Sleep Apnoea : its impact outside the chest. Dr Tom Mackay Consultant Respiratory Physician Royal Infirmary Edinburgh

Transcription

1 Sleep Apnoea : its impact outside the chest Dr Tom Mackay Consultant Respiratory Physician Royal Infirmary Edinburgh

2 Body Mass Index < 20 kg/m kg/m kg/m 2 > 30 kg/m 2 underweight normal overweight obese

3 Obesity Trends Among U.S. Adults 1995 BMI > 30 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

4 Obesity Trends Among U.S. Adults 2001 BMI > 30 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

5 Prevalence of obesity in different countries 35 Percent USA Europe China Brazil Kuwait Australia 0 Europe 16% Source: World Health Organization

6 Obesity trends in the UK The percentage of adults who are obese has doubled since the mid 1980 s Weight increases with age

7 Association of Age and Weight 2007 UK Figures % Overweight Age yrs yrs M : 28% M: 76% F: 27% F: 68%

8 Obesity Central apple shaped Visceral obesity Metabolically more active brown fat Increased waist-to-hip girth ratio WHR > 1.0 Peripheral pear shaped Less metabolically active white fat Normal waist-to-hip girth ratio WHR < 1.0

9 Central obesity (Vague J et al, Am J Clin Nut 1956)

10 Metabolic Syndrome Impaired glucose tolerance and / or insulin resistance hyperinsulinaemia PLUS two or more of: Hypertension Elevated triglyceride and / or reduced HDL cholesterol Visceral (central) obesity Microalbuminuria Expert Panel of WHO (1998) WHO Consultation, 1999: 31-33

11 Metabolic Syndrome Other Associated Features Hyperuricaemia / gout Increased LDL cholesterol Fibrinolysis activation exacerbates hypertension, atherosclerotic heart disease, cerebrovascular disease (? Via an inflammatory link)

12 Metabolic Syndrome Common / associated with obesity Obesity is increasing in the population? Malfunction of ancient genetic pathway feast or famine existence thrifty genes emerged to conserve energy and produce survival advantage lay down adipose tissue in times of plenty in anticipation of famine But produces survival disadvantage when food is abundant (as excess adipose tissue is laid down)

13 Possible mediator imbalance in the Metabolic Syndrome Neuropeptide Y (hypothalamic neuropeptide) Ghrelin (gastric fundus peptide) = Thrifty genes stimulate appetite weight gain Leptin peptide secreted by adipocytes usually acts as an appetite suppressant weight loss Leptin normally switches off Neuropeptide Y / Ghrelin production? Problem with normal feedback regulation in the Metabolic Syndrome Leptin fails to suppress Neuropeptide Y / Ghrelin levels Leptin level remains high Central Obesity

14 Obstructive Sleep Apnoea Hypopnoea Syndrome OSAHS

15 Epidemiology of OSAHS in Adults OSAHS is the commonest medical cause of excessive daytime sleepiness Affects 0.5-4% men, 0.5-2% women 50,000 adults affected in Scotland (10,000 currently receiving treatment)? 500,000 adults in UK Associated with central obesity

16 Central Obesity and OSAHS Vgontzas AN et al J Int Med 2003; 254: 32-44

17 OSAHS: CLINICAL FEATURES * Excessive Daytime Sleepiness ESS > 10 (* Cardinal symptom) Snoring/Apnoeas Unrefreshing sleep Poor concentration / Depression Nocturia 90% overweight (BMI > 25) 50% obese (BMI > 30)

18 Diagnosis of OSAHS Snoring, witnessed apnoeic episodes ESS > 10 (patient or partner s assessment) Sleep Study Oximetry: > 15 x 4% desats / hr Limited study: AH > 25 / hr in bed PSG: AHI > 15 / hr asleep

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20 MRI of Pharynx CONTROL OSAHS

21 MECHANISM OF OSAHS Fat deposition at the neck level (neck circumference >17 / 42cm) is closely related to visceral obesity Sleep decreases tone in upper airway dilating muscles Pharynx sucked shut

22 MECHANISM OF OBSTRUCTION Retrognathia Obesity Collar > 17 Pharyngeal Obstruction PHARYNGEAL SIZE Reduced activity of airway dilating muscles Sleep Stage / Position Alcohol

23 Describing Abnormalities of the Upper Airway Abnormalities of the upper airway can be categorised using the Mallampati score originally devised for anaesthetic practice (Mallampati 1983) 10

24 MECHANISM OF OSAHS Sleepiness Pharngeal narrowing Negative thoracic pressure Arousal Sleep disruption Blood pressure surge Road accidents Heart attacks Strokes Douglas Lancet 1994;334:653-5

25 Risks of Untreated OSAHS Immediate Problems Excessive Daytime Sleepiness Road traffic accidents Difficulties with activities of daytime living Longer Term Issues Metabolic Syndrome Hypertension Cardiovascular / Cerebrovascular Risk

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27 OSAHS Excessive sleepiness is a factor in many fatal road traffic accidents 6 fold risk of accidents Teran-Santos NEJM 1999;340: Estimated cost of fatal RTA is 1.25 million Cost of CPAP machine is 250 (+ 100 per year consumable costs)

28 OSAHS PATIENTS ARE DANGEROUS DRIVERS Steering error Control OSAHS George AJRCCM 1996;154:175-81

29 OSAHS PATIENTS ARE DANGEROUS DRIVERS Steering error Control Ethanol OSAHS George AJRCCM 1996;154:175-81

30 OSAHS and the Metabolic Syndrome : Snoring is a risk factor for diabetes in male general population Incidence of new diabetics, from 1984 to 1994, in four sub-populations based on combinations of habitual snoring and obesity. Younger group, men aged years at baseline Older group, men aged years at baseline. independently of BMI and other confounding factors Elmasry et al. J Intern Med 2000; 248: 13-20

31 Obesity and OSAHS: a cumulative risk for NIDDM Visceral obesity ( WHR > 1.0) and DM % NIDDM (n=150) Elmasry et al, J Intern Med 2001; 249:

32 OSAHS / Metabolic Syndrome and Inflammatory Mediators Increased levels of Leptin IL-6 TNF in OSAHS compared to age and BMI matched subjects (14 OSA, 11 obese and 12 normal weight men) Plasma inflammatory cytokines follow a circadian rhythm peak during sleep This may be secondary to recurrent episodes of hypoxia in untreated OSAHS Vgontzas AN et al J Clin Endocrinol Metab 2000: 85;

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34 Effect of CPAP treatment on Inflammatory Mediators

35 CPAP Treatment and Leptin Leptin levels fall in OSAHS patients following CPAP treatment After 3 days Chin et al Circulation 1999: 100: After 6 months Ip et al Chest 2000: 118; This may allow a rebalancing of the metabolic status of the individual

36 Comparison of serum leptin, insulin, and cortisol levels in OSAS patients before and after 3 to 4 days of NCPAP treatment Chin, K. et al. Circulation 1999;100: Copyright 1999 American Heart Association

37 Conclusions Central obesity is an important underlying factor in OSAHS Obesity may link the Respiratory problem with the Metabolic Syndrome The link between Metabolic Syndrome and increased cardiovascular and cerebrovascular morbidity may be driven by increased levels of mediators such as IL-6, leptin and TNF secondary to recurrent episodes of hypoxia Try to maintain a normal BMI if possible