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Jung SY, Shim HS, Hah YM, Kim SH, Yeo SG. Association of Metabolic Syndrome With Sudden Sensorineural Hearing Loss. JAMA Otolaryngol Head Neck Surg. 2018;144(4):308–314. doi:10.1001/jamaoto.2017.3144
Is metabolic syndrome associated with recovery from sudden sensorineural hearing loss?
In this medical record review of 124 patients with sudden sensorineural hearing loss, the rate of recovery was lower and the prognosis was poorer in patients with metabolic syndrome than in patients without metabolic syndrome and these measures were worse in patients with 4 or more factors of metabolic syndrome than in those with 3 factors.
The presence of metabolic syndrome may be associated with impaired recovery from sudden sensorineural hearing loss.
Each of the 5 diagnostic criteria or factors of metabolic syndrome—hyperglycemia or type 2 diabetes, hypertension, obesity, elevated triglyceride levels, and decreased high-density lipoprotein cholesterol level—is associated with the pathophysiologic features of sudden sensorineural hearing loss (SSNHL). Little is known, however, about the association of metabolic syndrome, defined as the presence of at least 3 of these factors, with the prognosis of SSNHL.
To evaluate the association of metabolic syndrome with the rate of recovery from SSNHL.
Design, Setting, and Participants
This retrospective medical record review of 124 patients treated for SSNHL at a single tertiary university hospital was performed from June 1, 2014, through May 31, 2016. Medical records were reviewed for demographic and clinical characteristics and audiologic variables.
Sudden sensorineural hearing loss.
Main Outcomes and Measures
Correlation among demographic and clinical characteristics, audiologic results, and prognosis.
Of the total 124 patients (52 men [41.9%]; 72 women [58.1%]; mean [SD] age, 56.0 [14.6] years), 70 had metabolic syndrome and 54 did not. Rates of type 2 diabetes (36 [51.4%] vs 6 [11.1%]; mean difference [MD], 40.3%; 95% CI, 24.4%-53.1%), hypertension (46 [65.7%] vs 9 [16.7%]; MD, 49.1%; 95% CI, 32.3%-61.7%), and obesity (47 [67.1%] vs 6 [11.1%]; MD%, 56.0; 95% CI, 40.0%-67.5%) and mean (SD) concentrations of triglycerides (192.9 [159.7] vs 133.4 [116.6] mg/dL; MD, 59.4 mg/dL; 95% CI, 53.0-65.9 mg/dL) were significantly higher and mean (SD) concentrations of high-density lipoprotein cholesterol (45.8 [9.4] vs 62.6 [17.7] mg/dL; MD, 16.8 mg/dL; 95% CI, 16.1-17.4 mg/dL) were significantly lower in the group with metabolic syndrome than in the group without metabolic syndrome. Mean (SD) pure-tone audiometry thresholds were similar at baseline in the groups with and without metabolic syndrome (65.0 [24.2] vs 60.8 [24.2] dB; MD, 4.3 dB; 95% CI, 3.2-5.4 dB), but recovery rates after treatment were significantly lower in the group with metabolic syndrome (16 [22.9%] vs 23 [42.6%]; MD, −19.7%; 95% CI, −35.4% to −3.2%). No differences were found in the 5 factors among patients with metabolic syndrome who did and did not recover. Level of hearing loss was higher in patients with than without metabolic syndrome, but the difference was not statistically significant. Audiogram patterns also differed but not significantly. Hearing recovery rates were similar in patients with 3 factors of metabolic syndrome and those with none but differed significantly between patients with 4 or more factors and those without metabolic syndrome (4 [19.0%] vs 27 [50.0%]; MD, −31.0%; 95% CI, −48.1% to −6.4%).
Conclusions and Relevance
The rate of recovery from SSNHL was lower among patients with metabolic syndrome than among those without metabolic syndrome, and prognosis was poorer in patients with 4 or more diagnostic factors of the metabolic syndrome.
Sudden sensorineural hearing loss (SSNHL) is generally defined as a sensorineural hearing loss of greater than 30 dB across 3 contiguous pure-tone frequencies occurring within 72 hours.1 Sudden sensorineural hearing loss has a prevalence of 10 per 100 000 persons in Korea and 5 to 20 per 100 000 persons in the United States, with about 4000 new patients in the United States annually.2 The main pathogenic causes of SSNHL are viral infection and vascular disorders; other causes include cochlear membrane rupture, autoimmune disease, inherited tendency, acoustic tumor, head injury, and combinations of multiple factors.3-5
Metabolic syndrome is defined as the occurrence of at least 3 of the following 5 factors: hyperglycemia or diabetes, hypertension, obesity, elevated triglyceride levels, and decreased high-density lipoprotein cholesterol (HDL-C) level.6 Metabolic syndrome is a risk factor for type 2 diabetes and cardiovascular diseases, including myocardial infarction and stroke, and cardiovascular disease–related mortality.7,8
One of the pathologic mechanisms of SSNHL is vascular dysfunction. For example, blood supply to the cochlea by the labyrinthine artery may decrease, reducing oxygen tension in the cochlear lymph and resulting in SSNHL. Microangiopathy has been observed pathologically in patients diagnosed with SSNHL.9 Moreover, various cardiovascular risk factors are associated with increased incidence of SSNHL,10 and a case-control study found that the rate of SSNHL was higher in patients with than without a personal or a family history of cardiovascular events.11 Because metabolic syndrome has been associated with microangiopathy, it could affect the incidence of and recovery from SSNHL. Most previous studies, however, have analyzed the effects of 1 or 2 factors of metabolic syndrome, such as type 2 diabetes,12-15 hypertension,13,16 abnormal lipid levels,12,15-17 and obesity,18,19 on SSNHL. Studies assessing the association of metabolic syndrome with SSNHL have compared findings in patients with and without SSNHL, limiting the ability to evaluate the association of metabolic syndrome with prognosis in patients with SSNHL.20 This study therefore investigated the association of metabolic syndrome, the components of which are known risk factors for SSNHL, with the onset and severity of and rate of recovery from SSNHL.
We performed a retrospective review of the medical records of patients admitted to the Department of Otorhinolaryngology–Head and Neck Surgery at Kyung Hee University, Seoul, Korea, with a diagnosis of SSNHL based on patient history and pure-tone audiometry (PTA), from June 1, 2014, through May 31, 2016. We defined SSNHL as sensorineural hearing loss of greater than 30 dB across 3 contiguous pure-tone frequencies occurring within 72 hours.1 All patients underwent audiologic tests, including PTA, impedance audiometry, speech audiometry, and auditory brainstem-evoked tests, before treatment, as well as physical examination and blood tests for the components of metabolic syndrome. We excluded the following patients from the study: those examined more than 15 days after the onset of disease; those with an accompanying central nervous system disease, infectious disease, head trauma, or head injury; those who had previously undergone otologic operation or showed ototoxic effects of medicine; and those with Meniere disease or a neurologic disorder. The study protocol was approved by the institutional review board of Kyung Hee University Medical Center. All analyses were based on existing anonymized data; therefore informed consent was not required.
All patients were treated with medication in the hospital or as outpatients. Adults were administered 80 mg/d oral prednisolone on days 1 to 4, 60 mg/d on days 5 and 6, 40 mg/d on days 7 and 8, 20 mg/d on days 9 and 10, and 10 mg/d on days 11 to 14. Patients with lower body weight (body mass index [BMI] [calculated as weight in kilograms divided by height in meters squared] <18.5; body weight, <40 kg) started treatment with 1 mg/d oral prednisolone, with this dosage gradually tapered.
Pure-tone audiometry was performed by measuring air and bone conduction, with hearing calculated as the mean of 3 frequencies (500, 1000, and 2000 Hz).21 Hearing was defined as normal if PTA was less than 25 dB, whereas hearing loss was defined as mild if it was 26 dB but less than 40 dB, moderate if it was greater than 41 dB but less than 55 dB, moderate to severe if it was greater than 56 dB but less than 70 dB, severe if it was greater than 71 dB but less than 90 dB, and profound if it was greater than 91 dB.22
The low frequencies included 125 and 250 Hz; the middle frequencies, 500, 1000, and 2000 Hz; and the high frequencies, 4000 and 8000 Hz. The audiogram patterns were classified as ascending type if the hearing threshold was better at high than at low frequencies, flat type if the threshold was similar at all frequencies, descending type if the threshold was better at low than at high frequencies, concave type if thresholds at middle frequencies were generally low, and convex type if thresholds at middle frequencies were generally high.
Final hearing tests were performed 3 months after the onset of SSNHL. Complete recovery was defined as a final hearing threshold of less than 25 dB; partial recovery, a greater than 15-dB improvement with a final hearing threshold of 25 to 45 dB; slight improvement, a greater than 15-dB improvement and a final hearing threshold of greater than 45 dB; and no improvement, a less than 15-dB improvement and a final hearing threshold of greater than 75 dB.21
The diagnostic criteria for metabolic syndrome were based on 4 criteria defined by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III),23 including hypertension (blood pressure ≥130/85 mm Hg), triglyceridemia (triglyceride level ≥150 mg/dL [to convert to millimoles per liter, multiply by 0.0113]), dyslipidemia (HDL-C level <40 mg/dL in men and <50 mg/dL in women [to convert to millimoles per liter, multiply by 0.0259]), and hyperglycemia (fasting plasma glucose level, ≥110 mg/dL [to convert to millimoles per liter, multiply by 0.0555]), and 1 criterion for obesity, defined by American Association of Clinical Endocrinologists (AACE) guidelines24 (BMI>25.0). Metabolic syndrome was defined as having 3 or more of these diagnostic criteria or factors.
All statistical analyses were performed using SPSS software (version 12.0 for Windows; SPSS, Inc), with P < .05 defined as statistically significant. Data are expressed as mean (SD) or as frequency and percentage. We used the Kolmogorov-Smirnov test to assess the compliance of numerical variables with a normal distribution. Normally distributed continuous variables in the 2 groups, including age, initial and final PTA results, BMI, and blood laboratory results, were compared using an unpaired t test. To compare categorical variables, the Pearson χ2 test was used when expected and observed counts were sufficient (sex, affected ear, smoking, alcohol use, hypertension, type 2 diabetes, BMI of at least 25.0, and accompanying symptoms), and the Fisher exact test was used when expected counts were insufficient. Normally distributed continuous variables in the 3 groups (without metabolic syndrome vs 3 vs ≥4 factors of metabolic syndrome), such as initial and final PTA results, were compared using analysis of variance. Effect sizes are presented to describe the magnitude of the differences between the compared groups and 95% CI around the effect size to describe the precision of the estimates and whether the results are consistent with clinically meaningful differences. A post hoc power analysis showed the adequacy of the sample size for further analyses.
Of the 124 patients with SSNHL (52 men [41.9%]; 72 women [58.1%]; mean [SD] age, 56.0 [14.6] years), 70 had metabolic syndrome and 54 did not. The 2 groups were similar in mean age, male to female ratio, the direction of the affected ear, smoking, use of alcohol, and accompanying otologic symptoms such as dizziness, tinnitus, and ear fullness. The percentages of patients with diabetes (36 [51.4%] vs 6 [11.1%]; mean difference [MD], 40.3%; 95% CI, 24.4%-53.1%), hypertension (46 [65.7%] vs 9 [16.7%]; MD, 49.1%; 95% CI, 32.3%-61.7%), and obesity (47 [67.1%] vs 6 [11.1%]; MD, 56.0%; 95% CI, 40.0%-67.5%) were significantly higher in the group with metabolic syndrome than in the group without metabolic syndrome. The mean (SD) concentrations of triglycerides (192.9 [159.7] vs 133.4 [116.6] mg/dL; MD, 59.4 mg/dL; 95% CI, 53.0-65.9 mg/dL) were significantly higher, and the mean (SD) concentrations of HDL-C (45.8 [9.4] vs 62.6 [17.7] mg/dL; MD, 16.8 mg/dL; 95% CI, 16.1-17.4 mg/dL) were significantly lower in the group with metabolic syndrome (Table 1).
Mean (SD) baseline hearing thresholds on PTA were similar in the groups with and without metabolic syndrome (65.0 [24.2] vs 60.8 [24.2] dB; MD, 4.3 dB; 95% CI, 3.2-5.4 dB) (Table 1). Although the degree of hearing loss, assessed as mild, moderate, moderate to severe, severe, and profound, was higher in patients with metabolic syndrome than in those without metabolic syndrome, this difference was not statistically significant. Evaluation of hearing patterns on audiograms showed that the rates of flat, descending, concave, and convex types were higher in patients with metabolic syndrome than in those without metabolic syndrome, but the differences were not statistically significant.
Final hearing threshold by PTA was determined at a mean of 3 months after SSNHL onset. The overall recovery rate determined by the measured final hearing threshold was significantly lower in the group with metabolic syndrome (16 [22.9%] vs 23 [42.6%]; MD, −19.7%; 95% CI, −35.4% to −3.2%) (Table 2).
Comparisons of patients who did and did not achieve a complete response showed no significant differences in mean age, male to female ratio, and all 5 factors constituting metabolic syndrome (Table 3). Of the 70 patients in the metabolic syndrome group, 49, 18, and 3 fulfilled 3, 4, and 5 metabolic syndrome factors, respectively. Patients were divided into the following 3 groups according to the number of diagnostic criteria for metabolic syndrome: none, 3, and 4 to 5. The recovery rate among patients who satisfied 3 diagnostic criteria of metabolic syndrome was similar to that among patients with none (18 [36.7%] vs 27 [50.0%]; MD, −13.3%; 95% CI, −30.9% to 5.76%). In contrast, the recovery rate was significantly lower among patients who satisfied 4 or 5 of the diagnostic criteria than among patients with none (4 [19.0%] vs 27 [50.0%]; MD, −31.0%; 95% CI, −48.1% to −6.4%).
Despite affecting 5 to 20 of 100 000 persons in the general US population, the exact causes of SSNHL remain unknown and its treatment is unclear.1 Although restoration of original hearing has been observed in about one-third of patients, the other two-thirds show no or only partial recovery.25 Methods are needed to prevent SSNHL or detect it early, and studies are actively under way to identify related diseases.
Metabolic syndrome, which affects 20% to 30% of the world’s population, includes risk factors for type 2 diabetes and cardiovascular disease.6-8 Among the various diagnostic criteria for metabolic syndrome are those proposed by the World Health Organization, the European Group for the Study of Insulin Resistance, the NCEP ATP III, the AACE, and the International Diabetes Federation. Common diagnostic criteria include insulin resistance, body weight, lipid concentrations, blood pressure, and hyperglycemia. In this study, 4 items—hypertension, triglyceridemia, dyslipidemia, and hyperglycemia—were determined using the NCEP ATP III criteria, whereas obesity (BMI) was defined according to AACE guidelines.
Although the present study found that initial PTA was similar in patients with and without metabolic syndrome, follow-up PTA showed poorer results in patients with metabolic syndrome than in those without metabolic syndrome. Rates of complete and partial recovery were lower, whereas the rate of no improvement was higher among patients with metabolic syndrome, confirming that metabolic syndrome has a negative association with the prognosis of patients with SSNHL. This finding was similar to those of a study20 showing that the rate of SSNHL was 3.54 times higher among patients with metabolic syndrome than among those without metabolic syndrome.
Patients with metabolic syndrome were subdivided into those with 3 and at least 4 factors, with findings in each subgroup compared with the results in patients without metabolic syndrome (ie, 0-2 factors). Recovery rates were similar among patients with 3 factors and those without metabolic syndrome. In contrast, rates of complete and partial responses were lower and rates of slight and no improvement were higher among patients with at least 4 factors than in the group without metabolic syndrome. In this study, the recovery rate from SSNHL decreased as the number of diagnostic components of metabolic syndrome increased. Thus, in agreement with previous results,20 we found that the prognosis of SSNHL was poorer for those with more metabolic syndrome factors than for those with fewer factors. Because metabolic syndrome is a complex condition that includes factors known to affect the onset and prognosis of SSNHL, such as diabetes, dyslipidemia, hypertension, and visceral obesity, the association of metabolic syndrome with SSNHL likely results from combinations of these individual factors.
Previous analyses of the association of metabolic syndrome with recovery from SSNHL were limited, because they compared metabolic syndrome in patients with and without SSNHL.20 In contrast, our study compares the severity of SSNHL and recovery from this condition in patients with and without metabolic syndrome. The association between each of the 5 components of metabolic syndrome and SSNHL have been analyzed. For example, the incidence of SSNHL was reported to be 1.54 times higher13 and rates of recovery from SSNHL 1.90 times lower in patients with diabetes than in those without diabetes.12,14,15 Although the mechanism linking these 2 conditions has not yet been clarified, diabetes was shown to induce hyperglycemia-mediated endothelial injury in other diseases, reducing recovery rates from comorbid diseases. Diabetes may also induce cochlear microangiopathy, resulting in SSNHL and reducing the recovery rate from this condition.9,12-15 Because atrophy of the spiral ganglion and demyelination of the eighth cranial nerve have been observed in individuals with diabetes, this type of diabetes-induced neuropathy may cause SSNHL.13,14
Dyslipidemia, characterized by hypercholesterolemia and/or triglyceridemia, is another risk factor for SSNHL. Dyslipidemia disrupts blood flow through the processes of plaque formation, vascular remodeling, and vascular luminal obstruction, inducing endothelial dysfunction and vascular inflammation and increasing the accumulation of lipid and cholesterol on the intima of vessel walls. This disruption ultimately impairs oxygen supply in target organs such as the cochlea.16,17 Correction of dyslipidemia in patients with chronic-phase SSNHL was found to improve hearing, providing further evidence that dyslipidemia is associated with the onset of impaired hearing and its prognosis.12
Hypertension is a risk factor for SSNHL, with the rate of SSNHL being higher and the recovery rate lower in patients with hypertension than in those without hypertension. High blood pressure leads to reduced blood vessel elasticity in the inner ear, resulting in atherosclerotic changes that cause narrowing of the vessels, a decrease in blood circulation, and increased cochlear damage. This damage may lead to hemorrhage in the inner ear, resulting in SSNHL.13,16
Few studies to date have analyzed the association between obesity and SSNHL. Obesity is an independent risk factor for presbycusis, with increasing BMI enhancing the severity of sensorineural hearing loss. Adipose tissue is thought to act as endocrine tissue, secreting hormones and cytokines, with obesity-induced inflammation causing end-organ damage by affecting atherosclerosis, insulin resistance, and energy metabolism.26 Moreover, lipotoxic effects and oxidative stress associated with obesity are thought to indirectly cause hearing loss through comorbidity-related angiopathy and neuropathy.19 Obesity-associated atherosclerosis may lead to reduced cochlear blood flow by inducing stiffening and constriction of internal auditory arteries. This process may ultimately lead to hearing loss through the induction of stria vascularis and cell death. Other studies, however, have reported that obesity does not affect the prognosis of patients with SSNHL.18
Microangiopathy is a pathologic mechanism associated with all 5 factors of metabolic syndrome, as well as vascular mechanisms, which constitute one of the causes of SSNHL. According to the vascular mechanism hypothesis, an interruption in the vascular supply to the cochlea, a highly metabolic organ, causes SSNHL. Because the blood supplied to the cochlea derives from the labyrinthine artery without collateral arterial blood flow, the cochlea is vulnerable to transient ischemia.12,15 Diabetes, hypertension, dyslipidemia, and obesity can induce atherosclerotic changes or alter the stiffness and/or elasticity of blood vessels, thereby inducing microangiopathy. Each pathologic change in the inner ear can increase the likelihood of SSNHL. Semipermanent changes in blood vessels are thought to have a negative association with outcomes in patients with SSNHL.
In this study, the severity and audiogram patterns on initial PTA in patients with SSNHL did not differ significantly between those with and without metabolic syndrome. However, analysis of recovery rates confirmed that metabolic syndrome had a negative association with the rate of recovery from SSNHL, with an increase in the number of factors of metabolic syndrome reducing recovery rates. Therefore, metabolic syndrome may be a prognostic factor in patients with SSNHL, and the presence of metabolic syndrome may help estimate the prognosis of these patients.
This study had several limitations. First, its cross-sectional design precluded a determination of any causal relationships between components of metabolic syndrome and hearing loss. As a result of the study design, we could not know the duration of illness or treatment for each disease included in the diagnostic criteria of metabolic syndrome, and it was difficult to realize the possibility of this problem affecting the rate of recovery from SSNHL.
Second, the results of hearing tests were calculated as the mean of 3 frequencies (500, 1000, and 2000 Hz) on the PTA. In general, SSNHL is defined as sensorineural hearing loss of greater than 30 dB across 3 contiguous pure-tone frequencies occurring within 72 hours.7 Trichotomy or quartering is a commonly used hearing assessment method, but it is inadequate for evaluating a loss of hearing threshold at low or high frequency alone. Additional studies are therefore required in patients with low-tone or high-tone hearing loss alone.
Rates of recovery from SSNHL were lower among patients with metabolic syndrome than among those without metabolic syndrome. Prognosis was poorer in patients with at least 4 factors of metabolic syndrome than in those with 3 or fewer of the 5 factors.
Accepted for Publication: December 4, 2017.
Corresponding Author: Seung Geun Yeo, MD, PhD, Department of Otorhinolaryngology–Head and Neck Surgery, School of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Korea (email@example.com).
Published Online: February 15, 2018. doi:10.1001/jamaoto.2017.3144
Author Contributions: Drs Jung and Shim contributed equally to this work. Dr Yeo had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Jung, Shim, Kim, Yeo.
Acquisition, analysis, or interpretation of data: Jung, Hah, Yeo.
Drafting of the manuscript: Jung, Hah, Kim, Yeo.
Critical revision of the manuscript for important intellectual content: Jung, Shim, Yeo.
Statistical analysis: Jung, Shim, Kim.
Obtained funding: Yeo.
Administrative, technical, or material support: Hah, Kim.
Study supervision: Yeo.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Funding/Support: This study was supported by grant KHU-20161705 from Kyung Hee University in 2016.
Role of the Funder/Sponsor: The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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