https://orcid.org/0009-0008-6834-3284
Figures
Abstract
Background
This study aimed to examine the epidemiological associations between hearing loss and the risk of all-cause mortality, cardiovascular mortality, and cancer mortality.
Methods
A comprehensive search was performed in PubMed, Cochrane Library, and Embase for cohort studies published from database inception to January 12, 2025, using relevant MeSH terms and keywords. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects model was applied for the meta-analysis. Sensitivity analysis was conducted by sequentially excluding individual studies to assess the robustness of the results. Subgroup analyses were performed based on hearing function measurement methods, study design, and continent. Publication bias was evaluated using funnel plots and Egger’s test. Statistical analyses were conducted using Stata 14.0.
Results
This meta-analysis included 36 cohort studies with a total of 6,364,914 participants, published between 1992 and 2024. Hearing loss was significantly associated with all-cause mortality (HR: 1.21; 95% CI: 1.13–1.31; I² = 95.7%, P < 0.001), cardiovascular mortality (HR: 1.22; 95% CI: 1.12–1.33; I² = 52.4%, P < 0.001), and cancer mortality (HR: 1.11; 95% CI: 1.02–1.22; I² = 51.2%, P = 0.016), after adjusting for demographics and comorbidities. Subgroup analysis showed that audiometrically measured hearing loss had a stronger effect than self-reported hearing loss (HR: 1.28; 95% CI: 1.10–1.49; I² = 97.7%, P = 0.002). The risk of all-cause mortality was higher in prospective cohorts compared to retrospective cohorts (HR: 1.24; 95% CI: 1.05–1.46; I² = 97.2%, P = 0.012). Additionally, the risk of all-cause mortality was slightly higher in studies from Asia compared to other continents (HR: 1.33; 95% CI: 1.09–1.62; I² = 98.3%, P = 0.005).
Citation: Jia J, Li H, Xu C (2025) Hearing loss and its association with all-cause and cause-specific mortality: A meta-analysis of cohort studies. PLoS One 20(10): e0333125. https://doi.org/10.1371/journal.pone.0333125
Editor: Yasin Sahin, Gaziantep Islam Science and Technology University, Medical Faculty, Division of Pediatric Gastroenterology, TÜRKIYE
Received: April 26, 2025; Accepted: September 9, 2025; Published: October 9, 2025
Copyright: © 2025 Jia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: This research was funded by Beijing Tiantan Hospital Research Fund Program, Code:2023-YQN-08. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Hearing loss (HL) represents a major global health issue, affecting more than 1.55 billion people worldwide in 2021 [1], with projections indicating that this number will rise to 2.5 billion by 2050 [2]. Unaddressed hearing loss costs the global economy approximately $980 billion annually, including healthcare, education, productivity losses, and societal costs [3]. Despite its widespread prevalence, HL has often been overlooked in public health priorities, partly due to its gradual onset and the subtle progression of auditory function [4]. Recent evidence, however, suggests a significant association between HL and an increased risk of mortality in adults [5,6]. This association may be mediated through various factors, including cognitive decline [7], walking disability, fall-related injuries [8], cardiovascular diseases [9], frailty [10] and social isolation [11]. However, some studies have reported no such association [12]. While previous meta-analyses [13] have explored this issue, most earlier studies primarily focused on all-cause mortality, with limited examination of cause-specific risks, such as cardiovascular or cancer-related mortality. Additionally, few reviews have addressed potential geographic or study design differences, which may impact the generalizability of their findings.
To fill these gaps, we present an updated meta-analysis that includes 36 cohort studies encompassing over 6.4 million participants. By synthesizing global evidence and conducting subgroup analyses based on measurement methods, study types, and geographic regions, this study aims to clarify the strength and consistency of the relationship between HL and mortality, offering valuable insights for clinical and public health interventions.
Methods
This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [14]. The protocol was pre-registered on the PROSPERO platform (registration number: CRD 42025637635) on January 13,2025.
Data sources and searches
We conducted a comprehensive search of PubMed, Embase, and Cochrane Library from inception to January 12, 2025, with no language restrictions. The search strategy combined MeSH terms and keywords related to HL and mortality. The full PubMed search strategy is detailed in S1 Table. We also reviewed reference lists of included studies and relevant meta-analyses to identify additional studies.
Eligibility criteria
We included cohort studies that examined the association between HL and all-cause or cause-specific mortality risk among adults aged 18 years and older. Studies were excluded if they met any of the following criteria: ①Did not report hazard ratios (HRs) with 95% confidence intervals (CIs) for mortality outcomes.②They were conference abstracts, study protocols, duplicate publications, or studies without relevant outcomes. ③Duplicate publications or sub-studies of the same cohort (only the most comprehensive study was retained). ④ Focused on specific subpopulations (e.g., cancer patients, post-stroke survivors) where HL was not the primary exposure.
Study selection
Two authors independently selected eligible studies (based on title and abstract, followed by full-text articles), extracted relevant data, and evaluated the risk of bias in a blinded manner, with conflicts resolved by a third author.
Study selection was performed by two reviewers (JLJ and CLX) who independently screened the literature based on the eligibility and exclusion criteria. Duplicate and irrelevant articles were first excluded according to their titles and abstracts. Thereafter, the full texts of the potentially eligible articles were downloaded and read to identify all eligible studies. Any disagreements were resolved by the third reviewer (HYL), who acted as an arbiter.The main reasons for excluding studies is displayed in S2 Table.
Data extraction
Data were independently extracted by two reviewers using pre-designed forms. Extracted data included study details (author, year, country, sample size, follow-up duration), HL definition, outcomes, and adjusted confounders. Disagreements were resolved by consensus with the third reviewer.
Risk of bias
The Newcastle-Ottawa Scale (NOS) [15] was used to assess study quality. Studies were rated on a scale of 0–9 stars, with higher scores indicating better quality. Scores of 0–3, 4–6, and 7–9 were considered low, moderate, and high quality, respectively.
Statistical analysis
We used adjusted HRs and 95% CIs to assess the association between HL and mortality risk. Heterogeneity was evaluated using the χ² test and I² values. Given the potential for both statistical and clinical heterogeneity, a random-effects model was applied [16,17]. Sensitivity analysis was conducted by excluding one study at a time to test the robustness of the findings. Statistical significance was defined as a two-sided P-value < 0.05 for all analyses. Funnel plots were visually inspected for publication bias, and Egger’s test was used for statistical assessment. Subgroup analyses were performed based on hearing assessment methods, study type, and continent. All statistical analyses were conducted using Stata 14.0.
Results
Literature search
The systematic search of cohort studies published before January 12, 2025, identified 2504 results. After title and abstract screening, 48 articles were considered potentially relevant. Thirty-six studies were included after full text review, of which 35 studies reported association between HL and all-cause mortality, 10 studies reported association between HL and cardiovascular mortality, and 6 studies reported association between HL and cancer mortality, The selection process is presented in Fig 1.
Study characteristics
Of the 36 included studies [5–7,9,12,18–48] all were observational, with 13 retrospective cohorts [5,7,18,21,26,29,36,37,43,45–48], 23 prospective cohorts [6,9,12,19,20,22–25,27,28,30–35,38–42,44]. When assessed using the NOS, 26 studies [5–7,9,12,18–22,24,26–32,35–37,39,41–44] and 10 studies [23,25,33,34,37,38,40,45–48] had a high and moderate risk of bias, respectively. The scores of the included studies are shown in S3 Table. Sensitivity analyses excluding the studies with a high risk of bias did not substantially alter our results. A total of 14 [5,6,9,18,29,32,33,35,37,41,43–46], 14 [12,19–21,23–28,38,39,42,48], 5 [22,30,31,34,47], and 3 studies [7,36,40] were conducted in North America, Asia, Europe, and Oceania, respectively. We included 36 studies in our meta-analysis. The main characteristics of the included trials are shown in Table 1.
Association of HL and mortality
Meta-analysis for all-cause mortality.
Thirty-five studies were included in the analysis of all-cause mortality. Participants with HL had a significantly higher pooled hazard ratio (HR) for all-cause mortality compared to those with normal hearing (HR, 1.21; 95% CI, 1.13–1.31; I² = 95.7%, P = 0.000, Fig 2). Sensitivity analysis confirmed the robustness of the results (S1 Fig).
Subgroup analyses revealed slightly higher HRs for audiometric assessments (HR, 1.28; 95% CI, 1.10–1.49; I² = 97.7%, P = 0.002) and for prospective cohorts (HR, 1.24; 95% CI, 1.05–1.46; I² = 97.2%, P = 0.012). The risk of all-cause mortality was higher in studies conducted in Asia compared to other continents (Table 2).
Meta-analysis for cardiovascular mortality.
Ten studies assessed the relationship between HL and cardiovascular mortality. The pooled results indicated a significant association between HL and increased cardiovascular mortality risk (HR, 1.22; 95% CI, 1.12–1.33; I² = 52.4%, P = 0.000, Fig 3). Sensitivity analysis showed consistent results across studies (S2 Fig).
Meta-analysis for cancer mortality.
Six studies examined the association between HL and cancer mortality. The pooled HR for cancer mortality was significantly elevated in those with HL (HR, 1.11; 95% CI, 1.02–1.22; I² = 51.2%, P = 0.016, Fig 4). Sensitivity analysis confirmed the robustness of these results (S3 Fig).
Publication bias
Visual inspection of the funnel plot indicated no significant publication bias for the association between HL and all-cause mortality (Fig 5). Egger’s regression test (P = 0.817) further supported the absence of publication bias. Similar results were observed for the association between HL and cardiovascular and cancer mortality, with no evidence of bias (S4 and S5 Figs).
Discussion
Interpretation of findings
The findings highlight HL as a critical yet underrecognized risk factor for mortality, emphasizing the need for integrating auditory health into broader public health strategies. A previous review [20] explored the relationship between HL and mortality, showing that HL increased the risk of all-cause and cardiovascular mortality. However, it did not find a relationship between HL and cancer mortality, identifying only three cohort studies in the analysis. In contrast, our current meta-analysis incorporates more recent studies, providing stronger evidence for the association between HL and cancer mortality. Furthermore, the significant heterogeneity observed in cancer mortality analysis (I² = 51.2%) and the lower bound of the 95% CI approaching 1.02 indicate residual uncertainty in this association, potentially attributable to methodological heterogeneity across studies including variations in cancer endpoint definitions and differential adjustment for critical confounders; consequently, future large-scale cohorts should adopt standardized cancer classification protocols, rigorously adjust for treatment-related confounders, and conduct subtype-specific analyses to elucidate underlying biological mechanisms.
Compared to previous meta-analyses, this study addresses several important gaps, such as incorporating a larger sample size (6.4 million participants), stratifying outcomes by cause-specific mortality, and systematically evaluating methodological and geographic heterogeneity. Earlier reviews predominantly focused on all-cause mortality, with limited exploration of cardiovascular or cancer-related risks. By including 10 studies on cardiovascular mortality and 6 on cancer mortality, our analysis reveals distinct associations, suggesting that HL may influence different disease pathways in specific ways. Moreover, the stronger effect size for audiometric HL compared to self-reported HL underscores the value of objective measurement in accurately capturing biological risks. These advances provide clinicians and policymakers with valuable insights, emphasizing the importance of routine HL screening in health assessments and targeted interventions (e.g., hearing aids, social support programs) to mitigate the associated mortality risks.
The relationship between HL and mortality may be mediated through several interconnected pathways. First, untreated HL often leads to social isolation and reduced environmental awareness, both of which are associated with neuroendocrine dysregulation (e.g., elevated cortisol levels) and chronic inflammation, as demonstrated in studies linking HL to elevated C-reactive protein and interleukin-6 levels [49,50]. Second, auditory processing deficits increase cognitive load, which may exacerbate systemic stress, impair cardiovascular function, and contribute to the development of atherosclerosis [51,52]. Third, shared risk factors such as vascular dysfunction and oxidative stress may underlie both HL and cancer progression, as evidenced by preclinical models demonstrating noise-induced cochlear damage and DNA repair deficiencies [53]. Additionally, research has indicated that autoimmune conditions such as celiac disease are associated with an increased prevalence of sensorineural hearing loss (SNHL). Potential mechanisms underlying this association include autoimmune-mediated attacks targeting inner ear structures, deposition of immune complexes, T lymphocyte-mediated cytotoxicity, and vasculitis affecting the cochlea. These processes may be driven by shared genetic susceptibility leading to a chronic inflammatory state. In celiac disease, anti-tissue transglutaminase antibodies might also contribute to neurological damage, including auditory pathways. Although often subclinical, such hearing impairment could signify early neural involvement and may progress with disease duration. Therefore, in some individuals, hearing loss could serve as an early indicator of underlying autoimmune or inflammatory processes, which have been linked to broader systemic complications and potentially increased mortality [54]. These mechanisms align with our findings, suggesting that HL serves both as a contributor to and a marker of multisystemic dysfunction.
We found that the risk of all-cause mortality was higher in Asia compared with other continents when performing subgroup analysis by continent. Based on the analysis of 13 Asian studies (7 Chinese, 3 Korean, 2 Japanese, 1 Indian), we propose the following evidence-supported hypotheses for this regional disparity:the concentration of studies in rapidly industrializing East Asian nations (China/Korea/Japan: 12/13 studies) aligns with WHO reports on escalating occupational noise hazards in developing economies. Manufacturing sector growth has increased exposure to chronic industrial noise (>85 dB), causing cumulative cochlear damage [55]. Industrial development generates concomitant air pollution and green space reduction, established environmental risk factors for hearing loss in extant literature [56]. Concurrently, East Asia faces accelerating population aging that compounds hearing loss burdens [57]. Inadequate screening programs and insufficient hearing protection measures collectively compound the severity of hearing loss and related disabilities, these systemic deficiencies may elevate all-cause mortality risk through multiple pathways.
Strengths and limitations
This study’s strengths include its adherence to PRISMA guidelines, extensive subgroup analyses (e.g., stratification by continent and study design), and the inclusion of a diverse range of populations spanning 30 years of research. However, there are limitations, such as residual confounding (e.g., unmeasured socioeconomic factors), high heterogeneity in some subgroups (I² > 95%), and reliance on observational data, which limits the ability to infer causality. Additionally, the predominance of studies from Asia and North America may limit the generalizability of the findings to other regions. Future research should focus on longitudinal studies with mechanistic designs and randomized trials to evaluate the impact of HL interventions on mortality. Furthermore, our findings are not generalizable to children, as no eligible studies addressed childhood hearing loss and mortality. Future research should prioritize longitudinal cohort studies specifically designed to examine the long-term mortality implications of pediatric hearing impairment, particularly through population-based registries linking early-life audiometric data to mortality registries.
Conclusion
This meta-analysis provides compelling evidence that hearing loss is independently associated with increased risks of all-cause, cardiovascular, and cancer mortality. The stronger associations observed with audiometric assessments and in Asian cohorts highlight the need for standardized diagnostic criteria and region-specific prevention strategies. Clinicians should consider HL not only as a sensory impairment but as a potential marker of broader systemic health deterioration, advocating for early screening and multidisciplinary management.
Supporting information
S1 Table. The retrieval strategies and retrieval results of each database.
https://doi.org/10.1371/journal.pone.0333125.s001
(DOCX)
S2 Table. Reasons for excluding studies from the final analysis after full text assessment.
https://doi.org/10.1371/journal.pone.0333125.s002
(DOCX)
S3 Table. The quality assessment of cohort studies.
https://doi.org/10.1371/journal.pone.0333125.s003
(DOCX)
S1 Fig. Sensitivity analysis of the risk of all-cause mortality caused by HL.
https://doi.org/10.1371/journal.pone.0333125.s004
(TIF)
S2 Fig. Sensitivity analysis of the risk of cardiovascular mortality caused by HL.
https://doi.org/10.1371/journal.pone.0333125.s005
(TIF)
S3 Fig. Sensitivity analysis of the risk of cancer mortality caused by HL.
https://doi.org/10.1371/journal.pone.0333125.s006
(TIF)
S4 Fig. Publication bias of the risk of cardiovascular mortality caused by HL.
https://doi.org/10.1371/journal.pone.0333125.s007
(TIF)
S5 Fig. Publication bias of the risk of cancer mortality caused by HL.
https://doi.org/10.1371/journal.pone.0333125.s008
(TIF)
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