Original Research
Metabolic Syndrome Increases the Risk of Sudden Sensorineural Hearing Loss in Taiwan: A Case-Control Study
Otolaryngology– Head and Neck Surgery 1–7 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599815575713 http://otojournal.org
Chen-Yu Chien, MD1,2,3,4, Shu-Yu Tai, MD1,5,6, Ling-Feng Wang, MD2,3,7, Edward Hsi, PhD8, Ning-Chia Chang, MD, PhD2,9, Ming-Tsang Wu, MD, PhD1,5,10,11, and Kuen-Yao Ho, MD1,2,3
No sponsorships or competing interests have been disclosed for this article.
Abstract Objective. Sudden sensorineural hearing loss has been reported to be associated with diabetes mellitus, hypertension, and hyperlipidemia in previous studies. The aim of this study was to examine whether metabolic syndrome increases the risk of sudden sensorineural hearing loss in Taiwan. Study Design. A case-control study. Setting. Tertiary university hospital. Subjects and Methods. We retrospectively investigated 181 cases of sudden sensorineural hearing loss and 181 controls from the Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, in southern Taiwan from 2010 to 2012, comparing their clinical variables. We analyzed the relationship between metabolic syndrome and sudden sensorineural hearing loss. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III with Asian modifications. The demographic and clinical characteristics, audiometry results, and outcome were reviewed. Results. Subjects with metabolic syndrome had a 3.54-fold increased risk (95% confidence interval [CI] = 2.00-6.43, P \ .01) of having sudden sensorineural hearing loss compared with those without metabolic syndrome, after adjusting for age, sex, smoking, diabetes mellitus, hypertension, and hyperlipidemia. With increases in the number of metabolic syndrome components, the risk of sudden sensorineural hearing loss increased (P for trend \.01). Vertigo was associated with a poor outcome (P = .02; 95% CI = 1.13~5.13, adjusted odds ratio = 2.39). The hearing loss pattern may influence the outcome of sudden sensorineural hearing loss (P \.01). Conclusion. These results suggest that metabolic syndrome is an independent risk factor for sudden sensorineural hearing loss in Taiwan. Vertigo and total hearing loss were indicators of a poor outcome in sudden sensorineural hearing loss. Keywords sudden deafness, metabolic syndrome, outcome, vertigo
Received August 14, 2014; revised February 3, 2015; accepted February 11, 2015.
S
udden sensorineural hearing loss (SSNHL) is defined as a 30-dB loss over 3 continuous frequencies occurring in less than 3 days.1 The incidence rates per 100,000 people in Taiwan are 8.85 for men and 7.79 for women.2 The cause of this disease is still not clear, but the proposed causes include viral infection, vascular disease, autoimmunity, and genetic factors.2,3 Metabolic syndrome (MetS) is a cluster of common pathologies, including abdominal obesity, hypertension, insulin resistance, and dyslipidemia. MetS is associated with an increased risk of cardiovascular disease, myocardial infarction, stroke,
1 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Department of Otorhinolaryngology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 4 Department of Otorhinolaryngology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 6 Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 7 Department of Otorhinolaryngology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 8 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 9 Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 10 Department of Family Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 11 Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan
Corresponding Author: Kuen-Yao Ho, Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 807, Taiwan. Email: [email protected]
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diabetes mellitus, and cardiovascular disease mortality.4,5 Acquired and inherited cardiovascular risk factors have been associated with an increased risk of developing SSNHL.6 A personal or familial history of cardiovascular events, including coronary insufficiency, myocardial infarction, stroke, and transient ischemic attack, have also been found to be more prevalent in patients with SSNHL than the control group.7,8 Several studies have identified microvascular damage in the pathology of SSNHL.9 Diabetes is a risk factor for SSNHL, possibly due to microangiopathy.10 With its associated microangiopathy, MetS could be a risk factor for SSNHL. However, few research studies have evaluated the association between MetS and SSNHL. We hypothesized that MetS may increase the risk of SSNHL. Previous studies of SSNHL did not focus on MetS patients. We conducted a retrospective review to elucidate the influence of MetS in SSNHL patients and the prognostic factors for SSNHL patients.
Materials and Methods Study Population We recruited 181 patients with SSNHL and 181 controls at the Kaohsiung Medical University Hospital between October 2010 and September 2012. The diagnostic criteria for SSNHL included sensorineural hearing loss of at least 30 dB in 3 contiguous frequencies using a pure-tone audiogram with an onset within 3 days.1-3 All patients denied previous episodes of SSNHL, and none received treatments before taking the hearing and blood tests. The exclusion criteria were hearing losses caused by acoustic neuroma, central lesions, Meniere’s disease, multiple sclerosis, infectious diseases, trauma, medication, noise, or prior ear surgery. Audiometric tests, including initial and follow-up pure-tone audiometry, speech audiometry, tympanometry, stapedial reflexes, auditory brainstem-evoked responses, and magnetic resonance imaging (to exclude acoustic neuroma) were performed in the SSNHL patients to verify the hearing loss was sensorineural hearing loss. The controls visited our department of otorhinolaryngology for health examination. Controls lacking a history of hearing loss or any other ear disorders were enrolled. The eligible controls were randomly selected and frequency matched with the case patients based on age and sex. Information on demographic characteristics was collected. A history of hypertension was defined as positive in persons taking antihypertension drugs to control blood pressure and a history of diabetes mellitus in those who had received drug or insulin therapy to control blood sugar. All 181 patients were hospitalized for 1 week. They received oral prednisolone (1 mg/kg for 2 days), which was tapered down over the following 2 weeks. They also received intravenous (1000 mL) low-molecular-weight dextran (MW 40,000, 10% 500 mL/Bot) daily during hospitalization. All patients underwent routine blood and biochemistry tests before treatment. This protocol was the standard treatment for SSNHL in our hospital.
The pattern of the audiogram was categorized by Sheehy classification.11 The audiograms were categorized into 4 patterns, which were low tone, high tone, flat, and total hearing loss types. The severity of hearing loss was evaluated with the average hearing level at 5 frequencies (250, 500, 1000, 2000, and 4000 Hz) on the pure-tone audiogram performed when SSNHL was diagnosed. The 5 frequencies were used for the hearing loss severity assessment to specifically categorize them under the Sheehy classification. The severity was then categorized into 1 of 4 grades based on the initial audiogram, which included mild (hearing loss of less than 40 dB), moderate (hearing loss of more than 40 dB but not exceeding 70 dB), severe (hearing loss of more than 70 dB but not exceeding 90 dB), and profound (hearing loss of more than 90 dB). Hearing improvement was evaluated by comparing the patient’s last follow-up audiogram with the audiogram taken when SSNHL was diagnosed. All patients were followed up at for least 3 months. The pure-tone average (PTA) was calculated by taking 4 frequencies, 500, 1000, 2000, and 3000 Hz. We followed the outcome assessment recommendations in ‘‘Clinical Practice Guideline: Sudden Hearing Loss’’ from the American Academy of Otolaryngology—Head and Neck Surgery (AAO-HNS) in 2012 to justify the treatment success.1 In this guideline, serviceable hearing is defined as a PTA 50 dB and word recognition score (WRS) 50% according to the American Academy of Otolaryngology— Head and Neck Surgery Foundation Hearing Classification System. The grades ‘‘complete recovery’’ and ‘‘meaningful partial recovery’’ were considered to have good outcome, whereas ‘‘not meaningful partial recovery’’ and ‘‘no recovery’’ were considered to have poor outcome.
Definition of MetS MetS was defined according to the National Cholesterol Education Program’s Adult Treatment Panel III criteria,12 with a cutoff value for defining abdominal obesity of 90 cm for males and 80 cm for females, as recommended by the World Health Organization guidelines for Chinese patients.13,14 Subjects with MetS must fulfill 3 or more of the following criteria: (1) waist circumference of 90 cm in males and 80 cm in females, (2) blood pressure of 130/85 mm Hg or receiving antihypertensive treatment, (3) fasting glucose of 100 mg/dL or known treatment for diabetes mellitus, (4) serum triglycerides of 150 mg/dL, and (5) high-density lipoprotein (HDL) cholesterol levels \40 mg/dL in males and \50 mg/dL in females. Individual criteria were scored, and the scores were totaled; a sum of 3 or greater was indicative of the presence of MetS.15 To evaluate the prognostic factors in SSNHL patients, we analyzed the differences in the distribution of the parameters between the good and poor outcome groups. The parameters included the following clinical and audiological variables: age, sex, side of lesion, duration from onset to treatment, diabetes mellitus, hypertension, hyperlipidemia, MetS status, smoking, drinking, vestibular symptoms, pattern of audiogram, and severity of hearing loss.
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Table 1. Basic Characteristics of the Subjects Included in the Study. Sudden Sensorineural Hearing Loss (n = 181)
Controls (n = 181)
P Value
48.7 6 14.1 91/90 28 (15.5) 20 (11.0) 71 (39.2) 43 (23.8) 84.2 6 11.6 130.0 6 20.5 78.1 6 12.6 123.7 6 40.1 104 (84-136)
46.4 6 11.0 99/82 26 (14.4) 13 (7.2) 43 (23.8) 35 (19.3) 78.7 6 9.8 122.0 6 15.9 75.1 6 12.4 98.8 6 17.2 91 (64-131)
.08a .40b .77b .20b \.01b .31b \.01a \.01a .02a \.01a \.01c
49 (38-57)
53 (46-63)
\.01c
Age, y, mean 6 SD Sex, male/female, n Smoking, n (%) Diabetes mellitus, n (%) Hypertension, n (%) Hyperlipidemia, n (%) Waist circumference, mean 6 SD Systolic blood pressure, mm Hg, mean 6 SD Diastolic blood pressure, mm Hg (mean 6 SD) Fasting glucose, mg/dL Triglyceride, mg/dL, median (25th-75th percentiles) High-density lipoprotein cholesterol, mg/dL, median (25th-75th percentiles) Side, right/left Outcome, n (%) Complete recovery Partial recovery Meaningful Not meaningful No recovery Good Poor
91/90 84 (46.4) 47 (26.0) 20 (11.1) 27 (14.9) 50 (27.6) 104 (57.5) 77 (42.5)
a
t test. x test. C Wilcoxon rank sum test. b 2
Ethical Concerns This study was approved by the Institutional Review Board of Kaohsiung Medical University Hospital (approval No. KMUH-IRB-20120270).
Statistical Analysis Continuous variables are expressed as the mean 6 standard deviation (SD) or median (25th-75th percentiles), as appropriate. Categorical data are expressed as frequencies. To compare the distributions of the baseline characteristics between subjects with and without SSNHL, among SSNHL patients with good and poor outcome, the t test, x2 test, Wilcoxon rank sum test, and Fisher exact test were used. Multivariate logistic regression analysis was used to calculate the adjusted odds ratios (aORs) and 95% confidence interval (95% CI) of the outcome factors of SSNHL. The JMP version 9.0 Stat View version 5.0 (SAS Institute Inc) was used for statistical analyses. All statistical tests were 2 sided, and P \ .05 was considered statistically significant.
Results Characteristics of the Study Participants The basic characteristics of the study subjects are listed in Table 1. The mean and SD of age were 48.7 6 14.1 years
in the 181 SSNHL patients (91 male and 90 female) and 46.4 6 11.0 years in the 181 controls (99 male and 82 female). According to the study design, there was no difference in the age and sex for the SSNHL versus control groups. The right ear was affected in 91 (50%) patients and the left in 90 (50%) patients. No side predominance was noted. The prevalence of hypertension was higher in the SSNHL patients than in the controls (P \ .01). The prevalence rates of smoking, diabetes mellitus, and hyperlipidemia were similar in the SSNHL patients and controls. The average waist circumference, systolic blood pressure, diastolic blood pressure, fasting glucose level, and triglyceride level were higher, whereas HDL cholesterol level was lower in the SSNHL patients than in the controls.
MetS and SSNHL The MetS characteristics for the SSNHL patients and controls are shown in Table 2. The 3 components of MetS including waist circumference (WC), blood pressure 130/ 85 mm Hg or had taken antihypertensive drugs, and fasting plasma glucose 100 mg/dL or had taken antidiabetic drugs were all significantly higher in SSNHL patients than in control group. The HDL cholesterol was significantly lower in SSNHL patients than in the control group. The triglyceride
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Table 2. Prevalence among Subjects of the Components of Metabolic Syndrome as Defined by National Cholesterol Education Program Adult Treatment Panel III with Asian Modification.
Waist circumference, n (%) Male 90 cm Female 80 cm Blood pressure 130/85 mm Hg or had taken antihypertensive drugs, n (%) Fasting glucose 100 mg/dL or had taken antidiabetic drugs, n (%) Triglyceride 150 mg/dL, n (%) HDL cholesterol, n (%) Male \40 mg/dL Female \50 mg/dL Metabolic syndrome, n (%)
SSNHL (n = 181)
Controls (n = 181)
P Value
78 (43.1)
38 (21.0)
\.01b
71 67 32 29
(39.2) (37.0) (17.7) (16.0)
.01b \.01b 1.00b \.01b
35 (19.3)
\.01c
94 142 32 70
(51.9) (78.4) (17.7) (38.7)
79 (43.7)
aORa (95% CI)
3.54 (2.00-6.43)
Abbreviations: aOR, adjusted odds ratio; HDL, high-density lipoprotein; SSNHL, sudden sensorineural hearing loss. a Age, sex, smoking, diabetes mellitus, hypertension, and hyperlipidemia adjusted. b 2 x test. c Multivariate logistic regression analysis.
Initial Presentations in the Audiometry and Hearing Improvement in Follow-up
Figure 1. Probability (odds ratio, 95% confidence interval) of sudden sensorineural hearing loss according to the number of metabolic syndrome components. Adjusted for age, sex, smoking, diabetes mellitus, hypertension, and hyperlipidemia; P for trend \.01.
component was similar in SSNHL patients and the control group. The prevalence of MetS was higher in SSNHL patients than in controls (43.7% vs 19.3%) using the National Cholesterol Education Program Adult Treatment Panel III with Asian modification criteria. After adjusting for age, sex, smoking, diabetes mellitus, hypertension, and hyperlipidemia, participants with MetS had a significantly increased risk of developing SSNHL (aOR = 3.54, 95% CI = 2.00~6.43, P \ .01). As depicted in Figure 1, the risk of developing SSNHL trended to increase stepwise as the number of MetS components increased (P for trend \.01).
The pretreatment PTAs (mean 6 SD) of the affected ear were 58.5 6 23.4 dB in good and 76.0 6 22.2 dB in poor outcome (P \ .01). The posttreatment PTAs (mean 6 SD) of the affected ear were 26.3 6 14.3 dB in good and 69.7 6 19.6 dB in poor outcome (P \ .01). The average hearing gain (mean 6 SD) of the affected ear in good and poor outcome were 32.2 6 19.4 dB and 6.3 6 16.8 dB, respectively (P \ .01). The hearing status of the unaffected ear in the SSNHL group was 19.7 6 10.1 dB. The hearing status of the control group was 18.2 6 6.9 dB in the right ear and 18.5 6 6.4 dB in the left ear. Each of the right (P = .11) and left (P = .20) ears of the control group had no significant difference compared with the unaffected ear in the SSNHL group. The pretreatment WRSs (%, mean 6 SD) of the affected ear were 53.0 6 25.9 in good and 27.1 6 25.5 in poor outcome (P \ .01). The posttreatment WRSs (%, mean 6 SD) of the affected ear were 91.1 6 9.5 in good and 38.0 6 22.0 in poor outcome (P \ .01). The average WRS gains (%, mean 6 SD) of the affected ear in good and poor outcome were 38.1 6 22.9 and 10.9 6 18.3, respectively (P \ .01). The severity and audiogram pattern of the hearing loss are shown in Table 3. The most common audiogram pattern was the flat type (56%), followed by the total hearing loss type (20%) and low-tone hearing loss type (14%). The hightone hearing loss type was rare (9%). Fifty-eight (32%) patients showed severe hearing loss on the initial audiogram in the lesion ear. Fifty-six (31%) patients had moderate hearing loss, and 38 (21%) patients had mild hearing loss, whereas 29 (16%) patients had profound hearing loss.
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Table 3. Factors That Influence Outcome after the Treatment of Sudden Sensorineural Hearing Loss. Outcome
Age, y, mean 6 SD Sex, male/female Side, right/left Duration from onset to treatment, d Diabetes mellitus, n (%) Hypertension, n (%) Hyperlipidemia, n (%) Metabolic syndrome, n (%) Smoking, n (%) Drinking, n (%) Symptoms, n (%) Vertigo Dizziness Tinnitus Fullness Hearing loss pattern, n (%) Low High Flat Total Hearing loss severity, n (%) Mild Moderate Severe Profound
Good (n = 104)
Poor (n = 77)
Total (n = 181)
48.0 6 13.8 54/50 52/52 5.1 6 3.8 10 (10) 42 (40) 24 (23) 47 (45) 20 (19) 13 (13)
49.7 6 14.4 37/40 39/38 4.7 6 4.3 10 (65) 29 (38) 19 (25) 32 (42) 8 (10) 8 (10)
20 (19) 32 (31) 97 (93) 63 (61)
33 (43) 23 (30) 66 (86) 44 (57)
53 55 163 107
(29) (30) (90) (59)
24 (23) 13 (13) 60 (57) 7 (7)
2 (3) 4 (5) 42 (54) 29 (38)
26 17 102 36
(14) (9) (56) (20)
91/90 91/90 4.9 6 4.0 20 (11) 71 (39) 43 (24) 79 (44) 28 (15) 21 (12)
P Value .42a .61b .93b .59a .47b .71b .80b .63b .10b .66b \.01b .90b .09b .64b \.01c
\.01b 28 (27) 38 (36) 31 (30) 7 (7)
10 (13) 18 (23) 27 (35) 22 (29)
38 56 58 29
(21) (31) (32) (16)
a
t test. x test. c Fisher exact test. b 2
Prognostic Factors of SSNHL After treatment, 104 (57.5%) patients had a good hearing outcome, while 77 (42.5%) patients had a poor hearing outcome (Table 1). The age, sex, lesion side, and duration from onset to treatment showed no significant difference between the good and poor outcome groups. Smoking, drinking alcohol, diabetes mellitus, hypertension, hyperlipidemia, and MetS were not correlated with hearing outcome. Some of the patients had associated symptoms such as vertigo (29%), dizziness (30%), tinnitus (90%), and aural fullness (59%). None of the presenting symptoms had a significant impact on the hearing outcome except vertigo (P \ .01). After adjusting for age, sex, duration from onset to treatment, vertigo, hearing loss pattern, and hearing loss severity, multivariate logistic regression analysis revealed that vertigo (aOR = 2.39, 95% CI = 1.13~5.13, P = .02) and hearing loss pattern (P \ .01) are related to a poor outcome, as listed in Table 4. The total (aOR = 137.02, 95% CI = 12.30~3917.25, P \ .01) and flat (aOR = 9.45, 95% CI = 2.16~69.34, P \ .01) hearing loss patterns had poor prognoses compared with the low-tone hearing loss pattern. Hearing loss severity was
not a significant predictive outcome factor after adjustment (P = .66). If we used the 4 frequencies included, 500, 1000, 2000, and 3000 Hz, of pretreatment PTA to calculate the severity of pretreatment hearing loss, the results in Table 4 would not change. The P value of vertigo was .03 (aOR = 2.35, 95% CI = 1.11-5.06), of hearing loss pattern was \.01, and of hearing loss severity was .62.
Discussion To the best of our knowledge, this study is the first attempt to investigate the influence of MetS on the risk of SSNHL. Our results indicate that MetS increases the risk of SSNHL. The MetS patients have a 3.54-fold increased risk of acquiring SSNHL after adjusting for age, sex, smoking, diabetes mellitus, hypertension, and hyperlipidemia. With increased numbers of MetS components, the risk of SSNHL increases. MetS is a condition that involves a clustering of risk factors, including visceral obesity, prehypertension, prediabetes, and prehyperlipidemia. The MetS status seems to be more predictive of SSNHL than diabetes mellitus, hypertension, or hyperlipidemia alone.
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Table 4. Multivariate Logistic Regression Analysis of the Results of Treatment on Hearing Outcome.a Outcome
Vertigo, n (%) Yes No Hearing loss pattern, n (%) Low High Flat Total Hearing loss severity, n (%) Mild Moderate Severe Profound
Good (n = 104)
Poor (n = 77)
aORb
95% CI
20 (19) 84 (81)
33 (43) 44 (57)
2.39 1 (ref)
1.13-5.13
24 13 60 7
(23) (13) (57) (7)
2 (3) 4 (5) 42 (54) 29 (38)
1 (ref) 3.52 9.45 137.02
28 38 31 7
(27) (36) (30) (7)
10 (13) 18 (23) 27 (35) 22 (29)
P Value
.02 \.01
0.58-28.83 2.16-69.34 12.30-3917.25
.17 \.01 \.01 .66
a
Adjusted odd ratios (aOR) of poor outcome by age, sex, duration from onset to treatment, vertigo, hearing loss pattern, and hearing loss severity among the 181 sudden sensorineural hearing loss patients. b Adjusted for age, sex, duration from onset to treatment, vertigo, hearing loss pattern, and hearing loss severity. ref = reference category.
Mottillo et al5 reported that MetS increased the risk of stroke (RR = 2.27) and myocardial infarction (RR = 1.99). Previous studies have revealed that SSNHL increases the risk of stroke and acute myocardial infarction.8,16,17 After adjusting for patient demographic characteristics and individual cardiovascular risk factors, the risk of stroke and acute myocardial infarction during the 5-year follow-up period was 60% and 50%, respectively, increasing the risk among SSNHL patients (P \ .001).16,17 Diabetes mellitus was significantly associated with an increased risk of developing SSNHL. The incidence of SSNHL was 1.54-fold higher in the diabetic group than in the nondiabetic group.18 Diabetes mellitus, hypertension, hyperlipidemia, and smoking are known risk factors for systemic atherosclerosis and have also been noted as potential risk factors for SSNHL.6,19 The actual mechanisms contributing to the increased risk of SSNHL in the presence of MetS are still unclear. The vascular component is one of the causes of SSNHL. We speculate that diabetes mellitus, hypertension, and hyperlipidemia may cause vascular problems that can lead to SSNHL. Lin et al16 found that the prevalence of diabetes mellitus, hypertension, and hyperlipidemia in Taiwan was higher in SSNHL patients (10.1%, 8.4%, and 0.8%, respectively) than in controls (4.3%, 5.7%, and 0.3%, respectively). Another study in Taiwan revealed that the prevalence levels of diabetes mellitus and hyperlipidemia were higher in SSNHL patients (12.64% and 7.54%, respectively) than in controls (7.76% and 4.87%, respectively), which was not true for hypertension (21.99% for both SSNHL patients and controls).8 These 2 studies in Taiwan evaluated the National Health Insurance Research Database, which was established in 1995 and covers 99% of the 25 million people in Taiwan. In our study, we found that the prevalence of MetS and hypertension is higher in SSNHL patients than controls
(43.7% vs 19.3% and 39.2% vs 23.8%, respectively), which is not true for diabetes mellitus and hyperlipidemia (11.0% vs 7.2% and 23.8% vs 19.3%, respectively). The overall prevalence rates of diabetes mellitus, hypertension, hyperlipidemia, and MetS in 2007, which were reported by Health Promotion Administration, Ministry of Health and Welfare of Taiwan, in 2011, were 9.5%, 27.7%, 19.9%, and 21.8%, respectively (http://www.hpa.gov.tw/BHPNet/Portal/File/ThemeDocFile/201 102140310199776/2007%e4%b8%89%e9%ab%98%e5%b0% 88%e8%bc%af_%e7%b0%a1%e5%96%ae%e7%89%88_ 20121218%e4%bf%ae.pdf). The prevalence rates of diabetes mellitus, hypertension, hyperlipidemia, and MetS in the control group (7.2%, 23.8%, 19.3%, 19.3%) in our study are similar to the general population data reported by the Health Promotion Administration, Ministry of Health and Welfare of Taiwan (9.5%, 27.7%, 19.9%, 21.8%). Given the difference in the characteristics of the study participants, our results provide a clinically relevant complement to previously published studies. The outcome of SSNHL remains a controversial issue and is usually assessed by analyses of factors that correlate with hearing improvement. The results were inconsistent due to the various therapeutic strategies and multiple outcome definitions for recovery. We used the recommendations of outcomes assessment in the ‘‘Clinical Practice Guideline: Sudden Hearing Loss’’ from the AAO-HNS in 2012 to justify the treatment success.1 Potential prognostic factors for SSNHL were evaluated in our study. All of the factors, such as age, sex, duration from onset to treatment, diabetes mellitus, hypertension, hyperlipidemia, MetS status, smoking, symptoms, hearing loss pattern, and hearing loss severity, were evaluated. We found that vertigo and hearing loss pattern (total and flat type) were poor prognostic factors for SSNHL after multivariate logistic regression analysis, as reported in previous studies.11,20-22 MetS, smoking, duration from onset to treatment,
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and hearing loss severity did not influence the outcome in our study. Using the low-tone hearing loss pattern as a reference, the total hearing loss pattern had the worst outcome, followed by the flat hearing loss pattern. This study is limited by its retrospective nature. A multicenter study would be needed to confirm these findings. This study was conducted in Taiwan, and we wonder whether the findings are generalizable to other countries. Our findings support the hypothesis that MetS is an independent risk factor of SSNHL. Thus, patients with SSNHL should be screened for MetS component factors to prevent cardiovascular and cerebrovascular disease in the future.
Conclusion This study revealed an association between MetS and SSNHL. Patients with MetS seem to have a higher risk of developing SSNHL. The risk of developing SSNHL tends to increase with an increasing number of MetS components. Our data also reveal that vertigo and the total hearing loss pattern are poor prognostic factors for SSNHL patients. Further studies are needed to confirm the true effects of the mechanism. Acknowledgments The authors thank the Statistical Analysis Laboratory, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, for their assistance.
Author Contributions Chen-Yu Chien, collected data, wrote article; Shu-Yu Tai, analyzed data, drafting; Ling-Feng Wang, collected data, drafting; Edward Hsi, analyzed data, drafting; Ning-Chia Chang, collected data, drafting; Ming-Tsang Wu, designed study, revised article; Kuen-Yao Ho, designed study, revised article.
Disclosures Competing interests: None. Sponsorships: None. Funding source: This study was supported by grants from the Kaohsiung Medical University Hospital (10115 and 10203), and Kaohsiung Municipal Hsiao-Kang Hospital (Kmhk-102-016), no role in study.
References 1. Stachler RJ, Chandrasekhar SS, Archer SM, et al. Clinical practice guideline: sudden hearing loss. Otolaryngol Head Neck Surg. 2012;146:S1-S35. 2. Wu CS, Lin HC, Chao PZ. Sudden sensorineural hearing loss: evidence from Taiwan. Audiol Neurootol. 2006;11:151-156. 3. Chien CY, Chang NC, Tai SY, et al. Heat shock protein 70 gene polymorphisms in sudden sensorineural hearing loss. Audiol Neurootol. 2012;17:381-385. 4. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287: 356-359.
5. Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010;56:1113-1132. 6. Lin RJ, Krall R, Westerberg BD, et al. Systematic review and meta-analysis of the risk factors for sudden sensorineural hearing loss in adults. Laryngoscope. 2012;122:624-635. 7. Mosnier I, Stepanian A, Baron G, et al. Cardiovascular and thromboembolic risk factors in idiopathic sudden sensorineural hearing loss: a case-control study. Audiol Neurootol. 2011;16: 55-66. 8. Lin C, Lin SW, Lin YS, et al. Sudden sensorineural hearing loss is correlated with an increased risk of acute myocardial infarction: a population-based cohort study. Laryngoscope. 2013;123:2254-2258. 9. Rudack C, Langer C, Stoll W, et al. Vascular risk factors in sudden hearing loss. Thromb Haemost. 2006;95:454-461. 10. Weng SF, Chen YS, Liu TC, et al. Prognostic factors of sudden sensorineural hearing loss in diabetic patients. Diabetes Care. 2004;27:2560-2561. 11. Sheehy JL. Vasodilator therapy in sensory-neural hearing loss. Laryngoscope. 1960;70:885-914. 12. Executive Summary of the Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497. 13. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363:157-163. 14. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome—a new worldwide definition. Lancet. 2005;366:1059-1062. 15. Sharma SK, Agrawal S, Damodaran D, et al. CPAP for the metabolic syndrome in patients with obstructive sleep apnea. N Engl J Med. 2011;365:2277-2286. 16. Lin HC, Chao PZ, Lee HC. Sudden sensorineural hearing loss increases the risk of stroke: a 5-year follow-up study. Stroke. 2008;39:2744-2748. 17. Keller JJ, Wu CS, Kang JH, et al. Association of acute myocardial infarction with sudden sensorineural hearing loss: a populationbased case-control study. Audiol Neurootol. 2013;18:3-8. 18. Lin SW, Lin YS, Weng SF, et al. Risk of developing sudden sensorineural hearing loss in diabetic patients: a populationbased cohort study. Otol Neurotol. 2012;33:1482-1488. 19. Chau JK, Lin JR, Atashband S, et al. Systematic review of the evidence for the etiology of adult sudden sensorineural hearing loss. Laryngoscope. 2010;120:1011-1021. 20. Chang NC, Ho KY, Kuo WR. Audiometric patterns and prognosis in sudden sensorineural hearing loss in southern Taiwan. Otolaryngol Head Neck Surg. 2005;133:916-922. 21. Byl FM, Jr. Sudden hearing loss: eight years’ experience and suggested prognostic table. Laryngoscope. 1984;94:647-661. 22. Fukui M, Kitagawa Y, Nakamura N, et al. Idiopathic sudden hearing loss in patients with type 2 diabetes. Diabetes Res Clin Pract. 2004;63:205-11.
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Metabolic Syndrome Increases the Risk of Sudden Sensorineural Hearing Loss in Taiwan: A Case-Control Study
Otolaryngology– Head and Neck Surgery 1–7 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599815575713 http://otojournal.org
Chen-Yu Chien, MD1,2,3,4, Shu-Yu Tai, MD1,5,6, Ling-Feng Wang, MD2,3,7, Edward Hsi, PhD8, Ning-Chia Chang, MD, PhD2,9, Ming-Tsang Wu, MD, PhD1,5,10,11, and Kuen-Yao Ho, MD1,2,3
No sponsorships or competing interests have been disclosed for this article.
Abstract Objective. Sudden sensorineural hearing loss has been reported to be associated with diabetes mellitus, hypertension, and hyperlipidemia in previous studies. The aim of this study was to examine whether metabolic syndrome increases the risk of sudden sensorineural hearing loss in Taiwan. Study Design. A case-control study. Setting. Tertiary university hospital. Subjects and Methods. We retrospectively investigated 181 cases of sudden sensorineural hearing loss and 181 controls from the Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, in southern Taiwan from 2010 to 2012, comparing their clinical variables. We analyzed the relationship between metabolic syndrome and sudden sensorineural hearing loss. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III with Asian modifications. The demographic and clinical characteristics, audiometry results, and outcome were reviewed. Results. Subjects with metabolic syndrome had a 3.54-fold increased risk (95% confidence interval [CI] = 2.00-6.43, P \ .01) of having sudden sensorineural hearing loss compared with those without metabolic syndrome, after adjusting for age, sex, smoking, diabetes mellitus, hypertension, and hyperlipidemia. With increases in the number of metabolic syndrome components, the risk of sudden sensorineural hearing loss increased (P for trend \.01). Vertigo was associated with a poor outcome (P = .02; 95% CI = 1.13~5.13, adjusted odds ratio = 2.39). The hearing loss pattern may influence the outcome of sudden sensorineural hearing loss (P \.01). Conclusion. These results suggest that metabolic syndrome is an independent risk factor for sudden sensorineural hearing loss in Taiwan. Vertigo and total hearing loss were indicators of a poor outcome in sudden sensorineural hearing loss. Keywords sudden deafness, metabolic syndrome, outcome, vertigo
Received August 14, 2014; revised February 3, 2015; accepted February 11, 2015.
S
udden sensorineural hearing loss (SSNHL) is defined as a 30-dB loss over 3 continuous frequencies occurring in less than 3 days.1 The incidence rates per 100,000 people in Taiwan are 8.85 for men and 7.79 for women.2 The cause of this disease is still not clear, but the proposed causes include viral infection, vascular disease, autoimmunity, and genetic factors.2,3 Metabolic syndrome (MetS) is a cluster of common pathologies, including abdominal obesity, hypertension, insulin resistance, and dyslipidemia. MetS is associated with an increased risk of cardiovascular disease, myocardial infarction, stroke,
1 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Department of Otorhinolaryngology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 4 Department of Otorhinolaryngology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 6 Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 7 Department of Otorhinolaryngology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 8 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 9 Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 10 Department of Family Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 11 Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan
Corresponding Author: Kuen-Yao Ho, Department of Otorhinolaryngology, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung 807, Taiwan. Email: [email protected]
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diabetes mellitus, and cardiovascular disease mortality.4,5 Acquired and inherited cardiovascular risk factors have been associated with an increased risk of developing SSNHL.6 A personal or familial history of cardiovascular events, including coronary insufficiency, myocardial infarction, stroke, and transient ischemic attack, have also been found to be more prevalent in patients with SSNHL than the control group.7,8 Several studies have identified microvascular damage in the pathology of SSNHL.9 Diabetes is a risk factor for SSNHL, possibly due to microangiopathy.10 With its associated microangiopathy, MetS could be a risk factor for SSNHL. However, few research studies have evaluated the association between MetS and SSNHL. We hypothesized that MetS may increase the risk of SSNHL. Previous studies of SSNHL did not focus on MetS patients. We conducted a retrospective review to elucidate the influence of MetS in SSNHL patients and the prognostic factors for SSNHL patients.
Materials and Methods Study Population We recruited 181 patients with SSNHL and 181 controls at the Kaohsiung Medical University Hospital between October 2010 and September 2012. The diagnostic criteria for SSNHL included sensorineural hearing loss of at least 30 dB in 3 contiguous frequencies using a pure-tone audiogram with an onset within 3 days.1-3 All patients denied previous episodes of SSNHL, and none received treatments before taking the hearing and blood tests. The exclusion criteria were hearing losses caused by acoustic neuroma, central lesions, Meniere’s disease, multiple sclerosis, infectious diseases, trauma, medication, noise, or prior ear surgery. Audiometric tests, including initial and follow-up pure-tone audiometry, speech audiometry, tympanometry, stapedial reflexes, auditory brainstem-evoked responses, and magnetic resonance imaging (to exclude acoustic neuroma) were performed in the SSNHL patients to verify the hearing loss was sensorineural hearing loss. The controls visited our department of otorhinolaryngology for health examination. Controls lacking a history of hearing loss or any other ear disorders were enrolled. The eligible controls were randomly selected and frequency matched with the case patients based on age and sex. Information on demographic characteristics was collected. A history of hypertension was defined as positive in persons taking antihypertension drugs to control blood pressure and a history of diabetes mellitus in those who had received drug or insulin therapy to control blood sugar. All 181 patients were hospitalized for 1 week. They received oral prednisolone (1 mg/kg for 2 days), which was tapered down over the following 2 weeks. They also received intravenous (1000 mL) low-molecular-weight dextran (MW 40,000, 10% 500 mL/Bot) daily during hospitalization. All patients underwent routine blood and biochemistry tests before treatment. This protocol was the standard treatment for SSNHL in our hospital.
The pattern of the audiogram was categorized by Sheehy classification.11 The audiograms were categorized into 4 patterns, which were low tone, high tone, flat, and total hearing loss types. The severity of hearing loss was evaluated with the average hearing level at 5 frequencies (250, 500, 1000, 2000, and 4000 Hz) on the pure-tone audiogram performed when SSNHL was diagnosed. The 5 frequencies were used for the hearing loss severity assessment to specifically categorize them under the Sheehy classification. The severity was then categorized into 1 of 4 grades based on the initial audiogram, which included mild (hearing loss of less than 40 dB), moderate (hearing loss of more than 40 dB but not exceeding 70 dB), severe (hearing loss of more than 70 dB but not exceeding 90 dB), and profound (hearing loss of more than 90 dB). Hearing improvement was evaluated by comparing the patient’s last follow-up audiogram with the audiogram taken when SSNHL was diagnosed. All patients were followed up at for least 3 months. The pure-tone average (PTA) was calculated by taking 4 frequencies, 500, 1000, 2000, and 3000 Hz. We followed the outcome assessment recommendations in ‘‘Clinical Practice Guideline: Sudden Hearing Loss’’ from the American Academy of Otolaryngology—Head and Neck Surgery (AAO-HNS) in 2012 to justify the treatment success.1 In this guideline, serviceable hearing is defined as a PTA 50 dB and word recognition score (WRS) 50% according to the American Academy of Otolaryngology— Head and Neck Surgery Foundation Hearing Classification System. The grades ‘‘complete recovery’’ and ‘‘meaningful partial recovery’’ were considered to have good outcome, whereas ‘‘not meaningful partial recovery’’ and ‘‘no recovery’’ were considered to have poor outcome.
Definition of MetS MetS was defined according to the National Cholesterol Education Program’s Adult Treatment Panel III criteria,12 with a cutoff value for defining abdominal obesity of 90 cm for males and 80 cm for females, as recommended by the World Health Organization guidelines for Chinese patients.13,14 Subjects with MetS must fulfill 3 or more of the following criteria: (1) waist circumference of 90 cm in males and 80 cm in females, (2) blood pressure of 130/85 mm Hg or receiving antihypertensive treatment, (3) fasting glucose of 100 mg/dL or known treatment for diabetes mellitus, (4) serum triglycerides of 150 mg/dL, and (5) high-density lipoprotein (HDL) cholesterol levels \40 mg/dL in males and \50 mg/dL in females. Individual criteria were scored, and the scores were totaled; a sum of 3 or greater was indicative of the presence of MetS.15 To evaluate the prognostic factors in SSNHL patients, we analyzed the differences in the distribution of the parameters between the good and poor outcome groups. The parameters included the following clinical and audiological variables: age, sex, side of lesion, duration from onset to treatment, diabetes mellitus, hypertension, hyperlipidemia, MetS status, smoking, drinking, vestibular symptoms, pattern of audiogram, and severity of hearing loss.
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Table 1. Basic Characteristics of the Subjects Included in the Study. Sudden Sensorineural Hearing Loss (n = 181)
Controls (n = 181)
P Value
48.7 6 14.1 91/90 28 (15.5) 20 (11.0) 71 (39.2) 43 (23.8) 84.2 6 11.6 130.0 6 20.5 78.1 6 12.6 123.7 6 40.1 104 (84-136)
46.4 6 11.0 99/82 26 (14.4) 13 (7.2) 43 (23.8) 35 (19.3) 78.7 6 9.8 122.0 6 15.9 75.1 6 12.4 98.8 6 17.2 91 (64-131)
.08a .40b .77b .20b \.01b .31b \.01a \.01a .02a \.01a \.01c
49 (38-57)
53 (46-63)
\.01c
Age, y, mean 6 SD Sex, male/female, n Smoking, n (%) Diabetes mellitus, n (%) Hypertension, n (%) Hyperlipidemia, n (%) Waist circumference, mean 6 SD Systolic blood pressure, mm Hg, mean 6 SD Diastolic blood pressure, mm Hg (mean 6 SD) Fasting glucose, mg/dL Triglyceride, mg/dL, median (25th-75th percentiles) High-density lipoprotein cholesterol, mg/dL, median (25th-75th percentiles) Side, right/left Outcome, n (%) Complete recovery Partial recovery Meaningful Not meaningful No recovery Good Poor
91/90 84 (46.4) 47 (26.0) 20 (11.1) 27 (14.9) 50 (27.6) 104 (57.5) 77 (42.5)
a
t test. x test. C Wilcoxon rank sum test. b 2
Ethical Concerns This study was approved by the Institutional Review Board of Kaohsiung Medical University Hospital (approval No. KMUH-IRB-20120270).
Statistical Analysis Continuous variables are expressed as the mean 6 standard deviation (SD) or median (25th-75th percentiles), as appropriate. Categorical data are expressed as frequencies. To compare the distributions of the baseline characteristics between subjects with and without SSNHL, among SSNHL patients with good and poor outcome, the t test, x2 test, Wilcoxon rank sum test, and Fisher exact test were used. Multivariate logistic regression analysis was used to calculate the adjusted odds ratios (aORs) and 95% confidence interval (95% CI) of the outcome factors of SSNHL. The JMP version 9.0 Stat View version 5.0 (SAS Institute Inc) was used for statistical analyses. All statistical tests were 2 sided, and P \ .05 was considered statistically significant.
Results Characteristics of the Study Participants The basic characteristics of the study subjects are listed in Table 1. The mean and SD of age were 48.7 6 14.1 years
in the 181 SSNHL patients (91 male and 90 female) and 46.4 6 11.0 years in the 181 controls (99 male and 82 female). According to the study design, there was no difference in the age and sex for the SSNHL versus control groups. The right ear was affected in 91 (50%) patients and the left in 90 (50%) patients. No side predominance was noted. The prevalence of hypertension was higher in the SSNHL patients than in the controls (P \ .01). The prevalence rates of smoking, diabetes mellitus, and hyperlipidemia were similar in the SSNHL patients and controls. The average waist circumference, systolic blood pressure, diastolic blood pressure, fasting glucose level, and triglyceride level were higher, whereas HDL cholesterol level was lower in the SSNHL patients than in the controls.
MetS and SSNHL The MetS characteristics for the SSNHL patients and controls are shown in Table 2. The 3 components of MetS including waist circumference (WC), blood pressure 130/ 85 mm Hg or had taken antihypertensive drugs, and fasting plasma glucose 100 mg/dL or had taken antidiabetic drugs were all significantly higher in SSNHL patients than in control group. The HDL cholesterol was significantly lower in SSNHL patients than in the control group. The triglyceride
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Table 2. Prevalence among Subjects of the Components of Metabolic Syndrome as Defined by National Cholesterol Education Program Adult Treatment Panel III with Asian Modification.
Waist circumference, n (%) Male 90 cm Female 80 cm Blood pressure 130/85 mm Hg or had taken antihypertensive drugs, n (%) Fasting glucose 100 mg/dL or had taken antidiabetic drugs, n (%) Triglyceride 150 mg/dL, n (%) HDL cholesterol, n (%) Male \40 mg/dL Female \50 mg/dL Metabolic syndrome, n (%)
SSNHL (n = 181)
Controls (n = 181)
P Value
78 (43.1)
38 (21.0)
\.01b
71 67 32 29
(39.2) (37.0) (17.7) (16.0)
.01b \.01b 1.00b \.01b
35 (19.3)
\.01c
94 142 32 70
(51.9) (78.4) (17.7) (38.7)
79 (43.7)
aORa (95% CI)
3.54 (2.00-6.43)
Abbreviations: aOR, adjusted odds ratio; HDL, high-density lipoprotein; SSNHL, sudden sensorineural hearing loss. a Age, sex, smoking, diabetes mellitus, hypertension, and hyperlipidemia adjusted. b 2 x test. c Multivariate logistic regression analysis.
Initial Presentations in the Audiometry and Hearing Improvement in Follow-up
Figure 1. Probability (odds ratio, 95% confidence interval) of sudden sensorineural hearing loss according to the number of metabolic syndrome components. Adjusted for age, sex, smoking, diabetes mellitus, hypertension, and hyperlipidemia; P for trend \.01.
component was similar in SSNHL patients and the control group. The prevalence of MetS was higher in SSNHL patients than in controls (43.7% vs 19.3%) using the National Cholesterol Education Program Adult Treatment Panel III with Asian modification criteria. After adjusting for age, sex, smoking, diabetes mellitus, hypertension, and hyperlipidemia, participants with MetS had a significantly increased risk of developing SSNHL (aOR = 3.54, 95% CI = 2.00~6.43, P \ .01). As depicted in Figure 1, the risk of developing SSNHL trended to increase stepwise as the number of MetS components increased (P for trend \.01).
The pretreatment PTAs (mean 6 SD) of the affected ear were 58.5 6 23.4 dB in good and 76.0 6 22.2 dB in poor outcome (P \ .01). The posttreatment PTAs (mean 6 SD) of the affected ear were 26.3 6 14.3 dB in good and 69.7 6 19.6 dB in poor outcome (P \ .01). The average hearing gain (mean 6 SD) of the affected ear in good and poor outcome were 32.2 6 19.4 dB and 6.3 6 16.8 dB, respectively (P \ .01). The hearing status of the unaffected ear in the SSNHL group was 19.7 6 10.1 dB. The hearing status of the control group was 18.2 6 6.9 dB in the right ear and 18.5 6 6.4 dB in the left ear. Each of the right (P = .11) and left (P = .20) ears of the control group had no significant difference compared with the unaffected ear in the SSNHL group. The pretreatment WRSs (%, mean 6 SD) of the affected ear were 53.0 6 25.9 in good and 27.1 6 25.5 in poor outcome (P \ .01). The posttreatment WRSs (%, mean 6 SD) of the affected ear were 91.1 6 9.5 in good and 38.0 6 22.0 in poor outcome (P \ .01). The average WRS gains (%, mean 6 SD) of the affected ear in good and poor outcome were 38.1 6 22.9 and 10.9 6 18.3, respectively (P \ .01). The severity and audiogram pattern of the hearing loss are shown in Table 3. The most common audiogram pattern was the flat type (56%), followed by the total hearing loss type (20%) and low-tone hearing loss type (14%). The hightone hearing loss type was rare (9%). Fifty-eight (32%) patients showed severe hearing loss on the initial audiogram in the lesion ear. Fifty-six (31%) patients had moderate hearing loss, and 38 (21%) patients had mild hearing loss, whereas 29 (16%) patients had profound hearing loss.
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Table 3. Factors That Influence Outcome after the Treatment of Sudden Sensorineural Hearing Loss. Outcome
Age, y, mean 6 SD Sex, male/female Side, right/left Duration from onset to treatment, d Diabetes mellitus, n (%) Hypertension, n (%) Hyperlipidemia, n (%) Metabolic syndrome, n (%) Smoking, n (%) Drinking, n (%) Symptoms, n (%) Vertigo Dizziness Tinnitus Fullness Hearing loss pattern, n (%) Low High Flat Total Hearing loss severity, n (%) Mild Moderate Severe Profound
Good (n = 104)
Poor (n = 77)
Total (n = 181)
48.0 6 13.8 54/50 52/52 5.1 6 3.8 10 (10) 42 (40) 24 (23) 47 (45) 20 (19) 13 (13)
49.7 6 14.4 37/40 39/38 4.7 6 4.3 10 (65) 29 (38) 19 (25) 32 (42) 8 (10) 8 (10)
20 (19) 32 (31) 97 (93) 63 (61)
33 (43) 23 (30) 66 (86) 44 (57)
53 55 163 107
(29) (30) (90) (59)
24 (23) 13 (13) 60 (57) 7 (7)
2 (3) 4 (5) 42 (54) 29 (38)
26 17 102 36
(14) (9) (56) (20)
91/90 91/90 4.9 6 4.0 20 (11) 71 (39) 43 (24) 79 (44) 28 (15) 21 (12)
P Value .42a .61b .93b .59a .47b .71b .80b .63b .10b .66b \.01b .90b .09b .64b \.01c
\.01b 28 (27) 38 (36) 31 (30) 7 (7)
10 (13) 18 (23) 27 (35) 22 (29)
38 56 58 29
(21) (31) (32) (16)
a
t test. x test. c Fisher exact test. b 2
Prognostic Factors of SSNHL After treatment, 104 (57.5%) patients had a good hearing outcome, while 77 (42.5%) patients had a poor hearing outcome (Table 1). The age, sex, lesion side, and duration from onset to treatment showed no significant difference between the good and poor outcome groups. Smoking, drinking alcohol, diabetes mellitus, hypertension, hyperlipidemia, and MetS were not correlated with hearing outcome. Some of the patients had associated symptoms such as vertigo (29%), dizziness (30%), tinnitus (90%), and aural fullness (59%). None of the presenting symptoms had a significant impact on the hearing outcome except vertigo (P \ .01). After adjusting for age, sex, duration from onset to treatment, vertigo, hearing loss pattern, and hearing loss severity, multivariate logistic regression analysis revealed that vertigo (aOR = 2.39, 95% CI = 1.13~5.13, P = .02) and hearing loss pattern (P \ .01) are related to a poor outcome, as listed in Table 4. The total (aOR = 137.02, 95% CI = 12.30~3917.25, P \ .01) and flat (aOR = 9.45, 95% CI = 2.16~69.34, P \ .01) hearing loss patterns had poor prognoses compared with the low-tone hearing loss pattern. Hearing loss severity was
not a significant predictive outcome factor after adjustment (P = .66). If we used the 4 frequencies included, 500, 1000, 2000, and 3000 Hz, of pretreatment PTA to calculate the severity of pretreatment hearing loss, the results in Table 4 would not change. The P value of vertigo was .03 (aOR = 2.35, 95% CI = 1.11-5.06), of hearing loss pattern was \.01, and of hearing loss severity was .62.
Discussion To the best of our knowledge, this study is the first attempt to investigate the influence of MetS on the risk of SSNHL. Our results indicate that MetS increases the risk of SSNHL. The MetS patients have a 3.54-fold increased risk of acquiring SSNHL after adjusting for age, sex, smoking, diabetes mellitus, hypertension, and hyperlipidemia. With increased numbers of MetS components, the risk of SSNHL increases. MetS is a condition that involves a clustering of risk factors, including visceral obesity, prehypertension, prediabetes, and prehyperlipidemia. The MetS status seems to be more predictive of SSNHL than diabetes mellitus, hypertension, or hyperlipidemia alone.
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Table 4. Multivariate Logistic Regression Analysis of the Results of Treatment on Hearing Outcome.a Outcome
Vertigo, n (%) Yes No Hearing loss pattern, n (%) Low High Flat Total Hearing loss severity, n (%) Mild Moderate Severe Profound
Good (n = 104)
Poor (n = 77)
aORb
95% CI
20 (19) 84 (81)
33 (43) 44 (57)
2.39 1 (ref)
1.13-5.13
24 13 60 7
(23) (13) (57) (7)
2 (3) 4 (5) 42 (54) 29 (38)
1 (ref) 3.52 9.45 137.02
28 38 31 7
(27) (36) (30) (7)
10 (13) 18 (23) 27 (35) 22 (29)
P Value
.02 \.01
0.58-28.83 2.16-69.34 12.30-3917.25
.17 \.01 \.01 .66
a
Adjusted odd ratios (aOR) of poor outcome by age, sex, duration from onset to treatment, vertigo, hearing loss pattern, and hearing loss severity among the 181 sudden sensorineural hearing loss patients. b Adjusted for age, sex, duration from onset to treatment, vertigo, hearing loss pattern, and hearing loss severity. ref = reference category.
Mottillo et al5 reported that MetS increased the risk of stroke (RR = 2.27) and myocardial infarction (RR = 1.99). Previous studies have revealed that SSNHL increases the risk of stroke and acute myocardial infarction.8,16,17 After adjusting for patient demographic characteristics and individual cardiovascular risk factors, the risk of stroke and acute myocardial infarction during the 5-year follow-up period was 60% and 50%, respectively, increasing the risk among SSNHL patients (P \ .001).16,17 Diabetes mellitus was significantly associated with an increased risk of developing SSNHL. The incidence of SSNHL was 1.54-fold higher in the diabetic group than in the nondiabetic group.18 Diabetes mellitus, hypertension, hyperlipidemia, and smoking are known risk factors for systemic atherosclerosis and have also been noted as potential risk factors for SSNHL.6,19 The actual mechanisms contributing to the increased risk of SSNHL in the presence of MetS are still unclear. The vascular component is one of the causes of SSNHL. We speculate that diabetes mellitus, hypertension, and hyperlipidemia may cause vascular problems that can lead to SSNHL. Lin et al16 found that the prevalence of diabetes mellitus, hypertension, and hyperlipidemia in Taiwan was higher in SSNHL patients (10.1%, 8.4%, and 0.8%, respectively) than in controls (4.3%, 5.7%, and 0.3%, respectively). Another study in Taiwan revealed that the prevalence levels of diabetes mellitus and hyperlipidemia were higher in SSNHL patients (12.64% and 7.54%, respectively) than in controls (7.76% and 4.87%, respectively), which was not true for hypertension (21.99% for both SSNHL patients and controls).8 These 2 studies in Taiwan evaluated the National Health Insurance Research Database, which was established in 1995 and covers 99% of the 25 million people in Taiwan. In our study, we found that the prevalence of MetS and hypertension is higher in SSNHL patients than controls
(43.7% vs 19.3% and 39.2% vs 23.8%, respectively), which is not true for diabetes mellitus and hyperlipidemia (11.0% vs 7.2% and 23.8% vs 19.3%, respectively). The overall prevalence rates of diabetes mellitus, hypertension, hyperlipidemia, and MetS in 2007, which were reported by Health Promotion Administration, Ministry of Health and Welfare of Taiwan, in 2011, were 9.5%, 27.7%, 19.9%, and 21.8%, respectively (http://www.hpa.gov.tw/BHPNet/Portal/File/ThemeDocFile/201 102140310199776/2007%e4%b8%89%e9%ab%98%e5%b0% 88%e8%bc%af_%e7%b0%a1%e5%96%ae%e7%89%88_ 20121218%e4%bf%ae.pdf). The prevalence rates of diabetes mellitus, hypertension, hyperlipidemia, and MetS in the control group (7.2%, 23.8%, 19.3%, 19.3%) in our study are similar to the general population data reported by the Health Promotion Administration, Ministry of Health and Welfare of Taiwan (9.5%, 27.7%, 19.9%, 21.8%). Given the difference in the characteristics of the study participants, our results provide a clinically relevant complement to previously published studies. The outcome of SSNHL remains a controversial issue and is usually assessed by analyses of factors that correlate with hearing improvement. The results were inconsistent due to the various therapeutic strategies and multiple outcome definitions for recovery. We used the recommendations of outcomes assessment in the ‘‘Clinical Practice Guideline: Sudden Hearing Loss’’ from the AAO-HNS in 2012 to justify the treatment success.1 Potential prognostic factors for SSNHL were evaluated in our study. All of the factors, such as age, sex, duration from onset to treatment, diabetes mellitus, hypertension, hyperlipidemia, MetS status, smoking, symptoms, hearing loss pattern, and hearing loss severity, were evaluated. We found that vertigo and hearing loss pattern (total and flat type) were poor prognostic factors for SSNHL after multivariate logistic regression analysis, as reported in previous studies.11,20-22 MetS, smoking, duration from onset to treatment,
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and hearing loss severity did not influence the outcome in our study. Using the low-tone hearing loss pattern as a reference, the total hearing loss pattern had the worst outcome, followed by the flat hearing loss pattern. This study is limited by its retrospective nature. A multicenter study would be needed to confirm these findings. This study was conducted in Taiwan, and we wonder whether the findings are generalizable to other countries. Our findings support the hypothesis that MetS is an independent risk factor of SSNHL. Thus, patients with SSNHL should be screened for MetS component factors to prevent cardiovascular and cerebrovascular disease in the future.
Conclusion This study revealed an association between MetS and SSNHL. Patients with MetS seem to have a higher risk of developing SSNHL. The risk of developing SSNHL tends to increase with an increasing number of MetS components. Our data also reveal that vertigo and the total hearing loss pattern are poor prognostic factors for SSNHL patients. Further studies are needed to confirm the true effects of the mechanism. Acknowledgments The authors thank the Statistical Analysis Laboratory, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, for their assistance.
Author Contributions Chen-Yu Chien, collected data, wrote article; Shu-Yu Tai, analyzed data, drafting; Ling-Feng Wang, collected data, drafting; Edward Hsi, analyzed data, drafting; Ning-Chia Chang, collected data, drafting; Ming-Tsang Wu, designed study, revised article; Kuen-Yao Ho, designed study, revised article.
Disclosures Competing interests: None. Sponsorships: None. Funding source: This study was supported by grants from the Kaohsiung Medical University Hospital (10115 and 10203), and Kaohsiung Municipal Hsiao-Kang Hospital (Kmhk-102-016), no role in study.
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