Research Proposal Prevalence of Sensorineural Hearing Loss in Dyslipidemias in Thai people Pawin Numthavaj, M.D.

Background and Rationale Dyslipidemia (DLP) is a major public health concern, especially in Thailand, where the prevalence of DLP is increasing in both urban and rural areas due to various reasons(1,2). The prevalence of sensorineural hearing loss (SNHL) in Thailand is also high (overall 3-5%; in some studies up to 22.7%)(3). The relationship between these two findings is unknown. There are reported cases that sudden hearing loss and vertigo is found associated with the occlusion of the vertebrobasilar arterial system, and, as is widely known, arterial occlusive disease is linked to DLP. However there is little known evidence regarding the relationship of DLP and hearing. Several preclinical data suggest that cochlear morphology and function may be disturbed in response to hyperlipidemia, particularly in chronic, long-standing hyperlipidemia(4,5,6). The population-based relationship between sensorineural hearing loss (SNHL) and DLP was first studied by Rosen in 1964(7), and has been studied since, but the results are conflicting. Jones N.S. and Davis A. have conducted several studies on SNHL and DLP. First, in 1999, they conducted a prospective case-controlled study comparing 197 50-60-year-old men already at risk of ischemic heart disease or hyperlipidemia and control subjects(8). They found no statistically significant differences between Page |1

the two groups in combined hearing thresholds. In the same year, they also studied the relationship between DLP and SNHL in 85 patients presenting with idiopathic SNHL(9). They reported no consistent association between hyperlipidemia and hearing loss. Yet in the year 2000, they retrospectively reviewed 1,490 patients who presented to a neuro-otology clinic regardless of the presenting problem. It was found that raised total cholesterol was associated with significantly better hearing threshold levels (10). Later in 2001, they compared people attending a lipid clinic with the control population. They found no consistent differences in the hearing thresholds, but the study was rather small (N=50)(11). Ning-Chia Chang et al. have also conducted a large (N=4,071) study concerning noise-induced hearing loss (NIHL) and hyperlipidemia in workers exposed to high noise levels in Taiwan(12). It was found that hypertrigleceridemia is linked to NIHL. Whether this data can be generalized to all populations is not known. Also, the relationships of SNHL between subgroups of dyslipidemia are controversial. Some reports found that the prevalence of SNHL is related to high cholesterol, some found it was the trigleceride level that is related to SNHL(13), and some found no relation between either. Aims of the study • To assess the relationship between sensorineural hearing loss and dyslipidemia in Thai people. • To assess the relationship between sensorineural hearing loss and subgroups of dyslipidemia, especially hypercholesterolemia and hypertrigleceridemia. • To determine the benefits of screening for sensorineural hearing loss in dyslipidemic patients. Study design Cross-sectional study

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Methods All patients in the dyslipidemia clinic in Ramathibodi hospital and/or other participating hospitals in Thailand will be offered an interview for entry into the study. The participants will be screened for other metabolic diseases including hypertension and diabetes. Their serum lipid levels (cholesterol, trigleceride, LDL, and HDL) will be obtained. Baseline characteristics of the individuals will be recorded. They will also be asked about their diets, lifestyle, any previous medical history, and noise exposure history. Participants will be examined by a clinician for any obvious ear malformations and conductive hearing loss. Participants will then obtain a screening audiogram by a certified audiologist or otologist. The data in the audiogram will be recorded and matched with the lipid levels. The analysis of the data will be done using a computer program to find any relationship between hearing and each variable. Expected benefits and application The relationship between sensorineural hearing loss and dyslipidemia will be clarified and if any relationship is found, the benefit of the screening audiogram will be determined. This study will provide a basis for further understanding in hearing loss and metabolic diseases, and possibly prevention and treatment. Expected Timing Case selection and data collection Analysis of the data

6-9 months 1 month

References (1) Pongchaiyakul C, Pongchaiyakul C, Pratipanawatr T. Prevalence of dyslipidemia in rural Thai adults: an epidemiologic study in Khon Kaen province. J Med Assoc Thai. 2005 Aug;88(8):1092-7. (2) Nillakupt K, Nathalang O, Arnutti P, Aimpun P, Rangsin R, Panichkul S, Areekul W. Dyslipidemia in Thai rural adults. J Med Assoc Thai. 2005 Jun;88(6):824-8.

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(3) Prasansuk S. Incidence/prevalence of sensorineural hearing impairment in Thailand and Southeast Asia. Audiology. 2000 Jul-Aug;39(4):207-11. (4) Guo Y, Zhang C, Du X, Nair U, Yoo TJ. Morphological and functional alterations of the cochlea in apolipoprotein E gene deficient mice. Hear Res. 2005 Oct;208(1-2):54-67. (5) Satar B, Ozkaptan Y, Sürücü HS, Oztürk H. Ultrastructural effects of hypercholesterolemia on the cochlea. Otol Neurotol. 2001 Nov;22(6):786-9. (6) Gratton MA, Wright CG. Alterations of inner ear morphology in experimental hypercholesterolemia. Hear Res. 1992 Aug;61(1-2):97-105. (7) Rosen S, Plester D, El-mofty A, Rosen HV. Relation of Hearing Loss to Cardiovascular Disease. Trans Am Acad Ophthalmol Otolaryngol. 1964 May-Jun;68:433-44. (8) Jones NS, Davis A. A prospective case-controlled study of 197 men, 50-60 years old, selected at random from a population at risk from hyperlipidaemia to examine the relationship between hyperlipidaemia and sensorineural hearing loss. Clin Otolaryngol Allied Sci. 1999 Sep;24(5):449-56. (9) Jones NS, Davis A. A prospective case-controlled study of patients presenting with idiopathic sensorineural hearing loss to examine the relationship between hyperlipidaemia and sensorineural hearing loss. Clin Otolaryngol Allied Sci. 1999 Dec;24(6):531-6. (10) Jones NS, Davis A. A retrospective case-controlled study of 1490 consecutive patients presenting to a neuro-otology clinic to examine the relationship between blood lipid levels and sensorineural hearing loss. Clin Otolaryngol Allied Sci. 2000 Dec;25(6):511-7. (11) Jones NS, Davis A. A prospective case-control study of 50 consecutive patients presenting with hyperlipidaemia. Clin Otolaryngol Allied Sci. 2001 Jun;26(3):189-96. (12) Chang NC, Yu ML, Ho KY, Ho CK. Hyperlipidemia in noise-induced hearing loss. Otolaryngol Head Neck Surg. 2007 Oct;137(4):603-6. (13) Evans MB, Tonini R, Shope CD, Oghalai JS, Jerger JF, Insull W Jr, Brownell WE. Dyslipidemia and auditory function. Otol Neurotol. 2006 Aug;27(5):609-14.

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