Chronic intermittent hypoxia caused by obstructive sleep apnea may play an important role in explaining the morbidity-mortality paradox of obesity

Summary Obesity has reached global pandemic that threatens the health of millions of people and is associated with numerous morbidities such as hypertension, type II diabetes mellitus, dyslipidemia, cor pulmonale, gallbladder disease, obstructive sleep apnea (OSA), certain cancers, osteoarthritis, increased surgical risk and postoperative complications, lower extremity venous and/or lymphatic problems, pulmonary embolism, stroke/cerebrovascular diseases and coronary arterial disease. Despite all these adverse associations, numerous studies and meta-analyses have documented an “obesity paradox” in which overweight and obese population with established cardiovascular disease have a better prognosis than do their lean counterparts. There are potential and plausible explanations offered by literature for these puzzling data; however, it still remains uncertain whether this phenomenon is attributable to a real protective effect of high body fat mass. In recent years, the survival advantage of patients with OSA, combined with the potential cardioprotective effects of chronic intermittent hypoxia, raise the possibility that apneas during sleep may activate preconditioning-like cardioprotective effect. Chronic intermittent hypoxia, one of the physiological markers of OSA, is characterized by transient periods of oxygen desaturation followed by reoxygenation, and is a major cause of its systemic harmful (oxidative stress, inflammation, sympathetic activity, vasculature remodelling and endothelial dysfunction) and/or protective (preconditioning-like cardioprotective) effects. Since many OSA subjects are obese, and obesity is an independent risk factor for many comorbidities associated with OSA; and also most OSA has never been diagnosed in obese patients, we hypothesed that the chronic intermittent hypoxia caused by OSA in obese patients may be one of the underlying mechanisms in morbi-mortality paradox of obesity.