Researchers discover how sleep apnea increases heart disease--and how statins might reverse it

John Murphy, MDLinx | January 08, 2016

Obstructive sleep apnea (OSA) triples the risk for cardiovascular diseases. Scientists have now discovered how this previously unknown event happens—and that statins may decrease this cardiovascular risk, according to a study published online January 6, 2016 in the journal Science Translational Medicine.

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Statins linked to sleep apnea related heart disease

In people with sleep apnea who don’t take statins, cholesterol draws the protective peptide CD59 inside the epithelial cell (left). But for those who do take statins, CD59 remains on the cell surface (right). (Images: Sanja Jelic, MD/Columbia University Medical Center)

“It has been well documented that sleep apnea is a powerful and independent risk factor for heart disease, but the underlying reason for this has remained unclear,” said the study’s corresponding author Sanja Jelic, MD, Associate Professor of Medicine in the Division of Pulmonary, Allergy, and Critical Care Medicine at Columbia University Medical Center (CUMC), in New York, NY.

“The aim of our study was to understand the mechanisms by which sleep apnea may lead to heart disease in an effort to reduce the risk,” Dr. Jelic said.

To that end, Dr. Jelic and colleagues enrolled 128 adults who underwent sleep studies at CUMC’s Sleep Disorders Center, including 76 people diagnosed with OSA and 52 control subjects who did not have OSA.

People with OSA suffer interruptions of breathing during sleep, resulting in intermittent hypoxia (IH). The investigators used a phage display peptide library in all subjects to investigate whether IH activates their endothelial cells (ECs) in a distinctive way. The researchers found that people with OSA had higher levels of the peptide CD59, which is known to protect ECs from the membrane attack complex (MAC) and resultant inflammation.

Surprisingly, CD59 was found mainly inside the epithelial cells in people with OSA, instead of on the cell surface, where it couldn’t provide its protective effect. Consequently, the ECs in subjects with OSA had larger deposits of inflammatory proteins.

“This unexpected finding suggests that repeatedly interrupting oxygen flow during sleep draws CD59 away from the cell surface, where it is better positioned to do its job in protecting cells from inflammation,” Dr. Jelic said.

However, in a small subset of OSA subjects, the researchers did find CD59 on the cell surface, similar to subjects who did not have sleep apnea. When the researchers investigated this, they learned that the people in this subset were taking statins.

Further testing revealed that cholesterol internalizes CD59, drawing it away from the cell surface, in patients with IH. Statins, on the other hand, turn the tables on this activity.

“We were surprised to discover that these commonly prescribed drugs appeared to reverse the process that leads to vascular injury, and ultimately heart disease, in people with sleep apnea,” Dr. Jelic said. “This striking result provides support for the concept that statins may be considered as a primary prevention strategy for reducing heart disease risk in people with sleep apnea, pending further clinical trials.”

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