Obstructive Sleep Apnea Is Associated With Increased Urinary Albumin Excretion

OBSTRUCTIVE SLEEP APNEA (OSA) IS A GROWING PUBLIC HEALTH PROBLEM IN THE UNITED STATES AND OTHER DEVELOPED COUNTRIES. THE NIGHTTIME apneas, hypoxemia, and arousals that characterize OSA are associated with daytime consequences that extend beyond the subjective fatigue and reduced quality of life commonly experienced by patients with OSA. Increasing research supports a causal role for OSA in diurnal hypertension,1 and the importance of this relationship is illustrated by the inclusion of sleep apnea as an identifiable cause of hypertension in current management guidelines.2 Additionally, individuals with OSA are more likely to suffer from heart failure, ischemic heart disease, stroke, and recurrent atrial fibrillation than are subjects without OSA.3–6 Individuals with untreated severe OSA also experience increased total mortality, including cardiovascular disease (CVD) mortality and sleep-related deaths.7,8 Although OSA is clearly associated with CVD, the pathophysiology that underlies this association remains unclear. Several physiologic links between OSA and CVD have been observed in recent years, including increased sympathetic nerve traffic, impaired vagal activity, and insulin resistance.9,10 Recent advances in our understanding of CVD risk at the molecular level suggest that regulation of homeostatic mechanisms such as systemic inflammation,11 coagulation,12 and endothelial function is altered in subjects with CVD, and such alterations may represent a state of “preclinical” CVD.13–15 Similar abnormalities have been described in OSA subjects even in the absence of known CVD or contributing comorbidities.16 Many of these abnormalities improve with continuous positive airway pressure (CPAP) therapy, suggesting that, if sleep-related pathophysiology does directly contribute to CVD risk, this risk may be attenuated to some degree by OSA treatment.15–17 Albuminuria independently predicts cardiovascular events in subjects with and without established cardiovascular risk factors.18,19 Albuminuria in subjects with diabetes may reflect a state of microvascular endothelial dysfunction, and therapies directed at reducing albumin excretion rates have been shown to slow the progression to overt kidney failure and attenuate cardiovascular disease risk in this population.20,21 Increased rates of urinary albumin excretion may also portend a greater risk for cardiovascular events in hypertensive individuals.22 The urinary albumin-to-creatinine ratio (ACR) has been shown to reliably estimate urine albumin excretion in a broad range of subjects.23 Furthermore, race- and sex-specific methods of urinary ACR calculation exist that adjust for baseline variation in creatinine excretion between these populations.24 While frank proteinuria has been previously observed in small, select populations of adult and pediatric subjects with OSA, the presence of overt glomerular dysfunction in many of these individuals confounds this observation.25,26 The relationship between OSA and microalbuminuria in adult individuals with intact glomerular filtration has not been previously described. The purpose of this study is to define the relationship between OSA severity and race- and sex-adjusted ACR (aACR). We hypothesize that increased OSA severity will be independently associated with increased urinary aACR levels. Additionally, we will explore the extent to which associations with urinary albumin excretion and OSA are moderated by diabetes and hypertension.