Many developed countries of the world experienced an obesity epidemic more than 20 years ago. Today, in the United States, more than 64% of adults are either overweight or obese, according to the 1999–2000 National Health and Nutrition Examination Survey (NHANES).^1-3 These startling statistics are even more dramatic when one considers that they represent a 14% increase from the 1988–1994 version of the survey and a 36% increase from the 1976–1980 version.

The greatest increase was noted for the obese group, defined as having a body mass index (BMI) of more than 301-5 and including more than 59 million US residents. Other statistics indicate that developing countries have problems with obesity and chronic disease as well. For example, in 1995, emerging economies reported the highest number of people with diabetes, with India, China, Latin America, and the Caribbean leading the way.⁶

Numerous chronic disease processes are associated with overweight and obesity. They include heart disease, respiratory disorders, high lipid levels, hypertension, type 2 diabetes, muscle and joint problems, cancer, depression, mood and anxiety disorders, and sleep-disordered breathing, to mention only a few.^6-8 In addition, obesity is linked to a decreased life span. Some professional football linemen exemplify a quartet of signs and symptoms that may be a trend; 34% have high BMIs, large neck circumferences, sleep-disordered breathing, and hypertension (compared with 14% of all players and 4% of the population at large).^9,10 This trend continues to emerge in other occupations and is advancing in the general population.

Depression and mood/anxiety disorders may be strongly associated with obesity and sleep-disordered breathing. Sleep disruption has long been associated with mood disorders, and depression is a common comorbidity in patients with obstructive sleep apnea (OSA). Specifically, sleep-disordered breathing results in significant sleep disruption, intermittent hypoxemia, and impaired daytime functioning, which may be linked to major depressive disorders.¹¹

Recent data¹² showed that consistent use of continuous positive airway pressure (CPAP) significantly reduced symptoms of depression. Whether improved OSA from consistent CPAP treatment decreased depressive symptoms by ameliorating the adverse effects of hypoxemia, by altering neurotransmitter levels, or through an unknown mechanism could not be determined in this study. What is evident, however, is the complexity of sleep-disordered breathing, obesity, and numerous comorbid conditions together promoting varying levels of dysfunction (and, in some cases, death).

Recent findings suggest that the relationship between obesity and sleep-disordered breathing may not be as clear as it was once thought to be. It was once believed that sleep-disordered breathing resulted from obesity, yet new data^13-16 suggest that a lack of sleep may, in fact, predispose individuals to obesity. More than 50% of individuals with sleep apnea are obese, while the number classified as overweight remains unknown; the combination of obesity and sleep-disordered breathing is correlated with an increased risk of heart and blood-vessel disease.¹⁷ Other risk factors include excessive alcohol consumption and smoking. Thus, there is still much that is unknown regarding obesity and sleep-disordered breathing.

OBESITY AND OSA

An estimated 18 million US residents suffer from sleep apnea. Of the sleep apnea syndromes, OSA is the most common. The upper airway has been the focus of many studies¹⁸-20 investigating the pathology of OSA. One effect on ventilation during sleep is a loss of upper-airway tone. This loss of tone, coupled with obesity, can lead to partial or complete upper-airway occlusions occurring throughout the night, with subsequent systemic hypoxia and hypercapnia.

The most common signs and symptoms of OSA are loud snoring, morning headaches, choking or gasping during sleep, and daytime hypersomnolence. Behavioral consequences of the condition include irritability, inability to concentrate, and memory and learning problems.^21-23 The prevalence of OSA is higher in males and in African Americans.

Obesity is a predisposing factor, even where the condition is worsened by alcohol and sleeping pills. In fact, OSA is two to eight times more prevalent in men, and is associated not only with obesity, but with increased neck circumference and reduced cross-sectional area of the upper airway.²⁴ Men possess greater fat deposition in the neck than women do, even when the comparison is corrected for the BMI. Obese subjects possess a larger fat pad, which is correlated with a higher apnea/hypopnea index (AHI).

Women have a greater ability to defend the upper airway against posture-related changes in airway diameter, and have higher upper-airway dilatory muscle tone, compared with males.²⁵ Some longitudinal studies^26,27 suggest that the prevalence of OSA increases with age, while others^28,29 have found that the AHI remains stable with advancing age and changes only with an increase in the BMI.

SLEEP DEPRIVATION AND OBESITY

Recent evidence^13,14,16 suggests that a lack of adequate sleep (7 to 9 hours per night) increases the risk of becoming obese. For example, people from the NHANES database who reported sleeping less than 7 hours per night were more likely to be obese on initial examination, and those who slept less than 5 hours per night were 73% more likely to develop obesity than those sleeping 7 to 9 hours per night.³⁰

Evidence from this study suggests a link between sleep and the neuropeptides leptin and grehlin, which regulate energy balance and food intake. Sleep deprivation lowers the level of leptin, which suppresses appetite, and raises the level of grehlin, resulting in an increased appetite. These researchers further suggest that the growing prevalence of sleep deprivation is a factor contributing to the growing obesity epidemic.

Image courtesy CalorieLab.com.

WEIGHT LOSS FOR OBSTRUCTIVE SLEEP APNEA

The efficacy of CPAP treatment in OSA is well established, but adherence is typically suboptimal.³¹ Slight improvements in patient adherence are realized when bilevel PAP is substituted for CPAP, but mask-fitting issues remain. While CPAP has shown clinical benefits for OSA patients, studies involving dietary-assisted or surgical weight loss also have demonstrated significant OSA improvement.^32,33 Weight loss is a common recommendation to obese patients, and OSA symptoms substantially and consistently decrease for those able to achieve and maintain the necessary weight loss³⁴; specifically, improvements are consistent for medical, dietary, and surgical methods of weight reduction.^35,36 Unfortunately, many patients are unable to lose sufficient weight to improve their OSA or comorbid conditions associated with obesity; meanwhile, the cost of treating these comorbid conditions is estimated to be twice the cost of the condition in patients without OSA.³⁷

Pharmacological adjunct therapies to assist weight loss are increasingly being utilized due to evidence that the use of weight-reducing medications increases weight loss in patients on diet programs as opposed to patients struggling to reach a desired weight with very low calorie diets alone.³⁸ For example, sibutramine hydrochloride, an orally administered serotonin (5-hydroxyltryptamine, 5HT) and noradrenaline re-uptake inhibitor (SNRI), has been found to induce dose-dependent weight loss, as well as enhance the effects of diets and exercise programs.³⁹ Projecting into the future, the increasing prevalence of obesity in our nation will result in more patients developing clinically relevant OSA, and, hence, the increase in clinically assisted and efficient weight loss treatment.

BARIATRIC SURGERY

Surgical procedures for weight loss can be classified as follows:

• Malabsorptive procedures (biliopancreatic diversion and jejunoileal bypass);
• Restrictive procedures (vertical banded gastroplasty, adjustable gastric banding, and sleeve gastrectomy); and
• Mixed procedures (gastric bypass, sleeve gastrectomy with duodenal switch, and implantable gastric stimulation).

One of these surgical procedures may be offered to patients with severe obesity and a body mass index >40 kg/m² or greater, who have failed diet and exercise programs (with or without drug therapy) and present with obesity-related comorbid conditions including sleep apnea.

Despite a variety of procedures, complications from weight loss surgery are frequent, and some are life-threatening. Recent data suggest that patients undergoing bariatric surgery presented with a 21.9% initial hospitalization complication rate and with a 40% rate when reviewed at 6 months postsurgery. The most common complications include dumping syndrome (20%), leaks at the surgical site (12%), incision hernia (7%), infections (6%), and pneumonia (4%).⁴⁰ As with many surgical procedures, the incidence rate for complications declines with experienced surgeons, staff, and hospitals along with careful patient selection.

Surgical effectiveness varies with the procedure used and postsurgical patient compliance. A recent meta-analysis explored weight loss as a function of the surgical procedure.⁴¹ The greatest weight loss occurred as a result of biliopancreatic diversion (53 kg) followed by gastric bypass-roux-en-Y (41 kg overall) with the open procedure accounting for 42 kg and the laparoscopic technique accounting for 38 kg, while adjustable gastric banding and vertical banded gastroplasty accounted for 35 and 32 kg of weight loss, respectively.

Despite the positive results of surgical procedures, weight loss alone may not be the complete answer if the underlying pathophysiological predisposition toward OSA remains. However, weight loss will significantly impact sleep architecture and improve comorbidities that place the patient at elevated risk for other life-threatening processes.⁴² For many patients undergoing bariatric surgery, continuation of CPAP should be considered and follow-up polysomnographs should be used to document success with the procedure and associated strategies to clinically manage sleep apnea.

FUTURE RESEARCH

It is clear that weight loss impacts the clinical presentation and severity of OSA. However, there are many questions that remain unanswered.

• Who is the best candidate for bariatric surgery, and what is the preferred technique?
• When should adolescents be considered for bariatric surgery?
• What are the most effective strategies for improving postsurgical adherence to continued weight loss and maintenance of weight loss?
• What are the phenotypes for individuals at greatest risk for obesity and OSA, and how can this data be used to reduce overall risk?
• Are there additional technologic advances in CPAP and airway pressure maintenance that will improve treatment and management of OSA?
• What surgical interventions are best suited for quality long-term outcomes?

James S. Williams, PhD, is associate professor and adjunct associate professor of physiology; Anna Tacon, PhD, is associate professor of health sciences; and Rick Carter, PhD, MBA, is professor and chair, Department of Health, Exercise and Sport Sciences, Texas Tech University, Lubbock. The authors can be reached at .

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