Statins May Reduce Sleep Apnea Cardiovascular Risk

Obstructive sleep apnea (OSA) is much more common in Western society than many of us consider. It affects approximately 25% of adults and has a very poor prognosis, increasing all-cause mortality by tripling the risk of hypertension, coronary artery disease, and venous embolism.^1-4 OSA manifests itself by repetitive episodes of mild hypoxia. Hypoxia activates the endothelium, causing platelet aggregation, white blood cell adhesion, and macrophage activation, leading to atherosclerosis development and progression.^5-7 Treatment of OSA is primarily by continuous positive airway pressure (CPAP). Interestingly, CPAP promotes regression of atherosclerosis. 

Which cardiovascular medications promote regression of atherosclerosis? Statins. In a small in vitro experiment, researchers from Columbia University Medical Center in New York City set out to determine whether intermittent hypoxia activates endothelial cells through the complement system.⁶ The peptide, complement inhibitor CD59, protects the endothelium from membrane attack.  Studying endothelial cells from patients with OSA, compliment inhibitor CD59 was decreased relative to patients’ endothelium without OSA. Lower levels of CD59 led to loss of vascular protection and was associated with greater levels of membrane attach complex. Increased internalization (loss of function) of compliment inhibitor CD59 protein appears to be cholesterol-dependent. In a subset of study patients who were taking statins lower concentrations of compliment inhibitor CD59 levels were reversed. This study will need to be confirmed in larger human in-vitro and in-vivo studies.

What does this mean? First, statins are not currently considered as a direct treatment for OSA. Treatment for sleep apnea is exercise, weight loss, and daily use of CPAP or other device. Second, this small basic science research study is preliminary and the results should not be taken to the clinical arena until confirmed. Third, if this research is true—that statins can regress atherosclerotic formation in sleep apnea patients—then the devastating OSA-induced cardiovascular event rate may be reduced.

Mark A. Munger, PharmD, FCCP, FACC, is a Professor of Pharmacotherapy and Adjunct Professor of Internal Medicine, at the University of Utah, where he also serves as the Associate Dean, Academic Affairs for the College of Pharmacy.

References:

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2. Marin JM, Carrizo SJ, Vincente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnea-hypopnea with or without treatment with continuous positive airway pressure. An observational study. Lancet. 2005;365(9464):1046-1053.

3. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med.2005;353(19):2034-2041.

4. Marshall NS, Wong KK, Liu PY, Cullen SR, Knuiman MW, Grunstein RR. Sleep apnea as an independent risk factor for all-cause mortality: The Busselton Health Study. Sleep. 2008;31(8):1079-1085. 

5. Arnaud C, Beguin PC, Lantuejoul S, et al. The inflammatory preatherosclerotic remodeling induced by intermittemt hypoxia is attenuated by RANTES/CCL5 inhibition. Am J Resp Crit Care Med. 2011;184(6):724-731. 

6. Dyugovskaya L, Lavie P, Lavie L. Increased adhesion molecules expression and production of reactive oxygen species in leukocytes of sleep apnea patients. Am J Resp Crit Care Med.2002;165(7):934-939.

7. Hopkins PN. Molecular biology of atherosclerosis. Physiol Rev. 2013;93(3):1317-1542.

8. Emin M, Wang G, Castagna F, et al. Increased internalization of complement inhibitor CD59 may contribute to endothelial inflammation in obstructive sleep apnea. Sci Translat Med. 2016;8(320):320ra1.