Cardiovascular Consequences of Sleep-Disordered Breathing: Past, Present and Future

Sleep-disordered breathing (SDB), which includes obstructive sleep apnea (OSA) as its most extreme variant, is characterized by intermittent episodes of partial or complete obstruction of the upper airway during sleep that disrupts normal ventilation and sleep architecture and is typically associated with snoring and daytime sleepiness. SDB is common, with an incidence in middle-aged men and women of 4% and 2%, respectively.1 Major risk factors for SDB include obesity, male gender, increasing age, and abnormalities of craniofacial morphology.2 There is an increasing perception that SDB/OSA via various mechanisms increases cardiovascular morbidity and mortality (Figure 1). However, many risk factors for SDB/ OSA, such as obesity and male gender, are the same as for hypertension and cardiovascular disease.3 Thus, only recently has there been converging evidence that SDB is a risk factor for their development.4–6 Moreover, there is increasing information to indicate that SDB/OSA is linked to metabolic, vascular, hematologic, and genetic markers associated with increased cardiovascular disease risk. In addition, central sleep apnea (CSA), another form of SDB, appears to be an important factor that influences morbidity and mortality among those with heart failure (HF). Nevertheless, responsible mechanisms, the role of SDB as a risk factor “independent” of associated comorbidities, and whether treatment of SDB will mitigate this risk are unknown and remain to be determined. This report summarizes the proceedings of a workshop sponsored by the National Center on Sleep Disorders Research and the National Heart, Lung, and Blood Institute on September 12 to 13, 2002, to assess a broad array of new physiological, molecular, and genetic information pertaining to the relationship between SDB and the risk of cardiovascular diseases. The major goal of the workshop was to recommend new directions for the research required to better understand the pathophysiological mechanisms underlying the relationship between SDB and cardiovascular diseases and the extent of this association from an epidemiological perspective. Hypertension, Vascular Disease, and Sleep-Disordered Breathing Epidemiology Consistent data indicate that individuals with SDB/OSA have a higher prevalence of hypertension.4,5 Findings from the Wisconsin Sleep Cohort Study demonstrate a 3-fold increased risk of incident hypertension over a period of 4 years independent of other known risk factors.4 Equally important are observations that experimentally induced OSA in a canines results in daytime hypertension.7 Hypertensive patients whose blood pressures do not fall appropriately at night, or “non-dippers,” are at increased risk for cardiovascular damage. Patients with SDB frequently have repetitive episodes of blood pressure elevation in conjunction with their apneic episodes,8 and they may be particularly likely to manifest a non-dipper pattern.9 Moreover, some individuals with SDB have hypertension that is not controlled despite the use of multiple antihypertensives.10 Recent data suggest that treating OSA lowers not only nighttime but also daytime blood pressure.11