Obstructive sleep apnea and cardiovascular disease: a perspective and future directions.

Data from animal and human studies provide a biological plausibility to the notion that obstructive sleep apnea activates pathways that lead to insulin resistance, atherosclerosis and hypertension. Sleep apnea thus activates the same pathways as does obesity. That obstructive sleep apnea is a risk factor for cardiovascular disease is supported by epidemiological association studies. Longitudinal cohort studies also provide evidence that patients with untreated severe sleep apnea have an increased rate of cardiovascular events. But these studies, while highly suggestive, do not provide the evidence needed to convince the skeptic. This would only be obtained by randomized treatment trials with hard cardiovascular endpoints such as cardiac events and deaths. While such studies are in the planning stages, they will be challenging. There are issues about randomizing individuals with severe sleep apnea and excessive sleepiness into no therapy, since they are at known increased risk for car crashes. Thus, lack of therapy puts others on the road at risk as well as the subject with sleep apnea. There is, moreover, the concern that treating obstructive sleep apnea in very obese individuals will have little impact, since any effect of therapy for OSA will be overwhelmed by the effects of obesity itself. Data from randomized treatment trials for cardiovascular endpoints will likely not be available for many years. In the interim, physicians need to consider how to treat such patients. It is proposed that given that CPAP treatment for obstructive sleep apnea is highly effective and essentially totally safe, and that the evidence is suggestive that sleep apnea is a risk factor for cardiovascular disease, then we propose all patients with severe sleep apnea should be treated to reduce cardiovascular risk.