Obstructive Sleep Apnea and the Metabolic Syndrome

Jamie C.M. Lam; Mary S.M. Ip

Disclosures

Expert Rev Resp Med. 2009;3(2):177-186. 

In This Article

Abstract and Introduction

Abstract

Obstructive sleep apnea (OSA) and the metabolic syndrome have a strong association with each other owing to their common feature of obesity, but an association independent of obesity has been demonstrated in several studies. There is also evidence, of varying strengths, from epidemiologic and clinical studies, for the independent association between OSA and individual core components of the metabolic syndrome, including hypertension, insulin resistance and dyslipidemia. To date, the data are strongest for hypertension, while data for adverse glucose or lipid metabolism are more controversial. Obesity and other factors, such as alcohol drinking and smoking, obviously pose major confounding hurdles to the clarification of the causal or aggravational role of OSA on cardiometabolic risks. Recurrent episodes of obstructed breathing notably result in intermittent hypoxemia and sleep fragmentation, and these may in turn lead to many adverse body responses, including sympathetic activation, neurohumeral changes and inflammation, which are the seeds for cardiometabolic dysfunctions, such as atherosclerosis and diabetes mellitus. Evidence from translational studies or animal/cell work are forthcoming in the delineation of these pathogenetic mechanisms.

Introduction

Obstructive sleep apnea (OSA) is a chronic condition, characterized by recurrent episodes of upper airway collapse during sleep, leading to intermittent hypoxemia and sleep fragmentation. OSA afflicts all age groups.[1,2] Its severity is usually graded according to the average number of apneic and hypopneic episodes per sleep hour (apnea-hypopnea index [AHI]) in sleep studies. In adults, OSA is defined by an AHI of 5 or more, and categorized as mild, moderate or severe OSA at AHI 5-15, greater than 15-30 or greater than 30, respectively.[3] In clinical practice, the severity of symptoms, in particular that of daytime sleepiness and also that of any comorbidities, need to be considered in the comprehensive assessment of the individual. In the middle-aged population, OSA has been estimated to symptomatically affect 3-7.5 and 1-4.5% of men and women, respecitvely,[4,5,6,7,8,9,10] while the prevalence of asymptomatic detection may be as high as one in four subjects, and increases with advancing age.[1,11] Excess bodyweight has been consistently identified as a major risk factor for adult OSA in different ethnicities[1] and is probably becoming an important risk factor in older children and adolescents.[2,12] There is accumulating evidence of increased cardiovascular morbidity and mortality in OSA, independent of obesity.[13,14,15]

The metabolic syndrome represents a cluster of closely related cardiometabolic features, including the essential components of visceral obesity, insulin resistance, hypertension and dyslipidemia, although various professional organizations have set slightly different criteria for definition of the syndrome.[16] According to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) report,[17] the syndrome is diagnosed when three out of five clinically identifiable variables are present: hypertension, glucose intolerance, low serum high-density lipoprotein (HDL)-cholesterol, elevated serum triglyceride and abdominal obesity. The WHO and the European Group for the Study of Insulin Resistance recommends insulin resistance or glucose intolerance to be an essential criterion, while the International Diabetes Federation recommends a diagnostic set similar to the NCEP ATP III version, using abdominal obesity as the anchoring feature.[18] The percentage of body fat and obesity-related health risks have been shown to occur at lower BMIs and waist circumferences in Asian populations, hence the threshold for defining obesity and abdominal obesity is lower for Asians.[19,20] The metabolic syndrome is also associated with an array of metabolic perturbations, such as microalbuminuria, elevated plasminogen activator inhibitor-1, thrombophilia, increased oxidative stress, endothelial dysfunction, liver steatosis, hyperuricemia, leptin resistance and hypoadiponectinemia.[16,21] On the basis of the NCEP ATP III definition, the prevalence of metabolic syndrome in adults in different countries and ethnic groups varies widely, from approximately 8% (India) to 44% (native Americans in the USA) in men, and from 7% (France) to 57% (native Americans in the USA) in women, and is highly age-dependent.[22]

The metabolic syndrome is associated with an increased risk of cardiovascular disease and Type 2 diabetes mellitus.[16] In recent years, there has been heated debate regarding the usefulness of defining the metabolic syndrome as a distinct entity.[23,24] Notwithstanding this controversy, the metabolic syndrome serves as a useful anchor for the evaluation of the relationship between OSA and cardiometabolic dysfunction.

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