Abstract
The aim of the present study was to investigate whether increased intima media thickness was associated with the severity of subjective non-pulsatile tinnitus and hearing loss. Data of the patients who came to Otorhinolaryngology Department of Isparta Government Hospital with subjective non-pulsatile tinnitus complaint, between January 2012 and June 2013, were evaluated retrospectively. A total of 215 patients were included in the present study. Hearing tests, biochemical analysis, tinnitus handicap inventory (THI), visual analogue scale (VAS) and doppler ultrasonography results of the patients were reviewed and recorded. The patients were classified into two groups as those having an increased intima media thickness and those having a normal intima media thickness. The said groups were compared with respect to age, gender, THI, VAS, hearing test findings and lipid values. Moreover, THI and VAS groups were compared with respect to intima-media thickness. In the group having increased intima-media thickness, THI and VAS average, frequency of hypertension, total cholesterol, low density lipoprotein and triglyceride averages and mean frequencies obtained by hearing test were significantly higher. Comparison of THI and VAS groups showed that intima-media thickness was significantly different between those having a mild tinnitus and those having a severe tinnitus. Increased intima-media thickness was associated with the severity of subjective non-pulsatile tinnitus and hearing loss. For this reason, the carotid system should be examined in subjective non-pulsatile tinnitus patients.
Keywords: Atherosclerosis, Hearing loss, Intima-media thickness, Tinnitus
Introduction
Tinnitus is described as the perception of a noise inside one’s head in the absence of auditory stimulation [1]. Both genders are affected equally while 50 % of the cases are bilateral [2]. The prevalence of tinnitus has been reported to be 10–15 % in the adult population [3]. The prevalence of tinnitus shows a tendency to increase with age as follow: 7 % in the 3rd decade and 21 % in the 7th decade [4]. Tinnitus is generally divided into two groups as objective tinnitus (perceived by another individual) and subjective tinnitus (perceived only by the patient). Objective tinnitus is the perception of sounds transmitted to the cochlea or the middle ear by the bones. Subjective tinnitus is the perception of sounds caused by abnormal neural activity that is not evoked by sound [5]. Most cases of tinnitus are subjective.
Subjective tinnitus is generally caused by pathologies in the central nervous system including the central auditory nervous system [6]. Vascular pathologies are thought to be one of the possible contributing factors. The cochlea is sensitive to the changes in the blood flow and a limited impairment of perfusion causes dysfunction of the organ of corti [7]. Atherosclerosis, which is associated with cerebrovascular diseases and ischemic heart diseases, has been thought to be among factors causing tinnitus. An increase in intima-media thickness (IMT) is accepted as an early sign of atherosclerosis [8, 9]. Doppler ultrasound of carotid artery is commonly used to measure the narrowness of carotid artery and IMT. There is a limited data on the association between subjective non-pulsatile tinnitus and atherosclerotic disease of the carotid artery. For this reason, our aim was to evaluate whether intima-media thickness and serum lipid levels had an effect on the severity of tinnitus and hearing loss in patients with subjective non-pulsatile tinnitus.
Subjects and Methods
Data of the patients who came to Otorhinolaryngology Department of Isparta Government Hospital with subjective non-pulsatile tinnitus complaint, between January 2012 and June 2013, were evaluated retrospectively. For this type of study formal consent is not required. The inclusion criteria were having bilateral subjective non-pulsatile tinnitus for at least 6 months, having no previous treatments for tinnitus, having no external or middle ear infection, having no history of neuro-otological surgery, having no systemic disease other than controlled hypertension or diabetes and having no history of any diseases causing tinnitus such as Meniere disease, otosclerosis, sudden hearing loss and acoustic tumour. Moreover, those found to have conductive hearing loss, mixed hearing loss and A–r, A–d, C and B type curves at audiometry and tympanometry were excluded too. Data of a total of 215 patients composed of 131 (aged 51.11 ± 14.32) female and 84 (aged 52.33 ± 11.40) male individuals aged between 18 and 75 years old were studied.
Threshold assessments were made at 250, 500, 1000, 2000, 4000, 6000 and 8000 Hz using pure tone audiometry. The pure tone thresholds for statistical purposes were classified as follows: mean of all tested frequencies (mean total: arithmetic mean of pure tone thresholds at 250, 500, 1000, 2000, 3000, 4000, 6000 and 8000 Hz.), mean at high frequencies (mean acute: arithmetic mean of pure tone thresholds at 4000, 6000 and 8000 Hz), conventional tritone mean (mean tri: arithmetic mean of pure tone thresholds at 500, 1000 and 2000 Hz), quadritone mean (mean quadri: arithmetic mean of pure tone thresholds at 500, 1000, 2000 and 4000 Hz).
Serum lipid levels, complete blood count, folic acid and vitamin B12 values of the patients were examined. Total cholesterol (Total-C) level less than 200 mg/dl was considered normal and ≥200 mg/dl was considered high. High density lipoprotein (HDL) level less than 40 mg/dl was considered and ≥40 mg/dl was considered desired. Low density lipoprotein (LDL) level less than 130 mg/dl was considered desired and >130 mg/dl was considered high. Triglyceride (TG) level less than 200 mg/dl was considered normal and >200 mg/gl was considered high [10].
Tinnitus Handicap Inventory (THI) and visual analogue scale (VAS) were used to evaluate the severity of tinnitus. The answers of the THI composed of 25 questions prepared for Turkey were: No: 0, Sometimes: 2 and Yes: 4 [11]. The lowest score was 0 and the highest score was 100. The five severity scores were: 0–16 points negligible (I), 18–36 points mild (II), 38–56 points moderate (III), 58–76 points severe (IV) and 78–100 points catastrophic (V). VAS scores were grouped similarly: 1–2 points negligible (I), 3–4 points mild (II), 5–6 points moderate (III), 7–8 points severe (IV) and 9–10 points catastrophic (V).
In all the patients, ultrasound evaluation of carotid artery was performed using 7.5-MHz linear-type B-mode probe by a radiologist blind to the medical status of the patients. Tests were performed at supine position. Measurements of the common, internal and external carotid arteries were made at both sides while the maximum IMT was defined as the distance from the leading edge of the lumen–intima interface to the leading edge of the media–adventitia interface of the far wall. Increased blood vessel wall thickness was diagnosed when IMT ≥1 mm [12]. The patients were divided into two groups as those having a normal IMT (<1 mm) and those having an increased IMT (≥1 mm).
The statistical analyses were performed between those having normal and increased IMT and between THI and VAS groups. It was examined whether IMT was associated with age, gender, pure tone audiometry and whether there was a significant association between THI and VAS results. SPSS.17 package program was used for the statistical analysis. Kolmogorov–Smirnov test was used to check the normal distribution of the data. In the comparison of inter-groups, Chi square was used for the personal data while Independent Sample T test and Mann Whitney U test were used for the measurement data. The correlation analyses were conducted using Pearson correlation analysis. Percentage and mean ± standard deviation values were given as descriptive statistics. p < 0.05 was regarded as significant.
Informed form was obtained from the participants of the study and their details was collected from the recorded data of the patients’ files.
Results
Fifty-three (24.6 %) of the patients were found to have increased intima-media thickness. Characteristics of the patients are shown in Table 1. While the mean age of the group having increased IMT was 59.40 ± 7.79, the mean age was 49.04 ± 13.67 in the group having normal IMT (p = 0.001). IMT was found to be increased in 35.7 % of the males and 17.6 % of the females (p = 0.003). Mean IMT was 0.96 mm in males and 0.86 mm in females (p = 0.003). In both genders, IMT increased significantly with age (p = 0.0001; r = 0.36). In the group having increased IMT, the mean THI and VAS scores, frequency of hypertension, total cholesterol, mean LDL and triglyceride values (Table 1) and mean frequencies (mean total, mean acute, mean tri, mean quadri) obtained in hearing tests (Table 2) were significantly higher. There was a significant correlation between IMT and hearing test and between THI and VAS findings (Table 3).
Table 1.
Demographic data of patients having normal and abnormal IMT
| IMT | p | ||
|---|---|---|---|
| <1 mm (n:162) mean ± SD | ≥1 mm (n:53) mean ± SD | ||
| Gender | |||
| Male | 54 (33.3 %) | 30 (56.6 %) | 0.003* |
| Female | 108 (66.7 %) | 23 (43.4 %) | |
| Age (years) | 49.04 ± 13.67 | 59.40 ± 7.79 | 0.001* |
| Duration of Tinnitus (month) | 42.29 ± 45.56 | 48.16 ± 47.57 | 0.421 |
| Hearing loss | |||
| Present | 111 (68.5 %) | 47 (88.7 %) | 0.004* |
| Non-present | 51 (31.5 %) | 6 (11.3 %) | |
| Diabetes | 14 (8.6 %) | 6 (11.3 %) | 0.560 |
| Hypertension | 26 (16.0 %) | 15 (28.3 %) | 0.049* |
| THI | 39.22 ± 17.77 | 45.07 ± 16.63 | 0.036* |
| VAS | 4.55 ± 1.79 | 5.37 ± 1.88 | 0.005* |
| Haemoglobin | 14.08 ± 1.86 | 14.56 ± 1.39 | 0.086 |
| Total-C (mg/dl) | 193.99 ± 41.52 | 212.83 ± 46.14 | 0.006* |
| VLDL (mg/dl) | 31.91 ± 18.67 | 39.21 ± 25.60 | 0.059 |
| LDL (mg/dl) | 113.18 ± 36.71 | 131.51 ± 38.12 | 0.002* |
| HDL (mg/dl) | 47.69 ± 11.63 | 45.60 ± 11.72 | 0.257 |
| Triglyceride (mg/dl) | 155.98 ± 85.66 | 196.28 ± 130.12 | 0.039* |
| B12 | 371.80 ± 219.84 | 386.54 ± 262.29 | 0.687 |
| Folic acid | 7.52 ± 3.61 | 7.32 ± 2.43 | 0.813 |
Total-C total cholesterol, VLDL very low density lipoprotein, LDL low density lipoprotein, HDL high density lipoprotein, HDL high density lipoprotein, THI tinnitus handicap inventory, VAS visual analogue scale
* p < 0.05
Table 2.
Distribution of audiological findings in patients having normal and abnormal IMT
| IMT | p | ||
|---|---|---|---|
| <1 mm mean ± SD | ≥1 mm mean ± SD | ||
| Mean total | |||
| Right | 24.22 ± 14.83 | 32.41 ± 15.73 | 0.001* |
| Left | 25.22 ± 16.86 | 31.95 ± 13.14 | 0.009* |
| Mean acute | |||
| Right | 32.91 ± 21.85 | 45.88 ± 21.80 | 0.001* |
| Left | 34.77 ± 23.32 | 46.42 ± 21.11 | 0.001* |
| Mean tri | |||
| Right | 17.98 ± 13.17 | 23.45 ± 15.80 | 0.013* |
| Left | 18.36 ± 15.74 | 22.01 ± 12.50 | 0.126 |
| Mean quadri | |||
| Right | 20.85 ± 13.52 | 28.56 ± 15.58 | 0.001* |
| Left | 21.71 ± 16.45 | 27.78 ± 12.82 | 0.015* |
* p < 0.05
Table 3.
Correlation analyses of IMT and hearing test, THI and VAS findings
| Pearson correlation* | p** | |
|---|---|---|
| THI | 0.234 | 0.001 |
| VAS | 0.257 | 0.001 |
| Mean total | ||
| Right | 0.260 | 0.001 |
| Left | 0.195 | 0.004 |
| Mean acute | ||
| Right | 0.298 | 0.001 |
| Left | 0.255 | 0.001 |
| Mean tri | ||
| Right | 0.177 | 0.009 |
| Left | 0.103 | 0.132 |
| Mean quadri | ||
| Right | 0.251 | 0.001 |
| Left | 0.174 | 0.011 |
THI tinnitus handicap inventory, VAS visual analogue scale
* Correlation is significant at the 0.01 level (2-tailed). ** Correlation is significant at the 0.05 level (2-tailed)
IMT was 0.93 ± 0.24 mm in 158 patients having hearing loss in at least one of the frequencies while it was 0.81 ± 0.15 mm in 57 patients having no hearing loss in any of the frequencies. The difference between the said groups was significant (p = 0.001) (Table 1). In the correlation test between THI and VAS, there was a moderately significant difference between the tests (Pearson correlation 0.565, p = 0.001). This finding shows that using both tests together in evaluating the severity of tinnitus may increase the reliability of a study.
When THI was used, 15 (7 %) patients had grade I, 79 (36.7 %) patients had grade II, 79 (39.7 %) patients had grade III, 36 (16.8 %) patients had grade IV and 6 (2.8 %) patients had grade V severity scores. Based on VAS scores, 34 (15.8 %) patients had grade I, 56 (26 %) patients had grade II, 84 (39 %) patients had grade III, 40 (18.6 %) patients had grade IV and 1 (0.5 %) patient had grade V severity scores. IMT values of THI and VAS groups are shown in Table 4. Moreover, the significance values obtained when THI and VAS groups were compared are given in Table 5. Especially, IMT showed a significant difference between those having a mild tinnitus and those having a severe tinnitus. These findings show that the severity of tinnitus increases parallel to an increase in IMT.
Table 4.
Intima media thicknesses in THI and VAS groups
| I | II | III | IV | V | |
|---|---|---|---|---|---|
| THI | |||||
| N | 15 | 79 | 79 | 36 | 6 |
| Mean ± SD | 0.86 ± 0.29 | 0.84 ± 0.18 | 0.93 ± 0.21 | 0.98 ± 0.30 | 0.86 ± 0.05 |
| VAS | |||||
| N | 34 | 56 | 84 | 40 | 1 |
| Mean ± SD | 0.81 ± 0.23 | 0.84 ± 0.15 | 0.93 ± 0.23 | 0.98 ± 0.28 | 0.80 ± |
N number of patients, Mean ± SD mm, THI tinnitus handicap inventory, VAS visual analogue scale
Table 5.
p values obtained when IMT values of THI and VAS groups were compared
| I–II | I–III | I–IV | I–V | II–III | II–IV | II–V | III–IV | III–V | IV–V | |
|---|---|---|---|---|---|---|---|---|---|---|
| THI | 0.812 | 0.195 | 0.145 | 0.527 | 0.002* | 0.010* | 0.329 | 0.798 | 0.535 | 0.631 |
| VAS | 0.340 | 0.014* | 0.015* | 0.920 | 0.029* | 0.030* | 0.635 | 0.656 | 0.401 | 0.438 |
VAS visual analogue scale
* p < 0.05, THI: tinnitus handicap inventory
Discussion
Damaged outer hair cells and more specifically modified stereocilia in hair cells is the most commonly accepted theory in the pathophysiology of tinnitus [6]. The cochlea is sensitive to the changes in the blood flow while a limited impairment of perfusion causes dysfunction of the organ of corti [7]. Atherosclerosis may cause changes in cochlear microcirculation and turbulence or decrease of blood flow in the inner ear [13, 14]. Tinnitus can be the first symptom of atherosclerosis [15, 16]. IMT is used as a criterion for atherosclerosis [8, 9]. Increased IMT detected by ultrasound reflects morphological changes including thickening and calcification of carotid artery [17]. Increased IMT is considered as an indicator of increased risk for myocardial infarction and stroke [9, 18]. We believe that IMT can be reflecting intracranial arterial sclerosis in patients who present with the complaint of tinnitus. In a study on 1348 patients attending a brain -scan program, Fukatsu et al. [19] reported that IMT was significantly higher in patients having tinnitus (242 patients) when compared to those having no tinnitus. In a study on 100 patients having pulsatile tinnitus, Sismanis and Smoker [15] reported the presence of atherosclerotic carotid artery disease as 15 %. Gutmann et al. [20] stated that the risk of atherosclerotic stenosis of the extracranial arteries was 18 % in patients having tinnitus and 1 % in asymptomatic patients. Waldvogel et al. [21] found atherosclerosis of the internal carotid artery in 8 % of 84 patients having pulsatile tinnitus. In our study, we found increased IMT in 24.6 % of the patients. THI and VAS scores, showing the severity of tinnitus, had a positive correlation with IMT while the severity of tinnitus increased parallel to an increase in IMT. As the aim of the present study was to evaluate the effect of an increased IMT on the severity of subjective non-pulsatile tinnitus, no control group composed of individual without tinnitus was formed.
It is known that tinnitus is associated with age, male gender, hearing loss and exposure to noise. Moreover, tinnitus is thought to be associated with some metabolic diseases such as hypertension, hypercholesterolemia and diabetes mellitus [22]. On the other hand, etiological mechanisms have to be explained clearly. In most of the patients having tinnitus, there can be at least one risk factor for atherosclerotic carotid artery disease [13]. High serum LDL and low HDL are regarded as the most important vascular risk factors. Daneshi et al. [23] reported that patients having pulsatile tinnitus had at least one risk factor for atherosclerotic carotid artery disease. Histochemical studies conducted on animals having hypercholesterolemia revealed vacuolar degeneration in vessels at stria vascularis [24] and clusters of amorphous material in outer hair cells and strial marginal cells [25]. Cholesterol, other than its role in atherosclerosis development and blood viscosity increase, may damage cochlear microcirculation by decreasing the release of nitric oxide (NO), which is a strong vasodilator, from the endothelial cell [26]. As it has been reported previously, we found that carotid IMT had a direct and significant correlation with total cholesterol, LDL cholesterol, triglyceride and HDL cholesterol (negative correlation) [27]. Moreover, in our study, IMT was higher in patients of male gender and hypertension while there was no significant difference in patients having diabetes. This finding is consistent with the ones obtained in previous studies [28].
There is a close association between tinnitus and hearing loss [29]. Tinnitus has been found in 50 % of those having sudden sensorineural hearing loss, 70 % of those having presbycusis and 50–90 % in those having chronic acoustic trauma [30]. The Pearson correlation analysis in our study verifies that there is a positive association between IMT and hearing loss ratios. In this regard, we believe that our results are consistent with the previous results.
Evaluating tinnitus patients with tinnitus inventories and scales helps assessing the impact of tinnitus and contributes to standardization in evaluating the treatment outcomes during patient follow-up. THI is a comprehensive method to assess the severity and impact of tinnitus. VAS is a simple method which is easy to apply especially in older people. In our study, we used THI and VAS together and evaluated the association of IMT to the severity of subjective non-pulsatile tinnitus and audiometric data. We believe that the significant correlation we found between THI and VAS increased the reliability of our study.
Conclusion
As a result, there was a significant association between increased IMT and severity of subjective non-pulsatile tinnitus and hearing loss. For this reason, the carotid system should be examined in subjective non-pulsatile tinnitus patients. At the same time, risks for cerebrovascular and cardiovascular diseases can be reduced.
Acknowledgments
Conflict of interest
We have no conflict of interest that we should disclose.
Contributor Information
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