Genetic Risk and Atrial Fibrillation in Patients with Heart Failure

Mariëlle Kloosterman, Bernadet T. Santema, Carolina Roselli, Christopher P. Nelson, Andrea Koekemoer, Simon P. R. Romaine, Isabelle C. Van Gelder, Carolyn S. P. Lam, Vicente A. Artola, Chim Lang, Leong L. Ng, Marco Metra, Stefan D. Anker, Gerasimos S. Filippatos, Kenneth Dickstein, Piotr Ponikowski, Pim van der Harst, Peter van der Meer, Dirk Jan Van Veldhuisen, Emelia J. BenjaminAdriaan A. Voors, Nilesh J. Samani, Michiel Rienstra

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Abstract

Aims: To study the association between an atrial fibrillation (AF) genetic risk score with prevalent AF and all-cause mortality in patients with heart failure.

Methods and results: An AF genetic risk score was calculated in 3759 European ancestry individuals (1783 with sinus rhythm, 1976 with AF) from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) by summing 97 single nucleotide polymorphism (SNP) alleles (ranging from 0-2) weighted by the natural logarithm of the relative SNP risk from the latest AF genome-wide association study. Further, we assessed AF risk variance explained by additive SNP variation, and performance of clinical or genetic risk factors, and the combination in classifying AF prevalence. AF was classified as AF or atrial flutter (AFL) at baseline electrocardiogram and/or a history of AF or AFL. The genetic risk score was associated with AF after multivariable adjustment. Odds ratio for AF prevalence per 1-unit increase genetic risk score was 2.12 (95% confidence interval 1.84-2.45, P = 2.15 × 10 -24 ) in the total cohort, 2.08 (1.72-2.50, P = 1.30 × 10 -14 ) in heart failure with reduced ejection fraction (HFrEF) and 2.02 (1.37-2.99, P = 4.37 × 10 -4 ) in heart failure with preserved ejection fraction (HFpEF). AF-associated loci explained 22.9% of overall AF SNP heritability. Addition of the genetic risk score to clinical risk factors increased the C-index by 2.2% to 0.721.

Conclusions: The AF genetic risk score was associated with increased AF prevalence in HFrEF and HFpEF. Genetic variation accounted for 22.9% of overall AF SNP heritability. Addition of genetic risk to clinical risk improved model performance in classifying AF prevalence.

Original languageEnglish
Number of pages9
JournalEuropean Journal of Heart Failure
Early online date9 Jan 2020
DOIs
Publication statusE-pub ahead of print - 9 Jan 2020

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Atrial Fibrillation
Heart Failure
Single Nucleotide Polymorphism
Atrial Flutter
Genome-Wide Association Study

Keywords

  • Atrial fibrillation
  • Genetic association studies
  • Heart failure
  • Risk factors
  • Single nucleotide polymorphism

Cite this

Kloosterman, M., Santema, B. T., Roselli, C., Nelson, C. P., Koekemoer, A., Romaine, S. P. R., ... Rienstra, M. (2020). Genetic Risk and Atrial Fibrillation in Patients with Heart Failure. European Journal of Heart Failure. https://doi.org/10.1002/ejhf.1735
Kloosterman, Mariëlle ; Santema, Bernadet T. ; Roselli, Carolina ; Nelson, Christopher P. ; Koekemoer, Andrea ; Romaine, Simon P. R. ; Van Gelder, Isabelle C. ; Lam, Carolyn S. P. ; Artola, Vicente A. ; Lang, Chim ; Ng, Leong L. ; Metra, Marco ; Anker, Stefan D. ; Filippatos, Gerasimos S. ; Dickstein, Kenneth ; Ponikowski, Piotr ; van der Harst, Pim ; Meer, Peter van der ; Van Veldhuisen, Dirk Jan ; Benjamin, Emelia J. ; Voors, Adriaan A. ; Samani, Nilesh J. ; Rienstra, Michiel. / Genetic Risk and Atrial Fibrillation in Patients with Heart Failure. In: European Journal of Heart Failure. 2020.
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abstract = "Aims: To study the association between an atrial fibrillation (AF) genetic risk score with prevalent AF and all-cause mortality in patients with heart failure.Methods and results: An AF genetic risk score was calculated in 3759 European ancestry individuals (1783 with sinus rhythm, 1976 with AF) from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) by summing 97 single nucleotide polymorphism (SNP) alleles (ranging from 0-2) weighted by the natural logarithm of the relative SNP risk from the latest AF genome-wide association study. Further, we assessed AF risk variance explained by additive SNP variation, and performance of clinical or genetic risk factors, and the combination in classifying AF prevalence. AF was classified as AF or atrial flutter (AFL) at baseline electrocardiogram and/or a history of AF or AFL. The genetic risk score was associated with AF after multivariable adjustment. Odds ratio for AF prevalence per 1-unit increase genetic risk score was 2.12 (95{\%} confidence interval 1.84-2.45, P = 2.15 × 10 -24 ) in the total cohort, 2.08 (1.72-2.50, P = 1.30 × 10 -14 ) in heart failure with reduced ejection fraction (HFrEF) and 2.02 (1.37-2.99, P = 4.37 × 10 -4 ) in heart failure with preserved ejection fraction (HFpEF). AF-associated loci explained 22.9{\%} of overall AF SNP heritability. Addition of the genetic risk score to clinical risk factors increased the C-index by 2.2{\%} to 0.721. Conclusions: The AF genetic risk score was associated with increased AF prevalence in HFrEF and HFpEF. Genetic variation accounted for 22.9{\%} of overall AF SNP heritability. Addition of genetic risk to clinical risk improved model performance in classifying AF prevalence.",
keywords = "Atrial fibrillation, Genetic association studies, Heart failure, Risk factors, Single nucleotide polymorphism",
author = "Mari{\"e}lle Kloosterman and Santema, {Bernadet T.} and Carolina Roselli and Nelson, {Christopher P.} and Andrea Koekemoer and Romaine, {Simon P. R.} and {Van Gelder}, {Isabelle C.} and Lam, {Carolyn S. P.} and Artola, {Vicente A.} and Chim Lang and Ng, {Leong L.} and Marco Metra and Anker, {Stefan D.} and Filippatos, {Gerasimos S.} and Kenneth Dickstein and Piotr Ponikowski and {van der Harst}, Pim and Meer, {Peter van der} and {Van Veldhuisen}, {Dirk Jan} and Benjamin, {Emelia J.} and Voors, {Adriaan A.} and Samani, {Nilesh J.} and Michiel Rienstra",
note = "Funding Information: British Heart Foundation; European Commission; Dutch Heart Foundation",
year = "2020",
month = "1",
day = "9",
doi = "10.1002/ejhf.1735",
language = "English",
journal = "European Journal of Heart Failure",
issn = "1388-9842",
publisher = "Wiley",

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Kloosterman, M, Santema, BT, Roselli, C, Nelson, CP, Koekemoer, A, Romaine, SPR, Van Gelder, IC, Lam, CSP, Artola, VA, Lang, C, Ng, LL, Metra, M, Anker, SD, Filippatos, GS, Dickstein, K, Ponikowski, P, van der Harst, P, Meer, PVD, Van Veldhuisen, DJ, Benjamin, EJ, Voors, AA, Samani, NJ & Rienstra, M 2020, 'Genetic Risk and Atrial Fibrillation in Patients with Heart Failure', European Journal of Heart Failure. https://doi.org/10.1002/ejhf.1735

Genetic Risk and Atrial Fibrillation in Patients with Heart Failure. / Kloosterman, Mariëlle; Santema, Bernadet T.; Roselli, Carolina; Nelson, Christopher P.; Koekemoer, Andrea; Romaine, Simon P. R.; Van Gelder, Isabelle C.; Lam, Carolyn S. P.; Artola, Vicente A.; Lang, Chim; Ng, Leong L.; Metra, Marco; Anker, Stefan D.; Filippatos, Gerasimos S.; Dickstein, Kenneth; Ponikowski, Piotr; van der Harst, Pim; Meer, Peter van der; Van Veldhuisen, Dirk Jan; Benjamin, Emelia J.; Voors, Adriaan A.; Samani, Nilesh J.; Rienstra, Michiel (Lead / Corresponding author).

In: European Journal of Heart Failure, 09.01.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic Risk and Atrial Fibrillation in Patients with Heart Failure

AU - Kloosterman, Mariëlle

AU - Santema, Bernadet T.

AU - Roselli, Carolina

AU - Nelson, Christopher P.

AU - Koekemoer, Andrea

AU - Romaine, Simon P. R.

AU - Van Gelder, Isabelle C.

AU - Lam, Carolyn S. P.

AU - Artola, Vicente A.

AU - Lang, Chim

AU - Ng, Leong L.

AU - Metra, Marco

AU - Anker, Stefan D.

AU - Filippatos, Gerasimos S.

AU - Dickstein, Kenneth

AU - Ponikowski, Piotr

AU - van der Harst, Pim

AU - Meer, Peter van der

AU - Van Veldhuisen, Dirk Jan

AU - Benjamin, Emelia J.

AU - Voors, Adriaan A.

AU - Samani, Nilesh J.

AU - Rienstra, Michiel

N1 - Funding Information: British Heart Foundation; European Commission; Dutch Heart Foundation

PY - 2020/1/9

Y1 - 2020/1/9

N2 - Aims: To study the association between an atrial fibrillation (AF) genetic risk score with prevalent AF and all-cause mortality in patients with heart failure.Methods and results: An AF genetic risk score was calculated in 3759 European ancestry individuals (1783 with sinus rhythm, 1976 with AF) from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) by summing 97 single nucleotide polymorphism (SNP) alleles (ranging from 0-2) weighted by the natural logarithm of the relative SNP risk from the latest AF genome-wide association study. Further, we assessed AF risk variance explained by additive SNP variation, and performance of clinical or genetic risk factors, and the combination in classifying AF prevalence. AF was classified as AF or atrial flutter (AFL) at baseline electrocardiogram and/or a history of AF or AFL. The genetic risk score was associated with AF after multivariable adjustment. Odds ratio for AF prevalence per 1-unit increase genetic risk score was 2.12 (95% confidence interval 1.84-2.45, P = 2.15 × 10 -24 ) in the total cohort, 2.08 (1.72-2.50, P = 1.30 × 10 -14 ) in heart failure with reduced ejection fraction (HFrEF) and 2.02 (1.37-2.99, P = 4.37 × 10 -4 ) in heart failure with preserved ejection fraction (HFpEF). AF-associated loci explained 22.9% of overall AF SNP heritability. Addition of the genetic risk score to clinical risk factors increased the C-index by 2.2% to 0.721. Conclusions: The AF genetic risk score was associated with increased AF prevalence in HFrEF and HFpEF. Genetic variation accounted for 22.9% of overall AF SNP heritability. Addition of genetic risk to clinical risk improved model performance in classifying AF prevalence.

AB - Aims: To study the association between an atrial fibrillation (AF) genetic risk score with prevalent AF and all-cause mortality in patients with heart failure.Methods and results: An AF genetic risk score was calculated in 3759 European ancestry individuals (1783 with sinus rhythm, 1976 with AF) from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) by summing 97 single nucleotide polymorphism (SNP) alleles (ranging from 0-2) weighted by the natural logarithm of the relative SNP risk from the latest AF genome-wide association study. Further, we assessed AF risk variance explained by additive SNP variation, and performance of clinical or genetic risk factors, and the combination in classifying AF prevalence. AF was classified as AF or atrial flutter (AFL) at baseline electrocardiogram and/or a history of AF or AFL. The genetic risk score was associated with AF after multivariable adjustment. Odds ratio for AF prevalence per 1-unit increase genetic risk score was 2.12 (95% confidence interval 1.84-2.45, P = 2.15 × 10 -24 ) in the total cohort, 2.08 (1.72-2.50, P = 1.30 × 10 -14 ) in heart failure with reduced ejection fraction (HFrEF) and 2.02 (1.37-2.99, P = 4.37 × 10 -4 ) in heart failure with preserved ejection fraction (HFpEF). AF-associated loci explained 22.9% of overall AF SNP heritability. Addition of the genetic risk score to clinical risk factors increased the C-index by 2.2% to 0.721. Conclusions: The AF genetic risk score was associated with increased AF prevalence in HFrEF and HFpEF. Genetic variation accounted for 22.9% of overall AF SNP heritability. Addition of genetic risk to clinical risk improved model performance in classifying AF prevalence.

KW - Atrial fibrillation

KW - Genetic association studies

KW - Heart failure

KW - Risk factors

KW - Single nucleotide polymorphism

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U2 - 10.1002/ejhf.1735

DO - 10.1002/ejhf.1735

M3 - Article

C2 - 31919934

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

SN - 1388-9842

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Kloosterman M, Santema BT, Roselli C, Nelson CP, Koekemoer A, Romaine SPR et al. Genetic Risk and Atrial Fibrillation in Patients with Heart Failure. European Journal of Heart Failure. 2020 Jan 9. https://doi.org/10.1002/ejhf.1735