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Identification of precursors of atrial fibrillation (AF) may lead to early detection and prevent associated morbidity and mortality. This study aimed to examine the association between frequent atrial premature complexes (APCs) and incidence of AF. For this retrospective cohort study, we analyzed Holter recordings obtained from 2000 to 2010 of 1,357 veterans free of AF at baseline. All pertinent data in electronic medical records were reviewed to ascertain baseline characteristics. Holter groups with frequent (≥100/day) and infrequent (<100/day) APCs were compared for development of new AF over a median follow-up of 7.5 years. Multivariate Cox regression analyses were performed before and after propensity score matching. Mean age was 64 years with 93% men. Mean body mass index, hemoglobin A1C, low-density lipoprotein, left atrial size, and heart rate were 31.24 kg/m(2), 6.42%, 107.92 mg/dl, 4.26 cm, and 73 beats/min, respectively. AF was noted in 21.8% of patients with frequent APCs compared to 5.6% of those with infrequent APCs. After adjusting for demographics, medication use, co-morbidities, and laboratory and echocardiographic findings, multivariate Cox regression analyses confirmed frequent APCs to be independently associated with higher incidence of AF (hazard ratio [HR] 2.97, 95% confidence interval [CI] 1.85 to 4.80; p <0.001). In propensity-matched groups, this association remained significant (HR 2.87, 95% CI 1.65 to 4.98; p <0.001). Additionally, atrial couplets (≥50/day), atrial bigeminy (≥50/day), frequent runs of ≥3 APCs (≥20 runs/day), and longer runs (≥10 beats/run) were significantly associated with AF (HR 3.11, 3.67, 2.94, and 1.73, respectively, all p <0.05). In conclusion, frequent APCs (≥100/day) are associated with greater risk of AF., (Copyright © 2015 Elsevier Inc. All rights reserved.)