biol Date: 2011-11-10 Impact factor: 8.311
Authors: David J Kennedy; W H Wilson Tang; Yiying Fan; Yuping Wu; Shirley Mann; Michael Pepoy; Stanley L Hazen Journal: J Am Heart Assoc Date: 2013-04-04 Impact factor: 5.501
Authors: Antonio P Arenas de Larriva; Faye L Norby; Lin Y Chen; Elsayed Z Soliman; Ron C Hoogeveen; Dan E Arking; Laura R Loehr; Alvaro Alonso Journal: Int J Cardiol Date: 2017-04-06 Impact factor: 4.164