心率变异性与普通人群中的心房颤动：一项纵向和孟德尔随机化研究。
Heart rate variability and atrial fibrillation in the general population: a longitudinal and Mendelian randomization study.
机构信息
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Medical Informatics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
出版信息
Clin Res Cardiol. 2023 Jun;112(6):747-758. doi: 10.1007/s00392-022-02072-5. Epub 2022 Aug 13.
BACKGROUND
Sex differences and causality of the association between heart rate variability (HRV) and atrial fibrillation (AF) in the general population remain unclear.
METHODS
12,334 participants free of AF from the population-based Rotterdam Study were included. Measures of HRV including the standard deviation of normal RR intervals (SDNN), SDNN corrected for heart rate (SDNNc), RR interval differences (RMSSD), RMSSD corrected for heart rate (RMSSDc), and heart rate were assessed at baseline and follow-up examinations. Joint models, adjusted for cardiovascular risk factors, were used to determine the association between longitudinal measures of HRV with new-onset AF. Genetic variants for HRV were used as instrumental variables in a Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) summary-level data.
RESULTS
During a median follow-up of 9.4 years, 1302 incident AF cases occurred among 12,334 participants (mean age 64.8 years, 58.3% women). In joint models, higher SDNN (fully-adjusted hazard ratio (HR), 95% confidence interval (CI) 1.24, 1.04-1.47, p = 0.0213), and higher RMSSD (fully-adjusted HR, 95% CI 1.33, 1.13-1.54, p = 0.0010) were significantly associated with new-onset AF. Sex-stratified analyses showed that the associations were mostly prominent among women. In MR analyses, a genetically determined increase in SDNN (odds ratio (OR), 95% CI 1.60, 1.27-2.02, p = 8.36 × 10), and RMSSD (OR, 95% CI 1.56, 1.31-1.86, p = 6.32 × 10) were significantly associated with an increased odds of AF.
CONCLUSION
Longitudinal measures of uncorrected HRV were significantly associated with new-onset AF, especially among women. MR analyses supported the causal relationship between uncorrected measures of HRV with AF. Our findings indicate that measures to modulate HRV might prevent AF in the general population, in particular in women. AF; atrial fibrillation, GWAS; genome-wide association study, IVW; inverse variance weighted, MR; Mendelian randomization, MR-PRESSO; MR-egger and mendelian randomization pleiotropy residual sum and outlier, RMSSD; root mean square of successive RR interval differences, RMSSDc; root mean square of successive RR interval differences corrected for heart rate, SDNN; standard deviation of normal to normal RR intervals, SDNNc; standard deviation of normal to normal RR intervals corrected for heart rate, WME; weighted median estimator. Rotterdam Study n=12,334 HRV GWAS n=53,174 AF GWAS n=1,030,836.
背景
心率变异性（HRV）与普通人群中心律失常（AF）之间的性别差异和因果关系仍不清楚。
方法
本研究纳入了来自基于人群的鹿特丹研究中的 12334 名无 AF 的参与者。在基线和随访检查时评估了 HRV 的指标，包括正常 RR 间隔的标准差（SDNN）、校正心率的 SDNN（SDNNc）、RR 间隔差异（RMSSD）、校正心率的 RMSSD（RMSSDc）和心率。使用调整心血管危险因素的联合模型来确定新发生的 AF 与 HRV 纵向测量值之间的关联。使用全基因组关联研究（GWAS）汇总水平数据的孟德尔随机化（MR）分析，将 HRV 的遗传变异作为工具变量。
结果
在中位随访 9.4 年期间，12334 名参与者中有 1302 例新发 AF（平均年龄 64.8 岁，58.3%为女性）。在联合模型中，SDNN 较高（完全调整后的风险比（HR），95%置信区间（CI）为 1.24，1.04-1.47，p=0.0213）和 RMSSD 较高（完全调整后的 HR，95%CI 为 1.33，1.13-1.54，p=0.0010）与新发 AF 显著相关。性别分层分析表明，这些关联在女性中更为明显。MR 分析表明，SDNN （比值比（OR），95%CI 为 1.60，1.27-2.02，p=8.36×10）和 RMSSD（OR，95%CI 为 1.56，1.31-1.86，p=6.32×10）的遗传决定增加与 AF 发生的几率增加显著相关。
结论
未校正 HRV 的纵向测量值与新发 AF 显著相关，尤其是在女性中。MR 分析支持未校正 HRV 指标与 AF 之间的因果关系。我们的研究结果表明，调节 HRV 的措施可能会预防普通人群中的 AF，特别是在女性中。AF；心房颤动，GWAS；全基因组关联研究，IVW；逆方差加权，MR；孟德尔随机化，MR-PRESSO；MR-egger 和孟德尔随机化偏倚剩余总和和异常值，RMSSD；连续 RR 间隔差异的均方根，RMSSDc；校正心率的连续 RR 间隔差异的均方根，SDNN；正常 RR 间隔的标准差，SDNNc；校正心率的正常 RR 间隔的标准差，WME；加权中位数估计值。鹿特丹研究 n=12334 HRV GWAS n=53174 AF GWAS n=1030836。
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