Several health conditions increase the likelihood of developing sleep apnoea, but OSA is more common in people who are overweight or obese.2 Excess weight creates fatty deposits in a person's neck, called pharyngeal fat. Pharyngeal fat can block a person's upper airway during sleep when the airway is already relaxed. Obstructive sleep apnoea (OSA) is a global disease with an increasing incidence along with its comorbidities, especially with metabolic syndrome. A major contributor to sleep apnoea is obesity, as well as type 2 diabetes mellitus (T2DM), hypercholesterolaemia and hypertension.
OSA is a treatable condition and the disease can be treated through the use of CPAP therapy. Awareness of this global problem is growing, and healthcare systems are providing preventive measures, diagnostics and treatment options. The main preventable risk factors for reducing obesity are lifestyle modification awareness (eating behaviours, smoking, alcohol consumption, etc.). If these lifestyle modifications are widely implemented, not only will the consequences of obesity and sleep apnoea be reduced, but also the incidence of cardiovascular disease will be greatly reduced.
Public awareness of the importance of weight loss through lifestyle modification or bariatric surgery is necessary to improve quality of life. These preventive actions, screening measures and treatment strategies for obesity and OSA can significantly reduce the incidence of obesity, as well as OSA and related comorbidities such as cardiovascular disease, atherosclerosis and depression. Finally, health care costs will also be reduced. Our understanding of the implications of obstructive sleep apnoea (OSA) on the pathophysiology of the disease has evolved rapidly.
OSA is thought to adversely affect multiple organs and systems and may be particularly relevant to cardiovascular disease, 1,2 It has been implicated in the aetiology of hypertension3,4 and in the progression of several established diseases, such as congestive heart failure, atrial fibrillation, diabetes and pulmonary hypertension, diabetes and pulmonary hypertension, 1 However, it has not yet been demonstrated whether OSA is causally related to the development of the latter diseases, 1,2 Currently, continuous positive airway pressure (CPAP) is considered the mainstay of OSA treatment. However, despite the benefits of CPAP treatment observed in numerous clinical trials,16 non-compliance is evident in a significant proportion of patients,17,18 suggesting that other therapies are needed. Several cardiometabolic disorders have been associated with OSA, independently of obesity and other possible confounding factors. Among the most important are glucose intolerance and insulin resistance, which are risk factors for the development of diabetes and cardiovascular disease,42,43 In addition, OSA has been associated with an elevated systemic inflammatory state, as demonstrated by increases in cytokines,38,44 serum amyloid A,45 and, in some but not all studies, C-reactive protein,46,47 OSA subjects who received effective CPAP treatment have shown improvement in some of these metabolic and inflammatory abnormalities,39,48 Interaction between obstructive sleep apnoea, obesity, sleep deprivation and metabolic abnormalities. Finally, hormones related to obesity, weight control, satiety and energy expenditure may be altered in OSA.
Leptin is a hormone produced by adipose tissue and binds to the ventral medial medial nucleus of the hypothalamus, known as the satiety centre. The binding of leptin to this nucleus signals to the brain that the body has eaten enough, a feeling of satiety, 55 Short-term sleep deprivation inhibits leptin production, suggesting a potential mechanism for the early development of obesity, 56 Paradoxically, obese subjects have higher levels of leptin, probably due to increased fat mass. This hyperleptinaemia is thought to be accompanied by a desensitisation of cellular responses to leptin, so that the effect of leptin is not achieved, 57 Leptin also modulates ventilatory control and may therefore be involved in the abnormal respiratory patterns of obesity, 58-60 Other adipokines, such as tumour necrosis factor α and interleukin-6, are also elevated in obesity and may be associated with depression of CNS activity and neuromuscular airway control, which may increase the severity of OSA. In fact, leptin levels in OSA patients are higher than would be expected due to obesity alone37,38 , and leptin levels are reduced after as little as 4 days of CPAP use39. Adiponectin is low in obesity and also in OSA.
Furthermore, adiponectin levels have been shown to increase with CPAP treatment, suggesting that treatment of OSA may reduce metabolic disturbances and potentially cardiovascular risk, 61,62 Ghrelin, a hormone produced by cells lining the stomach, stimulates appetite and is considered a counter-regulator of leptin, 63 Interestingly, ghrelin increases at night in obese subjects,64 and reduced sleep65 has been shown to increase ghrelin production, In recent years, three randomised trials have addressed the question of whether weight loss can improve OSA through non-surgical treatments, 66,67 Kajaste and colleagues, using a cognitive behavioural programme and an initial low-calorie diet with (n = 1) or without (n = 1) additional CPAP therapy, followed 31 obese men for 2 years to assess changes in OSA severity. Patients had lost a mean of 13.5 e of their initial body weight at 6 and 12 months compared to baseline, but at 24 months weight loss had decreased to 9n compared to baseline. At baseline, the oxygen desaturation index (desaturation events per hour of sleep greater than 4 at baseline) was 51 ± 31 and decreased to 23 ± 18 and 25 ± 23 at 6 and 12 months, respectively. After 24 months, patients started to regain lost weight and the oxygen desaturation index started to increase (32 ± 2, but was still significantly lower compared to baseline, 66 Interestingly, the group of patients in this study who also underwent CPAP treatment did not differ in weight loss and oxygen desaturation index compared to patients without additional CPAP treatment, although adherence was not objectively measured.
This randomised clinical trial suggests that weight loss in obese patients with OSA could be an important therapeutic intervention. However, as in most weight loss programmes, patients started to regain the lost weight after 2 years, followed by a worsening of the severity of their OSA. In addition, patients never reached a "normal oxygen desaturation index". CPAP is considered the mainstay of OSA treatment and has demonstrated benefits in dozens of randomised controlled trials.
These benefits include reduced daytime sleepiness, improved quality of life and lower blood pressure, 105 In addition, short-term data suggest that CPAP may attenuate some of the cardiometabolic disturbances present not only in OSA, but also in obesity and sleep deprivation. CPAP treatment has also been associated with reductions in visceral fat and total cholesterol and an increase in HDL, 106 For patients with concomitant OSA and type 2 diabetes, CPAP treatment has been associated with improved glycaemic control and insulin sensitivity, although these results have not been consistent, 107-109 Finally, CPAP has been associated with attenuation of inflammatory biomarkers and perhaps even improved endothelial function. Indeed, observational studies have reported improved survival and fewer cardiovascular events in CPAP-treated patients compared to patients with poor CPAP adherence or those who remained untreated, 18,110 However, important questions regarding CPAP treatment remain unanswered. Most trials have included male subjects and, therefore, we have limited insight into how women may benefit from CPAP treatment.
The benefits of CPAP treatment on metabolic parameters in subjects with mild and moderate OSA are also unclear. The therapeutic effects of CPAP depend on patient compliance, which can be problematic, 17,111,112 and most importantly, definitive evidence that CPAP prevents cardiovascular events and reduces mortality has not yet been obtained. Only carefully designed large prospective studies will be able to answer these important questions. Overweight is classified as a body mass index (BMI) of 25 or more, and obesity is a BMI of 30 or more.
Surgical procedures are vital treatment options, which may offer a better option to overcome obesity and its associated comorbidities. Weight loss has been accompanied by improvement in features related not only to obesity but also to OSA, suggesting that weight loss may be the cornerstone of treatment for both conditions. Thus, anatomical effects that predispose obese individuals to airway collapse include reduced airway cross-sectional area (reduced lumen size due to fatty tissue within the airways or on their side walls, reduced upper airway size secondary to the mass effect of the large abdomen on the chest wall and chest wall traction) and a change in airway shape to oval. The observation that circulating leptin increases in proportion to obesity26 suggests the presence of leptin resistance in obese subjects.
The effect of obesity on upper airway protective muscle activation probably plays an important role in the tendency of obese individuals to airway collapse. These results also highlight the need for regular use of weight loss therapies in conjunction with CPAP in all obese and overweight patients with OSA. The possible effects of leptin on respiratory control21 may also contribute to respiratory disorders in obese and hyperleptinaemic patients with OSA. The main factors contributing to obesity are the environment, eating behaviour and physical inactivity.
Obese individuals have elevated leptin levels,26 and their obesity persists due to a presumed resistance to the appetite-suppressing and metabolic effects of leptin ("leptin resistance"). Overweight and obesity remain the most important modifiable causes of sleep apnoea (Peppard et al, 201. According to these criteria, the prevalence of overweight and obesity is extremely high, approaching epidemic proportions. Patel et al40 reported a significant correlation between AHI and anthropomorphic measures of adiposity (ranging from 0.57 to 0.6), suggesting that obesity may explain almost 40 % of the genetic variance in sleep apnoea. The greater this relationship, the more significant the risk factors for sleep apnoea and other obesity-related disorders.
