睡眠醫學二十六之心肺健康

今晚如常到體育館練拳，迎面而來的竟是身型龐大的振華(假名)，我自不然要椰榆一下這位運動場稀客! 偉民當然亦不甘示弱，表示知道勤做運動可以提昇心肺健康，奈何自己患有糖尿病，高血壓同睡眠窒息症(OSA)，所以不能太操勞，實在身不由己!

話說回來，睡眠窒息症如何影響心肺健康( cardiorespiratory fitness, CRF) 也是百家爭鳴，其實這是個十分重要的健康問題，低的CRF值常常與心血管疾病及死亡率扯上關係(1-2)。CRF值比其他常引用的心血管疾病風險指標(Cardiovascular risk factor) 更能預測死亡風險(mortality)及願境(prognosis)(3-4)，CRF值通常用metabolic equivalents (METS) 或 peak oxygen consumption (V′O2peak)作單位的。

最近有學者(5)透過系統評價(systemic review)及薈萃分析(meta-analysis)對此醫學難題作出研究，發現睡眠窒息症病人的V′O2peak值真的較常人差。不論年青(五十歲以下) 或年長(五十歲以上)的睡眠窒息症病人也是如此。奇怪的是較瘦的睡眠窒息症病人(BMI<30Kg.m-2)較肥的OSA病人有更低的CRF值! 低的心肺健康值( cardiorespiratory fitness, CRF)正好解釋為何睡眠窒息症病人會出現較弱的體能和不濟的生活質素(6-10)。同一組學者(11)亦發現OSA病人每天的平均運動量(mean number of steps per day of 5388 )遠遠低於醫學界倡議的運動量(每天行一萬步)。其實運動訓練就算在沒有改善病人BMI下，仍能大幅改善睡眠窒息的頻率(Apnea-hypopnoea index)，日間嗜睡(Sleepiness)及提昇V′O2peak值的。究竟睡眠窒息症如何影響病人的運動量(exercise capacity) 不得而知，可能是OSA病人平日的運動量不足因而引致低CRF值吧。因此將來可能要考慮將運動治療(follower-up physical exercise programmes)納入醫治睡眠窒息症的常規方案。

夜了，正想搭振華的順風車回家，不過他說要去附近的東菇亨吃夜宵。唉!真的沒他辦法! 好在陳X記已經搬走了，費事話佢知先!

參考文獻:

1. Exercise capacity and mortality in black and white men. Circulation 2008;117: 614–622.

2. Cardiorespiratory fitness versus physical activity as predictors of all-cause mortality in men. Am Heart J 2018; 196: 156–162.

3. Importance of assessing cardiorespiratory fitness in clinical practice: a case for fitness as a clinical vital sign: a scientific statement from the American Heart Association. Circulation 2016; 134: e653–e699.

4. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 2002; 346: 793–801.

5. Maximal exercise capacity in patients with obstructive sleep apnoea syndrome: a systematic review and meta-analysis. Eur Respir J 2018; 51: 1702697.

6. Influence of gender on associations of obstructive sleep apnea symptoms with chronic conditions and quality of life. Int J Environ Res Public Health 2018; 15: 930.

7. Association between polysomnographic sleep measures and health-related quality of life in obstructive sleep apnea. J Sleep Res 2001; 10: 303–308.

8. Quality of life among untreated sleep apnea patients compared with the general population and changes after treatment with positive airway pressure. J Sleep Res 2015; 24:328–338.

9 Undiagnosed obstructive sleep apnea is independently associated with reductions in quality of life in middle-aged, but not elderly men of a population cohort. Sleep Breath 2015; 19: 1309–1316.

10. Quality of life in obstructive sleep apnea is related to female gender and comorbid insomnia. Sleep Breath 2018; in press [https://doi.org/10.1007/s11325-018-1621-y].

11. Obstructive sleep apnea syndrome, objectively measured physical activity and exercise training interventions: a systematic review and meta-analysis. Front Neurol 2018; 9: 73.

睡眠醫學二十五之男女大不同

我再次到振華(假名)家中作客，飽餐一頓後，振華太座Virginia 還端上一大盤水果，我當然大表渼慕! 振華卻不以為然並自嘲道:「我有糖尿、血壓高、失眠同睡眠窒息症喎! 梗係要好好照顧我啦，Virginia就晚晚不知瞓得幾好，日日鬼咁幾好精神。」這時我的正義感突然爆發:「華哥，我要為女士講句公道話，其實女士們也有很多睡眠問題的!」

當女性進入青春期，女性荷爾蒙(estradiol and progesterone) 週期性在血液中倍增，影響睡眠及多項身體功能(1)。隨著初潮(menarche) 來臨，女性比男性多兩倍風險患上情緒問題(2)，在十五至三十歲的年齡層中，女性亦比男性多28%機會有失眠現象(3)。

當女性懷孕，巨大的生理變化大大影響了她們的睡眠(4,5)，舉例說胃酸倒流現象會隨著懷孕惡化，且影響睡眠質素(6)。孕婦的骨絡因要為嬰兒出生作出變化，此等改變亦對睡眠有不良影響(7)。孕婦身體內的鐵質及葉酸含量同樣起了變動，亦引發了更多的腿不寧症(restless legs syndrome)(8)。孕婦睡眠的長短及質素亦隨著懷孕進展不斷變化(9)，當女性進入第二妊娠期(third trimester)，有28%的孕婦會睡少過七小時(10)。當孕婦進入第三妊娠期(third trimester)，她們的睡眠時間會比同齡的女士少三十分鐘(11) ，睡眠質素亦變得差了(12) 。研究發現較短的睡眠時間會產生較高機會需要剖腹產子(13,14) 及較長的生產時間(15)。

若果懷孕期間不幸患上睡眠窒息症的話，就會大增妊娠糖尿(16,17) 和妊娠高血壓問題(16-18) 。失眠(19) 及 睡眠窒息症(20,21) ，甚至劣質睡眠(22) 也可導致嬰兒早產!

當女性進入更年期，約四至六成婦女會出現睡眠問題，比較多發生在本身有抑鬱、嗜睡及使用精神科藥物的女士(23)。更年期的典型病徵如潮熱(hot flush) 及夜汗(night sweat) 就會嚴重影響睡眠質素(24,25) 。病徵越嚴重，就越大机會出現失眠現象(26,27)。若能妥善處理此等病徵，就可大大改善睡眠質素(28,29)。另外抑鬱亦常見於踏入更年期的女士(30,31)，而抑鬱當然也會影響睡眠。

人年紀大了，的確會容易出現失眠、淺睡、少了 Slow Wave Sleep 同REM sleep、易醒、睡眠效率減少等等(32) 。老年婦女更會經常難於入睡，睡得少、常常平夜驚醒(33) 。一般來說，超過一半更年期後的婦女都有不同程度的睡眠問題(34, 35) ，不可不知，此等劣質睡眠可引起炎症(36)，循環系統及新陳代謝毛病(37,38) 。

說到此時，振華突然良心發現，跑去幫太座洗碗!

**為保障個人私隱及達到教育效果，因此文中案例可能由真實及/或虛構病例改編而成***

參考文獻:

1.Ovarian steroids act as respiratory stimulant and antioxidant against the causes and consequences of sleep-apnea in women. Respir Physiol Neurobiol. 2017;239:46-54.

2.Epidemiology of DSM-III-R major depression and minor depression among adolescents and young adults in the National Comorbidity Survey. Depress Anxiety. 1998;7(1):3-14.

3.Sex differences in insomnia: a meta-analysis. Sleep. 2006;29(1):85-93.

4.Pulmonary Problems in Pregnancy. New York, NY: Humana Press; 2009:37-55.

5.Sleep and sleep disorders associated with pregnancy. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. Philadelphia, PA: Elsevier Health Sciences; 2017.

6.Predictors of gastroesophageal reflux symptoms in pregnant women screened for sleep disordered breathing: a secondary analysis. Clin Res Hepatol Gastroenterol. 2013;37(1):93-99.

7.Relaxin and its role in pregnancy. Endocrinol Metab Clin North Am. 1995;24(1):171-186

8.Restless legs syndrome and pregnancy. Neurology. 2004;63(6):1065-1069.

9. Sleep quality and nocturnal sleep duration in pregnancy and risk of gestational diabetes mellitus. Sleep. 2017;40(2).

10. Sleep during pregnancy: thenuMoM2b Pregnancy and Sleep Duration and Continuity Study. Sleep. 2017;40(5).

11. Prevalence of abnormal sleep duration and excessive daytime sleepiness in pregnancy and the role of socio-demographic factors: comparing pregnant women with women in the general population. Sleep Med. 2014;15(12): 1477-1483.

12. Sleep quality during pregnancy: a meta-analysis. Sleep Med Rev. 2018;38: 168-176.

13. Sleep disturbance in late pregnancy and type and duration of labour. J Obstet Gynaecol. 2011;31(6):489-491.

14. Sleep trajectories among pregnant women and the impact on outcomes: a population-based cohort study. Matern Child Health J. 2017;21(5):1139-1146

15. Nighttime sleep, daytime napping, and labor outcomes in healthy pregnant women in Taiwan. Res Nurs Health. 2013;36(6):612-622.

16. Obstructive sleep apnea and severe maternal-infant morbidity/mortality in the United States, 1998-2009. Sleep. 2014;37(5):843-849.

17. Obstructive sleep apnea in pregnancy is associated with adverse maternal outcomes: a national cohort. Sleep Med. 2017;38:50-57.

18. Population-based study of sleep apnea in pregnancy and maternal and infant outcomes. J Clin Sleep Med. 2016;12(6):871-877.

19. Sleep disorder diagnosis during pregnancy and risk of preterm birth. Obstet Gynecol. 2017;130(3):573-581

20.. Obstructive sleep apnea in gestational diabetes: a pilot study of the role of the hypothalamic pituitary adrenal axis. J Clin Sleep Med. 2018;14:87-93.

21 Obstructive sleep apnea and the risk of adverse pregnancy outcomes. Am J Obstet Gynecol. 2012;206(2):136.e1-136.e5.

22. Poor sleep quality is associated with preterm birth. Sleep. 2011;34(11):1493-1498.

23. Predictors of sleep disturbance in menopausal transition. Maturitas. 2016;94:137-142.

24. Adverse effects of induced hot flashes on objectively recorded and subjectively reported sleep: results of a gonadotropin-releasing hormone agonist experimental protocol. Menopause. 2013;20(9):905-914.

25. Somatic symptoms and psychological characteristics associated with insomnia in postmenopausal women. Sleep Med. 2013;14(1):71-78.

26. Health-related quality of life of women with menopausal hot flushes and night sweats. Climacteric. 2013;16(2):235-239.

27. Relationship between changes in vasomotor symptoms and changes in menopause-specific quality of life and sleep parameters. Menopause. 2016;23(10):1060-1066.

28.  The effect of different progestogens on sleep in postmenopausal women: a randomized trial. Gynecol Endocrinol. 2017;33(12):933-936.

29. Effects of oral versus transdermal menopausal hormone treatments on self-reported sleep domains and their association with vasomotor symptoms in recently menopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Menopause. 2018;25:145-153.

30. Longitudinal pattern of depressive symptoms around natural menopause. JAMA Psychiatry. 2014;71(1):36-43.

31. Depressive symptoms during the menopausal transition: the Study of Women’s Health Across the Nation (SWAN). J Affect Disord. 2007;103(1-3):267-272.

32.. Metaanalysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan. Sleep. 2004;27(7):1255-1273.

33.. A gonadotropin-releasing hormone agonist model demonstrates that nocturnal hot flashes interrupt objective sleep. Sleep. 2013;36(12):1977-1985.

34. Sleep-disordered breathing and the menopausal transition among participants in the Sleep in Midlife Women Study. Menopause. 2017;24(2):157-162.

35. Association of estradiol with sleep apnea in depressed perimenopausal and postmenopausal women: a preliminary study. Menopause. 2017;24(1):112-117.

36. Associations of self-reported sleep quality with circulating interferon gamma-inducible protein 10, interleukin 6, and high-sensitivity C-reactive protein in healthy menopausal women. PLoS One. 2017;12(1):e0169216.

37.. Sleep disorder, an independent risk associated with arterial stiffness in menopause. Sci Rep. 2017;7(1): 1904.

38.  Sleep quality and its association with postural stability and fear of falling among Spanish postmenopausal women. Menopause. 2018;25: 62-69