Center for Sleep and Circadian Neurobiology, University of Pennsylvania Perelman, School of Medicine, Philadelphia, PA, USA; Emory University, Nell Hodgson Woodruff School of Nursing, Atlanta, GA, USA.
Yale School of Public Health, New Haven, CT, USA.
Sleep Med. 2018 Apr;44:89-96. doi: 10.1016/j.sleep.2017.10.004. Epub 2017 Oct 26.
Sleepiness and cardiovascular disease share common molecular pathways; thus, metabolic risk factors for sleepiness may also predict cardiovascular disease risk. Daytime sleepiness predicts mortality and cardiovascular disease, although the mechanism is unidentified. This study explored the associations between subjective sleepiness and metabolite concentrations in human blood plasma within the oxidative and inflammatory pathways, in order to identify mechanisms that may contribute to sleepiness and cardiovascular disease risk.
An exploratory case-control sample of 36 subjects, categorized based on the Epworth Sleepiness Scale (ESS) questionnaire as sleepy (ESS ≥ 10) or non-sleepy (ESS < 10), was recruited among subjects undergoing an overnight sleep study for suspected sleep apnea at the University of Pennsylvania Sleep Center. The average age was 42.4 ± 10.5 years, the mean body mass index (BMI) was 40.0 ± 9.36 kg/m, median Apnea Hypopnea Index (AHI) was 8.2 (IQR: 2.5-26.5), and 52% were male. Fasting morning blood plasma samples were collected after an overnight sleep study. Biomarkers were explored in subjects with sleepiness versus those without using the multiple linear regression adjusting for age, BMI, smoking, Apnea Hypopnea Index (sleep apnea severity), study cohort, and hypertension.
The level of choline is significantly lower (P = 0.003) in sleepy subjects (N = 18; mean plasma choline concentration of 8.19 ± 2.62 μmol/L) compared with non-sleepy subjects (N = 18; mean plasma choline concentration of 9.14 ± 2.25 μmol/L). Other markers with suggestive differences (P < 0.1) include isovalerylcarnitine, Alpha-Amino apidipic acid, Spingosine 1 Phosphate, Aspartic Acid, Propionylcarnitine, and Ceramides (fatty acids; C14-C16 and C-18).
This pilot study is the first to show that lower levels of plasma choline metabolites are associated with sleepiness. Further exploration of choline and other noted metabolites and their associations with sleepiness will guide targeted symptom management.
目的：探索主观嗜睡与人体血液氧化和炎症通路中代谢物浓度之间的关联，以确定可能导致嗜睡和心血管疾病风险的机制。
方法：本研究纳入了宾夕法尼亚大学睡眠中心疑似睡眠呼吸暂停患者进行的过夜睡眠研究中，根据 Epworth 嗜睡量表（ESS）问卷将 36 名受试者分为嗜睡（ESS≥10）或非嗜睡（ESS<10），进行了一项探索性病例对照研究。受试者平均年龄为 42.4±10.5 岁，平均体重指数（BMI）为 40.0±9.36kg/m，中位呼吸暂停低通气指数（AHI）为 8.2（IQR：2.5-26.5），52%为男性。在进行过夜睡眠研究后采集空腹晨血血浆样本。采用多元线性回归模型，根据年龄、BMI、吸烟、呼吸暂停低通气指数（睡眠呼吸暂停严重程度）、研究队列和高血压对嗜睡和非嗜睡受试者进行调整，比较两组间生物标志物的差异。
结果：与非嗜睡受试者（N=18；平均血浆胆碱浓度为 9.14±2.25μmol/L）相比，嗜睡受试者（N=18；平均血浆胆碱浓度为 8.19±2.62μmol/L）的胆碱水平显著降低（P=0.003）。其他有提示意义的差异标志物（P<0.1）包括异戊酰肉碱、α-氨基己二酸、鞘氨醇 1 磷酸、天冬氨酸、丙酰肉碱和神经酰胺（脂肪酸；C14-C16 和 C-18）。
结论：这项初步研究首次表明，较低的血浆胆碱代谢物水平与嗜睡有关。进一步探讨胆碱和其他有提示意义的代谢物及其与嗜睡的关系，将有助于有针对性地进行症状管理。
