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

Area of Science:

• Cardiovascular Medicine
• Sleep Medicine
• Pharmacology

Background:

• Obstructive sleep apnea (OSA) is linked to increased cardiovascular risk, persisting even after continuous positive airway pressure (CPAP) therapy.
• Endothelial inflammation, initiated by impaired cholesterol-dependent endothelial protection against complement, contributes to this elevated risk in OSA.
• Novel therapies are needed to address residual cardiovascular risk in OSA patients unresponsive to CPAP.

Purpose of the Study:

• To determine if lowering cholesterol with statins can enhance endothelial protection against complement in patients with OSA.
• To investigate the impact of statins on complement deposition and downstream proinflammatory markers in OSA.

Main Methods:

• A randomized, double-blind, placebo-controlled trial involving 87 newly diagnosed OSA patients and 32 controls.
• Patients received either 10 mg atorvastatin or placebo for 4 weeks, following an initial 4-week CPAP therapy period.
• Primary outcome: change in CD59 expression (complement inhibitor) on endothelial cells. Secondary outcomes: complement deposition and angiopoietin-2 levels.

Main Results:

• OSA patients exhibited lower baseline CD59 expression and higher complement deposition and angiopoietin-2 levels compared to controls.
• CPAP therapy alone did not alter CD59 expression or complement deposition in OSA patients.
• Atorvastatin significantly increased CD59 expression and reduced complement deposition, while reversing CPAP-associated increases in angiopoietin-2.

Conclusions:

• Statins effectively restore endothelial protection against complement and mitigate downstream inflammation in OSA patients.
• This suggests statins may represent a viable strategy to reduce residual cardiovascular risk in OSA patients treated with CPAP.
• Clinical trial registered with www.clinicaltrials.gov (NCT03122639).