Metabolic Risk Factors for Vascular Disease in Obstructive Sleep Apnea: A Matched Controlled Study

Obstructive sleep apnea (OSA) is reported to have a metabolic profile predisposing to cardiovascular disease. However, previous case-control studies have not adequately controlled for confounders. To determine whether OSA is associated with increased insulin resistance and related metabolic risk factors. We performed a matched case-control study (n = 42) examining putative metabolic risks among men with OSA attending a sleep clinic (apnea-hypopnea index [AHI] > 15] compared with no OSA (AHI < 5). Participants were matched for age +/- 5 yr, body mass index +/- 10%, and current smoking status. They were free of diabetes, clinically demonstrable cardiovascular disease, marked hypertension, and dyslipidemia. Mean +/- SD AHI was higher in patients with OSA (40 +/- 27) than in control subjects (3 +/- 1.3, p = 0.02), and median (interquartile range) nocturnal oxygen saturation was lower (OSA, 83 [76-88]; control, 91 [90-93]%; p < 0.001). Patients with OSA had a higher median (interquartile range) homeostasis model assessment score for insulin resistance (OSA, 1.7 [0.8-4.1]; control, 1.0 [0.7-1.8] mU.mmol/L(2); p = 0.02), total cholesterol (OSA, 5.6 [4.8-6.2]; control, 4.8 [4.3-5.4] mmol/L; p = 0.049), and low-density-lipoprotein cholesterol (OSA, 3.8 [2.9-4.2]; control, 3.1 [2.6-3.6] mmol/L; p = 0.04). Patients with OSA had higher 24-h and nocturnal (12-h) urinary norepinephrine excretion and plasma leptin levels, and lower insulin-like growth factor (IGF)-1 levels (all, p < or = 0.02). Multiple linear regression, adjusting for central obesity, age, and alcohol consumption, confirmed an independent association between OSA and metabolic risks (all, p < 0.05), with a trend for IGF-1 (p = 0.053). In a sleep clinic population, men with OSA and no identifiable cardiovascular disease have increased insulin resistance and other metabolic changes that act to increase the risk of vascular disease, compared with age- and body mass index-matched attendees without OSA.