Among the risk factors for OSA, obesity is probably the most important. Several cross-sectional studies have consistently found an association between increased body weight and risk of OSA. Significant sleep apnoea is present in ≈40 e obese individuals, 17 and ≈70 e patients with OSA are obese. 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. Obesity is considered a major risk factor for the development and progression of OSA, 8,19,20,27,28 The prevalence of OSA in obese or severely obese patients is almost twice that of normal-weight adults.
Furthermore, patients with mild OSA who gain 10 e of their initial weight have a six-fold increased risk of OSA progression, and an equivalent weight loss can result in more than 20n improvement in OSA severity, 28 Furthermore, the higher prevalence of OSA in obese subjects is not limited to adults; recent data show that obese children have a 46 e prevalence of OSA compared to children seen in a general paediatric clinic (33%). These findings highlight the need to develop screening and prevention of these conditions, even in childhood. 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 evidenced 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 overnight 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 terms of weight loss or 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 its 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. But being overweight remains an elevated risk factor for the development of obstructive sleep apnoea.
On the one hand, extra weight can lead to breathing problems during sleep. On the other hand, a person with an untreated sleep disordered breathing, who is not obese, may start to gain weight as a result. Obesity has long been recognised as the most important reversible risk factor for obstructive sleep apnoea (OSA). Analyses from the Wisconsin Sleep Cohort Study suggest that 41 percent of adult OSA cases, including 58 percent of moderate to severe cases, are attributable to overweight or obesity, 1 and weight loss has long been recommended as an adjunctive treatment for OSA.
Longitudinal analyses from the Sleep Heart Health Study support the notion that weight loss is associated with improvements in OSA severity, 2 However, the beneficial impact of weight loss was much smaller than the adverse effect of the same amount of weight gain in that study, suggesting that the relationship between obesity and OSA is more complex than an acute (and reversible) unidirectional causal model can explain. Analyses from the Wisconsin Sleep Cohort Study suggest that 41 percent of adult OSA cases, including 58 percent of moderate to severe cases, are attributable to overweight or obesity. A neck circumference greater than 17 inches in men and 16 inches in women increases the risk of both obesity and sleep apnoea. Daytime sleepiness can lead to decreased mood and physical activity, which, if not associated with a reduction in caloric intake, will obviously worsen obesity.
Although childhood obesity can cause obstructive sleep apnoea, it is much less commonly associated with obstructive sleep apnoea than adult obesity. These close interactions between obesity, sleep deprivation and obstructive sleep apnoea (Fig) share the common pathophysiological feature of metabolic dysregulation. By maintaining a healthy weight, sleep apnoea and other obesity-related disorders can potentially be avoided. Overweight and obesity remain the most important modifiable causes of sleep apnoea (Peppard et al, 201).
Although weight loss cannot "cure other health conditions such as OSA, healthy weight loss and weight management can lead to better sleep, ease of mobility, higher energy levels, a more positive mood and less pain and discomfort. Several conditions associated with OSA, such as high blood pressure, insulin resistance, systemic inflammation, visceral fat deposition and dyslipidaemia, are also present in other conditions closely related to OSA, such as obesity and reduced sleep duration. The higher this ratio, the more significant the risk factors for sleep apnoea and other obesity-related disorders. Although obstructive sleep apnoea (OSA) can be diagnosed in people of all shapes and sizes, obesity appears to be an underlying risk factor.
Given the evidence that short sleep duration and poor sleep quality predict a higher rate of weight gain,3,4 many have postulated that OSA may itself predispose to obesity.
