Dataset Information

Circulating ceruloplasmin, ceruloplasmin-associated genes, and the incidence of atrial fibrillation in the atherosclerosis risk in communities study.

ABSTRACT: BACKGROUND:Ceruloplasmin (CP) may promote structural changes in the atrium making it more arrhythmogenic. We assessed the associations between CP, CP-associated genetic variants, and incident atrial fibrillation (AF) in the Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS:We studied 10,059 men and women without prevalent AF aged 53 to 75years in 1996-1998 and followed through 2012. Circulating CP was measured in stored blood samples obtained in 1996-1998. Polymorphisms rs11708215 and rs13072552, previously associated with CP concentrations, were measured in 10,059 and 8829 participants respectively. AF was ascertained from study electrocardiograms, hospital discharge codes, and death certificates. Multivariable Cox models were run to study the association between circulating CP, CP-associated polymorphisms, and the incidence of AF. Over 10.5years of mean follow-up, 1357 cases of AF were identified. After adjusting for traditional risk factors and biomarkers, higher levels of circulating CP were associated with incident AF (hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.11, 1.61 comparing top to bottom quartiles). Both rs11708215 and rs13072552 were significantly associated with CP levels. Presence of the CP-increasing alleles in rs11708215 and rs13072552, however, were significantly associated with lower risk of AF in whites (HR 0.84, 95%CI 0.76, 0.94, p=0.002 and HR 0.83; 95%CI 0.69, 0.99, p=0.043 respectively per CP-increasing allele in the final adjusted model) but not in African Americans. CONCLUSIONS:Even though higher CP concentrations were associated with increased AF risk, genetic variants associated with higher CP decreased the risk of AF in whites. Our results suggest that circulating CP levels may not be causally related to risk of incident AF.

SUBMITTER: Arenas de Larriva AP

PROVIDER: S-EPMC5515669 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Circulating ceruloplasmin, ceruloplasmin-associated genes, and the incidence of atrial fibrillation in the atherosclerosis risk in communities study.

Arenas de Larriva Antonio P AP Norby Faye L FL Chen Lin Y LY Soliman Elsayed Z EZ Hoogeveen Ron C RC Arking Dan E DE Loehr Laura R LR Alonso Alvaro A

International journal of cardiology 20170406

<h4>Background</h4>Ceruloplasmin (CP) may promote structural changes in the atrium making it more arrhythmogenic. We assessed the associations between CP, CP-associated genetic variants, and incident atrial fibrillation (AF) in the Atherosclerosis Risk in Communities (ARIC) study.<h4>Methods and results</h4>We studied 10,059 men and women without prevalent AF aged 53 to 75years in 1996-1998 and followed through 2012. Circulating CP was measured in stored blood samples obtained in 1996-1998. Poly ...[more]

PMID: 28427851

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Project description:Essentials Ceruloplasmin (CP) is an acute-phase reactant and a potential biomarker of atherothrombotic risk. We assessed associations between CP and venous thromboembolism (VTE) risk in 9933 individuals. Higher circulating CP but not CP-related genes were associated with greater incident VTE rates. Circulating CP could be considered a non-causal biomarker of VTE risk in the community. SUMMARY: Background Ceruloplasmin (CP) is an acute-phase reactant and a potential biomarker of atherothrombotic risk. We assessed the associations between CP, CP-associated genetic variants and incident venous thomboembolism (VTE) in the Atherosclerosis Risk in Communities study. Methods and results In an observational study, 9933 men and women aged 53-75 years without prevalent VTE were included in 1996-1998 and followed through 2011. Circulating CP was measured in stored blood samples obtained in 1996-1998. Polymorphisms rs11708215 and rs13072552, which have been previously associated with CP concentrations, were measured in 8439 participants. VTEs were identified from hospital discharge codes and validated by physician review of medical records and imaging reports. Over a mean of 10.5 years of follow-up, 376 cases of VTE were identified. The association between circulating CP, CP-associated polymorphisms and the incidence of VTE was estimated. After adjustment for traditional risk factors and biomarkers, higher concentrations of circulating CP were associated with greater incident VTE rates (hazard ratio 1.82, 95% confidence interval 1.12-2.95, comparing the 87.5-100th percentile with the bottom quartile). Both rs11708215 and rs13072552 were associated with CP concentrations but not with VTE risk. Conclusions Even though high CP concentrations were associated with an increased VTE risk, CP-associated genetic variants were not associated with a higher risk of VTE. Our results suggest that circulating CP concentrations may not be causally related to the risk of incident VTE.

Dataset Information

Circulating ceruloplasmin, ceruloplasmin-associated genes, and the incidence of atrial fibrillation in the atherosclerosis risk in communities study.

Publications

Circulating ceruloplasmin, ceruloplasmin-associated genes, and the incidence of atrial fibrillation in the atherosclerosis risk in communities study.

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