1. The Relationship of Weight
and
Obstructive Sleep Apnea
Mia Zaharna, MD, MPH
Stanford Sleep Center, Fellow

2. Objectives
• Background
• Discuss Obesity as a risk factor for OSA
• Discuss relationship of Obesity and OSA to health
effects
• Discuss Obesity as a consequence of OSA
• Discuss Treatment of OSA and its effect on
weight and vice versa
• Discuss ways that you can effectively control your
weight
Mia Zaharna - The Relationship of Weight and Obstructive SSlleeeepp AAppnneeaa

3. Background
• Obesity is the most powerful risk factor for obstructive
sleep apnea (OSA)
• Obesity is essentially the only reversible risk factor
• Potentially modifiable risk factors for OSA also include
alcohol, smoking, nasal congestion, and estrogen
depletion in menopause.
• Data suggest that obstructive sleep apnea is associated
with all these factors, but at present the only
intervention strategy supported with adequate
evidence is weight loss. ( Young et al. 2002)

4. Background: Obesity Prevalence
(Young et al. 2002)

5. Background: OSA Prevalence
• OSA present in 25-58% of men and 10-37% of women
(Young et al 1993), (Young et al 2002)
• Prevalence increases in middle age
• Symptomatic OSA (OSA with EDS) present in 4% of
middle aged men and 2% of women (Young et al 2002)
• OSA is associated with neurocognitive dysfunction,
cardiovascular disease, insulin resistance, dyslipidemia,
motor vehicle and occupational accidents
• OSA associated with metabolic syndrome (abdominal
obesity, dyslipidemia, impaired glucose tolerance,
hypertension) but causal link not proven

6. Obesity and OSA
• About 70% of those with OSA are obese (Malhotra
et al 2002)
• Prevalence of OSA in obese men and women
is about 40% (Young et al 2002)
• Higher BMI associated with higher prevalence
– BMI>30: 26% with AHI>15, 60% with AHI>5
– BMI>40: 33% with AHI>15, 98% with AHI>5
(Valencia-flores 2000)

7. Obesity and OSA
• Total body weight, BMI, and fat distribution all
correlate with odds of having OSA
– Every 10 kg increase in weight increases risk by 2X
– Every increase in BMI by 6 increases risk by 4X
– Every increase in waist or hip circumference by 13
to 15 cm increases risk by 4X (Young et al 1993)

8. Obesity as a Risk Factor For OSA:
Structural Factors
• Airway obstruction occurs when the nasopharynx and
oropharynx are occluded by posterior movement of the
tongue and palate against the posterior pharyngeal wall
• Narrower airways are more easily collapsible and prone to
airway occlusion
• Obese people have extrinsic narrowing of the area
surrounding collapsible region of the pharynx and regional
soft tissue enlargement (Fleetham 1992)
• Increased fat deposits posteriolateral to oropharyngeal
airspace at level of soft palate, in the soft palate, and in
submental area (Horner et al 1989)

9. Oropharynx in Normal and Obese Patient

10. Obesity as a Risk Factor For OSA:
Structural Factors
• Distribution of fat is an important correlate
• Fat accumulation in the central, android (apple
shape), and upper body correlate with metabolic
syndrome, atherosclerosis, and OSA
• Waist circumference more important than BMI,
weight, or total fat content
• Increased waist circumference predicts OSA even
in non-obese (Grunstein 1993)

11. Obesity as a Risk Factor For OSA:
Structural Factors
Apple shape is riskier than Pear shape

12. Central Obesity and OSA
• Anatomic respiratory effects: reduced upper
airway size secondary to mass effect of the
large abdomen on the chest wall and tracheal
traction (Pillar, Shehadeh 2008)
• Endocrine effects: The concept of leptin and
ghrelin

13. Leptin
• Leptin is an appetite suppressant
• Leptin associated with satiety, weight control, and fat
distribution (central obesity)
• Obese and pts with OSA (independently) have high leptin due
to leptin resistance rather than as a result of leptin deficiency
• Positive correlation between leptin and AHI in OSA
• Sleep deprivation/disordered sleep causes decreased leptin
making you feel more hungry (Patel et al 2004)
• Treatment of OSA with CPAP decreases leptin (after 2
months) and ghrelin levels (after 2 days) (Harsch et al 2003)
• ?? Treating OSA could lead to decreased appetite

14. Ghrelin
• Ghrelin is an appetite stimulant
• Ghrelin levels increase after weight loss
• Ghrelin levels higher in OSA pts
• Treatment of OSA may reduce ghrelin levels
leading to decreased appetite

15. Leptin and Ghrelin
↑Ghrelin ↓Ghrelin

16. Obesity, OSA, Disease conditions, and
Disease mechanisms
• Obesity and OSA are associated with common disease conditions with
overlapping pathogenesis and disease mechanisms, but causation still
unclear
Diseases Mechanisms
– Heart failure - Leptin
– Pulmonary htn - Insulin resistance
– Chronic CAD - Hypercoagulability
– Cerebrovasc.disease - Inflammation
– Hypertension - Sympathetic activity
– MI - Genetics
– Stroke and TIA

17. Obesity, OSA, Disease mechanisms, and Disease conditions
(Gami 2003)

18. Can Obesity be a consequence of OSA?
• OSA reduces physical activity and exercise
performance
• OSA reduces energy metabolism
• OSA reduces motivation (from underlying
comorbidities like depression: several studies
have found correlation between OSA and
depression) (Baran 2003)
• OSA reduces physical activity from sleepiness
(Basta 2008)

20. OSA and exercise performance
• Grote and colleagues studied 1149 pts with OSA
• BP and HR at rest and during graded bicycle exercise to assess
cardiovascular reactivity in those with and w/o OSA
• Results: Maximal exercise capacity was less in those with OSA
• Conclusions: OSA associated with reduced physical work capacity
and modified hemodynamic response to exercise
• Aguillard and colleagues studied 32 patients with OSA
• Performed PSGs and maximal exercise test which served as an
objective indicator of fatigue. Also completed FSS as subjective
measure of fatigue
• Conclusions: Those with poor quality sleep or inadequate
amount of sleep showed higher levels of fatigue both
subjectively and objectively

21. OSA and energy metabolism
• Reduced leptin and increased ghrelin lead to increased
hunger and decreased energy metabolism
• Vanuxem and colleagues studied 11 pts with OSA
– Asked to perform maximal effort and measured on
cycloergometer
– Decrease in maximum blood lactate concentration
suggesting an impairment of glycolytic metabolism and
decrease in the rate of lactate elimination indicating a
defect in oxidative metabolism seen in those with OSA
– Conclusion: OSA linked to impaired muscle energy
metabolism

22. Treatment of Obesity and Impact on OSA
• I will focus on dietary weight loss
• Medical weight loss with appetite
suppressants like sibutramine linked to
hypertension and arrythmias so unsuitable in
OSA patients
• Surgical weight loss such as bariatric surgery
for BMI >40 or BMI>35 with comorbidities
– Multiple studies have shown significant
improvements in AHI with lap band and Roux-en-Y

23. Dietary weight loss can improve OSA
• Reduces upper airway collapse by modifying anatomy
and function
– 13% weight loss decreased nasopharyngeal airway
collapsibility in obese patients with OSA after diet. All had
decrease in AHI. (Suratt 1987)
– Improved pharyngeal and glottic fxn and significant
decrease in AHI after 26 kg weight loss in obese patients
with OSA (Rubinstein 1988)
– 14 pts with BMI>40 showed significant reduction inn neck
fat on MRI and significant decrease in AHI (24.3 to 2.9)
after 10% weight loss (Hernandez 2009)
– In 15 obese pts found 8% weight loss decreased nocturnal
oxygen desat index significantly (Kansanen 1998)

24. Dietary weight loss can improve OSA
• Impact of weight loss is greater in those with
severe OSA (AHI>30) and those higher in BMI
– In obese patients, even minimal weight loss can be
beneficial
– Thought to be related to preferential loss of visceral
fat first as oppose to subcutaneous fat which has
metabolic advantages
– Study of 34 pts with BMI<30 and mild to moderate
OSA did not show significant decrease in AHI with
weight loss in most of the group (Only 8 pts had
decrease of AHI to <5) (Lam 2007)

25. Mean change in AHI by weight change
category (Peppard et al 2000)

26. Temporary relief of OSA from weight loss?
• Sampol and colleagues studied 24 initially
obese pts
– Despite initial cure of OSA after dietary weight
loss (Ave. BMI from 31.5 to 25.9) , OSA recurred in
50% after mean f/u of 94 months, regardless of
whether they had regained weight
– This favors a clear multifactorial etiology to OSA

27. Treatment of OSA and its effect on weight
• Weight loss may be helped by CPAP in obese with
OSA in compliant vs. noncompliant (use >4 hrs)
(Loube 1997)
• 6 mo. of CPAP could reduce intra-abdominal
visceral fat and serum leptin even in absence of
weight loss (Chin, 1999)
• 2 mo. of CPAP assoc. with reduced serum leptin
in absence of weight change (Harsch 2003)

28. Treatment of OSA and its effect on weight
• Other studies showed no change in visceral fat, weight,
and serum leptin despite adherence to CPAP therapy
in obese pts with OSA (Vgontzas, 2008)
– Small studies that lacked controls
– Lacked info on dietary habits and sleep duration
• Some studies suggest possible weight gain with CPAP
(Redenius, 2008)
– BMI of 228 pts measured pre and post CPAP for one year
and compared to pts who did not receive CPAP
– CPAP assoc. with weight gain in some. None lost weight.

29. How to manage your weight
• Reducing caloric intake is the most common
form, but difficult long term
– Overall median success rate of only 15% during up to
14 yrs of observation (Ayyad 1999)
• Reducing calorie intake is most important:
portion of fat vs. protein vs. carbs doesn’t matter
in regards to weight loss, satiety, hunger, and
satisfaction (Sacks et al. 2009)
• Diet + exercise is most effective method of
weight loss recommended by most doctors

30. How to manage your weight
• Diet alone may be just as good as diet and
exercise
– Metanalysis of 25 yrs of weight loss research on diet
alone, exercise alone, vs. diet + exercise
– Concluded: 15-week diet or diet plus exercise
program, produces a weight loss of about 24 lbs, with
a 15 and 19 lb maintained loss after one year,
respectively. (Miller 1997)
• Many studies suggest diet + exercise provides
about a 20% greater weight loss initially than diet
alone

31. How to manage your weight
• Exercise alone probably doesn’t work that
well (Caudwell 2009)
– 58 obese men and women ( Ave BMI = 31.8) were
prescribed exercise to expend approximately 500
Kcal per session, five times a week at an intensity
of 70 % maximum heart rate for 12 weeks
– Significant ave. wt loss of 3.2 kg but large
variability (loss of 14.7 kg to gain of 2.7 kg)
– Differences were accounted for by calorie intake

32. Exercise is important
• Exercise can improve sleep
– Study in a group of initially inactive adults showed
that moderate intensity exercise for 12 months
significantly improved both objective (PSG results)
and subjective measures of sleep (King et al. 2008)
• Exercise in the long run allows your body to be
more efficient at burning calories

33. The Weight Loss Rule
+ > >

34. Conclusions
• Complex interrelationship between weight
and OSA
• OSA may lead to weight gain and weight gain
leads to OSA
• Losing weight can improve OSA
• Unclear if treating OSA leads to weight loss
although some studies show this is the case
• Diet and exercise as well as diet alone are
good weight loss techniques

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38. Insulin Resistance/DM II
• OSA pts have higher fasting bl.glucose, insulin, and
HgbA1c than weight matched controls w/o OSA (Vgontzas
2000)
• Severity correlates with severity of AHI
• Correlation is independent of central obesity
• Study showed treatment with CPAP over 4 months
improved glucose metabolism (Brooks et al 1994)
• Effects of OSA and obesity on insulin resistance are
additive

39. Hypercoagulability
• Obese pts have higher plasma prothrombotic
factors like fibrinogen, vWF, factor VII,
plasminogen activator 1 (De Pergola, 2002)
• OSA pts have the above and increased platelet
aggregation and blood viscosity (Sanner 2000, Chin 1996, Nobili
2000)
• Exercise, low fat high fiber diet, and CPAP in OSA
pts can reverse abnormal coagulation profiles (De
Pergola 2002, Sanner 2000, Chin 1996)
• Linked to states such as MI, stroke, TIA, CAD, CVD

40. Inflammation
• Obesity is an inflammatory state (Roytblat 2000), (Visser 1999)
– High CRP and IL-6
– Central obesity has higher markers
• OSA is an inflammatory state (Shamsuzzaman 2002)
– High CPR, IL-6, TNF
• OSA inflammatory state may exist independently
of obesity
• Linked to states such as MI, stroke, TIA, CAD,
Cerebrovascular disease, hypercoagulability

41. Sympathetic activity
• Pts with OSA have high sympathetic activity
when awake, with further increases in blood
pressure and sympathetic activity during sleep
• Clinically means increased risk of stroke, htn,
cardiovascular disease, TIA, cerebrovascular
disease
• CPAP decreased blood pressure during sleep

42. Genetics
• OSA has genetic linkages
– Chrom 2p, 19 p
• Obesity has genetic linkages
– Chrom 2p, 17p, 12p
• Data suggests both shared and unshared
genetic factors in OSA and obesity (Palmer 2003)