The Association Between Age-Related Hearing Impairment and Metabolic Syndrome in Korean Women: 5-Year Follow-Up Observational Study

Abstract

Background:

Although several observational studies showed a relationship between various conditions of metabolic syndrome (MetS) and hearing threshold, there are no studies about longitudinal audiometric results related MetS. The aim of this study was to investigate the association between MetS and age-related hearing impairment (ARHI) through a large, average 5-year longitudinal follow-up, clinical comparative analysis.

Materials and Methods:

We recruited 1381 women older than 50 years who were enrolled in 2007 and reevaluated in 2012. They had normal or symmetrical sensorineural hearing loss. For the evaluation of the independent impact of MetS on hearing, multivariate analysis was used.

Results:

The average follow-up period was 5.0 ± 0.2 years. Subjects with MetS had higher hearing thresholds than subjects without MetS. The loss in high-frequency hearing (≥2000 Hz) progressed more rapidly in women with MetS over a 5-year period.

Conclusion:

Our analysis using longitudinal and large data revealed that MetS is associated with ARHI in women 50 years and older. High-frequency hearing loss tended to be greater in women with MetS than in those without MetS at the 5-year follow-up. Therefore, older women with MetS should be followed up closely for hearing evaluation.

Introduction

Age-related hearing impairment (ARHI) is a progressive, bilateral, symmetric sensorineural hearing loss (SNHL). ARHI is initially more pronounced at high frequencies. Approximately 23%–37% of adults 60–69 years, and 40%–60% of adults 71–80 years, have ARHI.¹ Between 2010 and 2030, Korea is projected to experience rapid growth in its older population. In the 2010 Korean census, an approximate 11% of the population was 65 years or older, and this proportion is anticipated to increase to 23% by 2030.² Thus, ARHI is expected to become an important public health problem within the next two decades. The cause of ARHI is complicated and still not clear, but the proposed causes include inflammatory processes, systemic disease, and oxidative stress.^3,4

Metabolic syndrome (MetS) is characterized by a complex condition, including abdominal obesity, glucose intolerance, hypertension (HTN), hypertriglyceridemia, and low high-density lipoprotein cholesterol (HDL-C), which may contribute to the development of ARHI. Several studies have demonstrated that metabolic disturbances can induce hearing loss. Abdominal obesity determined by waist circumference (WC) is an important risk factor for ARHI after adjusting for age, body mass index (BMI), and other clinical factors.⁵ Dyslipidemia and diabetes mellitus (DM) are also associated with ARHI,^6

–9 and hypercholesterolemia and DM are associated with both ARHI and an increased risk of sudden SNHL.¹⁰ HTN is a risk factor of SNHL in stroke patients.¹¹ Furthermore, our previous study showed metabolic risks increased hearing thresholds to establish an association between visceral adipose tissue and ARHI in women.¹²

To date, several studies have established a relationship between SNHL and MetS. The cohort study of 245,000 Swedish conscripts suggested that SNHL might be an associated clinical problem of MetS.¹³ Mets in Korean woman had relevance to increasing hearing level, age ≥18 years old.¹⁴ And, the increasing number of components of MetS was related with increasing hearing threshold in the U.S. population, age ≥20 years old.^13,15

Although several observational studies showed a direct relationship between various conditions of MetS and hearing threshold, there are no studies about longitudinal audiometric results-related MetS. It is important to analyze follow-up hearing results to determine the association with ARHI. We hypothesize that the presence of MetS in women would be associated with ARHI. This study investigated the association between MetS and ARHI through a large, longitudinal, clinical comparative analysis between subjects with MetS and without MetS in Korean women.

Materials and Methods

Study participants

In total, 1524 consecutive Korean women aged 50 years or older who had completed overall health examinations at the Health Screening and Promotion Center of the Asan Medical Center (AMC) in 2007 and follow-up examinations in 2012 were enrolled. Health screening protocol and obtaining the data from participants were done according to the previous report.^12,16

All subjects had visited the Health Screening and Promotion Center of the AMC spontaneously for a comprehensive health screening, which included anthropometric measurements (height, weight, and WC), a blood test (complete blood cell count, basic chemistry, serologic test, and blood coagulation test), stool/urine analysis, gastrointestinal fiberscopy, chest radiography, electrocardiography, and pure tone audiometry (PTA). A medical questionnaire was used to obtain medical histories of subjects. All subjects were assigned to enter up a medical questionnaire, which included questions on general, psychiatric, and neurological problems. All patients had undergone a medical examination based on their medical questionnaire.

Subjects with the following histories were excluded as previous studies^5,12,17: 106 patients were excluded due to otologic problems such as asymmetric SNHL [defined as a 15 decibel hearing level (dB HL) or greater asymmetry in two or more frequencies], external or middle ear problems, noise-induced hearing loss, and ototoxic drug-induced hearing loss. Twenty-four patients were excluded due to brain disorders such as stroke, major neurological or psychiatric diseases, or brain tumor, and 13 patients were excluded due to other medical problems such as liver cirrhosis, chronic renal failure under peritoneal dialysis or hemodialysis, and head or neck radiation exposure. After applying the exclusion criteria, 1381 subjects aged 50 years or older in 2007 were included in the final analysis.

The Institutional Review Board of Asan Medical Center (AMC IRB) approved the study method, and all subjects submitted an informed consent for the use of their medical records of health screening. The trial is registered with the Korean Clinical Research Information Service (CRIS) registry (KCT0001367).

Audiometric assessment

PTA was conducted in a double-walled soundproof room. Four frequencies at 0.5, 1, 2, and 4 kHz were assessed by routine PTA (MADSEN Itera II; GN Otometrics). Hearing levels at 0.5 and 1 kHz were averaged to describe the PTA-low, and hearing levels at 2 and 4 kHz were averaged to describe the PTA-high.¹²

Anthropometric and biochemical measurements

Anthropometric measurements for each patient were obtained after a 12-hr fast. BMI was calculated as the weight in kilograms divided by the height in meters squared (kg/m²). WC (cm) was measured on bare skin between the lower rib margin and the iliac crest at the end of a normal expiration. Blood pressure (BP, mmHg) was recorded twice after resting for more than 15 min using a mercury manometer with an appropriate cuff size, and the average of both measurements was used for analysis. Blood samples were obtained after a 12-hr fast and subsequently analyzed at certified laboratory of AMC. Serum levels of fasting total cholesterol, HDL-C and low-density lipoprotein cholesterol (LDL-C), and triglycerides were measured by an enzymatic colorimetric method using a Synchron LX20 (Beckman Coulter, Fullerton, CA). Serum fasting glucose was measured using a hexokinase method and a glucose analyzer (Beckman Coulter).

Definition of MetS

MetS was defined according to the 2005 revision of the criteria from the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III).¹⁸ Abdominal obesity was redefined on the basis of an Asian-specific cutoff point as recommended in the NCEP ATP III criteria. Subjects were considered to have MetS if they had three or more of the following abnormalities: WC ≥90 cm for men or ≥80 cm for women, hypertriglyceridemia ≥150 mg/dL (1.7 mmol/L), low HDL-C <40 mg/dL (1.0 mmol/L) for men or <50 mg/dL (1.3 mmol/L) for women, high BP (≥130/85 mmHg), or use of antidiabetic medication (e.g., insulin or oral agents).

Statistical analysis

Continuous variables were expressed as mean ± standard deviation (SD), and were compared using t-test. Categorical variables were presented as numbers (%) and compared using McNemar test or McNemar–Bowker test. Univariate linear regression was performed to assess the impact of MetS on PTA-low and PTA-high scores. Multiple regression analyses were used to determine the independent impact of MetS on PTA-low and PTA-high scores. To find a component of MetS that correlated with longitudinal hearing change we used multivariate regression coefficients. The covariates were age, BMI, smoking, and alcohol consumption. Multicollinearity was assessed using the variance inflation factor (VIF). VIF >10 indicates serious multicollinearity, and VIF >4 indicate possible cause for concern. P < 0.05 was considered statistically significant. All analyses were performed using SPSS (Version 21.0 for Windows; SPSS, Inc., Chicago, IL).

Results

Characteristics of the study population

Subject characteristics are listed in Table 1. The average follow-up period was 5.0 ± 0.2 years. The mean ages was 55.96 ± 5.51 (range: 50–83 years) in 2007. Age, height, WC, systolic BP, and hearing level were higher in 2012. However, BMI, weight, triglycerides, and HDL-C were lower in 2012. The prevalence of HTN, DM, and MetS was increased in 2012. Fasting glucose, Diastolic BP, smoking, and alcohol consumption have no differences between 2007 and 2012.

Table 1.

Baseline Characteristics of the Entire Study Population (n = 1381)

Variables	Female in 2007	Female in 2012	P^a
Age (years)	55.96 ± 5.51	60.95 ± 5.51	<0.001
Body mass index (kg/m²)	23.17 ± 2.85	22.97 ± 2.73	<0.001
Weight (kg)	57.13 ± 7.34	56.70 ± 7.09	<0.001
Height (cm)	156.69 ± 8.81	157.13 ± 4.90	0.025
Metabolic syndrome (%)	243 (17.6)	317 (22.9)	<0.001
Metabolic syndrome components
Waist circumference	75.11 ± 13.03	80.09 ± 7.88	<0.001
Fasting glucose	96.05 ± 14.10	96.03 ± 15.74	0.956
DM medication (%)	57 (4.1)	77 (5.6)	<0.001
Triglycerides (mg/dL)	111.31 ± 64.56	104.81 ± 51.61	<0.001
HDL-C (mg/dL)	62.95 ± 14.81	61.02 ± 14.28	<0.001
Systolic BP	117.81 ± 16.64	119.19 ± 14.10	<0.001
Diastolic BP	72.74 ± 8.98	73.02 ± 9.31	0.218
HTN medication (%)	295 (21.4)	406 (29.4)	<0.001
Smoking			0.368
Nonsmoker (%)	1332 (96.5)	1334 (96.6)
Ex-smoker (%)	25 (1.8)	26 (1.9)
Current smoker (%)	16 (1.2)	18 (1.3)
No data (%)	8 (0.6)	3 (0.2)
Alcohol consumption			0.371
Never (%)	819 (59.3)	818 (59.2)
≤1/Month (%)	328 (23.8)	330 (23.9)
2–4/Month (%)	165 (11.9)	167 (12.1)
2–3/Week (%)	52 (3.8)	54 (3.9)
≥4/Week (%)	9 (0.7)	9 (0.7)
No data (%)	8 (0.6)	3 (0.2)
Hearing level
PTA-low (dB HL)	12.40 ± 7.78	16.09 ± 8.59	<0.001
PTA-high (dB HL)	13.43 ± 9.18	19.12 ± 10.51	<0.001
Longitudinal hearing changes between 2007 and 2012
Diff-low	3.69 ± 6.37
Diff-high	5.69 ± 7.02

Data are expressed as numbers (percentages) for categorical variables and mean ± SD for continuous variables.

P values between in 2007 and in 2012 were tested using the t-test for continuous variables and McNemar test or McNemar–Bowker test for comparison of categorical variables.

BP, blood pressure; dB HL, decibel hearing level; DM, diabetes mellitus; HDL-C, high-density lipoprotein cholesterol; HTN, hypertension; PTA, pure tone audiometry; PTA-low, average hearing threshold of both ears at 0.5 and 1 kHz; PTA-high, average of hearing threshold of both ears at 2 and 4 kHz; SD, standard deviation; Diff-low, differences of PTA-low between 2007 and 2012; Diff-high, differences of PTA-high between 2007 and 2012.

Association between hearing thresholds and MetS

Hearing threshold of the MetS group was higher than that of the non-MetS group (Table 2). In 2007, the MetS group (n = 243) had significantly higher (worse) PTA-low (14.74 ± 9.11 vs. 11.90 ± 7.37; P < 0.001) and PTA-high (16.33 ± 11.31 vs. 12.81 ± 8.54; P < 0.001) than the non-MetS group (n = 1138), respectively. In 2012, the MetS group (n = 317) also had significantly higher (worse) PTA-low (18.29 ± 9.83 vs. 15.44 ± 8.08; P < 0.001) and PTA-high (22.22 ± 11.83 vs. 18.20 ± 9.91; P < 0.001) than the non-MetS group (n = 1064), respectively.

Table 2.

Difference in Hearing Thresholds According to the Presence of Metabolic Syndrome

	MetS (−)	MetS (+)	P^a
2007	n = 1138	n = 243
PTA-low (dB HL)	11.90 ± 7.37	14.74 ± 9.11	<0.001
PTA-high (dB HL)	12.81 ± 8.54	16.33 ± 11.31	<0.001
2012	n = 1064	n = 317
PTA-low (dB HL)	15.44 ± 8.08	18.29 ± 9.83	<0.001
PTA-high (dB HL)	18.20 ± 9.91	22.22 ± 11.83	<0.001

Data are expressed as mean ± SD.

P values between MetS (−) and MetS (+) were tested using the t-test.

MetS (−), absence of metabolic syndrome; MetS (+), presence of metabolic syndrome.

Univariate linear regression analysis showed that MetS correlated with hearing levels in both 2007 and 2012 (Table 3). Multivariate regressions were analyzed independent of age, BMI, smoking, and alcohol consumption. After adjustment of age, MetS correlated with hearing levels in both 2007 and 2012. But, after further adjustment of BMI, hearing level in 2007 was not correlated with presence of MetS in 2007. Multivariate analysis demonstrated that presence of MetS in 2012 strongly correlated with hearing level in 2012 (Table 3).

Table 3.

Cross-Sectional Results: Regression Analyses for Hearing Thresholds According to the Presence of Metabolic Syndrome

	Unadjusted		Model 1		Model 2		Model 3
	St-β ± SE	P	St-β ± SE	P	St-β ± SE	P	St-β ± SE	P
MetS (+) in 2007
PTA-low in 2007	2.834 ± 0.544	<0.001	1.615 ± 0.540	0.003	0.889 ± 0.569	0.118	0.912 ± 0.569	0.109
PTA-high in 2007	3.518 ± 0.642	<0.001	1.689 ± 0.622	0.007	1.207 ± 0.658	0.067	1.246 ± 0.657	0.058
MetS (+) in 2012
PTA-low in 2012	2.856 ± 0.545	<0.001	1.540 ± 0.514	0.003	1.256 ± 0.549	0.022	1.354 ± 0.548	0.014
PTA-high in 2012	4.020 ± 0.664	<0.001	2.193 ± 0.611	<0.001	1.988 ± 0.653	0.002	2.034 ± 0.654	0.002

Model 1, adjusted for age; Model 2, adjusted for age, body mass index; Model 3, adjusted for age, body mass index, smoking, and alcohol consumption.

SE, standard error; St-β, standardized-β.

We compared longitudinal hearing changes using presence of MetS in 2007 as an initial evaluation. Longitudinal hearing deteriorations at low and high frequency were significantly bigger in the subjects with MetS (4.51 ± 6.47 at low frequency and 7.16 ± 7.20 at high frequency) than in those without MetS (3.52 ± 6.34 at low frequency and 5.38 ± 6.94 at high frequency) (Table 4). After adjustment age, multivariate analysis showed MetS correlated with longitudinal hearing deteriorations at high frequency (Table 5).

Table 4.

Longitudinal Results: Differences in Hearing Changes According to the Presence of Metabolic Syndrome in 2007

	MetS (−) in 2007, n = 1138	MetS (+) in 2007, n = 243	P^a
Diff-low	3.52 ± 6.34	4.51 ± 6.47	0.028
Diff-high	5.38 ± 6.94	7.16 ± 7.20	<0.001

P value between MetS (−) and MetS (+) in 2007 were tested using the t-test.

Table 5.

Longitudinal Results: Regression Analyses for Hearing Changes According to the Presence of Metabolic Syndrome in 2007

	Unadjusted		Model 1		Model 2		Model 3
MetS (+) in 2007	St-β ± SE	P	St-β ± SE	P	St-β ± SE	P	St-β ± SE	P
Diff-low	0.990 ± 0.450	0.028	0.355 ± 0.456	0.437	0.767 ± 0.482	0.111	0.772 ± 0.482	0.109
Diff-high	1.785 ± 0.494	<0.001	1.052 ± 0.500	0.036	1.308 ± 0.529	0.014	1.306 ± 0.529	0.014

Model 1, adjusted for age; Model 2, adjusted for age, body mass index; Model 3, adjusted for age, body mass index, smoking, and alcohol consumption.

We evaluated the effect of each respective metabolic component on the longitudinal hearing deteriorations at high frequency. In univariate analysis, abdominal obesity and low level of HDL were correlated with longitudinal hearing deteriorations at high frequency. Multivariate analysis demonstrated that only abdominal obesity correlated with longitudinal hearing deteriorations at high frequency (Table 6).

Table 6.

Regression Coefficients of Component of Metabolic Syndrome in 2007 for Diff-high

		Diff-high
Component of MetS		Unadjusted	Model 1	Model 2	Model 3
Abdominal obesity	St-β ± SE	1.153 ± 0.406	0.923 ± 0.425	0.950 ± 0.512	0.943 ± 0.513
	P	0.005	0.032	0.036	0.039
Elevated fasting glucose	St-β ± SE	0.710 ± 0.422	0.171 ± 0.428	0.222 ± 0.428	0.200 ± 0.428
	P	0.093	0.690	0.605	0.640
Elevated triglycerides	St-β ± SE	0.880 ± 0.488	0.399 ± 0.509	0.392 ± 0.509	0.393 ± 0.509
	P	0.072	0.433	0.442	0.440
Low level of HDL	St-β ± SE	1.068 ± 0.480	0.603 ± 0.501	0.667 ± 0.502	0.682 ± 0.503
	P	0.026	0.229	0.184	0.175
Elevated BP	St-β ± SE	0.591 ± 0.397	−0.316 ± 0.413	−0.234 ± 0.415	−0.243 ± 0.416
	P	0.136	0.445	0.574	0.559

Model 1, adjusted for age; Model 2, adjusted for age, body mass index; Model 3, adjusted for age, body mass index, smoking, and alcohol consumption.

Discussion

This large, longitudinal study of 1381 Korean women 50 years or older showed that the MetS group have worse hearing than the non-MetS group. In addition, the loss in high-frequency hearing (>2000 Hz) progressed more rapidly in women with MetS over a 5-year period. To identify the causative role of MetS on hearing level, longitudinal follow-up is also necessary. To the best of our knowledge, this was the first study that investigated the association between MetS and ARHI by analyzing longitudinal hearing changes.

Previous studies showed gender-related hearing and metabolic problem. In most cases, the association between hearing thresholds and metabolic problems only exists among women.^12,14,19 And, the majority of studies that measure hearing levels in adults showed that older men have considerably greater loss of hearing in high frequency than older women.^20,21 In a Korean cohort, high-frequency hearing impairment differs between the sexes.²² This is often attributed to the greater noise exposure, both at work and recreationally, in men than in women. Although we excluded individuals who had substantial noise-induced hearing loss, these data suggested that such environmental factors are likely more important than metabolic risk in terms of increased hearing threshold in older men. Thus, this study enrolled only adult women for precise analysis between MetS and hearing.

MetS was reported to have an association with the development of various complications, such cardiovascular disease, DM, and dyslipidemia.²³ And, subjects with MetS had significantly increased hearing level than those without MetS.^14,24 Mechanisms contributing to ARHI were known as hypoxia-induced apoptosis, oxidative stress, and inflammation.^25,26 Although the cause of inner ear deterioration is not well known, it may be related to metabolic disturbances.²⁷ The biochemical pathways of auditory dysfunction in diabetes appear to involve oxidative stress and deposition of advanced glycation end products.²⁸ Low HDL and coronary heart disease in diabetes patients are also associated with high hearing thresholds.²⁹ Previous studies suggest that the pathogenesis of hearing deterioration may be due to neuropathy, micro-angiopathy, or a combination of these. Hearing difficulties may be affected by hypoxia, imbalance of redox status, and subsequent mitochondrial dysfunction of the cochlea.³⁰ Hypoxia of the cochlea may also contribute to the mitochondrial DNA (mtDNA) 4977 deletion and to other mtDNA mutants, which result in further decrease of mitochondrial oxidative phosphorylation and dysfunction of the acoustic neural system.^1,31 The mtDNA damage leads to ketosis, hyperlipidemia, and increased fat storage that promote MetS.³² Therefore, the underlying cause of MetS with ARHI is likely complex and involves micro-angiopathy, redox imbalance, and neuropathy.

Adiponectin (APN) is hormone related to MetS. Subjects with MetS have lower APN than those without MetS.³³ APN is a protein hormone that control metabolic processes, including glucose metabolism and fatty acid oxidation,³⁴ and exerts prosurvival effects, and anti-inflammatory and antioxidant activities, in various cell types.³⁵ In the organ of Corti of the inner ear, apoptosis is promoted by APN deficiency. A low concentration of plasma APN is also associated with decreased hearing capacity in women ≥55 years,¹⁹ and APN plays an important role in preventing ARHI.³⁶ Apparently, healthy Korean adults with low circulating APN are at a significantly high risk of dyslipidemia and MetS.^37,38 In particular, MetS-related abnormal APN may have a role in hearing loss. Therefore, further studies are needed to identify the cause of hearing loss associated with MetS.

Our results presented that hearing changes at high frequency between 2007 and 2012 were significantly higher in the subjects with MetS in 2007 than in those without MetS in 2007. ARHI typically begins with high-frequency hearing loss and affects lower frequencies in the later stages. In ARHI, hearing loss at low frequency have a slower rate than at high frequency.³⁹ Similarly, our 5-year follow-up data showed women with MetS tended to have a faster worsening rate not at low-frequency hearing but at high-frequency hearing by multivariate analysis for reducing the confounding effect. We anticipate low-frequency hearing capacity would show a similar trend in follow-up data carried out over a long period of time.

Our previous study showed visceral adipose tissue increased hearing thresholds in Korean women older than 40 years.¹² In this study, multivariate analysis showed that only abdominal obesity correlated with longitudinal hearing deteriorations at high frequency. From these results, we speculated obesity related with metabolic disorders might be an important factor with hearing deterioration.

In conclusion, our analysis using longitudinal and large data revealed that MetS is associated with ARHI in women 50 years and older. Individuals with MetS had lower hearing capacity than individuals without MetS. Also, high-frequency (>2000 Hz) hearing loss tended to be greater in women with MetS than in those without MetS at the 5-year follow-up. Therefore, older women with MetS should be followed up closely for hearing level.

Footnotes

Author Disclosure Statement

No conflicting financial interests exist.

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