Uncle Alan chooses to snore instead of using his Constant Positive Airway Pressure (CPAP) machine. The machine prevents sleep apnea—a disease in which people stop breathing for periods of 10 seconds or more during the night—by keeping the soft palate in the back of the mouth from collapsing. Uncle Alan says it aggravates his chronic sinus condition.
But without it, he may be risking more life-threatening illnesses, such as hypertension, heart disease, osteoporosis, and inflammatory disease, say psychiatrists Edward Bixler and Alexandros Vgontzas of Penn State's College of Medicine. Bixler has created a model, based on a recent study, which suggests that if you snore, you are 1.6 times more likely to have hypertension. If you have mild to moderate apnea, you are 2 to 5 times more likely; severe apnea, 6 times. According to Vgontzas, the correlation may be caused by elevated levels of Interleukin-6 (IL-6), an inflammatory chemical that causes fevers, tiredness, and loss of appetite. Vgontzas' work shows that when people don't sleep long enough or well enough, their IL-6 levels rise.
Bixler and Vgontzas conduct their studies at the Sleep Research Treatment Center at Penn State's Hershey Medical Center. Each of the six motel-like rooms is equipped with video cameras and ports in the walls for electrode leads to pass through. The electrodes, affixed to a sleeping subject's body, help Vgontzas and Bixler monitor the length and quality of the five stages of sleep.
In the control room, crowded among video monitors, boxes of electrical wires, and various pieces of CPAP machines, six machines record the data on long rolls of paper. One, an electroencephalograph (EEG), monitors brain output. Another, an electrocardiograph (EKG), records heart patterns. Other machines measure eye movement, muscle tone, blood oxygenation, breathing patterns, and snoring. In one night of sleep, Bixler and Vgontzas record 480 minutes (1500 pages) of records. Their graduate students hand-analyze the charts using a scoring method that sleep-study pioneers devised in the 1960s.
"Four percent of the male population suffers from sleep apnea," Bixler says. His model shows that the association of apnea with hypertension is strongest in men, aged 50 to 55, who are obese—the same type of patient who is most frequently seen in sleep disorder clinics. "You don't see the elderly in the sleep clinics, even though the figures in the literature indicate that the number of apnea occurrences increases with age," Bixler notes. Nine years ago, he began a study to investigate this discrepancy. He and his graduate students interviewed more than 4,000 men, asking if they were sleepy during the day, if they snored, what their heights and weights were, and whether they had hypertension. Bixler tried to bring 100 percent of the men who had all four symptoms into the sleep lab for evaluation and treatment, since they had the highest risk for complications. But he also evaluated those who had fewer symptoms. Ultimately 741 men spent a night in the lab.
Bixler and his students found that the total number of apnea events does increase with age, just as other studies had suggested; however, elderly subjects most often have a non-obstructive type of apnea in which they stop breathing, then simply start again without struggling. Bixler is not yet sure how this type of apnea affects body chemistry, but only by excluding the non-obstructive events is he able to obtain an epidemiological breakdown that matches clinical observations.
The primary function of IL-6 is to incite inflammation in the body, but until recently, inflammation caused by lack of sleep was hard to substantiate with laboratory testing. A new highly sensitive assay for IL-6 has allowed Vgontzas and his students to detect elevated levels of IL-6 and tumor necrosis factor-alpha, another inflammatory chemical, in patients with sleep disorders such as apnea and narcolepsy—a disease in which spontaneous sleeping occurs at inappropriate times. Other recent research shows that IL-6 is also high in people who suffer from African sleeping sickness and adrenal insufficiency.
IL-6 is made by white blood cells and brain cells, but also by what's called "omental" fat tissue—the kind that situates itself primarily around the bellies and thighs. "The more fat," Vgontzas explains, "the more IL-6 produced. In obese people ten percent of the body's IL-6 is provided by fat." The IL-6 produced by fat compounds the apnea-induced elevation. That may be why obese men with apnea tend to have complications which lead them to seek treatment in sleep clinics. Estrogen, Bixler has found, protects premenopausal women from apnea, and thus to some extent from its consequences. "But," he points out, "obesity can over-ride this protection."
To determine how long one must be sleep-deprived to suffer physical consequences, Vgontzas and his students invited normal, healthy volunteers to sleep in the lab for six nights, and observed the subjects sleeping normally for the first four. Subjects were not allowed to sleep at all the fifth night, but slept normally again the sixth. IL-6 levels were higher the day following the sleepless night than they had been following the nights of rest. In addition, sounder-sleeping volunteers had lower daytime IL-6 levels.
Since high levels of IL-6 give you that all-over sick feeling, sleeping soundly and for the right amount of time improves your sense of well-being. "Even now," notes Vgontzas, "the most common remedy for illness is sleep." But bad sleep makes you more than rundown. The high levels of IL-6 that result makes you more susceptible to osteoporosis, heart attacks, and rheumatoid arthritis.
"People sleep less well in old age," Vgontzas says. "Maybe that is why these problems are prevalent in the elderly." He now has a study in progress to determine if older people have higher levels of IL-6.
Edward Bixler, Ph.D., is professor of psychiatry in the College of Medicine at Hershey Medical Center, 500 University Dr., Box 850, Hershey, PA 17033; 717-531-8515; eob1@psu.edu. Alexandros Vgontzas, Ph.D., is associate professor of psychiatry; 531-8136; axv3@psu.edu. Bixler's research is funded by the National Institutes of Health. Writer Heather L. Fletcher is a graduate student in chemistry at Penn State.