Occupational Noise, Smoking, and a High Body Mass Index are Risk Factors for Age-related Hearing Impairment and Moderate Alcohol Consumption is Protective: A European Population-based Multicenter Study

ERIK FRANSEN 1 3 5 VEDAT TOPSAKAL 1 2 3 JAN-JAAP HENDRICKX 1 2 3 5 LUT VAN LAER 1 3 5 JEROEN R. HUYGHE 1 3 5 ELS VAN EYKEN 1 3 5 NELE LEMKENS 1 2 3 SAMULI HANNULA 0 1 3 ELINA MKI-TORKKO 0 1 3 MONA JENSEN 1 3 8 KELLY DEMEESTER 1 2 3 ANKE TROPITZSCH 1 3 7 AMANDA BONACONSA 1 3 6 MANUELA MAZZOLI 1 3 6 ANGELES ESPESO 1 3 10 KATIA VERBRUGGEN 1 3 9 JOKE HUYGHE 1 3 9 PATRICK L. M. HUYGEN 1 3 SYLVIA KUNST 1 3 MINNA MANNINEN 1 3 4 AMALIA DIAZ-LACAVA 1 3 11 MICHAEL STEFFENS 1 3 11 THOMAS F. WIENKER 1 3 11 ILMARI PYYKK 1 3 4 COR W. R. J. CREMERS 1 3 HANNIE KREMER 1 3 INGEBORG DHOOGE 1 3 9 DAFYDD STEPHENS 1 3 10 EVA ORZAN 1 3 6 MARKUS PFISTER 1 3 7 MICHAEL BILLE 1 3 8 AGNETE PARVING 1 3 8 MARTTI SORRI 0 1 3 PAUL VAN DE HEYNING 1 2 3 GUY VAN CAMP 1 3 5 0 Department of Otorhinolaryngology, University of Oulu , 90014 Oulu, Finland 1 Electronic supplementary material The online version of this article (doi:10.1007/s10162-008-0123-1) contains supplementary material, which is available to authorized users. University of Antwerp 2 Department of Otorhinolaryngology, University Hospital of Antwerp , 2650 Antwerp, Belgium 3 A multicenter study was set up to elucidate the envi- ronmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine sub- samples, collected by nine audiological centers across Europe , added up to a total of 4, 083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors 4 Department of Otorhinolaryngology, University of Tampere , 33014 Tampere, Finland 5 Department of Medical Genetics, University of Antwerp, Universiteitsplein , 2610 Antwerp, Belgium 6 Department of Oto-Surgery, University Hospital Padova , 35128 Padova, Italy 7 Department of Otorhinolaryngology, University of Tbingen , 72074 Tbingen, Germany 8 Department of Audiology, Bispebjerg Hospital , 2400 NV Copenhagen, Denmark 9 Department of Otorhinolaryngology, University Hospital of Ghent , 9000 Ghent, Belgium 10 College of Medicine, Cardiff University , CF14 4XW Cardiff, UK 11 Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn , 53105 Bonn, Germany - medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (91 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dosedependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (G2 kHz). A high body mass index (BMI) correlated with hearing loss across the frequency range tested. Moderate alcohol consumption was inversely correlated with hearing loss. Significant associations were found in the high as well as in the low frequencies. The results suggest that a healthy lifestyle can protect against age-related hearing impairment. Several factors contribute to the decline in hearing acuity with increasing age. Apart from biological degeneration because of aging in itself, age-related hearing impairment (ARHI) is influenced by genetic risk factors, exposure to noise and toxic substances, and the occurrence of certain diseases. The relative contributions of the different risk factors are difficult to estimate, and the interactions between them remain unclear. Typically, ARHI is sensorineural, bilaterally symmetrical and more pronounced at high frequencies with males more severely affected than females. There is a large variation between individuals, which is larger in males than in females (Lee et al. 2005). Variability increases with age and is greater at the high frequencies. ARHI starts slowly around the fifth decade and worsens gradually, becoming the most common sensory impairment in the elderly. Between the ages of 60 and 70 years, about one third of the population has an average hearing loss (HL) of 25 dB or more for pure tones at 0.5, 1, 2, and 4 kHz. Between the age of 70 and 80 years, the proportion of individuals with a pure-tone average (PTA) showing over 25 dB HL increases to 50% (Davis 1994). Although this is considered mild hearing loss, it seriously affects an individuals ability to communicate in a noisy environment. When comparing ARHI in men and women of different ages, one needs to correct for gender and age differences between the subjects, and this correction is different depending on the frequencies studied. The expected median hearing threshold as a function of age, sex, and frequency, plus the standard deviation around this median, is given by the ISO 7029 standard (International Organisation of Standardization 1984). In a previous paper, we developed a method to quantify how severely a person is affected by age-related hearing loss, given his/her age and sex (Fransen et al. 2004). In this method, a Z score is defined as the standardized difference between an individuals observed hearing threshold at a given frequency and the age- and sex-specific median for that frequency. This allows the comparison of individuals of different age and sex. Ideally, in a randomly collected highly screened population, Z scores should have a standard normal distribution with no differences between males and females and no relation to age. However, several studies indicate that typical unscreened populations have slightly worse hearing than predicted by the ISO 7029 standard, whereby the former seem to have an apparent excess aging by 1015 years compared to the population described by the ISO 7029 standard (Robinson 1988; Lutman and Davis 1994; Engdahl et al. 2005). Importance of genetics The relative importance of genes in ARHI is agedependent. A heritability estimate by Karlsson et al. (1997) indicated that in the age stratum 5665, 58% of the variance in hearing thresholds was attributable to the influence of genes, declining to 47% in the stratum over 65. In the Framingham cohort, Gates et al. (1999) found a clear familial aggregation of the hearing thresholds. The heritability also seems to be frequency-dependent with a higher heritability in the low frequencies. The advent of high-throughput methods for genetic analysis provides tools for identifying genetic variants implicated in ARHI. A genome-wide linkage study in the Framingham cohort identified several loci with suggestive evidence for linkage (DeStefano et al. 2003). Garringer et al. (2006) reported suggestive linkage in the DFNA18 region in the general population. Polymorphisms in the N-acetyltransferase 2 (NAT2) and KCNQ4 genes were found to be associated with ARHI in two independent populations (nal et al. 2005; Van Eyken et al. 2006, 2007). Environmental risk factors Whereas research into genetic variants associated with ARHI is (...truncated)