Statins may improve endothelial protection against complement activity and reduce its downstream proinflammatory effects in patients with obstructive sleep apnea (OSA), according to a study in the Annals of the American Thoracic Society.
Researchers sought to determine whether lowering cholesterol through statins in patients with OSA could improve endothelial protection against complement and its associated inflammatory effects.
The 4-week, randomized, double-blind, parallel-group, placebo-controlled clinical trial (ClinicalTrials.gov Identifier: NCT03122639) included patients referred for evaluation of sleep-disordered breathing from September 2017 to January 2020 at a university medical center. A control group included individuals without OSA with an apnea-hypopnea index (AHI) of less than 5. At 4 weeks after commencement of continuous positive airway pressure (CPAP), the patients with OSA were randomized 1:1 to atorvastatin 10 mg daily or placebo for 4 weeks.
The primary outcome was the proportion of complement inhibitor CD59 on the endothelial cell (EC) plasma membrane in the participants.
The intention-to-treat analysis included 87 patients with OSA and 35 individuals in the control group. The mean (SD) age of patients with OSA was 46 (13) years, and 47% were female. The mean age in the control group was 38 (14) years, and 63% were female.
After 4 weeks of statin therapy, the proportion of complement inhibitor CD59 on the EC surface was significantly increased (P <.001), and membrane attack complex (MAC) deposition on ECs was significantly lower (P <.001) vs placebo among all patients with OSA after adjustment. Compared with placebo, CD59 expression on the EC surface was greater (P =.001) and MAC deposition on ECs was lower (P <.001) after 4 weeks of statin use in the CPAP-adherent (P <.001) and CPAP-nonadherent (P =.004) patients with OSA after adjustment.
No significant correlation was found between changes in lipid profile and CD59 endothelial cell surface expression, MAC deposition, or angiopoietin-2. The proportion of a major complement inhibitor CD59 on the EC surface was significantly decreased at baseline in untreated patients with OSA vs control individuals.
Among untreated patients with OSA, circulating levels of angiopoietin-2 were significantly greater vs those in control individuals. After adjustment for baseline values and prespecified covariates, the comparison was unchanged (P <.001). Circulating levels of angiopoietin-2 after 4 weeks of CPAP therapy were increased vs baseline among the patients with OSA and was primarily accounted for by an increase in angiopoietin-2 levels in CPAP-adherent patients with OSA, as those who did not adhere with CPAP had angiopoietin-2 levels comparable to baseline.
Study limitations include the use of venous ECs, which preclude conclusions about atherosclerosis in OSA, and the inability to determine whether a change in lipid profile precedes a change in CD59 expression because all measurements were conducted at the same time points.
“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,” the study authors concluded.
This article originally appeared on Pulmonology Advisor
Shah R, Patel N, Emin M, et al. Statins restore endothelial protection against complement activity in obstructive sleep apnea: a randomized trial. Ann Am Thorac Soc. Published online March 13, 2023. doi:10.1513/AnnalsATS.202209-761OC