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New research in RLS, sleep apnea

Thursday, December 13 2007 | Comments

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What's This? Dr. Michael Silber, president of the American Academy of Sleep Medicine and a neurologist from the Mayo Clinic in Rochester, Minn, discussed the implications of several noteworthy studies focused on restless legs syndrome and sleep apnea.

One study he discussed examined the risk of restless leg syndrome and its relationship to pregnancy. Although it is known that RLS is common during pregnancy, researchers evaluated the risk of RLS in women who previously had been pregnant. The case-controlled, family study included patients who had received a diagnosis of RLS and control probands who did not have RLS (530 men, 532 women).

Researchers found that 26.6% of men and 32.2% of nulliparous women had RLS. In comparison, 41.2% of women who had a history of pregnancy had RLS. These differences were apparent across all age groups.

"Even though we know that women have a higher frequency of RLS than men [do], it seems to be confined to women who have once been pregnant," Dr. Silber commented. "We know RLS is common in pregnancy, but this effect seems to persist. Risk apparently increases after a single pregnancy." Further research is needed to explain how pregnancy may alter the pathophysiology of RLS, he added. (Hening WA, et al. S49.003.)

Another study examined the association between RLS and cardiovascular disease. Researchers conducted a cross-sectional observational study of 3,406 men and women (mean age, 68 years) who were enrolled in the Sleep Heart Health Study. RLS was defined as experiencing RLS events ≥5 times/month, with symptoms that caused at least moderate distress. CVD included coronary artery disease, heart failure, and stroke.

After adjustment, the odds for CVS were 2-fold among men and women who had RLS relative to those who did not have RLS. The association was even greater for patients whose RLS symptoms occurred >15 times/month and for those with severely distressing RLS symptoms.

"Because this is cross-sectional data, it is unclear whether RLS causes vascular disease, whether vascular disease causes RLS, or whether the 2 are simply in association with some third underlying factor. It remains to be demonstrated whether treatment of RLS will reduce vascular risk," Dr. Silber cautioned. "One potential mechanism for a direct association between RLS and CVD may involve sympathetic hyperactivity [seen with] associated periodic limb movements of sleep, which occur in 80% to 90% of patients with RLS," Dr. Silber said. (Winkelman JW, et al. S49.002.)

Another study Dr. Silber discussed focused on the potential connection between sleep apnea and cognitive impairment. "We know sleep apnea is associated with vascular risk," he noted, "but is it associated with cognitive impairment?"

To explore this possibility, researchers examined 448 older, community-dwelling women (mean age, 83 years) who were also enrolled in a study of osteoporotic fractures. The primary predictor was the apnea-hypopnea index (AHI). Researchers measured cognitive impairment using the Mini-Mental State Examination (MMSE) and defined cognitive impairment as MMSE results that were 1.5 standard deviations from the sample mean. Multivariate analysis adjusted for age, education, and use of selective serotonin reuptake inhibitors.

The odds of cognitive impairment were 1.4-fold for patients with milder sleep apnea and 3.4-fold with an AHI of ≥30.

In addition, researchers examined whether the apolipoprotein E (APOE) e4 genetic marker influenced the association between cognitive impairment and sleep apnea. "The APOE e4 marker is a known marker for Alzheimer's disease, but also a less well-known marker for sleep apnea," Dr. Silber said. For the 11% of patients who were APOE e4-positive, the odds of cognitive impairment increased to 4.6-fold among those with sleep apnea.

"These results were not adjusted for vascular disease," Dr. Silber said. "Heart disease and hypertension may well be some confounding risk factors here." In addition, researchers did not assess all cognitive domains and the subjects were mostly white women. (Spira AP, et al. S49.008.)

A fourth study Dr. Silber discussed found that sleep apnea may impair immune response to influenza vaccinations. "We all have learned that sleep seems to be necessary for immune competence," he stated. "There's been, in fact, research that shows sleep deprivation impairs the response to some vaccinations."

In this study, researchers hypothesized that antibody titers after a flu vaccination would be reduced in patients with sleep apnea (AHI>10). The study included 33 subjects (12 patients with sleep apnea and 21 controls). The apneic subjects had a mean Respiratory Disturbance Index of 42 events/hour. Researchers took blood samples at baseline, and at 10 days and 30 days after vaccination.

The subjects with sleep apnea had significantly lower immunoglobulin M antibody titers than the control group did at day 10 and day 30 (P=0.027 and P=0.036, respectively).

Although the study was relatively small and there were some discrepancies between age and weight of the control and experimental groups, Dr. Silber said the results indicate that individuals with sleep apnea are less able or slower to mount an effective immune response to vaccinations. "This may have clinical implications especially for older subjects getting flu or pneumoccocal vaccinations," Dr. Silber concluded. (Consens FB, et al. S49.007.)

By Katherine Kahn

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