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Biomarkers of Systemic Inflammation and Risk of Incident Hearing Loss

Gupta, Shruti1,2; Curhan, Sharon G.1,3; Curhan, Gary C.1,2,3,4

doi: 10.1097/AUD.0000000000000678
Research Article: PDF Only

Background: Chronic inflammation may lead to cochlear damage, and the only longitudinal study that examined biomarkers of systemic inflammation and risk of hearing loss found an association with a single biomarker in individuals <60 years of age. The purpose of our study was to determine whether plasma inflammatory markers are associated with incident hearing loss in two large prospective cohorts, Nurses’ Health Studies (NHS) I and II.

Methods: We examined the independent associations between plasma levels of markers of systemic inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and soluble tumor necrosis factor receptor 2 [TNFR-2]) and self-reported hearing loss. The participants in NHS I (n = 6194 women) were 42 to 69 years of age at the start of the analysis in 1990, while the participants in NHS II (n = 2885 women) were 32 to 53 years in 1995. After excluding women with self-reported hearing loss before the time of blood-draw, incident cases of hearing loss were defined as those women who reported hearing loss on questionnaires administered in 2012 in NHS I and 2009 or 2013 in NHS II. The primary outcome was hearing loss that was reported as moderate or worse in severity, pooled across the NHS I and NHS II cohorts. We also examined the pooled multivariable-adjusted hazard ratios for mild or worse hearing loss. Cox proportional hazards regression was used to adjust for potential confounders.

Results: At baseline, women ranged from 42 to 69 years of age in NHS I and 32 to 53 years of age in NHS II. Among the NHS I and II women with measured plasma CRP, there were 628 incident cases of moderate or worse hearing loss during 100,277 person-years of follow-up. There was no significant association between the plasma levels of any of the three inflammatory markers and incident moderate or worse hearing loss (multivariable-adjusted pooled p trend for CRP = 0.33; p trend IL-6 = 0.54; p trend TNFR-2 = 0.70). There was also no significant relation between inflammatory marker levels and mild or worse hearing loss. While there was no significant effect modification by age for CRP or IL-6 in NHS I, there was a statistically significant higher risk of moderate or worse hearing loss (p interaction = 0.02) as well as mild or worse hearing loss (p interaction = 0.004) in women ≥60 years of age who had higher plasma TNFR-2 levels.

Conclusions: Overall, there was no significant association between plasma markers of inflammation and risk of hearing loss.

1Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA

2Renal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA

3Harvard Medical School, Boston, Massachusetts, USA

4Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and text of this article on the journal’s Web site (www.ear-hearing.com).

ACKNOWLEDGMENTS: G.C. received grant support from Shoebox Audiometry. This work was supported by the following NIH Grants: 4T32DK007527, DK091417, DC010811, UM1 CA186107, R01 CA49449, UM1 CA176726, and R01 CA67262.

S.G.C. is a consultant for Decibel Therapeutics. The authors have no other financial disclosures.

All authors contributed equally to this study. S.G. was responsible for data compilation, statistical analysis, interpretation of results, and manuscript preparation. S.G.C. assisted with interpretation of results, manuscript preparation, and critical revisions. G.C.C. provided guidance for statistical analysis, interpretation of results, manuscript preparation, and presentation of results, and also provided critical revisions. All authors discussed the results and implications and commented on the manuscript at all stages.

Address for correspondence: Shruti Gupta, Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 181 Longwood Avenue. E-mail: Sgupta21@bwh.harvard.edu

Received April 26, 2018; accepted October 3, 2018.

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