Older age is a primary risk factor for greater cardiovascular disease (CVD) risk, which is attributable, in part, to stiffening of the aorta (Mitchell, 2021). Aortic stiffness, when assessed by carotid–femoral pulse wave velocity (cfPWV), is associated with higher resting blood pressure of the peripheral (brachial) and central (aortic) arteries and predicts future CVD events (Mitchell et al., 2010). As such, age-related aortic stiffening has the potential to promote excess flow pulsatility contributing to a greater hemodynamic load, resulting in microvasculature dysfunction and damage to high-flow, low-resistance organs and tissues (Chirinos et al., 2019). Specifically, dysfunction of the heart, brain, and kidneys has been associated with a greater pulsatile load due to aortic stiffening.

Age-related hearing loss, or presbycusis, is typically seen in both ears and is characterized by the loss of pure tone hearing sensitivity and the reduction of speech understanding (Lee, 2013). Presbycusis affects ∼33% of adults over the age of 65 years, contributing to frailty, depression, cognitive dysfunction and increased risk of dementia, social isolation, and loneliness, especially if left untreated (Lv et al., 2023). A key organ in the peripheral auditory system involved in the encoding of sound is the cochlea. Given the rich blood supply to the stria vascularis, a highly vascularized tissue lining the cochlea, it is reasonable to infer that factors affecting blood flow and blood pressure, such as aortic stiffness, could influence hearing sensitivity and auditory function. Furthermore, thickening of the capillary wall in the stria vascularis increases with aging, contributing to inadequate blood supply to the cochlea (Yoshioka et al., 2010; Thulasiram et al., 2022). Limited evidence supports the notion that changes in cochlear structure and function are related to microvascular changes in blood supply, with conflicting findings indicating that hearing loss and sensitivity may or may not be associated with elevated blood pressure (Gates et al., 1993; Friedland et al., 2009; Tan et al., 2018; Wattamwar et al., 2018). More recent evidence suggests that central blood pressure due to greater aortic stiffening may have a greater influence on target organ damage (McEniery et al., 2014). Although few studies (Helzner et al., 2011; Chung et al., 2016) have examined the relationship between age-related hearing loss and arterial stiffness, the augmentation index normalized to heart rate 75 (AIxHR75), central blood pressure, and the factors potentially influencing this relationship remain unknown.

A primary mechanism underlying age-related increases in aortic stiffness and blood pressure is inflammation (Sun, 2015; Fleenor et al., 2022; Murray et al., 2023). Preclinical animal and clinical human studies have identified inflammation as a pathophysiological mechanism contributing to presbycusis (Paplou et al., 2021). Specifically, systemic inflammation (e.g., C-reactive protein) in adults with hearing loss is associated with elevated hearing thresholds, indicating the loss of hearing sensitivity (Verschuur et al., 2012; Verschuur et al., 2014). Novel age-related markers of inflammation including adipocytokines such as resistin, vaspin, and matrix metalloproteinases (MMPs) may also contribute to auditory dysfunction (Manicone and McGuire, 2008; Tripathi et al., 2020; Park and Shimokawa, 2024). Previous evidence demonstrates that resistin is a primary regulator of inflammation in several vascular cell types and is associated with aortic stiffness and hypertension, whereas vaspin is anti-inflammatory (Norman et al., 2016; Zhang et al., 2017; Radzik-Zając et al., 2023). Furthermore, MMPs play a role in regulating the cochlear response to acoustic trauma and in vascular remodeling through the degradation of the extracellular matrix such as collagen and elastin, which are present in the cochlea (Filková et al., 2009; Chen et al., 2013; Wu et al., 2017; Simões et al., 2022). Collectively, these findings support the notion for inflammation as an underlying mechanism contributing to age-related hearing loss. However, it is currently unknown if the relationship between aortic stiffness, central blood pressure, and hearing loss is influenced by inflammation.

The purpose of this exploratory study was to determine if age-related increases in aortic stiffness and central blood pressure are related to hearing loss/sensitivity and examine the potential impact of inflammation on this relationship. We hypothesize that 1) aortic stiffness and central blood pressure will be correlated with poorer hearing sensitivity by measures of speech recognition threshold (SRT) and low- and high-frequency pure tone average (PTA) and 2) the relationship between aortic stiffness, central blood pressure, and hearing loss will be influenced, in part, by resistin, vaspin, and MMP-2.

All procedures for this study were reviewed and approved by the Ball State University Institutional Review Board. The benefits and risks associated with the study procedures were explained to all participants prior to obtaining written informed consent before starting the study. All participants reported to the Clinical Exercise Physiology (CEP) Laboratory at Ball State University for all vascular hemodynamic assessments and measurements of aortic stiffness. All cardiovascular assessments were performed after an overnight fast (8 h–12 h) from food, exercise, caffeine, and alcohol. All audiometric measures were performed in the Speech Pathology and Audiology Clinic in the Health Professionals Building at Ball State University.

A total of 22 participants completed the study. Participant characteristics, vascular hemodynamics, and audiological measurements of the participant population are presented in Table 1. Compared to younger adults, older adults had higher resting heart rate, cholesterol, LDL, aSBP, aortic PP, AIxHR75, and cfPWV (all, p < 0.05, Table 1). Bilateral hearing sensitivity was also lower in older adults than in younger adults, which was reflected as having a higher SRT and LFPTA and HFPTA in both the right and left ears (all, p < 0.05, Table 1). No differences were observed between markers of inflammation between younger and older adults (all, p > 0.05, Table 1).

Age was correlated with cfPWV (r = 0.61, p = 0.003), AIxHR75 (r = 0.73, p < 0.001), aSBP (r = 0.59, p = 0.004), RE (r = 0.82, p < 0.001) and LE (r = 0.81, p < 0.001) SRT, RE (r = 0.74, p < 0.001) and LE (r = 0.72, p < 0.001) LFPTA, and RE (r = 0.77, p < 0.001) and LE (r = 0.82, p < 0.001) HFPTA.

cfPWV was not correlated with SRT in either the RE (r = 0.40, p = 0.08) or LE (r = 0.38, p = 0.09) (both, Figure 1A). However, AIxHR75 and aSBP were both correlated with SRT in the RE (AIxHR75: r = 0.60, p = 0.004; aSBP: r = 0.47, p = 0.03) and LE (AIxHR75: r = 0.54, p = 0.01; aSBP: r = 0.44, p = 0.04) (all, Figures 1C,E). cfPWV was correlated with RE LFPTA (r = 0.45, p = 0.04) and both RE (r = 0.53, p = 0.01) and LE (r = 0.52, p = 0.02) HFPTA (all, Figure 1B) but not with LE LFPTA (r = 0.33, p = 0.14, Figure 1B). AIxHR75 and aSBP were correlated with RE (AIxHR75: r = 0.56, p < 0.01; aSBP: r = 0.41, p = 0.05) LFPTA and RE (AIxHR75: r = 0.68, p < 0.001; aSBP: r = 0.53, p = 0.01) and LE (AIxHR75: r = 0.66, p < 0.001; aSBP: r = 0.46, p = 0.03) HFPTA (all, Figures 1D,F). aSBP was not correlated with LE LFPTA (r = 0.28, p = 0.22, Figure 1F). There were no correlations between AIxHR75, cfPWV and aSBP, and hearing loss variables after adjusting for age (all, p > 0.05, Supplementary Table S1). Brachial systolic blood pressure was not related to SRT or PTA (both, p > 0.05, data not shown); however, brachial pulse pressure was correlated with RE (r = 0.49, p = 0.02) and LE (r = 0.55, p = 0.007) HFPTA.

Resistin tended to be correlated with AIxHR75 (r = 0.37, p = 0.10), LE LFPTA (r = −0.38, p = 0.09), and LE HFPTA (r = −0.44, p = 0.05); vaspin tended to be correlated with cfPWV (r = 0.35, p = 0.14); and MMP-2 tended to be correlated with LE HFPTA (r = −0.40, p = 0.08).

AIxHR75, cfPWV, and aSBP were independently correlated with hearing loss-related variables; however, no correlation was observed after independent adjustment for age (all, p > 0.05, Supplementary Table S1). The correlation between cfPWV and RE LFPTA and HFPTA in both ears did not remain after adjusting for MMP-2 or resistin (both, p > 0.05, Table 2). However, the relationship between AIxHR75 and SRT and LFPTA and HFPTA PTA in both ears remained after minimally adjusting for each inflammatory biomarker, namely, MMP-2, resistin, and vaspin (all, p < 0.05, Table 2). The relationship between aSBP and RE SRT and RE HFPTA remained (both, p < 0.05, Table 2) after adjusting for MMP-2, resistin, and vaspin. The relationship between aSBP and LE SRT and LE HFPTA also remained significant after adjusting for resistin (both, p < 0.05, Table 2). Additional inflammatory markers including CRP did not influence the relationship between cfPWV, AIxHR75, aSBP and SRT, or LFPTA and HFPTA (all, p > 0.05, data not shown).

This study provides evidence for the association of AIxHR75 and aSBP with age-related hearing loss. Specifically, our findings demonstrate that 1) AIxHR75 and aSBP but not cfPWV are associated with a higher SRT; 2) cfPWV, AIxHR75, and aSBP are associated with poorer hearing sensitivity (i.e., higher PTA) in both the low- and high-frequency domains; and 3) the relationship between both cfPWV and aSBP and LFPTA and HFPTA is influenced by age and MMP-2. Collectively, these preliminary findings demonstrate that higher aortic stiffness and aSBP are associated with lower hearing sensitivity with aging, which is influenced, in part, by MMP-2 in an apparently healthy, nonclinical population.

Aging is the primary risk factor contributing to the development of CVD and is associated with greater aortic stiffening and higher aortic blood pressure. Our findings demonstrate that AIxHR75 and aSBP, but not cfPWV, were positively correlated with a higher SRT, suggesting diminished hearing. SRT is used to measure the minimum intensity for speech processing, representing the minimum hearing level for speech at which individuals can recognize 50% of the speech material (Lee et al., 2024). Elevations in vascular hemodynamics compromise the structural and functional components of the microcirculation, leading to impaired blood flow to target organs such as the cochlea (Ungvari et al., 2021). Specifically, blood pressure has been shown to affect speed processing, working memory function, and short-term memory; however, the majority of studies examining the effects of blood pressure on SRT are limited to brachial blood pressure (Sánchez-Nieto et al., 2021). This is noteworthy as we extend these findings demonstrating that central (aortic) blood pressure and AIxHR75, but not cfPWV, are associated with a higher SRT in both the low- and high-frequency domains. These correlations did not remain significant after adjusting for age, suggesting age-dependency, thus supporting our primary hypothesis. Furthermore, the SRT test uses both auditory and language centers of the brain, which may explain, in part, the similarity between the performance of both the RE and LE and the correlation with cardiovascular parameters. As such, higher central blood pressure and AIxHR75 are predictors of mortality and thereby may serve as early indicators of hearing loss (Roman et al., 2007; Janner et al., 2013). Thus, these findings suggest that central blood pressure and AIxHR75 are important markers that may provide potential prognostic value with regard to auditory function and cognitive processing with aging.

Importantly, our findings demonstrate that cfPWV, the “gold standard” for assessing aortic stiffness, is associated with RE LFPTA and RE and LE HFPTA. Thus, these data support the notion that aortic stiffness plays a modulatory role with regard to hearing sensitivity in both the low- and high-frequency domains, which appears to be independent of ear dominance. Additionally, we demonstrate for the first time that AIxHR75 is associated with higher LFPTA and HFPTA and aSBP is associated with a greater HFPTA hearing threshold. Notably, cfPWV and AIxHR75 did not remain significantly correlated with hearing loss variables, supporting age as the key variable aligned with our hypothesis. Our results are supported by other studies, demonstrating that higher aortic pulse wave velocity is associated with higher PTA in older women, and not men, but only in the dominant hearing ear (Helzner et al., 2011). Brachial–ankle pulse wave velocity has also been shown to be associated with hearing loss with LFPTA in the dominant ear and with initial hearing levels in adults with idiopathic sudden sensorineural hearing loss (Chung et al., 2016; Tan et al., 2018). These data are noteworthy as aortic stiffness, augmentation index, and central blood pressure are not only predictors of increased CVD risk but are also associated with poorer cognitive performance and cognitive aging (Pase et al., 2013; Ou et al., 2020). As such, central blood pressure and augmentation index have been identified as sensitive indicators for the prediction of age-related cognitive performance that has not been predicted by brachial blood pressure (Pase et al., 2013). Thus, these data provide preliminary evidence for higher central arterial stiffness and aortic systolic blood pressure as contributors to age-related hearing loss.

Increases in aortic systolic blood pressure due to aortic stiffening with aging results in increased pulsatile pressure wave transmission to the microcirculation, which is reflective of higher augmentation index. Evidence from preclinical animal studies support this notion, demonstrating an impaired myogenic response of resistance arteries contributing to microvascular dysfunction as a potential mechanism underlying auditory dysfunction (Springo et al., 2015). Moreover, arteries distal to the large elastic arteries, such as the labyrinthine artery that supplies blood to the cochlea, are more susceptible to increased pulsatile energy, particularly when local microvascular arterial tone and resistance are low (Gratton et al., 1996; Shi, 2011). These data suggest that higher AIxHR75 and aSBP are important central vascular hemodynamics contributing to impaired hearing ability with aging.

Aortic stiffness, increases in central blood pressure, and hearing loss with aging are partly attributable to inflammatory processes (Verschuur et al., 2012; Verschuur et al., 2014; Jablonski et al., 2015; Zanoli et al., 2020; Pierce et al., 2022). A novel finding of this study was that the inflammatory molecules, MMP-2 and resistin, each attenuated the relationship between cfPWV and LFPTA and HFPTA, suggesting that these inflammatory biomolecules may be a link between arterial stiffness and hearing loss. A similar attenuation occurred for the relationship between aSBP and LE SRT and LE HFPTA after separately adjusting for MMP-2 and vaspin. Notably, current evidence demonstrates that higher circulating levels of MMP-2 and resistin are associated with aortic stiffness and hypertension and have been linked as a pathophysiological mechanism underlying presbycusis (Vlachopoulos et al., 2007; Norman et al., 2016; Wu et al., 2017; Zhang et al., 2017; Prado et al., 2021). As such, higher concentrations of MMP-2 and resistin are also associated with CVD and ischemic cerebrovascular disease-related events in older adults (Gencer et al., 2016; Wang et al., 2017). Therefore, it is reasonable to suggest that MMP-2 and resistin are important inflammatory biomarkers that may influence age-related hearing loss in adults without known CVD. Furthermore, while inflammation was not different at baseline between younger and older adults, this does not rule out low-grade inflammation contributing to hearing loss. Inflammation with aging has been shown to damage the inner structure of the cochlea and its sensory cells and promote blood vessel constriction, leading to reduced blood flow to the inner ear and ischemia contributing to the pathogenesis of hearing loss. Therefore, future studies are needed to further our understanding of the influence of inflammation on the relationship between cardiovascular dysfunction and hearing loss and aging (Eisenhut, 2019; Frosolini et al., 2022).

These findings provide novel evidence for the association of greater aortic stiffness and higher aortic systolic blood pressure with age-related hearing loss. Notably, these correlations were attenuated, in part, by both age and MMP-2 and resistin, highlighting both age and inflammation as potential contributing factors to aortic stiffness-related auditory dysfunction. Thus, these findings provide insights for aortic stiffness, aortic systolic blood pressure, and MMP-2 as clinically relevant therapeutic targets to prevent and/or mitigate presbycusis in adults without overt CVD.