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
Pages (from-to)519-527
Number of pages9
JournalEuropean Journal of Heart Failure
Volume22
Issue number3
Early online date9 Jan 2020
DOIs
Publication statusPublished - 27 Mar 2020

Keywords

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

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  • Cite this

    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., Ng, L. L., Metra, M., Anker, S. D., Filippatos, G. S., Dickstein, K., Ponikowski, P., van der Harst, P., Meer, P. V. D., 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