Stephen F Smagula1, Katie L Stone, Susan Redline, Sonia Ancoli-Israel, Elizabeth Barrett-Connor, Nancy E Lane, Eric S Orwoll, Jane A Cauley. 1. From the Department of Epidemiology, Graduate School of Public Health (Smagula, Cauley), and Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center (Smagula, Cauley), University of Pittsburgh, Pittsburgh, Pennsylvania; Research Institute (Stone), California Pacific Medical Center, San Francisco, California; Division of Sleep Medicine (Redline), Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Boston, Massachusetts; Departments of Psychiatry and Medicine (Ancoli-Israel) and Family and Preventive Medicine, Division of Epidemiology (Barrett-Connor), University of California San Diego, La Jolla, California; Department of Veterans Affairs San Diego Center of Excellence for Stress and Mental Health (CESAMH; Ancoli-Israel), San Diego, California; Aging Center, Medicine and Rheumatology (Lane), University of California at Davis School of Medicine, Sacramento, CA; Division of Endocrinology, Diabetes, and Clinical Nutrition, Department of Medicine (Orwoll), Oregon Health and Science University, Portland, Oregon.
Abstract
OBJECTIVES: To evaluate whether objectively measured sleep characteristics are associated with mortality risk independent of inflammatory burden and comorbidity. METHODS: The Osteoporotic Fractures in Men Sleep Study (conducted in 2003-2005) included community-dwelling older men (n = 2531; average [standard deviation {SD}] age = 76.3 (5.5) years). Sleep measures from in-home polysomnography and wrist actigraphy and assessments of serum inflammatory markers levels (C-reactive protein, interleukin-6, tumor necrosis factor α, tumor necrosis factor α soluble receptor II, and interferon-γ) were obtained. Vital status was ascertained over an average (SD) follow-up of 7.4 (1.9 SD) years. RESULTS: Three of the seven main sleep measures examined were independently associated with greater inflammatory burden. Mortality risk associated with prolonged (≥10% total sleep time) blood oxygen desaturation and short (<5 hours) sleep duration was attenuated to nonsignificance after adjusting for inflammatory burden or medical burden/lifestyle factors. Severe blood oxygen desaturation (adjusted hazard ratio [aHR] = 1.57, 95% confidence interval [CI] = 1.11-2.22), sleep fragmentation (aHR = 1.32, 95% CI = 1.12-1.57), and a lower percentage of sleep in rapid eye movement (aHR per SD = 0.90, 95% CI = 0.93-0.97) were independently associated with mortality. CONCLUSIONS: Short sleep duration and prolonged blood oxygen desaturation were independently associated with inflammatory burden, which attenuated associations between these sleep characteristics and mortality. Medical and life-style factors also substantially attenuated most sleep-mortality associations, suggesting complex relations between sleep, inflammation, and disease. Sleep fragmentation, severe blood oxygen desaturation, and the percentage of sleep time in rapid eye movement were independently related to mortality risk. Future studies with repeated measures of mediators/confounds will be necessary to achieve a mechanistic understanding of sleep-related mortality risk.
OBJECTIVES: To evaluate whether objectively measured sleep characteristics are associated with mortality risk independent of inflammatory burden and comorbidity. METHODS: The Osteoporotic Fractures in Men Sleep Study (conducted in 2003-2005) included community-dwelling older men (n = 2531; average [standard deviation {SD}] age = 76.3 (5.5) years). Sleep measures from in-home polysomnography and wrist actigraphy and assessments of serum inflammatory markers levels (C-reactive protein, interleukin-6, tumornecrosis factor α, tumornecrosis factor α soluble receptor II, and interferon-γ) were obtained. Vital status was ascertained over an average (SD) follow-up of 7.4 (1.9 SD) years. RESULTS: Three of the seven main sleep measures examined were independently associated with greater inflammatory burden. Mortality risk associated with prolonged (≥10% total sleep time) blood oxygen desaturation and short (<5 hours) sleep duration was attenuated to nonsignificance after adjusting for inflammatory burden or medical burden/lifestyle factors. Severe blood oxygen desaturation (adjusted hazard ratio [aHR] = 1.57, 95% confidence interval [CI] = 1.11-2.22), sleep fragmentation (aHR = 1.32, 95% CI = 1.12-1.57), and a lower percentage of sleep in rapid eye movement (aHR per SD = 0.90, 95% CI = 0.93-0.97) were independently associated with mortality. CONCLUSIONS: Short sleep duration and prolonged blood oxygen desaturation were independently associated with inflammatory burden, which attenuated associations between these sleep characteristics and mortality. Medical and life-style factors also substantially attenuated most sleep-mortality associations, suggesting complex relations between sleep, inflammation, and disease. Sleep fragmentation, severe blood oxygen desaturation, and the percentage of sleep time in rapid eye movement were independently related to mortality risk. Future studies with repeated measures of mediators/confounds will be necessary to achieve a mechanistic understanding of sleep-related mortality risk.
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