By Kurt Ullman
Severe obstructive sleep apnea was associated with a risk of cardiovascular death in women, but continuous positive airway pressure (CPAP) seemed to reduce the risk, according to a small Spanish study.
In a 116-patient, observational study, those with severe obstructive sleep apnea had a cardiovascular mortality rate of 3.71 per 100 person-years compared with the control group's rate of 0.28 per 100 person years (P< 0.001), Francisco Campos-Rodriguez, MD, from Valme University Hospital in Seville, Spain, and colleagues found.
Women with mild to moderate apnea had a mortality rate of 0.94 per 100 person-years (P=0.034 compared with the control group), they reported in the Annals of Internal Medicine.
Despite prevalence data suggesting that 2% to 3% of middle-age women have obstructive sleep apnea, most of the studies on both apnea and cardiovascular effects have been done exclusively in men. The researchers were interested in investigating this issue in a large group of women.
The study population consisted of women referred to the sleep units of two hospitals in Spain between December 1998 and December 2007. Following a sleep study, CPAP was offered to the patients with apnea-hypopnea index (AHI) of 30 or greater without regard to symptoms.
Those with AHI scores between 10 and 29 were prescribed CPAP if they also had daytime hypersomnolence. These also were the cutoffs for having mild to moderate (AHI 10 to 29) or severe (30 or more) OSA. Controls were pulled from those having an AHI of 9 or under.
Adherence to CPAP was assessed using a time counter on the device. This information was compiled by the home health provider with primary responsibility for respiratory therapies.
Patients were reviewed at three-month intervals at the sleep center during the first year and every 12 months thereafter. Median follow-up was 72 months. The study's endpoint was cardiovascular death, defined as death from stroke, myocardial infarction, heart failure, or arrhythmia.
Compared with controls, the fully adjusted HR for cardiovascular mortality was 3.50 (95% CI 1.23 to 9.98) for the untreated group with severe sleep apnea. For the CPAP-treated severe sleep apnea group, the fully adjusted HR was 0.55 (95% CI 0.17 to 1.74).
For those untreated patients with mild to moderate sleep apnea, the fully adjusted HR was 1.60 (95% CI 0.52 to 4.90) and 0.19 (95% CI 0.02 to 1.67) for those with mild to moderate sleep apnea who underwent treatment.
Cumulative cardiovascular mortality was increased significantly in both untreated groups compared with controls. This measure in the treated cohort was similar to what was seen in the controls.
Age, body mass index (BMI), hypertension, diabetes, previous cardiovascular events, and sleep apnea status were associated with cardiac mortality in the univariate analysis. In the multivariate analysis, untreated, severe obstructive sleep apnea was an independent predictor of mortality (fully adjusted HR 3.50, 95% CI 1.23 to 9.98). Both CPAP-treated groups did not differ from the control group.
Adherence as a continuous variable was independently associated with lower cardiovascular mortality risk in those who started CPAP treatment (fully adjusted HR 0.72, 95% CI 0.63 to 0.83). AHI as a continuous variable was independently associated with increased mortality among those who were not treated (fully adjusted HR 1.18, 95% CI: 1.06 to 1.32).
The study could not be randomized and this may have introduced a selection bias, which was a limitation, the authors stated. Selection bias also was a concern as all participants were enrolled only after referral to the sleep clinic. A stratified analysis could not be performed because of the small number of cardiac deaths.
Nonetheless, they pointed out that this is most likely the first evidence of a link between severe obstructive sleep apnea and cardiovascular mortality in women. They called for randomized, controlled trials in a larger patient population to conﬁrm whether severe obstructive sleep apnea is truly an independent risk factor for cardiovascular death and whether CPAP can effectively decrease mortality.
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