Börschel Christin S, Ohlrogge Amelie H, Geelhoed Bastiaan, Niiranen Teemu, Havulinna Aki S, Palosaari Tarja, Jousilahti Pekka, Rienstra Michiel, van der Harst Pim, Blankenberg Stefan, Zeller Tanja, Salomaa Veikko, Schnabel Renate B
Department of Cardiology, University Heart and Vascular Centre Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, 20246 Hamburg, Germany.
Europace. 2021 May 21;23(5):674-681. doi: 10.1093/europace/euaa334.
Classical cardiovascular risk factors (CVRFs), biomarkers, and common genetic variation have been suggested for risk assessment of atrial fibrillation (AF). To evaluate their clinical potential, we analysed their individual and combined ability of AF prediction.
In N = 6945 individuals of the FINRISK 1997 cohort, we assessed the predictive value of CVRF, N-terminal pro B-type natriuretic peptide (NT-proBNP), and 145 recently identified single-nucleotide polymorphisms (SNPs) combined in a developed polygenic risk score (PRS) for incident AF. Over a median follow-up of 17.8 years, n = 551 participants (7.9%) developed AF. In multivariable-adjusted Cox proportional hazard models, NT-proBNP [hazard ratio (HR) of log transformed values 4.77; 95% confidence interval (CI) 3.66-6.22; P < 0.001] and the PRS (HR 2.18; 95% CI 1.88-2.53; P < 0.001) were significantly related to incident AF. The discriminatory ability improved asymptotically with increasing numbers of SNPs. Compared with a clinical model, AF risk prediction was significantly improved by addition of NT-proBNP and the PRS. The C-statistic for the combination of CVRF, NT-proBNP, and the PRS reached 0.83 compared with 0.79 for CVRF only (P < 0.001). A replication in the Dutch Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort revealed similar results. Comparing the highest vs. lowest quartile, NT-proBNP and the PRS both showed a more than three-fold increased AF risk. Age remained the strongest risk factor with a 16.7-fold increased risk of AF in the highest quartile.
The PRS and the established biomarker NT-proBNP showed comparable predictive ability. Both provided incremental predictive value over standard clinical variables. Further improvements for the PRS are likely with the discovery of additional SNPs.
经典心血管危险因素（CVRFs）、生物标志物和常见基因变异已被用于心房颤动（AF）的风险评估。为评估它们的临床潜力，我们分析了它们预测AF的个体及联合能力。
在FINRISK 1997队列的6945名个体中，我们评估了CVRF、N末端B型利钠肽原（NT-proBNP）以及在一个开发的多基因风险评分（PRS）中组合的145个最近鉴定出的单核苷酸多态性（SNP）对新发AF的预测价值。在中位随访17.8年期间，n = 551名参与者（7.9%）发生了AF。在多变量调整的Cox比例风险模型中，NT-proBNP [对数转换值的风险比（HR）为4.77；95%置信区间（CI）3.66 - 6.22；P < 0.001]和PRS（HR 2.18；95% CI 1.88 - 2.53；P < 0.001）与新发AF显著相关。随着SNP数量增加，鉴别能力逐渐提高。与临床模型相比，添加NT-proBNP和PRS可显著改善AF风险预测。CVRF + NT-proBNP + PRS组合的C统计量达到0.83，而仅CVRF为0.79（P < 0.001）。在荷兰预防终末期肾病和血管疾病（PREVEND）队列中的重复研究显示了相似结果。比较最高四分位数与最低四分位数，NT-proBNP和PRS均显示AF风险增加超过三倍。年龄仍然是最强的风险因素，最高四分位数中AF风险增加16.7倍。
PRS和已确立的生物标志物NT-proBNP显示出相当的预测能力。两者均比标准临床变量提供了额外的预测价值。随着更多SNP的发现，PRS可能会进一步改善。
