Tianyi Huang1, Matthew Goodman2, Xiaoyu Li2, Scott A Sands3, Jun Li4, Meir J Stampfer5, Richa Saxena6, Shelley S Tworoger7, Susan Redline3. 1. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Division of Sleep Medicine, Harvard Medical School, Boston, MA. Electronic address: tih541@mail.harvard.edu. 2. Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 3. Division of Sleep Medicine, Harvard Medical School, Boston, MA; Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 4. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA. 5. Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA. 6. Division of Sleep and Circadian Disorders, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA. 7. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
Abstract
BACKGROUND: Individuals with OSA have elevated levels of inflammatory markers, but no prospective study has examined the role of inflammation in the development of OSA. RESEARCH QUESTION: Is C-reactive protein (CRP) prospectively associated with risk of developing OSA? STUDY DESIGN AND METHODS: We followed 1,882 women from the Nurses' Health Study (NHS) (2002-2012), 3,854 women from Nurses' Health Study II (NHSII) (1995-2013), 3,075 men from the Health Professionals Follow-up Study (HPFS) (1996-2012), and 1,919 women and men from the Multi-Ethnic Study of Atherosclerosis (MESA) (2000-2012) who did not have diagnosed OSA at baseline and for whom CRP levels were available. In NHS/NHSII/HPFS, physician-diagnosed OSA was self-reported. In MESA, at-home polysomnography was performed and OSA was identified as an apnea-hypopnea index ≥ 30. Logistic regression was used to estimate the OR for OSA risk according to baseline CRP level, adjusted for multiple inflammation-related factors. RESULTS: After multivariable adjustment not including BMI, the pooled OR for OSA risk per doubling of baseline CRP level was 1.24 (95% CI, 1.18-1.30). Additional adjustment for BMI substantially attenuated the association (pooled OR, 1.07; 95% CI, 1.01-1.12). The fully adjusted association was consistently stronger in individuals < 55 vs ≥ 55 years of age (P interaction = .01), in individuals with BMI < 25 vs ≥ 25 kg/m2 (P interaction = .02), and in pre- vs postmenopausal women (P interaction = .002). CRP was more strongly associated with risk of OSA associated with excessive daytime sleepiness, high airway collapsibility, and low arousal threshold (P heterogeneity < .05). INTERPRETATION: Higher CRP was prospectively associated with increased OSA risk, particularly among younger individuals, underweight/normal-weight individuals, or premenopausal women. The differential associations by OSA phenotype/endotype suggest possible mechanisms through which inflammation operates to modulate OSA risk. Given our reliance on a single CRP level measured a decade before OSA assessment, future studies with repeated CRP measurements are warranted to confirm these prospective associations.
BACKGROUND: Individuals with OSA have elevated levels of inflammatory markers, but no prospective study has examined the role of inflammation in the development of OSA. RESEARCH QUESTION: Is C-reactive protein (CRP) prospectively associated with risk of developing OSA? STUDY DESIGN AND METHODS: We followed 1,882 women from the Nurses' Health Study (NHS) (2002-2012), 3,854 women from Nurses' Health Study II (NHSII) (1995-2013), 3,075 men from the Health Professionals Follow-up Study (HPFS) (1996-2012), and 1,919 women and men from the Multi-Ethnic Study of Atherosclerosis (MESA) (2000-2012) who did not have diagnosed OSA at baseline and for whom CRP levels were available. In NHS/NHSII/HPFS, physician-diagnosed OSA was self-reported. In MESA, at-home polysomnography was performed and OSA was identified as an apnea-hypopnea index ≥ 30. Logistic regression was used to estimate the OR for OSA risk according to baseline CRP level, adjusted for multiple inflammation-related factors. RESULTS: After multivariable adjustment not including BMI, the pooled OR for OSA risk per doubling of baseline CRP level was 1.24 (95% CI, 1.18-1.30). Additional adjustment for BMI substantially attenuated the association (pooled OR, 1.07; 95% CI, 1.01-1.12). The fully adjusted association was consistently stronger in individuals < 55 vs ≥ 55 years of age (P interaction = .01), in individuals with BMI < 25 vs ≥ 25 kg/m2 (P interaction = .02), and in pre- vs postmenopausal women (P interaction = .002). CRP was more strongly associated with risk of OSA associated with excessive daytime sleepiness, high airway collapsibility, and low arousal threshold (P heterogeneity < .05). INTERPRETATION: Higher CRP was prospectively associated with increased OSA risk, particularly among younger individuals, underweight/normal-weight individuals, or premenopausal women. The differential associations by OSA phenotype/endotype suggest possible mechanisms through which inflammation operates to modulate OSA risk. Given our reliance on a single CRP level measured a decade before OSA assessment, future studies with repeated CRP measurements are warranted to confirm these prospective associations.
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