Statins Restore Endothelial Protection against Complement Activity in Obstructive Sleep Apnea: A Randomized Trial.

RATIONALE: Increased cardiovascular risk in obstructive sleep apnea (OSA) persists after continuous positive airway pressure (CPAP) and alternative therapies are needed. Impaired endothelial protection against complement is a cholesterol-dependent process that initiates endothelial inflammation in OSA, which increases cardiovascular risk.

OBJECTIVES: To investigate directly whether cholesterol lowering improves endothelial protection against complement and its pro-inflammatory effects in OSA.

METHODS: Newly diagnosed OSA patients (n=87) and OSA-free controls (n=32) participated. Endothelial cell and blood were collected at baseline, after 4 weeks of CPAP and again after 4 weeks of atorvastatin 10 mg vs. placebo using randomized, double-blind, parallel group design. Primary outcome was the proportion of a complement inhibitor CD59 on the endothelial cell plasma membrane in OSA patients after 4 weeks of statins vs. placebo. Secondary outcomes were complement deposition on endothelial cells and circulating levels of its downstream pro-inflammatory factor angiopoietin-2 after statins vs. placebo.

RESULTS: Baseline expression of CD59 was lower whereas complement deposition on endothelial cells and levels of angiopoietin-2 were greater in OSA patients then controls. CPAP did not affect expression of CD59 or complement deposition on endothelial cells in OSA patients regardless of adherence. Compared with placebo, statins increased expression of endothelial complement protector CD59 and lowered complement deposition in OSA patients. Good CPAP adherence was associated with increased angiopoietin-2 levels, which was reversed by statins.

CONCLUSIONS: Statins restore endothelial protection against complement and reduce its downstream pro-inflammatory effects, suggesting a potential approach to reduce residual cardiovascular risk after CPAP in OSA. Clinical trial registered at ClinicalTrials.gov (NCT03122639).