A group of Johns Hopkins scientists have uncovered a link between sleep apnea and cardiometabolic dysfunction that could help explain heart disease in sleep patients, according to a recent study in the Journal of Clinical Endocrinology and Metabolism.

It’s well-known that obstructive sleep apnea (OSA) is associated with diabetes and cardiovascular disease, according to the study, but until now scientists haven’t been able to tell whether OSA is a cause, consequence or marker of cardiovascular disease.

“Sleep apnea is a common condition that I see on a daily basis as a pulmonary physician,” lead researcher Jonathan Jun, MD, said in an email. “Many of my sleep apnea patients have diabetes and metabolic syndrome. I—and many others before me—have wondered whether OSA is causing these problems, or if OSA is just an ‘innocent bystander’ to obesity.”

In his study, Jun and his colleagues measured levels of plasma free fatty acids (FFAs), glucose, insulin, triglycerides (TGs) and cortisol in a group of 31 patients while they slept, both with the aid of continuous positive airway pressure (CPAP) and without.

In their study, Jun and co-authors noted most studies of metabolic function in individuals with OSA have taken place during wakefulness, not actual sleep.

“Because sleep comprises one third of the human lifespan, altered metabolism during this period may have substantial health implications,” they wrote.

Jun said he’s completed several experiments with lab mice in which OSA was simulated in the rodents. He said he noticed immediate metabolic changes in the mice, especially in FFA and glucose levels, during exposure to hypoxia. The experiments were what prompted him to design a similar study for people.

All 31 of Jun’s human subjects suffered from moderate to severe OSA, according to the study, and were an average 50 years old. The majority of the population was male and white, and more than half had a history of hypertension and hyperlipidemia. A quarter had a history of non-insulin-dependent diabetes.

Jun’s team enrolled only CPAP-acclimatized patients who would use the device on their own, and analyzed sleep patterns for two nights: one with CPAP, and the other two days later, without the machine. The researchers ultimately found that OSA, after a three-day hiatus from CPAP, increased blood pressure, heart rate and arterial stiffness in patients, boosting cardiovascular stress.

They also noted that OSA increased levels of plasma FFA, glucose and cortisol, paralleling the distribution of respiratory events, hypoxemia, increasing heart rate and sleep fragmentation during sleep. In nondiabetic patients, glucose production didn’t increase, but plasma insulin and reduced glucose clearance did.

Jun and co-authors described this as “a form of sleep-induced metabolic syndrome” in individuals with OSA. If a patient has consistently dramatic metabolic responses to the breathing condition, they wrote, that patient might be at increased risk for cardiovascular disease and diabetes. Though other elements factor into those risks, Jun wrote that OSA can be used as a kind of “metabolic stress test” to help discern risk of cardiometabolic disease in patients.

“Cardiovascular disease is inextricably linked with metabolism, as evidenced by the impacts of visceral obesity, diabetes and hyperlipidemia on atherosclerotic heart disease,” Jun said. “I think this study sheds light on the metabolic complications that can be caused by sleep apnea. Recently, some randomized controlled trials have failed to show a benefit of CPAP therapy on cardiovascular outcomes. I think it is important to realize that one, CPAP is not well tolerated, and two, these studies did not enroll highly symptomatic OSA patients. So, the impacts of sleep apnea on cardiovascular health are still unclear.”