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 C Lang; Leon L Ng; Marco Metra; Stefan Anker; Gerasimos Filippatos; Kenneth Dickstein; Piotr Ponikowski; Pim van der Harst; Peter van der Meer; Dirk J van Veldhuisen; Emelia J Benjamin; Adriaan A Voors; Nilesh J Samani; Michiel Rienstra

doi:10.1002/ejhf.1735

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 C Lang, Leon L Ng, Marco Metra, Stefan Anker, Gerasimos Filippatos, Kenneth Dickstein, Piotr Ponikowski, Pim van der Harst, Peter van der Meer, Dirk J van Veldhuisen, Emelia J BenjaminAdriaan A Voors, Nilesh J Samani, Michiel Rienstra^*

^*Corresponding author for this work

Cardiovascular Centre (CVC)

Research output: Contribution to journal › Article › Academic › peer-review

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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 language	English
Pages (from-to)	519-527
Number of pages	9
Journal	European Journal of Heart Failure
Volume	22
Issue number	3
Early online date	9-Jan-2020
DOIs	https://doi.org/10.1002/ejhf.1735
Publication status	Published - Mar-2020

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Kloosterman, M., Santema, B. T., Roselli, C., Nelson, C. P., Koekemoer, A., Romaine, S. P. R., Van Gelder, I. C., Lam, C. S. P., Artola, V. A., Lang, C. C., Ng, L. L., Metra, M., Anker, S., Filippatos, G., Dickstein, K., Ponikowski, P., van der Harst, P., van der Meer, P., van Veldhuisen, D. J., ... Rienstra, M. (2020). Genetic risk and atrial fibrillation in patients with heart failure. European Journal of Heart Failure, 22(3), 519-527. https://doi.org/10.1002/ejhf.1735

@article{ff07b88ccf1c49039b947dc25155a743,

title = "Genetic risk and atrial fibrillation in patients with heart failure",

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.",

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 Lang, {Chim C} and Ng, {Leon L} and Marco Metra and Stefan Anker and Gerasimos Filippatos and Kenneth Dickstein and Piotr Ponikowski and {van der Harst}, Pim and {van der Meer}, Peter and {van Veldhuisen}, {Dirk J} and Benjamin, {Emelia J} and Voors, {Adriaan A} and Samani, {Nilesh J} and Michiel Rienstra",

note = "{\textcopyright} 2020 The Authors. European Journal of Heart Failure {\textcopyright} 2020 European Society of Cardiology.",

year = "2020",

month = mar,

doi = "10.1002/ejhf.1735",

language = "English",

volume = "22",

pages = "519--527",

journal = "European Journal of Heart Failure",

issn = "1388-9842",

publisher = "Wiley",

number = "3",

}

Kloosterman, M , Santema, BT, Roselli, C, Nelson, CP, Koekemoer, A, Romaine, SPR, Van Gelder, IC , Lam, CSP, Artola, VA, Lang, CC, Ng, LL, Metra, M, Anker, S, Filippatos, G, Dickstein, K, Ponikowski, P, van der Harst, P , van der Meer, P , 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, vol. 22, no. 3, pp. 519-527. https://doi.org/10.1002/ejhf.1735

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 C

AU - Ng, Leon L

AU - Metra, Marco

AU - Anker, Stefan

AU - Filippatos, Gerasimos

AU - Dickstein, Kenneth

AU - Ponikowski, Piotr

AU - van der Harst, Pim

AU - van der Meer, Peter

AU - van Veldhuisen, Dirk J

AU - Benjamin, Emelia J

AU - Voors, Adriaan A

AU - Samani, Nilesh J

AU - Rienstra, Michiel

PY - 2020/3

Y1 - 2020/3

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.

U2 - 10.1002/ejhf.1735

DO - 10.1002/ejhf.1735

M3 - Article

C2 - 31919934

SN - 1388-9842

VL - 22

SP - 519

EP - 527

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

IS - 3

ER -

Genetic risk and atrial fibrillation in patients with heart failure

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