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 - 2020/3/27
Y1 - 2020/3/27
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
UR - http://www.scopus.com/inward/record.url?scp=85078053327&partnerID=8YFLogxK
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 -