MacDonald David M, Mkorombindo Takudzwa, Ling Sharon X, Adabag Selcuk, Casaburi Richard, Connett John E, Helgeson Erika S, Porszasz Janos, Rossiter Harry B, Stringer William W, Voelker Helen, Zhao Dongxing, Dransfield Mark T, Kunisaki Ken M
Pulmonary Section, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States.
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Minnesota, Minneapolis, Minnesota, United States.
Chronic Obstr Pulm Dis. 2022 Apr 29;9(2):226-236. doi: 10.15326/jcopdf.2021.0264.
Autonomic dysfunction is common in chronic obstructive pulmonary disease (COPD), and worse autonomic function may be a marker of risk for acute exacerbations of COPD (AECOPD). Heart rate variability (HRV) is a measure of autonomic function. Our objective was to test whether lower (worse) HRV is a risk factor for AECOPD.
We measured standard deviation of normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) on 10-second electrocardiograms (ECGs) performed at screening and day 42 in participants in the Beta Blockers for the Prevention of Acute Exacerbations of COPD trial ( BLOCK-COPD), a placebo-controlled trial of metoprolol for prevention of AECOPD. We used Cox-proportional hazards models to test if these HRV measures were associated with risk of any AECOPD, and separately, hospitalized AECOPD. We tested associations using baseline HRV measures and incorporating HRV measures from day 42 as a time-varying covariate. We also tested for interactions with metoprolol assignment.
Of 532 trial participants, 529 (forced expiratory volume in 1 second [FEV ]41 ± 16.3 % predicted) were included in this analysis. We did not find a significant association between HRV measures and risk of AECOPD when all participants were analyzed together. There was a significant interaction between RMSSD and assignment to metoprolol on time to first hospitalized AECOPD; in the placebo group greater RMSSD was associated with a lower risk of hospitalized AECOPD (adjusted hazard ratio0.71, 95% confidence interval: 0.52 to 0.96, per 10 ms increase) but there was no association in the metoprolol group.
Autonomic dysfunction as measured by HRV may be a risk factor for AECOPD. Future studies should analyze longer HRV recordings and their performance in broader samples of people with COPD, including those on beta-blockers.
自主神经功能障碍在慢性阻塞性肺疾病（COPD）中很常见，而更差的自主神经功能可能是慢性阻塞性肺疾病急性加重（AECOPD）风险的一个标志。心率变异性（HRV）是自主神经功能的一种测量指标。我们的目的是测试较低（较差）的HRV是否是AECOPD的一个危险因素。
在“β受体阻滞剂预防慢性阻塞性肺疾病急性加重试验”（BLOCK - COPD）的参与者中，我们在筛查时和第42天测量了10秒心电图（ECG）上正常RR间期的标准差（SDNN）和连续RR间期差值的均方根（RMSSD），该试验是一项使用美托洛尔预防AECOPD的安慰剂对照试验。我们使用Cox比例风险模型来测试这些HRV测量指标是否与任何AECOPD的风险相关，以及分别与住院AECOPD的风险相关。我们使用基线HRV测量指标并将第42天的HRV测量指标作为时变协变量来测试关联。我们还测试了与美托洛尔分配的相互作用。
在532名试验参与者中，529名（一秒用力呼气容积[FEV₁]为预测值的41±16.3%）被纳入该分析。当对所有参与者进行综合分析时，我们未发现HRV测量指标与AECOPD风险之间存在显著关联。RMSSD与美托洛尔分配对首次住院AECOPD时间存在显著相互作用；在安慰剂组中，较高的RMSSD与较低的住院AECOPD风险相关（调整后的风险比为0.71，95%置信区间：0.52至0.96，每增加10毫秒），但在美托洛尔组中无关联。
通过HRV测量的自主神经功能障碍可能是AECOPD的一个危险因素。未来的研究应分析更长的HRV记录及其在更广泛的COPD患者样本中的表现，包括那些使用β受体阻滞剂的患者。
