C-reactive Protein and Risk of OSA in Four US Cohorts

Tianyi Huang¹, Matthew Goodman², Xiaoyu Li², Scott A Sands³, Jun Li⁴, Meir J Stampfer⁵, Richa Saxena⁶, Shelley S Tworoger⁷, Susan Redline³

Affiliations

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.

PMID: 33529772
PMCID: PMC8213962
DOI: 10.1016/j.chest.2021.01.060

Multicenter Study

C-reactive Protein and Risk of OSA in Four US Cohorts

Tianyi Huang et al. Chest. 2021 Jun.

. 2021 Jun;159(6):2439-2448.

doi: 10.1016/j.chest.2021.01.060. Epub 2021 Jan 30.

Authors

Tianyi Huang¹, Matthew Goodman², Xiaoyu Li², Scott A Sands³, Jun Li⁴, Meir J Stampfer⁵, Richa Saxena⁶, Shelley S Tworoger⁷, Susan Redline³

Affiliations

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.

PMID: 33529772
PMCID: PMC8213962
DOI: 10.1016/j.chest.2021.01.060

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.

Keywords: C-reactive protein; OSA; endotypes; inflammation; risk factors.

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Comment in

Relationship Between C-reactive Protein and Risk of OSA in the Framework of Causal Inference.
Ye T. Ye T. Chest. 2021 Jun;159(6):2515-2516. doi: 10.1016/j.chest.2021.02.029. Chest. 2021. PMID: 34099145 No abstract available.
Response.
Huang T, Redline S. Huang T, et al. Chest. 2021 Jun;159(6):2516-2517. doi: 10.1016/j.chest.2021.02.030. Chest. 2021. PMID: 34099146 Free PMC article. No abstract available.

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C-reactive Protein and Risk of OSA in Four US Cohorts

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C-reactive Protein and Risk of OSA in Four US Cohorts

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