scholarly journals Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort

EP Europace ◽  
2020 ◽  
Vol 22 (10) ◽  
pp. 1463-1469
Author(s):  
Bastiaan Geelhoed ◽  
Christin S Börschel ◽  
Teemu Niiranen ◽  
Tarja Palosaari ◽  
Aki S Havulinna ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Causal Relationship ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Mendelian Randomization ◽  
Causal Relation ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
Polygenic Risk

Abstract Aims Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and previous studies several single-nucleotide polymorphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. We investigated the causal relationship between natriuretic peptides and AF as well as HF using a Mendelian randomization approach. Methods and results N-terminal pro B-type natriuretic peptide (NT-proBNP) (N = 6669), B-type natriuretic peptide (BNP) (N = 6674), and mid-regional pro atrial natriuretic peptide (MR-proANP) (N = 6813) were measured in the FINRISK 1997 cohort. N = 30 common SNPs related to NT-proBNP, BNP, and MR-proANP were selected from studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF, separately. Polygenic risk scores (PRSs) based on multiple SNPs were used as genetic instrumental variable in Mendelian randomizations. Polygenic risk scores were significantly associated with the three natriuretic peptides. Polygenic risk scores were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation except for small causal betas is unlikely. Conclusion In our Mendelian randomization approach, we confirmed an association between common genetic variation at the NPPA-NPPB locus and natriuretic peptides. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF at the community-level was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms.

scholarly journals Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure – a Mendelian randomization study in the FINRISK cohort

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Boerschel ◽  
B Geelhoed ◽  
T Niiranen ◽  
A.S Havulinna ◽  
C.J.K Fouodo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Causal Relationship ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Mendelian Randomization ◽  
Causal Relation ◽  
Risk Scores ◽  
Funding Source ◽  
Nucleotide Polymorphisms

Abstract Background Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and in previous studies several single nucleotide polymorphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. Purpose We investigated whether a causal relationship exists between natriuretic peptides and AF as well as HF using a Mendelian randomization approach. Methods N-terminal pro B-type natriuretic peptide (NT-proBNP) (N=6669), B-type natriuretic peptide (BNP) (N=6674) and mid-regional pro atrial natriuretic peptide (MR-proANP) (N=6813) were measured in the FINRISK 1997 cohort. Thirty common SNPs related to NT-proBNP, BNP and MR-proANP were selected from prior studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF separately. Polygenic risk scores (PRS) based on multiple SNPs were used as the genetic instrumental variable in Mendelian randomizations. Results PRS were significantly associated with the three natriuretic peptides. PRS were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation, other than a weak one, is unlikely. Conclusion In our Mendelian randomization approach, based on common genetic variation at the NPPA-NPPB locus, associations of the common polymorphisms with natriuretic peptides and the protein biomarkers themselves with incident disease could be confirmed. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms. Comparison of hazard ratios Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme, German Ministry of Research and Education

Opportunistic screening for heart failure with natriuretic peptides in patients with atrial fibrillation: a meta-analysis of individual participant data of four screening studies

Heart ◽  
2018 ◽  
Vol 104 (15) ◽  
pp. 1236.1-1237 ◽  
Author(s):  
Sander van Doorn ◽  
Geert-Jan Geersing ◽  
Rogier F Kievit ◽  
Yvonne van Mourik ◽  
Loes C Bertens ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Meta Analysis ◽  
Diagnostic Value ◽  
Community Dwelling ◽  
Individual Participant Data ◽  
Cut Point ◽  
Individual Participant

ObjectiveHeart failure (HF) often coexists in atrial fibrillation (AF) but is frequently unrecognised due to overlapping symptomatology. Furthermore, AF can cause elevated natriuretic peptide levels, impairing its diagnostic value for HF detection. We aimed to assess the prevalence of previously unknown HF in community-dwelling patients with AF, and to determine the diagnostic value of the amino-terminal pro B-type natriuretic peptide (NTproBNP) for HF screening in patients with AF.MethodsIndividual participant data from four HF-screening studies in older community-dwelling persons were combined. Presence or absence of HF was in each study established by an expert panel following the criteria of the European Society of Cardiology. We performed a two-stage patient-level meta-analysis to calculate traditional diagnostic indices.ResultsOf the 1941 individuals included in the four studies, 196 (10.1%) had AF at baseline. HF was uncovered in 83 (43%) of these 196 patients with AF, versus 381 (19.7%) in those without AF at baseline. Median NTproBNP levels of patients with AF with and without HF were 744 pg/mL and 211 pg/mL, respectively. At the cut-point of 125 pg/mL, sensitivity was 93%, specificity 35%, and positive and negative predictive values 51% and 86%, respectively. Only 23% of all patients with AF had an NTproBNP level below the 125 pg/mL cut-point, with still a 13% prevalence of HF in this group.ConclusionsWith a prevalence of nearly 50%, unrecognised HF is common among community-dwelling patients with AF. Given the high prior change, natriuretic peptides are diagnostically not helpful, and straightforward echocardiography seems to be the preferred strategy for HF screening in patients with AF.

scholarly journals Genetic support of a causal relationship between Iron status and atrial fibrillation: a Mendelian randomization study

2021 ◽  
Author(s):  
Tianyi Wang ◽  
Jun Cheng ◽  
Yanggan Wang
Keyword(s):  
Atrial Fibrillation ◽  
Causal Relationship ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Nucleotide Polymorphisms ◽  
Positive Effects ◽  
A Genome

Background Atrial fibrillation is the most common arrhythmia disease.Animal and observational studies have found a link between iron status and atrial fibrillation. However, the causal relationship between iron status and the risk of atrial fibrillation may be biased by confounding and reverse causality.The purpose of this investigation was to use Mendelian randomization (MR) analysis, which has been widely appied to estimate the causal effect,to reveal whether systemic iron status was causally related to atrial fibrillation. Methods Single nucleotide polymorphisms (SNPs) strongly associated (P< 5.10-8) with four biomarkers of systemic iron status were obtained from a genome-wide association study involving 48,972 subjects conducted by the Genetics of Iron Status consortium. Summary-level data for the genetic associations with atrial fibrillation were acquired from AFGen (Atrial Fibrillation Genetics) consortium study( including 65,446 atrial fibrillation cases and 522,744 controls) .We used a two-sample MR analysis to obtain a causal estimate, and further verified credibility through sensitivity analysis. Results Genetically instrumented serum iron [OR:1.09;95%; confidence interval (CI)1.02-1.16; p=0.01], ferritin [OR:1.16;95%CI:1.02-1.33; p=0.02], and transferrin saturation [OR:1.05;95%CI:1.01-1.11; p=0.01] had positive effects on atrial fibrillation. Genetically instrumented transferrin levels [OR:0.90;95%CI:0.86-0.97; p=0.006] was an inverse correlation with atrial fibrillation. Conclusion In conclusion,our results strongly elucidated a causal link between genetically determined higher iron status and increased the risk of atrial fibrillation.This provided new ideas for clinical prevention and treatment of atrial fibrillation.

Prognostic significance of natriuretic peptide levels in atrial fibrillation without heart failure

Heart ◽  
2020 ◽  
pp. heartjnl-2020-317735
Author(s):  
Yasuhiro Hamatani ◽  
Moritake Iguchi ◽  
Kentaro Ueno ◽  
Yuya Aono ◽  
Masahiro Esato ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Natriuretic Peptide ◽  
Prognostic Marker ◽  
Natriuretic Peptides ◽  
Prognostic Significance ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

ObjectivesNatriuretic peptides are an important prognostic marker in patients with heart failure (HF). However, little is known regarding their prognostic significance in patients with atrial fibrillation (AF) without HF and natriuretic peptides levels are underused in these patients in daily practice.MethodsThe Fushimi AF Registry is a community-based prospective survey of patients with AF in Fushimi-ku, Kyoto, Japan. We investigated patients with AF without HF (defined as prior HF hospitalisation, New York Heart Association functional class≥2 or left ventricular ejection fraction<40%) using the data of B-type natriuretic peptide (BNP, n=388) or N-terminal pro-B-type natriuretic peptide (NT-proBNP, n=771) at enrolment. BNPs were converted to NT-proBNP using a conversion formula. We divided the patients according to quartiles of NT-proBNP levels and compared the backgrounds and outcomes.ResultsOf 1159 patients (mean age: 72.1±10.2 years, median CHA2DS2-VASc score: 3 and oral anticoagulant (OAC) prescription: 671 (56%)), the median NT-proBNP level was 488 (IQR 169–1015) ng/L. Patients with high NT-proBNP levels were older, had higher CHA2DS2-VASc scores and had more OAC prescription (all p<0.001). Kaplan-Meier curves demonstrated that NT-proBNP levels were significantly associated with higher incidences of stroke/systemic embolism, all-cause death and HF hospitalisation during a median follow-up period of 5.0 years (log rank, all p<0.001). Multivariable Cox regression analyses revealed that NT-proBNP levels were an independent predictor of adverse outcomes even after adjustment by various confounders.ConclusionNT-proBNP levels are a significant prognostic marker for adverse outcomes in patients with AF without HF and may have clinical value.Trial registration numberUMIN000005834.

scholarly journals Association of Lipoprotein (a) variants with risk of cardiovascular disease: a Mendelian randomization study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Juan Xia ◽  
Chunyue Guo ◽  
Kuo Liu ◽  
Yunyi Xie ◽  
Han Cao ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Chinese Population ◽  
Left Ventricular Mass Index ◽  
Mendelian Randomization ◽  
Left Ventricular ◽  
Han Chinese ◽  
Han Chinese Population ◽  
Internal Dimension

Abstract Background There is a well-documented empirical relationship between lipoprotein (a) [Lp(a)] and cardiovascular disease (CVD); however, causal evidence, especially from the Chinese population, is lacking. Therefore, this study aims to estimate the causal association between variants in genes affecting Lp(a) concentrations and CVD in people of Han Chinese ethnicity. Methods Two-sample Mendelian randomization analysis was used to assess the causal effect of Lp(a) concentrations on the risk of CVD. Summary statistics for Lp(a) variants were obtained from 1256 individuals in the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei. Data on associations between single-nucleotide polymorphisms (SNPs) and CVD were obtained from recently published genome-wide association studies. Results Thirteen SNPs associated with Lp(a) levels in the Han Chinese population were used as instrumental variables. Genetically elevated Lp(a) was inversely associated with the risk of atrial fibrillation [odds ratio (OR), 0.94; 95% confidence interval (95%CI), 0.901–0.987; P = 0.012)], the risk of arrhythmia (OR, 0.96; 95%CI, 0.941–0.990; P = 0.005), the left ventricular mass index (OR, 0.97; 95%CI, 0.949–1.000; P = 0.048), and the left ventricular internal dimension in diastole (OR, 0.97; 95%CI, 0.950–0.997; P = 0.028) according to the inverse-variance weighted method. No significant association was observed for congestive heart failure (OR, 0.99; 95% CI, 0.950–1.038; P = 0.766), ischemic stroke (OR, 1.01; 95%CI, 0.981–1.046; P = 0.422), and left ventricular internal dimension in systole (OR, 0.98; 95%CI, 0.960–1.009; P = 0.214). Conclusions This study provided evidence that genetically elevated Lp(a) was inversely associated with atrial fibrillation, arrhythmia, the left ventricular mass index and the left ventricular internal dimension in diastole, but not with congestive heart failure, ischemic stroke, and the left ventricular internal dimension in systole in the Han Chinese population. Further research is needed to identify the mechanism underlying these results and determine whether genetically elevated Lp(a) increases the risk of coronary heart disease or other CVD subtypes.

Atrial fibrillation, a difficulty in the heart failure screening with natriuretic peptides

Heart ◽  
2018 ◽  
Vol 104 (15) ◽  
pp. 1236.2-1237 ◽  
Author(s):  
Paulo Bettencourt ◽  
Patrícia Lourenço
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Natriuretic Peptides

scholarly journals Natriuretic Peptides and Analytical Barriers

2017 ◽  
Vol 63 (1) ◽  
pp. 50-58 ◽  
Author(s):  
Vlad C Vasile ◽  
Allan S Jaffe
Keyword(s):  
Heart Failure ◽  
Clinical Practice ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Myocardial Function ◽  
Specific Assay ◽  
Peptide System ◽  
Cardiovascular Homeostasis ◽  
Natriuretic Peptide System

Abstract BACKGROUND The natriuretic peptide system is an endocrine, autocrine and paracrine system that plays an important role in the maintenance of cardiovascular homeostasis. Biomarkers based on these peptides are important diagnostic and prognostic tools for myocardial function. CONTENT Although natriuretic peptides were discovered more than 2 decades ago, their intricate and complex biology is associated with important questions not yet elucidated. The diversity of circulating forms of natriuretic peptides, the distinct expression of these forms in particular patients, and the heterogeneity of heart failure forms, along with specific assay-related and preanalytic issues, cause assays to be poorly harmonized. SUMMARY This review presents the relevant issues related to the biology of natriuretic peptides and differences between assays with immediate implications for clinical practice.

B-Type natriuretic peptide predicts major adverse cardiac and cerebrovascular events after catheter ablation of atrial fibrillation: insights from AF frontier ablation registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Kato ◽  
K Usuda ◽  
H Tada ◽  
T Tsuda ◽  
K Takeuchi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Natriuretic Peptide ◽  
Cardiovascular Events ◽  
Curve Analysis ◽  
Funding Source ◽  
Coronary Syndrome ◽  
Cerebrovascular Events

Abstract Background High plasma B-Type natriuretic peptide (BNP) level is associated with cardiac events or stroke in patients with atrial fibrillation (AF). However, it is still unknown whether BNP predicts worse clinical outcomes after catheter ablation ofAF. Purpose We aimed to see if plasma BNP level is associated with major adverse cardiac and cerebrovascular events (MACCE) after catheter ablation of AF. Methods We retrospectively analyzed 1,853 participants (73.1% men, mean age 63.3±10.3 years, 60.7% paroxysmal AF) who received first catheter ablation of AF with pre-ablation plasma BNP level measurement and completed follow-up more than 3 months after the procedure from AF Frontier Ablation Registry, a multicenter cohort study in Japan. We evaluated an association between plasma BNP level before catheter ablation and first MACCE in cox-regression hazard models adjusted for known risk factors. MACCE were defined as stroke/transient ischemic attack (TIA), cardiovascular events or all-cause death. Results The mean plasma BNP level was 120.2±3.7 pg/mL. During a mean follow-up period of 21.9 months, 57 patients (3.1%) suffered MACCE (ischemic stroke 8 [14.0%], hemorrhagic stroke 5 [8.8%], TIA 5 [8.8%], hospitalization for heart failure 11 [19.2%], acute coronary syndrome 9 [15.8%], hospitalization for other cardiovascular events 8 [14.0%] and all-cause death 11 [19.2%]). Plasma BNP level of patients with MACCE were significantly higher than those without MACCE (291.7±47.0 vs 114.7±3.42 pg/mL, P&lt;0.001). Multivariate analysis revealed that plasma BNP level (hazard ratio [HR] per 10 pg/mL increase 1.014; 95% confidence interval [CI] 1.005–1.023; P=0.001), baseline age (HR 1.052; 95% CI 1.022–1.084; P=0.001), heart failure (HR 2.698; 95% CI 1.512–4.815; P=0.001), old myocardial infarction (HR 3.593; 95% CI 1.675–7.708; P=0.001) and non-ischemic cardiomyopathy (HR 2.676; 95% CI 1.337 - 5.355; P=0.005) were independently associated with MACCE. At receiver-operating characteristic curve analysis, plasma BNP level before catheter ablation ≥162.7 pg/mL was the best threshold to predict MACCE (area under the curve: 0.71). Kaplan-Meier curve analysis (Figure) showed that the cumulative incidence of MACCE was significantly higher in patients with a BNP ≥162.7 pg/mL than in those with a BNP below 162.7 pg/mL (HR 4.85; 95% CI 2.86–8.21; P&lt;0.001). Conclusions Elevation of plasma BNP level was independently related to the increased risk of MACCE after catheter ablation ofAF. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bristol-Meiers Squibb

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