TY - JOUR
TI - Genetic risk and atrial fibrillation in patients with heart failure
AU - Kloosterman, M.
AU - Santema, B.T.
AU - Roselli, C.
AU - Nelson, C.P.
AU - Koekemoer, A.
AU - Romaine, S.P.R.
AU - Van Gelder, I.C.
AU - Lam, C.S.P.
AU - Artola, V.A.
AU - Lang, C.C.
AU - Ng, L.L.
AU - Metra, M.
AU - Anker, S.
AU - Filippatos, G.
AU - Dickstein, K.
AU - Ponikowski, P.
AU - van der Harst, P.
AU - van der Meer, P.
AU - van Veldhuisen, D.J.
AU - Benjamin, E.J.
AU - Voors, A.A.
AU - Samani, N.J.
AU - Rienstra, M.
JO - European Journal of Heart Failure
PY - 2020
VL - 22
TODO - 3
SP - 519-527
PB - John Wiley and Sons Ltd
SN - null
TODO - 10.1002/ejhf.1735
TODO - aged;  all cause mortality;  allele;  Article;  atrial fibrillation;  cardiovascular risk;  cohort analysis;  controlled study;  disease association;  electrocardiogram;  European;  female;  gene locus;  genetic association study;  genetic risk;  genetic risk score;  genetic variation;  genome-wide association study;  heart atrium flutter;  heart failure with preserved ejection fraction;  heart failure with reduced ejection fraction;  heritability;  human;  major clinical study;  male;  observational study;  prevalence;  priority journal;  prospective study;  single nucleotide polymorphism;  sinus rhythm;  atrial fibrillation;  genetics;  heart failure;  heart left ventricle function;  heart stroke volume;  middle aged;  prognosis;  risk factor;  very elderly, angiotensin receptor antagonist;  dipeptidyl carboxypeptidase inhibitor, Aged;  Aged, 80 and over;  Angiotensin Receptor Antagonists;  Angiotensin-Converting Enzyme Inhibitors;  Atrial Fibrillation;  Female;  Genome-Wide Association Study;  Heart Failure;  Humans;  Middle Aged;  Prognosis;  Risk Factors;  Stroke Volume;  Ventricular Function, Left
TODO - 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. © 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
ER -