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Increased carotid artery intima-media thickness in patients with tympanosclerosis: Common risk factors with atherosclerosis?
Kaohsiung Journal of Medical Sciences (2015) 31, 199e202
Available online at www.sciencedirect.com
ScienceDirect journal homepage: http://www.kjms-online.com
ORIGINAL ARTICLE
Increased carotid artery intima-media thickness in patients with tympanosclerosis: Common risk factors with atherosclerosis? Sumeyra Doluoglu a,*, Celil Gocer a, Ugur Toprak b, Ayse Iriz a, Melek Uyar a, Adil Eryilmaz a a
Department of ENT, III Clinic of Ankara Numune Education and Research Hospital, Ankara, Turkey b Department of Radiology, II Clinic of Ankara Numune Education and Research Hospital, Ankara, Turkey Received 31 July 2014; accepted 6 January 2015
Available online 9 February 2015
KEYWORDS Atherosclerosis; Carotid artery; Tympanosclerosis
Abstract We investigated the relationship between tympanosclerosis, known atherosclerotic risk factors, and the intima-media thickness of bilateral carotid arteries using ultrasonography. A total of 122 patients admitted to our clinic with chronic otitis media between 2005 and 2010 were included in the study. The study group consisted of 61 patients with tympanosclerosis; the control group comprised 61 patients without tympanosclerosis. Internal carotid artery intima-media thickness (CAIMT), total cholesterol, triglyceride, low- and high-density lipoprotein cholesterol, C-reactive protein, and homocysteine levels were measured in all patients. Homocysteine, low-density lipoprotein, total cholesterol, and triglyceride levels in the study group were higher compared with those of the control group (p < 0.05). Right and left CAIMT was greater in the study group versus the control group (p 0.001). In conclusion, atherosclerosis and tympanosclerosis were associated with identical risk factors; in the tympanosclerosis group, CAIMT was increased significantly. Copyright ª 2015, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. All rights reserved.
Introduction
Conflicts of interest: All authors declare no conflicts of interest. * Corresponding author. Department of ENT, Clinic of Ankara Numune Education and Research Hospital, 06100 Ankara, Turkey. E-mail address: [email protected] (S. Doluoglu).
Tympanosclerosis (TS) is characterized by hyaline degeneration of the middle ear and mastoid air cells. Although numerous studies have been conducted on TS, its etiology and pathogenesis remain poorly understood. Immunological reactions, genetic predisposition, infection, Helicobacter
http://dx.doi.org/10.1016/j.kjms.2015.01.003 1607-551X/Copyright ª 2015, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. All rights reserved.
200 pylori, and trauma have all been proposed as possible etiologic factors [1,2]. A number of etiopathogenetic risk factors have been identified for atherosclerotic vascular disease, of which a positive family history is the most important. Other notable risk factors include lifestyle, smoking, diabetes mellitus, high blood cholesterol and high C-reactive protein (CRP), and homocysteine levels [3,4]. Endothelial dysfunction and increased intima-media thickness in the whole vascular bed represent the most important structural alterations during the early subclinical phase of atherosclerotic disease [5]. Endothelial dysfunction and increased intima-media thickness can be assessed using simple, inexpensive, and noninvasive methods [6] such that therapeutic measures may be used before extensive atherosclerosis develops. TS incidence is higher in patients with coronary artery atherosclerosis [7e9]. Despite the involvement of different organs, the inflammatory response is similar in both diseases, suggesting a common etiopathogenesis. We investigate herein the relationship between TS, known atherosclerotic risk factors, and internal carotid artery intima-media thickness (CAIMT).
Methods The study population consisted of patients admitted to our clinic with chronic otitis media (COM), subsequently divided into two groups according to presence or absence of TS. The study group consisted of 61 patients with TS; TS was diagnosed when hyaline plates were observed on the tympanic membrane remnant or when tympanosclerotic foci were detected in the middle ear and mastoid during surgery. In patients who did not undergo surgery, hyalinizationdi.e., a sclerotic appearance in the middle ear on otoscopy in the presence of a tympanic membrane perforationdrepresented the TS diagnosis criterion. The control group comprised 61 patients without hyaline plates on the tympanic membrane remnant or tympanosclerotic foci in the middle ear and mastoid during surgery, and patients with a tympanic membrane perforation without hyalinization. The exclusion criteria included receiving therapy, or dieting, for hypercholesterolemia, and supplementation with vitamin B12, folic acid, or antioxidants. A total of 122 patients were included in the study. Written informed consent was obtained from all participants, and ethics committee approval was granted. Total cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, CRP, and homocysteine levels were measured in the venous blood samples of all patients after a 12-hour fast. Patients were questioned for family history of myocardial infarction at a young age, and cerebrovascular and obstructive peripheral vascular disease; family history was regarded as positive for atherosclerosis in the presence of at least one of these factors. All patients underwent ultrasonography using a Logiq 7 (GE Healthcare, Wauwatosa, WI, USA) device, performed by the same radiologist. A 12-MHz, high-resolution linear probe calibrated for the vascular system was used. Gray-scale imaging was performed using the tissue harmonic mode, and
S. Doluoglu et al. Doppler imaging was performed using the color pulse wave method. Vessel diameter and intima-media thickness measurements were obtained at maximum magnification. The diameter of the common carotid artery was measured 2 cm proximal to the bifurcation, during the diastole. Intimal thickness was measured in the same area, and in two additional areas 1 cm and 2 cm proximal to this location; a total of three measurements were taken, all from the posterior wall of the vessel. Measurements 0.9 mm were regarded as normal, and CAIMT >0.9 mm was considered pathological; the location, length, and thickness of plaques were noted in pathological cases. Plaques were classified as fatty, heterogeneous, or fibrous. The presence of calcification, surface characteristics of plaques (i.e., smooth or irregular), and presence of ulcers were recorded. Data analysis was performed using the SPSS for Windows software package (version 16.0; SPSS Inc., Chicago, IL, USA). Continuous variables were presented as median (minimumemaximum) values, and categorical variables were presented as percentages. Differences in intergroup means were assessed using the ManneWhitney U test. Chisquare or Fisher’s exact test were used to compare categorical data. A p value <0.05 was taken to indicate statistical significance.
Results The study group included 30 (49.18%) males and 31 (50.82%) females, and the control group consisted of 26 (42.62%) males and 35 (57.38%) females. The male/female ratios of the two groups were similar (p > 0.05). The median (minimumemaximum) age of the study group was 46 years (range, 13e74 years) versus 39 years (range, 17e63 years) in the control group. The mean ages of the groups did not differ (p Z 0.15). Homocysteine, LDL, and total cholesterol and triglyceride levels in the study group were higher compared with those of the control group (p < 0.05; Table 1). CRP and HDL levels did not differ between groups. In the study group, 32 of 61 (52.5%) patients, compared with 26 of 61 controls, were positive for smoking history (p Z 0.27). In total, 38 of 61 patients (62.30%) in the study group, and 28 of 61 controls (45.9%), were characterized by a positive family history (p Z 0.069). CAIMT was higher, on the right and left side, in the study group compared with that found in the control group (both p Z 0.0001; Table 2), and there were more plaques in the right and left common carotid arteries of the study group versus the control group (both p Z 0.0001; Table 3).
Discussion TS is an inactive otitis media sequel characterized by hyaline and calcified tissue accumulation beneath the mucosa. Although its etiopathogenesis is unclear, it is known that middle ear infection and tympanic membrane trauma precipitate TS. However, not all patients with middle ear infection, or who have a ventilation tube inserted, develop TS, suggesting that a molecular mechanism with genetic variations may play a role in the development of TS.
Atherosclerosis and tympanosclerosis Table 1
201
Homocysteine, CRP, LDL, HDL, total cholesterol, and triglyceride levels in the study group and control group. Study group (n Z 61)
Homocysteine (mmol/L) CRP (mg/L) LDL (mg/dL) HDL (mg/dL) Total cholesterol (mg/dL) Triglyceride (mg/dL)
Control group (n Z 61)
p
Mean SD
Median
MineMax
Mean
Median
MineMax
12 0,5 122 37 193 119
2.2e50 0.3e4.2 58e206 22e70 113e270 26e432
10.784 0.62 107.31 42.69 170.02 106.07
9.87 0.5 103 41 167 94
2.7e33.4 0.5e2.2 65e188 24e84 104e281 23e282
13.7 0.74 121.8 40.5 190.1 140.6
7.1 0.6 31.2 10.5 39.6 92.6
0.003 0.055 0.006 0.385 0.001 0.044
CRP Z C-reactive protein; HDL Z high-density lipoprotein; LDL Z low-density lipoprotein; SD Z standard deviation.
Table 2
Comparison of carotid artery intima-media thickness between the groups. Study group
>0.9 mm 0.9 mm Total
Table 3
Control group
Right
Left
Right
Left
Right
Left
31 (50.82%) 30 (49.18%) 61 (100%)
35 (57.37%) 26 (42.63%) 61 (100%)
0 (0%) 61 (100%) 61 (100%)
0 (0%) 61 (100%) 61 (100%)
31 (25.4%) 91 (74.59%) 122 (100%)
35 (28.68%) 87 (71.32%) 122 (100%)
Comparison of atherosclerotic plaques between the groups. Study group
Present None Total
Total
Control group
Total
Right
Left
Right
Left
Right
Left
13 (21.31%) 48 (79.69%) 61 (100%)
14 (22.95%) 47 (77.05%) 61 (100%)
0 (0%) 61 (100%) 61 (100%)
0 (0%) 61 (100%) 61 (100%)
13 (10.65%) 109 (89.3%) 122 (100%)
14 (11.47%) 108 (88.5%) 122 (100%)
Clinical and experimental studies suggest that free oxygen radicals, produced by bacteria and inflammatory cells and appearing in otitis media, play important roles in the development of TS [10,11]. Free oxygen radicals-related tissue injury occurs in a number of conditions including cataract, cerebrovascular disease, atherosclerosis, arthritis, and ischemiaereperfusion injury; tissue injury is necessary for TS to develop. TS incidence is higher in patients with atherosclerosis [12]. Koc ¸ et al (1989) investigated the genetic predisposition for TS and atherosclerosis and compared the TS prevalence between atherosclerotic patients and healthy controls. Otoscopy was performed on 1024 patients with atherosclerosis, of whom 682 (66.6%) patients were positive for myringosclerosis. Myringosclerosis was evident in 36 (12%) of 300 controls (p < 0.0001) [11]. Genetic predisposition is the most important risk factor for the development of coronary artery atherosclerosis. In another study, Koc ¸ and Uneri [13] demonstrated that TS was more frequent in males, a trend that has also been reported elsewhere. However, in our study group (31 females and 30 males), both sexes were affected similarly. Uneri and Koc ¸ [7] compared the ultrastructural features of tympanosclerotic and atherosclerotic foci; both lesions were examined under light and electron microscopes, which revealed that their ultrastructural appearances were similar. The authors suggest that these two diseases
represent a common reaction in two separate tissues due to different causal factors [7]. Despite the involvement of different organs, the inflammatory reaction is the same in both entities. In a study designed to investigate the co-occurrence of these two diseases, TS prevalence was assessed in a group of patients who had undergone carotid artery surgery for severe atherosclerosis and in age-matched healthy controls. TS was detected in 32 of 84 patients (38.1%) in the study group compared with 11 of 84 controls (13%; p Z 0.005) [8]. Right and left CAIMT were significantly greater in the TS group in our study (p Z 0.0001), which supports the co-occurrence of these two diseases. Family history is the most important risk factor for atherosclerosis. In our study, there was a trend toward a higher rate of positive family history in the TS group versus the control group (62.30% and 45.9%, respectively), but this difference was not significant (p Z 0.069). We suggest that a significant association between family history and tympanosclerotic middle ear disease might have been observed in the context of a larger sample. Smoking is also an important risk factor for atherosclerosis development [3,4]; smoking was more prevalent in our TS group but not significantly so (p Z 0.27). High LDL levels in the blood are another important risk factor for atherosclerosis [14]. LDL is oxidized by macrophages located in the media layer of middle- and large-
202 sized arteries, which become foam cells resulting in endothelial dysfunction, inflammation, and typical atheroma plaques. These plaques increase the likelihood of bleeding, laceration, and thrombocyte adhesion in these regions [2]. Mean LDL was significantly higher in our study group compared with the control group (p Z 0.006). Although less important than high LDL, a high cholesterol level is also a strong risk factor for atherosclerosis [15]. In our study, total cholesterol was higher in the study group (p Z 0.001), in accordance with the literature. Recently, CRP, an important marker of atherosclerosis, has been studied extensively. CRP is a biochemical marker of systemic inflammation; high CRP levels are associated with atherosclerosis [16]. Measuring CRP confers significant advantages during the follow up of patients with known atherosclerotic vascular disease [17]. In our study, the mean CRP level was higher in the TS group than in the control group, but not significantly so (p Z 0.055). We suggest that this finding could reach significance with a larger sample. Homocysteine is a sulfhydryl-containing amino acid derivative produced following the demethylation of methionine, and present in abundance in animal proteins [18]. High homocysteine levels are observed in atherosclerotic vascular disease patients, who exhibit peripheral vascular and cerebrovascular diseases more frequently than coronary artery disease [19,20]. Another study performed in our clinic demonstrated that homocysteine, in addition to atherosclerosis, is an important risk factor for TS [9]. In accordance with the literature, homocysteine levels were significantly higher in our study group versus the control group (p Z 0.003). Furthermore, in accordance with previous studies, the absence and presence of pathological CAIMT in the control group, and in a considerable number of patients, respectively, strongly supports the hypothesis that these diseases possess common risk factors. As mentioned previously, the existence of common risk factors for atherosclerosis and TS suggests that common mechanisms may underlie the development of these two diseases. In support of this hypothesis, well-known risk factors for atherosclerosis such as homocysteine, LDL, total cholesterol, and triglyceride levels were significantly higher in our study group. Pathophysiological studies are required to further delineate the relationship between risk factors and TS. Studies have typically sought to determine atherosclerotic risk factors so that they may be controlled. However, because atherosclerosis can be simultaneously present in TS patients, a more careful and detailed examination of the cardiovascular system must be performed. In conclusion, we demonstrate herein that atherosclerosis and tympanosclerosis possess identical risk factors; in our tympanosclerosis group, CAIMT was significantly increased. Prospective, randomized controlled studies are required to further delineate the pathophysiological relationship between the risk factors of tympanosclerosis and atherosclerosis.
S. Doluoglu et al.
References [1] Tos M, Stangerup SE. Hearing loss in tympanosclerosis caused by grommets. Arch Otolaryngol Head Neck Surg 1989;115:931e5. [2] Iriz A, Eryilmaz A, Gocer C, Acar A, Boynuegri S, Dursun E. Could Helicobacter pylori play a role in the aetipathogenesis of tympanosclerosis? J Laryngol Otol 2011;125:1121e4. http: //dx.doi.org/10.1017/S0022215111002301. [3] Heinecke JW. Oxidants and antioxidants in the pathogenesis of atherosclerosis: implications for the oxidized low density lipoprotein hypothesis. Atherosclerosis 1998;141:1e15. [4] Woo CW, Siow YL, Pierce GN. Hyperhomocysteinemia induces hepatic cholesterol biosynthesis and lipid accumulation via activation of transcription factors. Am J Physiol Endocrinol Metab 2005;288:1002e10. [5] Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987;316:1371e5. [6] Gostomzyk JG, Heller WD, Gerhardt P, Lee PN, Keil U. B-scan ultrasound examination of the carotid arteries within a representative population (MONICA project Augsburg). Klin Wochenschr 1988;66:58e65. [7] Uneri C, Koc ¸ A. Ultrastructural comparison between tympanosclerosis and atherosclerosis. Tu ¨rk Otolaringol Ars‚ivi 2005; 43:137e44. [8] Ferri M, Faggioli GL, Feri GG, Pirodda A. Is carotid stenosis correlated with tympanosclerosis? Int Angiol 2004;23:144e6. [9] Acar A, Eryılmaz A, Gocer C, Genc U, Bakir F, Boynuegri S, et al. Is tympanosclerosis affected by risk factors for atherosclerosis? Int Adv Otol 2009;5:166e70. [10] Dawes PJD, Bingham BJ, Rhys R, Griffiths MV. Aspirating middle ear effusions when inserting ventilation tubes: does it influence post-operative otorrhoea, tube obstruction or the development of tympanosclerosis? Clin Otolaryngol Allied Sci 1991;16:457e61. [11] McRae D, Gatland DJ, Youngs R, Cook J. Aspiration of middle ear effusions prior to grommet insertion an etiological factor in tympanosclerosis. J Otolaryngol 1989;18:229e31. [12] Koc ¸ A, Uneri C. Genetic predisposition for tympanosclerotic degeneration. Eur Arch Otorhinolaryngol 2002;259:180e3. [13] Koc ¸ A, Uneri C. Sex distribution in children with tympanosclerosis after insertion of a tympanostomy tube. Eur Arch Otorhinolaryngol 2001;258:16e9. [14] Berliner JA, Heinecke JW. The role of oxidized lipoproteins in atherogenesis. Free Radic Biol Med 1996;20:707e27. [15] Crouse 3rd JR, Byington RP, Bond MG, Espeland MA, Craven TE, Sprinkle JW, et al. Pravastatin, lipids, and atherosclerosis in the carotid arteries (PLAC-II). Am J Cardiol 1995;75:455e9. [16] Rıdker PM. High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation 2001;103:1813e8. [17] Danesh J, Wheeler JG, Hirschfleld GM, Eda S, Eiriksdottir G, Rumley A, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 2004;350:1387e97. [18] Ueland PM. Homocysteine species as components of plasma redox thiol status. Clin Chem 1995;41:340e2. [19] McCully KS. Homocysteine and vascular disease. Nat Med 1996;2:386e9. [20] Veerkamp MJ, dee Graaf J, den Heijer M, Blom HJ, Stalenhoef AF. Plasma homocysteine in subjects with familial combined hyperlipidemia. Atherosclerosis 2003;166:111e7.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: http://www.kjms-online.com
ORIGINAL ARTICLE
Increased carotid artery intima-media thickness in patients with tympanosclerosis: Common risk factors with atherosclerosis? Sumeyra Doluoglu a,*, Celil Gocer a, Ugur Toprak b, Ayse Iriz a, Melek Uyar a, Adil Eryilmaz a a
Department of ENT, III Clinic of Ankara Numune Education and Research Hospital, Ankara, Turkey b Department of Radiology, II Clinic of Ankara Numune Education and Research Hospital, Ankara, Turkey Received 31 July 2014; accepted 6 January 2015
Available online 9 February 2015
KEYWORDS Atherosclerosis; Carotid artery; Tympanosclerosis
Abstract We investigated the relationship between tympanosclerosis, known atherosclerotic risk factors, and the intima-media thickness of bilateral carotid arteries using ultrasonography. A total of 122 patients admitted to our clinic with chronic otitis media between 2005 and 2010 were included in the study. The study group consisted of 61 patients with tympanosclerosis; the control group comprised 61 patients without tympanosclerosis. Internal carotid artery intima-media thickness (CAIMT), total cholesterol, triglyceride, low- and high-density lipoprotein cholesterol, C-reactive protein, and homocysteine levels were measured in all patients. Homocysteine, low-density lipoprotein, total cholesterol, and triglyceride levels in the study group were higher compared with those of the control group (p < 0.05). Right and left CAIMT was greater in the study group versus the control group (p 0.001). In conclusion, atherosclerosis and tympanosclerosis were associated with identical risk factors; in the tympanosclerosis group, CAIMT was increased significantly. Copyright ª 2015, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. All rights reserved.
Introduction
Conflicts of interest: All authors declare no conflicts of interest. * Corresponding author. Department of ENT, Clinic of Ankara Numune Education and Research Hospital, 06100 Ankara, Turkey. E-mail address: [email protected] (S. Doluoglu).
Tympanosclerosis (TS) is characterized by hyaline degeneration of the middle ear and mastoid air cells. Although numerous studies have been conducted on TS, its etiology and pathogenesis remain poorly understood. Immunological reactions, genetic predisposition, infection, Helicobacter
http://dx.doi.org/10.1016/j.kjms.2015.01.003 1607-551X/Copyright ª 2015, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. All rights reserved.
200 pylori, and trauma have all been proposed as possible etiologic factors [1,2]. A number of etiopathogenetic risk factors have been identified for atherosclerotic vascular disease, of which a positive family history is the most important. Other notable risk factors include lifestyle, smoking, diabetes mellitus, high blood cholesterol and high C-reactive protein (CRP), and homocysteine levels [3,4]. Endothelial dysfunction and increased intima-media thickness in the whole vascular bed represent the most important structural alterations during the early subclinical phase of atherosclerotic disease [5]. Endothelial dysfunction and increased intima-media thickness can be assessed using simple, inexpensive, and noninvasive methods [6] such that therapeutic measures may be used before extensive atherosclerosis develops. TS incidence is higher in patients with coronary artery atherosclerosis [7e9]. Despite the involvement of different organs, the inflammatory response is similar in both diseases, suggesting a common etiopathogenesis. We investigate herein the relationship between TS, known atherosclerotic risk factors, and internal carotid artery intima-media thickness (CAIMT).
Methods The study population consisted of patients admitted to our clinic with chronic otitis media (COM), subsequently divided into two groups according to presence or absence of TS. The study group consisted of 61 patients with TS; TS was diagnosed when hyaline plates were observed on the tympanic membrane remnant or when tympanosclerotic foci were detected in the middle ear and mastoid during surgery. In patients who did not undergo surgery, hyalinizationdi.e., a sclerotic appearance in the middle ear on otoscopy in the presence of a tympanic membrane perforationdrepresented the TS diagnosis criterion. The control group comprised 61 patients without hyaline plates on the tympanic membrane remnant or tympanosclerotic foci in the middle ear and mastoid during surgery, and patients with a tympanic membrane perforation without hyalinization. The exclusion criteria included receiving therapy, or dieting, for hypercholesterolemia, and supplementation with vitamin B12, folic acid, or antioxidants. A total of 122 patients were included in the study. Written informed consent was obtained from all participants, and ethics committee approval was granted. Total cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, CRP, and homocysteine levels were measured in the venous blood samples of all patients after a 12-hour fast. Patients were questioned for family history of myocardial infarction at a young age, and cerebrovascular and obstructive peripheral vascular disease; family history was regarded as positive for atherosclerosis in the presence of at least one of these factors. All patients underwent ultrasonography using a Logiq 7 (GE Healthcare, Wauwatosa, WI, USA) device, performed by the same radiologist. A 12-MHz, high-resolution linear probe calibrated for the vascular system was used. Gray-scale imaging was performed using the tissue harmonic mode, and
S. Doluoglu et al. Doppler imaging was performed using the color pulse wave method. Vessel diameter and intima-media thickness measurements were obtained at maximum magnification. The diameter of the common carotid artery was measured 2 cm proximal to the bifurcation, during the diastole. Intimal thickness was measured in the same area, and in two additional areas 1 cm and 2 cm proximal to this location; a total of three measurements were taken, all from the posterior wall of the vessel. Measurements 0.9 mm were regarded as normal, and CAIMT >0.9 mm was considered pathological; the location, length, and thickness of plaques were noted in pathological cases. Plaques were classified as fatty, heterogeneous, or fibrous. The presence of calcification, surface characteristics of plaques (i.e., smooth or irregular), and presence of ulcers were recorded. Data analysis was performed using the SPSS for Windows software package (version 16.0; SPSS Inc., Chicago, IL, USA). Continuous variables were presented as median (minimumemaximum) values, and categorical variables were presented as percentages. Differences in intergroup means were assessed using the ManneWhitney U test. Chisquare or Fisher’s exact test were used to compare categorical data. A p value <0.05 was taken to indicate statistical significance.
Results The study group included 30 (49.18%) males and 31 (50.82%) females, and the control group consisted of 26 (42.62%) males and 35 (57.38%) females. The male/female ratios of the two groups were similar (p > 0.05). The median (minimumemaximum) age of the study group was 46 years (range, 13e74 years) versus 39 years (range, 17e63 years) in the control group. The mean ages of the groups did not differ (p Z 0.15). Homocysteine, LDL, and total cholesterol and triglyceride levels in the study group were higher compared with those of the control group (p < 0.05; Table 1). CRP and HDL levels did not differ between groups. In the study group, 32 of 61 (52.5%) patients, compared with 26 of 61 controls, were positive for smoking history (p Z 0.27). In total, 38 of 61 patients (62.30%) in the study group, and 28 of 61 controls (45.9%), were characterized by a positive family history (p Z 0.069). CAIMT was higher, on the right and left side, in the study group compared with that found in the control group (both p Z 0.0001; Table 2), and there were more plaques in the right and left common carotid arteries of the study group versus the control group (both p Z 0.0001; Table 3).
Discussion TS is an inactive otitis media sequel characterized by hyaline and calcified tissue accumulation beneath the mucosa. Although its etiopathogenesis is unclear, it is known that middle ear infection and tympanic membrane trauma precipitate TS. However, not all patients with middle ear infection, or who have a ventilation tube inserted, develop TS, suggesting that a molecular mechanism with genetic variations may play a role in the development of TS.
Atherosclerosis and tympanosclerosis Table 1
201
Homocysteine, CRP, LDL, HDL, total cholesterol, and triglyceride levels in the study group and control group. Study group (n Z 61)
Homocysteine (mmol/L) CRP (mg/L) LDL (mg/dL) HDL (mg/dL) Total cholesterol (mg/dL) Triglyceride (mg/dL)
Control group (n Z 61)
p
Mean SD
Median
MineMax
Mean
Median
MineMax
12 0,5 122 37 193 119
2.2e50 0.3e4.2 58e206 22e70 113e270 26e432
10.784 0.62 107.31 42.69 170.02 106.07
9.87 0.5 103 41 167 94
2.7e33.4 0.5e2.2 65e188 24e84 104e281 23e282
13.7 0.74 121.8 40.5 190.1 140.6
7.1 0.6 31.2 10.5 39.6 92.6
0.003 0.055 0.006 0.385 0.001 0.044
CRP Z C-reactive protein; HDL Z high-density lipoprotein; LDL Z low-density lipoprotein; SD Z standard deviation.
Table 2
Comparison of carotid artery intima-media thickness between the groups. Study group
>0.9 mm 0.9 mm Total
Table 3
Control group
Right
Left
Right
Left
Right
Left
31 (50.82%) 30 (49.18%) 61 (100%)
35 (57.37%) 26 (42.63%) 61 (100%)
0 (0%) 61 (100%) 61 (100%)
0 (0%) 61 (100%) 61 (100%)
31 (25.4%) 91 (74.59%) 122 (100%)
35 (28.68%) 87 (71.32%) 122 (100%)
Comparison of atherosclerotic plaques between the groups. Study group
Present None Total
Total
Control group
Total
Right
Left
Right
Left
Right
Left
13 (21.31%) 48 (79.69%) 61 (100%)
14 (22.95%) 47 (77.05%) 61 (100%)
0 (0%) 61 (100%) 61 (100%)
0 (0%) 61 (100%) 61 (100%)
13 (10.65%) 109 (89.3%) 122 (100%)
14 (11.47%) 108 (88.5%) 122 (100%)
Clinical and experimental studies suggest that free oxygen radicals, produced by bacteria and inflammatory cells and appearing in otitis media, play important roles in the development of TS [10,11]. Free oxygen radicals-related tissue injury occurs in a number of conditions including cataract, cerebrovascular disease, atherosclerosis, arthritis, and ischemiaereperfusion injury; tissue injury is necessary for TS to develop. TS incidence is higher in patients with atherosclerosis [12]. Koc ¸ et al (1989) investigated the genetic predisposition for TS and atherosclerosis and compared the TS prevalence between atherosclerotic patients and healthy controls. Otoscopy was performed on 1024 patients with atherosclerosis, of whom 682 (66.6%) patients were positive for myringosclerosis. Myringosclerosis was evident in 36 (12%) of 300 controls (p < 0.0001) [11]. Genetic predisposition is the most important risk factor for the development of coronary artery atherosclerosis. In another study, Koc ¸ and Uneri [13] demonstrated that TS was more frequent in males, a trend that has also been reported elsewhere. However, in our study group (31 females and 30 males), both sexes were affected similarly. Uneri and Koc ¸ [7] compared the ultrastructural features of tympanosclerotic and atherosclerotic foci; both lesions were examined under light and electron microscopes, which revealed that their ultrastructural appearances were similar. The authors suggest that these two diseases
represent a common reaction in two separate tissues due to different causal factors [7]. Despite the involvement of different organs, the inflammatory reaction is the same in both entities. In a study designed to investigate the co-occurrence of these two diseases, TS prevalence was assessed in a group of patients who had undergone carotid artery surgery for severe atherosclerosis and in age-matched healthy controls. TS was detected in 32 of 84 patients (38.1%) in the study group compared with 11 of 84 controls (13%; p Z 0.005) [8]. Right and left CAIMT were significantly greater in the TS group in our study (p Z 0.0001), which supports the co-occurrence of these two diseases. Family history is the most important risk factor for atherosclerosis. In our study, there was a trend toward a higher rate of positive family history in the TS group versus the control group (62.30% and 45.9%, respectively), but this difference was not significant (p Z 0.069). We suggest that a significant association between family history and tympanosclerotic middle ear disease might have been observed in the context of a larger sample. Smoking is also an important risk factor for atherosclerosis development [3,4]; smoking was more prevalent in our TS group but not significantly so (p Z 0.27). High LDL levels in the blood are another important risk factor for atherosclerosis [14]. LDL is oxidized by macrophages located in the media layer of middle- and large-
202 sized arteries, which become foam cells resulting in endothelial dysfunction, inflammation, and typical atheroma plaques. These plaques increase the likelihood of bleeding, laceration, and thrombocyte adhesion in these regions [2]. Mean LDL was significantly higher in our study group compared with the control group (p Z 0.006). Although less important than high LDL, a high cholesterol level is also a strong risk factor for atherosclerosis [15]. In our study, total cholesterol was higher in the study group (p Z 0.001), in accordance with the literature. Recently, CRP, an important marker of atherosclerosis, has been studied extensively. CRP is a biochemical marker of systemic inflammation; high CRP levels are associated with atherosclerosis [16]. Measuring CRP confers significant advantages during the follow up of patients with known atherosclerotic vascular disease [17]. In our study, the mean CRP level was higher in the TS group than in the control group, but not significantly so (p Z 0.055). We suggest that this finding could reach significance with a larger sample. Homocysteine is a sulfhydryl-containing amino acid derivative produced following the demethylation of methionine, and present in abundance in animal proteins [18]. High homocysteine levels are observed in atherosclerotic vascular disease patients, who exhibit peripheral vascular and cerebrovascular diseases more frequently than coronary artery disease [19,20]. Another study performed in our clinic demonstrated that homocysteine, in addition to atherosclerosis, is an important risk factor for TS [9]. In accordance with the literature, homocysteine levels were significantly higher in our study group versus the control group (p Z 0.003). Furthermore, in accordance with previous studies, the absence and presence of pathological CAIMT in the control group, and in a considerable number of patients, respectively, strongly supports the hypothesis that these diseases possess common risk factors. As mentioned previously, the existence of common risk factors for atherosclerosis and TS suggests that common mechanisms may underlie the development of these two diseases. In support of this hypothesis, well-known risk factors for atherosclerosis such as homocysteine, LDL, total cholesterol, and triglyceride levels were significantly higher in our study group. Pathophysiological studies are required to further delineate the relationship between risk factors and TS. Studies have typically sought to determine atherosclerotic risk factors so that they may be controlled. However, because atherosclerosis can be simultaneously present in TS patients, a more careful and detailed examination of the cardiovascular system must be performed. In conclusion, we demonstrate herein that atherosclerosis and tympanosclerosis possess identical risk factors; in our tympanosclerosis group, CAIMT was significantly increased. Prospective, randomized controlled studies are required to further delineate the pathophysiological relationship between the risk factors of tympanosclerosis and atherosclerosis.
S. Doluoglu et al.
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