Ceruloplasmin and atrial fibrillation: evidence of causality from a population‐based Mendelian randomization study

Eryd, Samuel Adamsson; Sjögren, Marketa; Smith, J. G.; Nilsson, Peter M.; Melander, Olle; Hedblad, Bo; Engström, Gunnar

doi:10.1111/joim.12144

Cited by 14 publications

(16 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(7) Our study confirms and extends these findings to the large, middle-aged, biracial cohort of men and women in the ARIC study. After adjusting for traditional risk factors and different biomarkers, higher levels of circulating CP were associated with incident AF.…”

Section: Discussionsupporting

confidence: 87%

“…In this same study, a variant of rs11708215, a single nucleotide polymorphism (SNP) located in the CP gene promoter, was associated with both higher CP concentrations in blood and increased AF risk. (7) These results, however, have not been replicated in other studies. Another SNP, rs13072552, also in the CP gene, has been associated with CP plasma concentration.…”

Section: Introductionmentioning

confidence: 73%

“…If this relationship between AF and CP is confirmed, new prevention approaches could be researched and we could identify individuals at increased risk of AF. (7)…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Larriva

Norby

Chen

et al. 2017

International Journal of Cardiology

View full text Add to dashboard Cite

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 75 years 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 8,829 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 10.5 years 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.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 73%

See 1 more Smart Citation

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

Larriva

Norby

Chen

et al. 2017

International Journal of Cardiology

View full text Add to dashboard Cite

show abstract

“…Maternal obesity has also been linked to inflammation 23. Since inflammation is a well‐known AF risk factor, one can speculate that some of the risk of AF associated with high maternal BMI could perhaps be mediated through upregulation of inflammatory pathways in the offspring 24. Prevalence of obesity among fertile women is rising, with implications for the health of future generations 25.…”

Section: Discussionmentioning

confidence: 99%

Early Life Risk Factors for Incident Atrial Fibrillation in the Helsinki Birth Cohort Study

Johnson

Salonen

Kajantie

et al. 2017

JAHA

View full text Add to dashboard Cite

BackgroundEarly life risk factors are associated with cardiometabolic disease, but have not been fully studied in atrial fibrillation (AF). There are discordant results from existing studies of birth weight and AF, and the impact of maternal body size, gestational age, placental size, and birth length is unknown.Methods and ResultsThe Helsinki Birth Cohort Study includes 13 345 people born as singletons in Helsinki in the years 1934–1944. Follow‐up was through national registries, and ended on December 31, 2013, with 907 incident cases. Cox regression analyses stratified on year of birth were constructed for perinatal variables and incident AF, adjusting for offspring sex, gestational age, and socioeconomic status at birth. There was a significant U‐shaped association between birth weight and AF (P for quadratic term=0.01). The lowest risk of AF was found among those with a birth weight of 3.4 kg (3.8 kg for women [85th percentile] and 3.0 kg for men [17th percentile]). High maternal body mass index (≥30 kg/m2) predicted offspring AF; hazard ratio 1.36 (95% CI 1.07–1.74, P=0.01) compared with normal body mass index (<25 kg/m2). Maternal height was associated with early‐onset AF (<65.3 years), hazard ratio 1.47 (95% CI 1.24–1.74, P<0.0001), but not with later onset AF. Results were independent of incident coronary artery disease, hypertension, or diabetes mellitus.ConclusionsHigh maternal body mass index during pregnancy and maternal height are previously undescribed predictors of offspring AF. Efforts to prevent maternal obesity might reduce later AF in offspring. Birth weight has a U‐shaped relation to incident AF independent of other perinatal variables.

show abstract

“…However, recent studies have demonstrated that Cp may act as an oxidase to nitric oxide [4], and may adversely impact on endothelial function [5]. An emerging literature also supports an important role of Cp in the development of neurodegenerative diseases [6] and in atrial fibrillation [7], suggesting a potential pathogenic role of Cp.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Elevated Serum Ceruloplasmin Levels in Patients With Heart Failure

Hammadah

Fan

et al. 2014

Journal of Cardiac Failure

View full text Add to dashboard Cite

Background Ceruloplasmin (Cp) is a copper-binding acute-phase protein that is increased in inflammatory states and deficient in Wilson’s disease. Recent studies demonstrate increased levels of Cp are associated with increased risk of developing heart failure. Our objective is to test the hypothesis that serum Cp provides incremental and independent prediction of survival in stable patients with heart failure. Methods and Results We measured serum Cp levels in 890 patients with stable heart failure undergoing elective cardiac evaluation that included coronary angiography. We examine the role of Cp levels in predicting survival over 5-years of follow-up. Mean Cp level was 26.6±6.9 mg/dL, and demonstrated relatively weak correlation with BNP (r=0.187, p<0.001). Increased Cp levels were associated with increased 5 year all-cause mortality (Q4 vs Q1 HR 1.9, 95%CI 1.4–2.8, p<0.001). When controlled for coronary disease traditional risk factors, creatinine clearance, dialysis, body mass index, medications, history of myocardial infarction, BNP, LVEF, heart rate, QRS duration, left bundle branch blockage and ICD, higher Cp remained an independent predictor of increased mortality (Q4 vs Q1 HR1.7, 95%CI 1.1 – 2.6, p<0.05). Model quality was improved with addition of Cp to aforementioned co-variables (NRI of 9.3%, p<0.001) Conclusions Ceruloplasmin is an independent predictor of all-cause mortality in patients with heart failure. Use of Cp may help to identify patients at heightened mortality risk.

show abstract

Ceruloplasmin and atrial fibrillation: evidence of causality from a population‐based Mendelian randomization study

Cited by 14 publications

References 44 publications

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

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

Early Life Risk Factors for Incident Atrial Fibrillation in the Helsinki Birth Cohort Study

Prognostic Value of Elevated Serum Ceruloplasmin Levels in Patients With Heart Failure

Contact Info

Product

Resources

About