Hearing Loss As A Surrogate Marker For Early Atherosclerosis in A High-Risk Population: A Prospective Study

This study explores the potential of audiometry as a tool for monitoring atherosclerosis in a high-risk population with inflammatory atherosclerosis, focusing on patients with rheumatoid arthritis (RA).1Avina-Zubieta JA Thomas J Sadatsafavi M Lehman AJ Lacaille D. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies.Ann Rheum Dis. 2012; 71: 1524-1529Crossref PubMed Scopus (673) Google Scholar Multiple studies suggest that hearing loss might serve as a marker for atherosclerosis.2Fischer ME Schubert CR Nondahl DM Dalton DS Huang GH Keating BJ Klein BE Klein R Tweed TS Cruickshanks KJ. Subclinical atherosclerosis and increased risk of hearing impairment.Atherosclerosis. 2015; 238: 344-349Abstract Full Text Full Text PDF PubMed Google Scholar This study aims to assess the correlation between audiometry and traditional measures of atherosclerosis, using 18-fluorodeoxyglucose positron emission tomography computed tomography (FDG-PET/CT) at the heart and great vessels prospectively at baseline and 6 months. The study involved 115 patients with RA subjected to a 6-month randomized regimen between 2 immune therapies, methotrexate plus a tumor necrosis factor versus methotrexate plus oral azulfidene and hydroxychloroquine, which proved to have equal suppression of inflammation.3Solomon D Giles J Liao K Ridker P Rist P Glynn R Broderick R Lu F Murray MT Vanni K Santacroce LM Abohashem S Robson PM Fayad Z Mani V Tawakol A Bathon J Trial Consortium TARGET Reducing cardiovascular risk with immunomodulators: a randomized active comparator trial among patients with rheumatoid arthritis.Ann Rheum Dis. 2023; 82: 324-330Crossref PubMed Scopus (7) Google Scholar The protocol prohibited any change in medication for 6 months. Subjects were aged >50 years, and none had previous cardiovascular disease. A subgroup of 22 subjects underwent hearing tests at 1 site alongside imaging scans to evaluate arterial inflammation measured as standardized uptake volume (SUV) adjusted to abdominal aorta values. Carotid and aorta were measured with tomograms at 5-mm intervals, and the ascending aorta was chosen as the signal arterial segment for analysis. Data on carotid ultrasound and CT calcium scores were also collected. Hearing loss was recorded in decibels (dB) at 8 frequencies by standard pure tone audiogram and word identification scores. The audiograms assessed the health of the eighth cranial nerve, and auditory processing in the temporal, parietal, and frontal lobes.4Purves D Augustine G Fitzpatrick D Katz LC LaMantia AS McNamara JO Williams SM The Auditory Cortex. Neuroscience. 2nd ed. Sinauer Associates, Sunderland, MA2001Google Scholar,5Uchida Y Nishita Y Otsuka R Sugiura S Sone M Yamasoba T Kato T Iwata K Nakamura A. Aging brian and hearing: a mini-review.Front Aging Neurosci. 2021; 13791604Google Scholar The baseline measurements revealed a significant correlation between hearing loss and arterial inflammation measured on imaging (r = 0.620, p <0.002). There was also a significant correlation for changes at 6 months in the 2 measurement tools (r = 0.708, p <0.0003) (Figure 1). In the study, hearing loss >30 dB was associated with arterial inflammation at 3.5 SUV. At 6 months, both hearing and inflammation showed improvement, with 82% of subjects experiencing improved hearing and 76% showing reduced inflammation. There were 5 subjects without improvement by imaging, and 3 of these same subjects had no improvement in hearing. There was an 80% concordance for each subject for hearing and imaging. There were no changes noted for cardiac calcium scores or carotid intima-media thickness at 6 months, perhaps because these do not measure early phases of atherosclerosis. This study focused on the early phases of atherosclerosis characterized by inflammation detected through FDG-PET/CT imaging.6Moghbel M Al-Zaghal A Werner TJ Constantinescu CM Høilund-Carlsen PF Alavi A. The role of PET in evaluating atherosclerosis: a critical review.Semin Nucl Med. 2018; 48: 488-497Crossref PubMed Scopus (49) Google Scholar Patients with RA provided a unique population for a model to observe changes in inflammatory atherosclerosis within a 6-month timeframe.7Amigues I Tugcu A Russo C Giles JT Morgenstein R Zartoshti A Schulze C Flores R Bokhari S Bathon JM. Myocardial inflammation, measured using 18-fluorodeoxyglucose positron emission tomography with computed tomography, is associated with disease activity in rheumatoid arthritis.Arthritis Rheumatol. 2019; 71: 496-506Crossref PubMed Scopus (27) Google Scholar Audiometry emerged as a potential surrogate marker for systemic early atherosclerosis.8Iwatsuka R Matsue Y Yonetsu T O'Uchi T Matsumura A Hashimoto Y Hirao K Arterial inflammation measured by 18F-FDG-PET/CT to predict coronary events in older subjects.Atherosclerosis. 2018; 268: 49-54Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar The study's limitations include a small sample size and the absence of a control group. A sample size of 18 to 25 subjects provides at best a 90% chance that the results are real, with a 10% margin of error. There was no adjustment for multiple confounding factors owing to the small sample. However, multiple large cross-sectional studies confirm the association of hearing loss with atherosclerosis, independent from hypertension, cholesterol, or diabetes.9Nash SD Cruickshanks KJ Klein R Klein BE Nieto FJ Huang GH Pankow JS Tweed TS. The prevalence of hearing impairment and associated risk factors: the Beaver Dam offspring study.Arch Otolaryngol Head Neck Surg. 2011; 137: 432-439Crossref PubMed Scopus (166) Google Scholar Although the results showed consistency, larger trials involving diverse populations are necessary to validate the potential of audiometry as a screening tool for atherosclerosis. This study's use of patients with RA may limit the generalizability of the findings to the broader population. Audiograms may prove useful as a screening tool for early atherosclerosis. Unique to this study is the finding that an individual hearing test correlates with that subject's arterial inflammation, comparable to using cholesterol tests for a patient. The study suggests that audiometry could potentially be integrated into cardiovascular risk calculators.10Friedland DR Cederberg C Tarima S. Audiometric pattern as a predictor of cardiovascular status: development of a model for assessment of risk.Laryngoscope. 2009; 119: 473-486Crossref PubMed Scopus (83) Google Scholar A concrete test finding of hearing loss may provide a tangible concept to patients, motivating better adherence to lifestyle changes and medications to prevent atherosclerosis. The authors have no competing interests to declare.