Plasma Ceruloplasmin, a Regulator of Nitric Oxide Activity, and Incident Cardiovascular Risk in Patients with CKD

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). ConclusionIn 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.

Oxidase Enzyme Activities and Their Correlations with Antioxidative Stress Biomarkers in Patients with Acute Coronary Syndrome in Bangladesh

“…This observation is in agreement with a study by Samokyszyn et al [39] which suggested that Cp can inhibit XO. According to Kennedy et al [40], Cp can show both pro-oxidant and antioxidant capacity and there might be a homeostatic balance between the two states that prevails under different conditions. As a pro-oxidant, NO oxidase function of Cp may predominate which promotes nitrative stress and disease progression, while as an antioxidant, Cp can remove free ferrous iron and therefore can reduce a major producer of superoxide and hydroxyl radicals.…”

Biomarkers of antioxidant status and lipid peroxidation in elderly patients with hypertension

“…Increased serum activity has been linked to long-term adverse cardiovascular events. This relationship was strong even after multivariable model adjustment for traditional clinical and biological risk factors [23]. Antihypertensive treatment has been shown to decrease Cp activity [24].…”

Prediction of development and maintenance of high albuminuria during chronic renin–angiotensin suppression by plasma proteomics

“…The levels of this protein are increased by proinflammatory agonists of the acute-phase reaction [22]. Elevated serum CP has been associated with increased cardiovascular risk [23] and albuminuria in men with type 2 diabetes mellitus [24].…”