Exploring fatigue in Marfan and hypermobile Ehlers-Danlos syndromes: an analytical cross-sectional study in two Italian healthcare centres

Abstract Objective: This study investigates the prevalence and underlying factors of fatigue in individuals with Marfan syndrome (MFS) and hypermobile Ehlers-Danlos syndromes (hEDS), highlighting the necessity for focused research on this symptom within these patient populations. Design: Cross-sectional, multicentre study. Setting: Data were collected from participants diagnosed with MFS or hEDS across multiple healthcare centres. Participants: The study enrolled 282 participants (127 with MFS and 155 with hEDS). Primary and secondary outcome measures: Fatigue was measured using the Fatigue Severity Scale (FSS). Additional assessments included the Patient Health Questionnaire-9 (PHQ-9) for depression and the Insomnia Severity Index (ISI) for sleep disturbances. Results: Participants with hEDS exhibited significantly higher median fatigue scores (FSS median=5.9, IQR=5.00-6.44) compared with the MFS group (FSS median=4.0, IQR=2.88-5.00). Significant predictors of fatigue included being female, having hEDS, participating in psychotherapy, and elevated scores on depression and insomnia scales. In the overall sample, hEDS significantly predicted fatigue (B=0.430, p=0.022), with depression and insomnia as strong influencers (PHQ-9: B=0.12, p<0.001; ISI: B=0.092, p<0.001). Notably, 80% of the hEDS group reported clinically relevant fatigue levels, compared with 31.5% in the MFS group. Daily persistence of fatigue was especially pronounced in hEDS, with 72.2% reporting everyday fatigue versus 25.2% in MFS. Temporal fatigue patterns also differed, with a more evenly distributed pattern throughout the day in hEDS, correlating with higher insomnia scores. Conclusions: The results underscore the severe impact of fatigue on individuals with hEDS compared with those with MFS, suggesting the need for targeted, multidisciplinary management strategies to enhance quality of life. Trial registration number: NCT05712564. Keywords: CARDIOLOGY; Fatigue; Frailty; Nursing Care.摘要 研究目的：本研究旨在探讨马方综合征（Marfan syndrome, MFS）与高活动型埃勒斯-当洛斯综合征（hypermobile Ehlers-Danlos syndromes, hEDS）患者的疲劳患病率及潜在影响因素，强调针对此类患者群体开展该症状专项研究的必要性。 研究设计：横断面多中心研究。 研究场景：数据采集自多家医疗中心确诊为MFS或hEDS的受试者。 研究对象：本研究共纳入282名受试者，其中127名MFS患者、155名hEDS患者。 主要及次要结局指标：采用疲劳严重度量表（Fatigue Severity Scale, FSS）评估疲劳程度；附加评估工具包括用于筛查抑郁的患者健康问卷9项版（Patient Health Questionnaire-9, PHQ-9），以及用于评估睡眠障碍的失眠严重指数量表（Insomnia Severity Index, ISI）。 研究结果：与MFS组相比，hEDS组受试者的疲劳评分中位数显著更高（FSS中位数=5.9，四分位距=5.00~6.44；MFS组FSS中位数=4.0，四分位距=2.88~5.00）。疲劳的显著预测因素包括女性性别、确诊hEDS、接受心理治疗，以及抑郁与失眠量表得分升高。在全部受试者中，hEDS可显著预测疲劳程度（B=0.430，p=0.022），抑郁与失眠为较强的影响因素（PHQ-9：B=0.12，p<0.001；ISI：B=0.092，p<0.001）。值得注意的是，hEDS组中有80%的受试者报告存在具有临床意义的疲劳症状，而MFS组这一比例为31.5%。hEDS组受试者的疲劳每日持续性尤为显著，72.2%的受试者报告日常存在疲劳，而MFS组该比例仅为25.2%。疲劳的时间分布模式也存在差异：hEDS组的疲劳在全天分布更为均匀，且与更高的失眠量表得分相关。 研究结论：本研究结果证实，相较于MFS患者，hEDS患者所受疲劳的影响更为严重，提示需制定针对性的多学科管理策略以提升患者的生活质量。 试验注册号：NCT05712564。 关键词：心脏病学；疲劳；虚弱；护理。