When in Doubt, Pressurize the Snout!

Abstract & Commentary

By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips reports no financial relationship to this field of study.

Synopsis: Patients with mild-to-moderate obstructive sleep apnea (OSA) who were treated with Continuous Positive Airway Pressure (CPAP) experienced an absolute risk reduction in cardiovascular risk compared with those who were not treated.

Source: Buchner NJ, et al. Continuous Positive Airway Pressure Treatment of Mild to Moderate Obstructive Sleep Apnea Reduces Cardiovascular Risk. Am J Respir Crit Care Med. 2007;176:1274-1280.

This report results from a 6 year follow-up of an unselected cohort of patients who were referred to a sleep laboratory with suspected obstructive sleep apnea (OSA). Severity of sleep-disordered breathing was based on the Apnea plus Hypopnea Index (AHI) as follows: mild OSA was defined as AHI 5 to < 15/h, moderate OSA was defined as AHI 15 to < 30/h, and severe OSA was defined as AHI > 30/h. (For well-informed readers, apneas required only 10 seconds of cessation of airflow (not defined further in this paper), and hypopneas required at least a 50% reduction in airflow with an arousal or 4% oxygen desaturation. These definitions are a mishmash of old and new scoring criteria, with a little research criteria thrown in. (It is unlikely that interscorer reliability of these events would be very high, but never mind.) All patients with an AHI of at least 5 and sleepiness (not defined in this paper) were offered CPAP; those with mild OSA who were not sleepy or who refused CPAP were offered an oral appliance. The authors controlled for current smoking, arterial hypertension, diabetes, hypercholesterolemia, cardiovascular disease history or documentation (including coronary artery disease, myocardial infarction, and stroke), and body mass index [BMI].

Once enrolled, patients were followed yearly, and underwent cardiovascular workups as indicated. Compliance was defined as CPAP use for at least 4 hours a night; this was not objectively confirmed in all cases. Primary outcomes were nonfatal and fatal (death from myocardial infarction or stroke) cardiovascular events. Nonfatal events included myocardial infarction, stroke, and acute coronary syndrome requiring revascularization procedures.

Of 449 patients recruited, 364 accepted positive airway pressure (mostly CPAP, but some bilevel pressure; 20 chose an oral appliance). Their mean age was about 56 years and about 15% were women. Those who were treated were statistically significantly heavier than those who were not (BMI 31.2 vs 29.3 kg/m2, P = 0.003), and had higher AHI's and lower oxygen desaturation. Of those who accepted CPAP initially, 21.5% were "noncompliant." Although the mean duration of follow-up was 72 months, the untreated patients were followed for shorter periods (mean 50 months vs 70 months for treated patients).

During follow-up, 76 events occurred in the treated patients, including nine myocardial infarctions (2.4%), 25 revascularization procedures (6.8%), 10 strokes (2.7%), eight cardiovascular deaths (2.2%), and 24 deaths of all cause (6.6%). Among the untreated patients, there were five myocardial infarctions (5.8%), 11 revascularization procedures (12.9%), five strokes (5.8%), and three deaths due to cardiovascular causes (3.5%). Of the treated patients, 14.2% had an event vs 28.3% for the untreated ones, with an absolute risk reduction of 27.9%.

In evaluating only those patients with mild-to-moderate sleep apnea, the reduction in event risk for treatment was similar: more events occurred in untreated (25.3% [n = 20]) than in treated patients (14.4% [n = 30]; P = 0.024). After controlling for confounding variables such as BMI, age, smoking, etc, the risk reduction associated with treatment of OSA was 64%, both for the entire group and for those with mild-to-moderate OSA.

Commentary

There is no doubt that obstructive sleep apnea is associated with cardiovascular morbidity and mortality.1-4 The association with hypertension is particularly strong.4 While there have been previous observational studies demonstrating a reduction in cardiovascular mortality with CPAP treatment,5-8 little is known about the benefits of treatment of older patients and of patients with milder disease. By stratifying their patients by disease severity and by including an older cohort (mean age 56 years), these authors have expanded the group of sleep apnea patients who are likely to benefit from treatment.

There are a couple of important caveats here. This study is not a randomized, placebo-controlled trial (and it becomes increasingly unlikely that such a trial will ever happen). Those patients who choose to use CPAP are likely to be different from those who do not. As Gary Taubes put it in a recent New York Times article, "the problem is that people who faithfully engage in activities that are good for them—taking a drug as prescribed, for instance, or eating what they believe is a healthy diet—are fundamentally different from those who don't."8 Further, people who do what their doctors ask are healthier than those who don't. And there are other, difficult to quantify factors between those who follow medical advice and those who don't. I recently had a patient who told me where to stick a CPAP machine in no uncertain terms, then stormed out of the clinic. My guess is that his prognosis is poor for a lot of reasons.

It is notable, however, that the untreated patients in this study had worse outcomes, even though they had fewer risk factors, since they were less likely to be obese and had milder sleep apnea.

There are a lot of "muddy" issues in this paper, including no discussion of how sleepy and nonsleepy patients were distinguished, lack of objective measurement of adherence, and shorter follow-up for untreated than for untreated patient. These problems would tend to bias the results toward reduced differences in outcomes for the treated patients, however, and tend to strengthen the authors' conclusions.

On the basis of this and other studies, recommendation of CPAP treatment for those patients with even mild sleep apnea is the most prudent course at present.

References

1. Mooe T, et al. Sleep-disordered breathing and coronary artery disease: long-term prognosis. Am J Respir Crit Care Med. 2001;164:1910-1913.

2. Shahar E, et al. Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the sleep heart health study. Am J Respir Crit Care Med. 2001;163:19-25.

3. Nieto FJ, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study: sleep heart health study. JAMA. 2000;283:1829-1836.

4. Peppard PE, et al. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342:1378-1384.

5. Campos-Rodriguez F, et al. Mortality in obstructive sleep apnea-hypopnea patients treated with positive airway pressure. Chest. 2005;128:624-633.

6. Doherty LS, et al. Long-term effects of nasal continuous positive airway pressure therapy on cardiovascular outcomes in sleep apnea syndrome. Chest. 2005;127:2076-2084.

7. Marin JM, et al. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005;365:1046-1053.

8. Taubes G. Do we really know what makes us healthy? New York Times Magazine. Sept 16, 2007.