P6235The metabolism of triglyceride-rich lipoproteins is impaired in patients with obstructive sleep apnoea: effects of treatment with continuous positive airway pressure

Abstract

Background: There is growing evidence that Obstructive Sleep Apnoea (OSA) may cause fasting dyslipidemia and atherosclerosis. In animal models, intermittent hypoxia is associated with delayed triglyceride-rich lipoprotein (TRLP) plasma clearance and atherosclerosis. Evidence in OSA patients is still lacking. Purpose: To investigate whether the metabolism of TRLP is impaired in patients with OSA and whether eventual disturbances in this metabolism could be reversed by OSA treatment. Methods: We studied 16 male apparently healthy patients with severe OSA (apnoea-hypopnoea index ≥30 events/hour) and 12 volunteers without OSA (apnea-hypopnea index <5 events/hour) determined by polysomnography. The groups were matched for age, body mass index and waist circumference. After 12 hours fasting, a triglyceride-rich chylomicron-like emulsion, labeled with [14C]- cholesterol ester (that tracks remnant removal) and [3H]-triglycerides (that tracks emulsion lipolysis) was injected intravenously. Blood samples were collected at 2, 4, 6, 10, 15, 20, 30, 45 and 60 minutes after the injection. The fractional clearance rate (FCR) of the radiolabeled lipid was estimated by radioisotope decay. We performed laboratory measurements of glucose, lipid profile and free fatty acids. In addition, we measured carotid intima-media thickness (CIMT). A subgroup of patients with OSA repeated measurements after three months of CPAP. All measurements were blinded to the clinical status. Results: Compared to healthy subjects, patients with OSA presented a huge delay in both FCR-cholesterol esters (0.013±0.001 vs. 0.0028±0.002min-1; p=0.032) and FCR-triglycerides (0.035±0.012 vs. 0.0050±0.002min-1; p=0.003), respectively. CIMT was higher in OSA group: 620±17 vs. 725±29 μm; p=0.004. Cholesterol esters FCR were inversely related to total sleep time <90% (r=-0.42; P=0.029) and CIMT (r=-0.44; P=0.022). The triglyceride FCR was inversely correlated with Apnoea-Hypopnoea Index (r=-0.39; P=0.04). Seven patients were treated with CPAP. After treatment, the emulsion triglyceride FCR increased fivefold, from 0.0065±0.0088 to 0.0302±0.0245 min-1; p=0.025, but the cholesterol ester FCR was unchanged (p=0.395). Conclusions: Severe OSA present delayed clearance of cholesterol esters and triglycerides. CPAP treatment promoted improvements in triglycerides clearance. These findings may contribute to explain mechanisms by which OSA promotes atherosclerosis.