Sleep Apnea and CardioMetabolic Syndrome in women

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1 Sleep Apnea and CardioMetabolic Syndrome in women 신원철 강동경희대병원신경과, 수면센터 1

2 Today s Talks 폐쇄성수면무호흡증의정의와발생기전 수면무호흡증의합병증 : 고혈압, 관상동맥질환, 부정맥, 뇌졸중, 돌연사, 당뇨, 대사증후군 여성에서의폐쇄성수면무호흡증

3 폐쇄성수면무호흡증 (Obstructive Sleep Apnea: OSA) 수면무호흡 : 수면중 10 초이상숨을쉬지않는것. 수면무호흡 - 저호흡증후군 ; 잠자는중, 수면무호흡이시간당 5 번이상발생할때. - mild OSA : 5< AHI < 15/hr - Moderate OSA : 16 < AHI < 30/hr - Severe OSA : AHI > 30/hr 40 세이상한국인 5000 명대상조사 Apnea-hypopnea index (AHI) : >5/hr sleep 남자 : 27% (4.5%), 여자 : 16.5% (3.5%) AHI > 10 ( 외국보고 ) 성인남자 15%, 여자 5% 노인 : 남자 70%, 여자 56%

4 Obstructive sleep apnea

5 Four OSA pathophysiologic trait for pharyngeal patency Different pathophysiology phenotype causing upper airway obstruction 1) High Critical closing pressure (Pcrit) 2) Low Upper airway reflex 3) Elevated loop gain or unstable ventilatory control 4) Low Arousal threshold

6 Obstructive apnea 각성 무호흡 저산소증

7 저산소혈증이산화탄소농도상승 교감신경항진스트레스호르몬분비 ; 당뇨저항성증가동맥경화증심장의부담증가 수면무호흡 비만, 작은턱, 굵은목, 술, 담배, 나이 뇌각성 상기도근육긴장도상승 수면 호흡재개 수면의질저하주간졸음, 아침두통, 기억력저하, 집중력저하

8 폐쇄성수면무호흡증 뇌기능에대한영향 인지기능저하 심한주간졸림증 만성피로 교통사고증가 우울증증가 Sympathetic over activity High cortisol level Decreased glucose intolerance High blood pressure 심뇌혈관계에대한영향 고혈압유발 관상동맥질환 / 심근경색증가 심부전증가 부정맥발생증가 뇌졸중유발 치매유발 수면중돌연사의원인 내분비계에대한영향 당뇨병유발 고지혈증유발 대사증후군증가 수면무호흡증이유발하는문제들

9 Sympathetic Hyperactivity in OSA Naughton MT. Drug Discovery Today:Therapeutic strategies 1:329,2004 During apnea ; blood pressure with varying effect on heart rate Following apnea ; blood pressure and heart rate 24-h sympathetic nervous system activity Heart rate variability HR variability risk of future hypertension mortality in patients with HF BP variability risk for damage to target organs Endothelial damage and dysfunction Platelet activation and blood coagulability Insulin resistance

10 Oxidative stress in OSA Intermittent hypoxia & reperfusion Activation of polymorphonuclear neutrophils Generation of highly reactive free oxygen radicals Inflammation in OSA Odds ratio P 5 AHI< AHI< AHI obesity HOMAIR HTN DM Metabolic syndrome

11 J Clin Endocrinol Metab 96: )

12 Hypertension in OSA JAMA 2012:307;

13 Bratton DJ. JAMA 2015; 314;2280

14 Secondary causes in resistant Hypertension Gonzaga C, Bertolami A, Bertolami M, Amodeo C, Calhoun D. Obstructive sleep apnea, hypertension and cardiovascular diseases. J Hum Hypertens Dec;29(12):

15 Coronary artery disease in OSA

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17 Treatment OSA on Cardiac death after coronary intervention

18 OSA vs Arrhythmia ; Atrial fibrillation 75% 40%

19 OSA on Mortality 중등도수면무호흡증 : 사망률 70% 증가, 심한수면무호흡증 : 사망률 4 배증가 Sleep 2008;31(8):

20 DM in OSA Am J Respir Crit Care Med Dec 15;172(12):1590-5

21 Comparison of clinical characteristics between Non-OSA & OSA groups Non-OSA (N=60) OSA (N=155) P Age(years) 44.2± ± Gender(number of Men, n(%)) 20(64.5) 51(78.5) BMI(Kg/m 2 ) 25.2± ± Waist Circumference(cm) 87.6± ± Systolic blood pressure(mmhg) 131.2± ± Diastolic blood pressure(mmhg) 87.2± ± Glucose(mg/dl) 96.1± ± Insulin(μIU/ml) 8.3± ± HOMA IR 1.9± ± HOMA beta(%) 103.5± ± Leptin(ng/ml) 6.2± ± Adiponectin(μg/ml) 1.6± ± Log hscrp(mg/dl) 1.4± ± Total cholesterol(mg/dl) 191.0± ± Triglyseride(mg/dl) 183.8± ± HDL(mg/dl) 51.4± ± LDL(mg/dl) 121.0± ± Metabolic syndrome,n(%) 7(35%) 25(40%) 0.671

22 CPAP effect on insulin sensitivity J Clin Endocrinol Metab 96: , 2011)

23 OSA in Women Prevalence ; Male Vs female : 24 Vs 9% > 50% of women aged years had OSA (AHI 5/h) years; 14% had severe OSA (AHI 30/h) Rate of severe OSA in obese patients aged years ; 31% Franklin, K.A., et al. Eur Respir J, 2012

24 Clinical complains in Women with OSA Men : more likely to report snoring and apneic episodes Women - insomnia, restless legs, depression, nightmares, palpitations and hallucinations - higher prevalence of atypical symptoms such as headache, anxiety and depression under-evaluation of OSA in women, Sleep, (3):312

25 Gender differences in the upper airway and respiratory stability in OSA Significantly lower overall AHI compared with men (20.2/h vs 31.8/h; p<0.001) AHI during non-rem sleep was also significantly lower in women vs men (14.6/h vs 29.6/h; p<0.001) No difference between females and males with respect to AHI during REM sleep (42.7/h vs 39.9/h) O Connor, C. et al. Am J Respir Crit Care Med, (5): p

26 Gender differences in the upper airway and respiratory stability in OSA Airway length, the tongue, the soft palate, and the total amount of soft tissue in the throat are all smaller in women men have a longer, softer oropharynx, and a larger, fatter, more posterior tongue, increasing the susceptibility of the large airway to collapse Smaller airway might be expected to occlude more easily than a larger one Upper airway collapsibility ; less in women versus men Jordan, A.S., et al., J Appl Physiol, (5):p

27 Gender differences in the upper airway, fat distribution and respiratory stability in OSA ; Fat distribution difference Obesity ; fat distribution - well-recognized risk factor for OSA, and higher body mass index (BMI) indicates a greater severity of OSA for both sexes - for the same AHI, women tend to be more obese than men differences in fat distribution between the sexes For the same BMI, men tend to have higher mean body weight, free fat mass and neck circumference compared with women Upper body and visceral adiposity - associated with reductions in lung function, including total lung capacity, forced vital capacity and forced expiratory volume. J Appl Physiol, (5): p / SLEEP 2010;33(4):

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29 Gender differences in the upper airway, fat distribution and respiratory stability in OSA ; Hormone effect female sex hormones have a protective effect on upper airway patency and/or ventilatory drive Progesterone is a known respiratory stimulant which increases chemoreceptor responses to hypercapnia and hypoxia, and has been shown to increase upper airway muscle tone

30 Gender differences in the upper airway, fat distribution and respiratory stability in OSA ; Hormone effect Chest 2001; 120:

31 Pregnancy and OSA Women may be at increased risk of OSA during pregnancy due to a number of factors. Growing uterus elevates the diaphragm, changing pulmonary mechanics During pregnancy, neck circumference increases, nasal patency is reduced and pharyngeal edema occurs Substantial increases in snoring, snorting/gasping and witnessed apneas have been documented in pregnant women ; Snoring during pregnancy appears to be a risk factor for both pregnancy-induced hypertension and intrauterine growth retardation Medical Hypotheses 82 (2014)

32 Am J Perinatol November ; 31(10):

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34 Tx of OSA

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36 Take Home message 수면무호흡증은수면중, 상기도의폐쇄가발생하여나타나게된다. 수면무호흡증은수면중, 잦은각성으로인한수면의질저하, 빈번한저산소증을일으켜수면의질저하와교감신경항진을초래하여주간졸음뿐만아니라고혈압, 당뇨, 심장질환, 뇌졸중, 치매를일으킬수있다. 여성들은남성과다른폐쇄성수면무호흡증을보인다. - 폐경이후및임신여성들은비만, 지방침착의차이, 여성호르몬의 변화에의해서수면무호흡증이증가한다.

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