ABSTRACT: BACKGROUND:A general-population approach has been advocated to improve the screening of patients with atrial fibrillation (AF). A more pragmatic alternative may be targeted screening of patients at high risk of developing AF. We assess the value of a simple clinical risk score, C2HEST (C2, coronary artery disease/chronic obstructive pulmonary disease; COPD (1 point each); H, hypertension; E, elderly (age ?75, doubled); S, systolic heart failure; HF (doubled); T, hyperthyroidism)); to facilitate population screening and detection of incident AF in the general population, in a prespecified ancillary analysis of the Huawei Heart Study. METHODS:The Huawei Heart Study investigated general population screening for AF, identified using photoplethysmography (PPG)-based HUAWEI smart devices. We compared the value of a general population approach to a target screening approach between 26 October 2018 and 20 November 2019. RESULTS:There were 644,124 individuals (mean age ± standard deviation, SD 34 ± 11; female 15.9%) who monitored their pulse rhythm using smart devices, among which 209,274 individuals (mean age 34 years, SD11; 10.6% female) completed the questionnaire on cardiovascular risk factors, with 739 detecting AF. Of these, 31.4% (n = 65,810) subjects reported palpitations. The median (interquartile range, IQR) duration to first detected AF was 11 (1-46), 6 (1-49), and 4 (1-24) in the population with low, intermediate, and high C2HEST score category, respectively (p = 0.03). Detected AF events rates increased with increasing C2HEST score points, stratified by age (p for trend, p < 0.001). Hazard ratios of the components of the C2HEST score for detected AF were between 1.31 and 2.75. A combination of symptomatic palpitations and C2HEST score increased prediction of AF detection, compared to using C2HEST score alone (c-indexes 0.72 vs. 0.76, Delong test, p < 0.001). CONCLUSIONS:The C2HEST score, especially when combined with symptoms, could facilitate a targeted population-based screening and preventive strategy for AF.