Project Summary This study examines the relationship of sleep disturbance with cardiovascular and pain indicators in patients with sickle cell disease (SCD). Reduced sleep duration and sleep disordered breathing are strongly correlated with hypertension and cardiovascular disease in the general population, and especially in African Americans. In SCD, these adverse effects are anticipated to be further compounded by the sickling of red blood cells and microvascular thrombosis unique to the disease. Despite extensive research currently exploring the physiologic and epidemiologic linkage of sleep and cardiovascular disease in the general population, limited data exist in SCD, particularly in adults. Similarly, while sleep quality is known to affect pain perception in many settings, it is relatively unexplored in SCD. Patients presenting for routine follow-up at the Howard University Sickle Cell Center will be invited to participate in this study. To assess disease burden and functional impairment, they will be carefully characterized regarding medical background including severity of anemia, comorbid disease, and frequency of pain crises. Cardiovascular parameters evaluated will include blood pressure, echocardiography and 6 minute walk distance. Sympathetic nervous system (SNS) activity will be assessed utilizing heart rate variability analysis. Biomarkers of inflammation and endothelial injury will be obtained. Finally, peripheral and central pain sensitivity responses will be evaluated in a subgroup of subjects representing a spectrum of sleep apnea severity using quantitative sensory testing. This detailed characterization of disease burden and functional impairment will be correlated with careful analysis of both subjective and objective measures of sleep duration and sleep disturbance. This will include self-reports of sleep quality and daytime sleepiness, actigraphy determined sleep duration and efficiency, and overnight sleep laboratory polysomnography. The first aim is to assess the prevalence and severity of sleep impairment, namely reduced habitual sleep duration, arousal frequency, sleep apnea, and nocturnal hypoxemia, in a clinic population of patients with SCD recruited without selection for sleep complaints. The second aim is to correlate sleep disorders with indicators of cardiovascular dysfunction and pain. The third aim is to define the response of cardiovascular and pain indicators to the treatment of any identified sleep disorders. Sickle Cell Disease (SCD) affects 1 in 500 African Americans and is associated with cardiovascular complications that degrade quality of life and increase mortality. Sleep apnea, nocturnal hypoxemia, and insufficient sleep promote cardiovascular disease, and preliminary information suggests they are common in SCD. This study assesses the frequency of sleep disorders and the cardiovascular and pain related consequences of these disorders for SCD patients.