基于LASSO的列线图用于预测阻塞性睡眠呼吸暂停中SAS定义的焦虑症状的开发与内部验证

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中文摘要

背景： 焦虑症状在阻塞性睡眠呼吸暂停（OSA）患者中常见，但常被低估。传统多导睡眠图严重程度指标可能无法完全反映OSA的心理负担。本研究旨在开发并内部验证用于预测OSA患者临床显著焦虑症状的列线图。
方法： 共787例OSA患者按7:3比例随机分为训练队列（n=551）和验证队列（n=236）。收集人口学特征、合并症、实验室参数、患者报告量表和多导睡眠图变量。采用十折交叉验证的LASSO logistic回归从36个候选变量中筛选预测因子。构建post-LASSO多变量logistic模型以开发列线图。通过ROC分析、bootstrap校准、Hosmer-Lemeshow检验和决策曲线分析评估区分度、校准度和临床实用性。限制性立方样条分析检验最长阻塞性呼吸暂停持续时间与焦虑症状之间的关联。
结果： 在纳入的787例患者中，71例（9.0%）存在临床显著焦虑症状。保留六个预测因子：性别、心血管疾病、血红蛋白、中性粒细胞与淋巴细胞比值、体重指数和最长阻塞性呼吸暂停持续时间。有焦虑症状的患者主观睡眠质量较差，但OSA相关参数相对较轻，包括较低的AHI和ODI、较短的最长阻塞性呼吸暂停持续时间以及较高的最低SpO2。限制性立方样条分析显示最长阻塞性呼吸暂停持续时间与焦虑症状之间存在显著总体关联（Wald χ²=12.21，df=3，P=0.0067），非线性呈边缘性（P=0.0583）。与60-100秒组相比，持续时间<60秒的患者焦虑风险更高（OR=2.84，95% CI 1.43-5.62，P=0.0028）。列线图显示出可接受的区分度，训练队列和验证队列的AUC分别为0.735和0.751。校准度可接受，Hosmer-Lemeshow检验无统计学意义（P=0.1056和0.4948）。决策曲线分析表明在广泛阈值范围内具有正净获益。
结论： 该基于LASSO的列线图在预测OSA患者SAS定义的临床显著焦虑症状方面表现出可接受的性能。焦虑风险可能无法仅由传统呼吸严重程度指标完全反映，可能反映多因素风险特征。需要外部验证。

英文摘要

BACKGROUND: Anxiety symptoms are common but often under-recognized in patients with obstructive sleep apnea (OSA). Conventional polysomnographic severity indices may not fully capture the psychological burden of OSA. This study aimed to develop and internally validate a nomogram for clinically significant anxiety symptoms in patients with OSA.
METHODS: A total of 787 patients with OSA were randomly divided into a training cohort (n=551) and a validation cohort (n=236) at a 7:3 ratio. Demographic characteristics, comorbidities, laboratory parameters, patient-reported scales, and polysomnographic variables were collected. Ten-fold cross-validated LASSO logistic regression was used to select predictors from 36 candidate variables. A post-LASSO multivariable logistic model was constructed to develop the nomogram. Discrimination, calibration, and clinical utility were assessed using ROC analysis, bootstrap calibration, Hosmer-Lemeshow testing, and decision curve analysis. Restricted cubic spline analysis examined the association between longest obstructive apnea duration and anxiety symptoms.
RESULTS: Among the 787 included patients, 71 patients (9.0%) had clinically significant anxiety symptoms. Six predictors were retained: gender, cardiovascular disease, hemoglobin, neutrophil-to-lymphocyte ratio, body mass index, and longest obstructive apnea duration. Patients with anxiety symptoms had poorer subjective sleep quality but relatively milder OSA-related parameters, including lower AHI and ODI, shorter longest obstructive apnea duration, and higher minimum SpO2. Restricted cubic spline analysis showed a significant overall association between longest obstructive apnea duration and anxiety symptoms (Wald χ²=12.21, df=3, P = 0.0067), with borderline non-linearity (P = 0.0583). Compared with the 60-100-second group, patients with a duration <60 seconds had a higher anxiety risk (OR = 2.84, 95% CI 1.43-5.62, P = 0.0028). The nomogram showed acceptable discrimination, with AUCs of 0.735 and 0.751 in the training and validation cohorts, respectively. Calibration was acceptable, with non-significant Hosmer-Lemeshow tests (P = 0.1056 and 0.4948). Decision curve analysis indicated positive net benefit across broad threshold ranges.
CONCLUSION: This LASSO-based nomogram showed acceptable performance for predicting SAS-defined clinically significant anxiety symptoms in patients with OSA. Anxiety risk may not be fully captured by conventional respiratory severity indices alone and may reflect a multifactorial risk profile. External validation is warranted.