PREDICTORS OF ELEVATED TUMOUR NECROSIS FACTOR a LEVEL IN OBSTRUCTIVE SLEEP APNOEA SYNDROME

WINNING ABSTRACT: Circulating levels of TNF-a are elevated in Obstructive Sleep Apnoea Syndrome (OSAS) and likely contribute to associated cardiovascular diseases. Furthermore, TNF-a has been suggested as a mediator of excessive daytime sleepiness (EDS). We investigated the predictors of TNF-a in OSAS in large, well-selected patient and control cohorts. We undertook a prospective study of 30 non-OSAS (including 22 non-sleepy controls and 8 sleepy non-apnoeic snorers), 36 mild-moderate OSAS and 31 severe OSAS male subjects. All groups were closely matched in age, BMI, smoking status, blood pressure and lipid profile. All subjects were free of other disease and were not taking regular medication. Serum for TNF-a assay was drawn following polysomnography (PSG) in all subjects. 49 patients were commenced on CPAP therapy within one week following PSG; sleep studies and TNF-a measurements were repeated 6 weeks later. TNF-a was higher in OSAS patients than controls (p,0.001). In multivariate analysis, TNF-a was independently associated with the desaturation index (r50.399, p,0.001), the Epworth Sleepiness Score (ESS) (r50.243, p50.005) and total cholesterol (r50.216, p50.018). Furthermore, levels were higher in sleepy non-OSAS patients than in controls (4.49[3.35,6.94] pg?ml vs 2.46[1.66,3.40]; p50.002) but lower than in severe OSAS patients (6.32[5.70,8.17]; p50.03). CPAP significantly lowered TNF-a (from 5.56¡2.10 to 4.13¡2.99 pg?ml; p50.004). The severity of intermittent hypoxia is the strongest predictor of TNF-a level supporting a key role of inflammation in the cardiovascular pathophysiology of OSAS. Furthermore, TNF-a is independently associated with EDS.