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Body Mass Index, Waist Circumference, Physical Activity, and Risk of Hearing Loss in Women

  • Sharon G. Curhan
    Correspondence
    Requests for reprints should be addressed to Sharon G. Curhan, MD, MSc, Channing Division of Network Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115.
    Affiliations
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass
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  • Roland Eavey
    Affiliations
    Vanderbilt Bill Wilkerson Center for Otolaryngology and Communication Sciences, Vanderbilt University School of Medicine, Nashville, Tenn
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  • Molin Wang
    Affiliations
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass

    Department of Biostatistics, Harvard School of Public Health, Boston, Mass

    Department of Epidemiology, Harvard School of Public Health, Boston, Mass
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  • Meir J. Stampfer
    Affiliations
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass

    Department of Epidemiology, Harvard School of Public Health, Boston, Mass
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  • Gary C. Curhan
    Affiliations
    Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass

    Department of Epidemiology, Harvard School of Public Health, Boston, Mass

    Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Mass
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Published:October 14, 2013DOI:https://doi.org/10.1016/j.amjmed.2013.04.026

      Abstract

      Background

      Acquired hearing loss is highly prevalent, but prospective data on potentially modifiable risk factors are limited. In cross-sectional studies, higher body mass index (BMI), larger waist circumference, and lower physical activity have been associated with poorer hearing, but these have not been examined prospectively.

      Methods

      We examined the independent associations between BMI, waist circumference, and physical activity, and self-reported hearing loss in 68,421 women in the Nurses' Health Study II from 1989 to 2009. Baseline and updated information on BMI, waist circumference, and physical activity was obtained from biennial questionnaires.

      Results

      After more than 1.1 million person-years of follow-up, 11,286 cases of hearing loss were reported to have occurred. Higher BMI and larger waist circumference were associated with increased risk of hearing loss. Compared with women with BMI <25 kg/m2, the multivariate-adjusted relative risk (RR) for women with BMI ≥40 was 1.25 (95% confidence interval [CI], 1.14-1.37). Compared with women with waist circumference <71 cm, the multivariate-adjusted RR for waist circumference >88 cm was 1.27 (95% CI, 1.17-1.38). Higher physical activity was related inversely to risk; compared with women in the lowest quintile of physical activity, the multivariate-adjusted RR for women in the highest quintile was 0.83 (95% CI, 0.78-0.88). Walking 2 hours per week or more was associated inversely with risk. Simultaneous adjustment for BMI, waist circumference, and physical activity slightly attenuated the associations but they remained statistically significant.

      Conclusions

      Higher BMI and larger waist circumference are associated with increased risk, and higher physical activity is associated with reduced risk of hearing loss in women. These findings provide evidence that maintaining healthy weight and staying physically active, potentially modifiable lifestyle factors, may help reduce the risk of hearing loss.

      Keywords

      • Higher body mass index and larger waist circumference may increase the risk of hearing loss in women.
      • Higher levels of physical activity may reduce the risk of hearing loss in women.
      • Walking 2 hours per week or more may reduce the risk of hearing loss in women.
      Acquired hearing loss is a highly prevalent disabling chronic condition. In the US, it is estimated that up to 1/3 of women in their fifties and 2/3 of women in their sixties suffer from some degree of hearing loss.
      • Agrawal Y.
      • Platz E.A.
      • Niparko J.K.
      Prevalence of hearing loss and differences by demographic characteristics among US adults: data from the National Health and Nutrition Examination Survey, 1999-2004.
      Hearing loss can impair communication and social interaction, and adversely affect psychosocial well-being and quality of life.
      • Cacciatore F.
      • Napoli C.
      • Abete P.
      • Marciano E.
      • Triassi M.
      • Rengo F.
      Quality of life determinants and hearing function in an elderly population: Osservatorio Geriatrico Campano Study Group.
      • Mulrow C.D.
      • Aguilar C.
      • Endicott J.E.
      • et al.
      Association between hearing impairment and the quality of life of elderly individuals.
      Therefore, identification of potentially modifiable risk factors for hearing loss is a compelling public health goal.
      Obesity and its comorbidities, cardiovascular disease,
      • Agrawal Y.
      • Platz E.A.
      • Niparko J.K.
      Prevalence of hearing loss and differences by demographic characteristics among US adults: data from the National Health and Nutrition Examination Survey, 1999-2004.
      • Torre 3rd, P.
      • Cruickshanks K.J.
      • Klein B.E.
      • Klein R.
      • Nondahl D.M.
      The association between cardiovascular disease and cochlear function in older adults.
      • Nash S.D.
      • Cruickshanks K.J.
      • Klein R.
      • et al.
      The prevalence of hearing impairment and associated risk factors: the Beaver Dam Offspring Study.
      • Gates G.A.
      • Cobb J.L.
      • D'Agostino R.B.
      • Wolf P.A.
      The relation of hearing in the elderly to the presence of cardiovascular disease and cardiovascular risk factors.
      cerebrovascular disease,
      • Kiely K.M.
      • Gopinath B.
      • Mitchell P.
      • Luszcz M.
      • Anstey K.J.
      Cognitive, health, and sociodemographic predictors of longitudinal decline in hearing acuity among older adults.
      • Helzner E.P.
      • Cauley J.A.
      • Pratt S.R.
      • et al.
      Race and sex differences in age-related hearing loss: the Health, Aging and Body Composition Study.
      diabetes,
      • Bainbridge K.E.
      • Hoffman H.J.
      • Cowie C.C.
      Diabetes and hearing impairment in the United States: audiometric evidence from the National Health and Nutrition Examination Survey, 1999 to 2004.
      • Kakarlapudi V.
      • Sawyer R.
      • Staecker H.
      The effect of diabetes on sensorineural hearing loss.
      hypertension,
      • Gates G.A.
      • Cobb J.L.
      • D'Agostino R.B.
      • Wolf P.A.
      The relation of hearing in the elderly to the presence of cardiovascular disease and cardiovascular risk factors.
      • Brant L.J.
      • Gordon-Salant S.
      • Pearson J.D.
      • et al.
      Risk factors related to age-associated hearing loss in the speech frequencies.
      and dyslipidemia,
      • Gates G.A.
      • Cobb J.L.
      • D'Agostino R.B.
      • Wolf P.A.
      The relation of hearing in the elderly to the presence of cardiovascular disease and cardiovascular risk factors.
      may be related to the development of hearing loss, potentially due to compromised vascular supply to the stria vascularis and impaired cochlear function. Obese leptin-deficient mice develop sensorineural hearing loss earlier than their wild-type counterparts.
      • Lee H.S.
      • Kim K.R.
      • Chung W.H.
      • Cho Y.S.
      • Hong S.H.
      Early sensorineural hearing loss in ob/ob mouse, an animal model of type 2 diabetes.
      In human cross-sectional studies, higher body mass index (BMI), a measure of overall obesity, and larger waist circumference, a measure of central adiposity, have been associated with poorer hearing thresholds.
      • Helzner E.P.
      • Patel A.S.
      • Pratt S.
      • et al.
      Hearing sensitivity in older adults: associations with cardiovascular risk factors in the health, aging and body composition study.
      • Fransen E.
      • Topsakal V.
      • Hendrickx J.J.
      • et al.
      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.
      • Hwang J.H.
      • Wu C.C.
      • Hsu C.J.
      • Liu T.C.
      • Yang W.S.
      Association of central obesity with the severity and audiometric configurations of age-related hearing impairment.
      However, the relation between obesity and hearing loss has not been examined prospectively.
      Higher levels of physical activity may protect against hearing loss. Physical activity may have beneficial effects on the cochlear vascular endothelium, enhance detoxification of free radicals, and reduce inflammation. Small cross-sectional studies have reported relations between higher levels of physical activity, higher cardiorespiratory fitness, and better hearing sensitivity.
      • Hutchinson K.M.
      • Alessio H.
      • Baiduc R.R.
      Association between cardiovascular health and hearing function: pure-tone and distortion product otoacoustic emission measures.
      • Loprinzi P.D.
      • Cardinal B.J.
      • Gilham B.
      Association between cardiorespiratory fitness and hearing sensitivity.
      A number of conditions implicated in hearing loss, such as diabetes and cardiovascular disease, are associated inversely with higher levels of physical activity.
      • Hu F.B.
      • Sigal R.J.
      • Rich-Edwards J.W.
      • et al.
      Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study.
      • Manson J.E.
      • Hu F.B.
      • Rich-Edwards J.W.
      • et al.
      A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women.
      Yet, it is unclear whether physical activity is an independent risk factor for hearing loss.
      We prospectively analyzed the association between these potentially modifiable factors and the risk of hearing loss in 68,421 female participants in the Nurses' Health Study II (NHS II).

      Methods

      Study Participants

      The Nurses' Health Study II is comprised of 116,430 female registered nurses aged 25-42 years from 14 states who answered a mailed questionnaire in 1989. Questionnaires were administered every other year and the average follow-up rate over 22 years exceeds 90%. The questionnaires elicited information on anthropometric measures, lifestyle factors, medication use, and medical conditions. Detailed information on diet was obtained every 4 years. The 2009 questionnaire asked participants whether they have a hearing problem and at what age a change in hearing was first noticed. We excluded women who reported a hearing problem (n = 2530) or cancer (n = 654) that began before 1989. We also excluded women who developed cancer during follow-up and before the onset of hearing loss (n = 4118). To refine the categorization of hearing “problem” as hearing “loss,” we excluded participants who reported tinnitus that occurred more than once/week at baseline or during follow-up and before the onset of hearing loss (n = 6490), because tinnitus is a strong risk factor for hearing loss.
      • Henry J.A.
      • Dennis K.C.
      • Schechter M.A.
      General review of tinnitus: prevalence, mechanisms, effects, and management.
      • Nondahl D.M.
      • Cruickshanks K.J.
      • Wiley T.L.
      • Klein R.
      • Klein B.E.
      • Tweed T.S.
      Prevalence and 5-year incidence of tinnitus among older adults: the epidemiology of hearing loss study.
      • Hasson D.
      • Theorell T.
      • Westerlund H.
      • Canlon B.
      Prevalence and characteristics of hearing problems in a working and non-working Swedish population.
      We performed secondary analyses that included these women and stratified by tinnitus. The study protocol was approved by the Institutional Review Board of Brigham and Women's Hospital.

      Assessment of BMI

      BMI was calculated based on height, reported at study entry in 1989, and weight, reported on each biennial questionnaire, and these measurements were used to calculate biennially updated BMI. In a validation study, self-reported height and weight and direct measurements were highly correlated (height, r = 0.94 and weight, r = 0.96)
      • Willett W.
      • Stampfer M.J.
      • Bain C.
      • et al.
      Cigarette smoking, relative weight, and menopause.
      • Troy L.M.
      • Hunter D.J.
      • Manson J.E.
      • Colditz G.A.
      • Stampfer M.J.
      • Willett W.C.
      The validity of recalled weight among younger women.
      in a similar cohort of women.

      Assessment of Waist Circumference

      Waist circumference was assessed at 2 time points, in 1993 and 2005. Participants were sent a measuring tape and asked to report their waist circumference to the nearest ¼ inch. Self-measured waist circumference was found to be correlated with technician-measured waist circumference measurements (r = 0.89).
      • Rimm E.B.
      • Stampfer M.J.
      • Colditz G.A.
      • Chute C.G.
      • Litin L.B.
      • Willett W.C.
      Validity of self-reported waist and hip circumferences in men and women.
      Information on waist circumference was available for 50% of study participants.

      Assessment of Physical Activity

      Information on physical activity was first collected in 1989 and again in 1991, 1997, 2001, 2005, and 2009. Participants completed a physical activity grid, modified slightly on successive questionnaires, and reported average time spent per week in the previous year in a variety of recreational activities: walking for exercise, walking to work, hiking outdoors, jogging (>10 min/mile), running (≤10 min/mile), bicycling (including stationary machine), calisthenics/aerobics/aerobic dance/rowing machine, tennis, squash, racquetball, lap swimming, other aerobic activity (eg, aerobics, dance, ski/stair machine), lower-intensity exercise (eg, yoga, stretching, toning), other vigorous activities, weight training, or resistance exercise. Participants also reported flights of stairs climbed daily. Energy expenditure in metabolic-equivalent tasks (METs) in hours/week
      • Rockhill B.
      • Willett W.C.
      • Manson J.E.
      • et al.
      Physical activity and mortality: a prospective study among women.
      was calculated using the Ainsworth classification .
      • Ainsworth B.E.
      • Haskell W.L.
      • Herrmann S.D.
      • et al.
      2011 Compendium of Physical Activities: a second update of codes and MET values.
      One MET is the amount of energy expended while sitting quietly, hence an activity with MET score of 5 requires 5 times the energy as sitting quietly. Total physical activity was derived from the reported hours spent per week in recreational activities plus the reported number flights of stairs climbed daily. Walking pace was used to determine the MET score for calculating MET h/week from walking.
      • Ainsworth B.E.
      • Haskell W.L.
      • Leon A.S.
      • et al.
      Compendium of physical activities: classification of energy costs of human physical activities.
      The reproducibility and validity of the physical activity questionnaire have been demonstrated in a representative sample of 147 NHS II participants. The questionnaire-based estimate of physical activity was highly correlated with 1-week recall (r = 0.79) and 4 1-week diaries completed over the course of 1 year (r = 0.62).
      • Wolf A.M.
      • Hunter D.J.
      • Colditz G.A.
      • et al.
      Reproducibility and validity of a self-administered physical activity questionnaire.

      Assessment of Hearing Loss

      The primary outcome, self-reported hearing loss, was determined based on responses to the 2009 question “Do you have a hearing problem?” with response categories: “no,” “mild,” “moderate,” or “severe,” and, “If so, at what age did you first notice a change in your hearing?” Of the 80,096 women who responded to this questionnaire, 23.3% reported a hearing problem.
      We defined an incident case as hearing problem first noticed after 1989. We excluded those who reported tinnitus; therefore, we considered the remaining cases of self-reported hearing problem to be hearing loss. Although hearing loss is usually insidious in onset, we defined incident cases as hearing loss when first noticed by the participant. We did not have information on severity of hearing loss at the time of onset, thus we were not able to perform prospective analyses that considered severity of hearing loss as the outcome. Pure-tone audiometry is considered the gold standard for hearing loss evaluation, but cost and logistic limitations precluded such assessment in this large population. Studies that assessed the reliability of self-reported hearing loss using a single question found this method to be a reasonably reliable measure.
      • Gomez M.I.
      • Hwang S.A.
      • Sobotova L.
      • Stark A.D.
      • May J.J.
      A comparison of self-reported hearing loss and audiometry in a cohort of New York farmers.
      • Schow R.L.
      • Gatehouse S.
      Fundamental issues in self-assessment of hearing.
      • Sindhusake D.
      • Mitchell P.
      • Newall P.
      • Golding M.
      • Rochtchina E.
      • Rubin G.
      Prevalence and characteristics of tinnitus in older adults: the Blue Mountains Hearing Study.
      A recent validation study of individuals aged 30-65 years evaluated the performance of a single question as compared with results from pure-tone audiometry and found the sensitivity and specificity were 79.6% and 77.4%, respectively.
      • Ferrite S.
      • Santana V.S.
      • Marshall S.W.
      Validity of self-reported hearing loss in adults: performance of three single questions.

      Assessment of Covariates

      We considered covariates purported to be risk factors for hearing loss, including age,
      • Agrawal Y.
      • Platz E.A.
      • Niparko J.K.
      Prevalence of hearing loss and differences by demographic characteristics among US adults: data from the National Health and Nutrition Examination Survey, 1999-2004.
      race,
      • Agrawal Y.
      • Platz E.A.
      • Niparko J.K.
      Prevalence of hearing loss and differences by demographic characteristics among US adults: data from the National Health and Nutrition Examination Survey, 1999-2004.
      smoking,
      • Itoh A.
      • Nakashima T.
      • Arao H.
      • et al.
      Smoking and drinking habits as risk factors for hearing loss in the elderly: epidemiological study of subjects undergoing routine health checks in Aichi, Japan.
      intake of alcohol,
      • Itoh A.
      • Nakashima T.
      • Arao H.
      • et al.
      Smoking and drinking habits as risk factors for hearing loss in the elderly: epidemiological study of subjects undergoing routine health checks in Aichi, Japan.
      folate,
      • Durga J.
      • Verhoef P.
      • Anteunis L.J.
      • Schouten E.
      • Kok F.J.
      Effects of folic acid supplementation on hearing in older adults: a randomized, controlled trial.
      vitamin B12,
      • Houston D.K.
      • Johnson M.A.
      • Nozza R.J.
      • et al.
      Age-related hearing loss, vitamin B-12, and folate in elderly women.
      magnesium,
      • Haupt H.
      • Scheibe F.
      • Mazurek B.
      Therapeutic efficacy of magnesium in acoustic trauma in the guinea pig.
      potassium, vitamin A,
      • Le Prell C.G.
      • Hughes L.F.
      • Miller J.M.
      Free radical scavengers vitamins A, C, and E plus magnesium reduce noise trauma.
      hypertension,
      • Gates G.A.
      • Cobb J.L.
      • D'Agostino R.B.
      • Wolf P.A.
      The relation of hearing in the elderly to the presence of cardiovascular disease and cardiovascular risk factors.
      diabetes,
      • Bainbridge K.E.
      • Hoffman H.J.
      • Cowie C.C.
      Diabetes and hearing impairment in the United States: audiometric evidence from the National Health and Nutrition Examination Survey, 1999 to 2004.
      acetaminophen use, and ibuprofen use.
      • Curhan S.
      • Shargorodsky J.
      • Eavey R.
      • Curhan G.
      Analgesic use and the risk of hearing loss in women.
      Covariate information was obtained from the biennial questionnaires. Intakes of alcohol, folate, B12, potassium, magnesium, and vitamin A were calculated from semiquantitative food frequency questionnaires mailed first in 1991 and every 4 years thereafter. Beginning in 1995 and every 2 years thereafter, participants were asked about average frequency of use of analgesics.

      Statistical Analysis

      All analyses were prospective, using exposure information collected before the reported onset of the hearing problem. BMI was calculated and categorized as <25, 25-29, 30-34, 35-39, and 40+, which conform with World Health Organization categories for healthy weight (BMI <25), pre-obese (BMI 25-29), obese class I (30-34), obese class II (35-39), and obese class III (BMI 40+). Waist circumference was categorized according to previously used cutoff points: <71 cm, 71-79 cm, 80-88 cm, and >88 cm.
      • Flint A.J.
      • Rexrode K.M.
      • Hu F.B.
      • et al.
      Body mass index, waist circumference, and risk of coronary heart disease: a prospective study among men and women.
      Physical activity, expressed as METs/week, was categorized in quintiles. Intensity of physical activity was categorized as strenuous (activities with a MET value >6) and moderate (activities with a MET value of 3.5-6). Hours per week of walking was categorized into 4 categories: <1 h/week, 1-1.5 h/week, 2-4 h/week, and 4+ h/week, in a way that is consistent with previous examinations of the relation between walking and other health outcomes in this cohort.
      • Feskanich D.
      • Willett W.
      • Colditz G.
      Walking and leisure-time activity and risk of hip fracture in postmenopausal women.
      • Maruti S.S.
      • Willett W.C.
      • Feskanich D.
      • Rosner B.
      • Colditz G.A.
      A prospective study of age-specific physical activity and premenopausal breast cancer.
      For each participant, person-time was allocated based on the most recent responses to the weight, waist circumference, and physical activity questions at the beginning of each follow-up period. Participants were censored at the age of reported hearing loss or cancer, whichever came first. Missing categories were created for data on covariates that were not available. Age- and multivariate-adjusted relative risks (RRs) were estimated using Cox proportional hazards regression models, with the Anderson-Gill data structure.
      • Therneau T.M.
      Extending the Cox Model.
      To control as finely as possible for confounding by age, calendar time, and any possible 2-way interactions between these 2 time scales, we stratified the analysis jointly by age in months at start of follow-up and calendar year of the current questionnaire cycle. To examine whether the associations vary by age, we performed likelihood ratio tests comparing models with and without the age*exposure interaction terms.
      For all RRs, we calculated 95% confidence intervals (CIs). All P values are 2-tailed. Tests of linear trend across increasing categories of exposure were conducted by treating the BMI, waist circumference, and physical activity categories as continuous variables and assigning the median value for each category. All analyses were performed using SAS statistical software, version 9.2 (SAS Institute Inc., Cary, NC).

      Results

      Characteristics of participants at baseline are summarized in Table 1. The mean age was 34.5 years, the median BMI was 22.6 kg/m2 (interquartile range [IQR] 20.7-25.6), the median waist circumference in 1993 was 73.7 cm (IQR 68.6-83.8), and the median level of physical activity was 13.9 METs/week (IQR 5.4-30.2). Walking for exercise 1 h/week or more was reported by 58% of the women. Participants who answered the 2009 main questionnaire, on which hearing loss was first assessed, did not differ appreciably with respect to baseline characteristics from those participants who did not.
      Table 1Baseline Characteristics of Nurses' Health Study II Women
      CharacteristicN = 68,421
      Age, years34.5 (4.6)
      Caucasian, %93.1
      Body mass index, kg/m²22.6 (20.7-25.6)
      Waist circumference, cm73.7 (68.6-83.8)
      Physical activity, METs
      Metabolic equivalent tasks (MET) from recreational and leisure-time activities.
      /week
      13.9 (5.4-30.2)
      Never smoker, %66.7
      Past smoker, %21.3
      Current smoker, %11.6
      Alcohol, g/d0.9 (0.0-3.50)
      Vitamin B12, μg/d7.0 (5.0-11.0)
      Folate, μg/d372 (280-609)
      Potassium, mg/d2940 (533)
      Magnesium, mg/d316 (74)
      Vitamin A, IU/d11,113 (7702-15,722)
      History of hypertension, %5.0
      History of diabetes, %0.6
      Ibuprofen use
      Regular use 2+ times per week.
      , %
      18.3
      Acetaminophen use
      Regular use 2+ times per week.
      , %
      20.6
      Walking, %
       <1 h/week41.9
       1-1.5 h/week24.8
       2-3 h/week17.0
       4+ h/week16.3
      Values are means (SD), medians (interquartile range), or percentages.
      Dietary factors assessed in 1991.
      Waist circumference assessed in 1993.
      Ibuprofen and acetaminophen use assessed in 1995.
      Metabolic equivalent tasks (MET) from recreational and leisure-time activities.
      Regular use 2+ times per week.
      After 1,159,460 person-years of follow-up, 11,286 cases of hearing loss were reported to have occurred. The age- and multivariate-adjusted RRs of hearing loss according to category of BMI are presented in Table 2. Higher BMI was associated independently with an increased risk of hearing loss. In a multivariate-adjusted model that did not include physical activity, compared with women with BMI <25, the RR for hearing loss in those with BMI ≥40 was 1.25 (95% CI, 1.14-1.37; P-trend <.001). Further adjusting for physical activity and for waist circumference slightly attenuated the association; however, a BMI of 25 or greater remained independently associated with risk of hearing loss.
      Table 2Body Mass Index and Risk of Self-reported Hearing Loss among Women in the Nurses' Health Study II (1989-2009)
      Categories of Body Mass Index (kg/m2)P-Trend
      <2525-2930-3435-3940+
      Cases489930591577762535
      Age-adjusted RR (95% CI)1.00 (ref)1.14 (1.09-1.19)1.21 (1.14-1.28)1.29 (1.19-1.39)1.34 (1.23-1.47)<.001
      Multivariate-adjusted
      Adjusted for age, race, smoking, alcohol intake, intake of B12, magnesium, potassium, vitamin A, and folate, baseline hypertension, baseline diabetes, acetaminophen use, and ibuprofen use.
      RR (95% CI) (without PA or WC)
      1.00 (ref)1.12 (1.07-1.17)1.17 (1.10-1.24)1.22 (1.12-1.31)1.25 (1.14-1.37)<.001
      Multivariate-adjusted
      Adjusted for all of the above, as well as for physical activity (PA).
      RR (95% CI) (with PA)
      1.00 (ref)1.11 (1.06-1.16)1.14 (1.08-1.21)1.18 (1.09-1.28)1.21 (1.10-1.32)<.001
      Multivariate-adjusted
      Adjusted for all of the above, as well as for physical activity (PA) and waist circumference (WC).
      RR (95% CI) (with PA and WC)
      1.00(ref)1.08 (1.03-1.14)1.11 (1.03-1.18)1.16 (1.06-1.26)1.19 (1.07-1.32)<.001
      CI = confidence interval; RR = relative risk.
      Information on WC was first obtained in 1993. Information on analgesic use was first obtained in 1995.
      Adjusted for age, race, smoking, alcohol intake, intake of B12, magnesium, potassium, vitamin A, and folate, baseline hypertension, baseline diabetes, acetaminophen use, and ibuprofen use.
      Adjusted for all of the above, as well as for physical activity (PA).
      Adjusted for all of the above, as well as for physical activity (PA) and waist circumference (WC).
      Larger waist circumference also was associated independently with an increased risk of hearing loss (Table 3). In a multivariate-adjusted model that did not include BMI or physical activity, compared with women with waist circumference <71 cm, the RR for hearing loss in those with waist circumference >88 cm was 1.27 (95% CI, 1.17-1.38; P-trend <.001). Further adjusting for physical activity and for BMI attenuated the association; however, waist circumference >88 cm remained associated independently with risk of hearing loss (multivariate-adjusted RR = 1.17; 95% CI, 1.06-1.29).
      Table 3Waist Circumference and Risk of Self-reported Hearing Loss Among Women in the Nurses' Health Study II (1993-2009)
      Categories of Waist Circumference (cm)P-Trend
      <7171-7980-88>88
      Cases777216019492866
      Age-adjusted RR (95% CI)1.00 (ref)1.16 (1.07-1.26)1.24 (1.14-1.35)1.48 (1.36-1.61)<.001
      Multivariate-adjusted
      Adjusted for: age, race, smoking, alcohol intake, intake of B12, magnesium, potassium, vitamin A, and folate, baseline hypertension, baseline diabetes, acetaminophen use, and ibuprofen use.
      RR (95% CI) (without BMI or PA)
      1.00 (ref)1.07 (0.99-1.16)1.11 (1.02-1.21)1.27 (1.17-1.38)<.001
      Multivariate-adjusted
      Adjusted for all of the above as well as for physical activity (PA).
      RR (95% CI) (with PA)
      1.00 (ref)1.07 (0.98-1.16)1.09 (1.00-1.19)1.23 (1.14-1.34)<.001
      Multivariate-adjusted
      Adjusted for all of the above as well as for body mass index (BMI) and physical activity (PA).
      RR (95% CI) (with BMI and PA)
      1.00 (ref)1.05 (0.97-1.14)1.05 (0.95-1.15)1.17 (1.06-1.29).001
      CI = confidence interval; RR = relative risk.
      Information on waist circumference was first obtained in 1993. Information on analgesic use was first obtained in 1995.
      Adjusted for: age, race, smoking, alcohol intake, intake of B12, magnesium, potassium, vitamin A, and folate, baseline hypertension, baseline diabetes, acetaminophen use, and ibuprofen use.
      Adjusted for all of the above as well as for physical activity (PA).
      Adjusted for all of the above as well as for body mass index (BMI) and physical activity (PA).
      Higher level of physical activity was associated inversely with the risk of hearing loss (Table 4). In a multivariate model that did not include BMI or waist circumference, the RR for hearing loss for women in the highest quintile compared with the lowest quintile of physical activity was 0.83 (95% CI, 0.78-0.88; P-trend <.001). Further adjusting for BMI slightly attenuated the association (multivariate-adjusted RR = 0.86; 95% CI, 0.81-0.92).
      Table 4Physical Activity and Risk of Self-reported Hearing Loss Among Women In the Nurses' Health Study II (1989-2009)
      Physical Activity (METs/week) QuintilesP-Trend
      12345
      1989 METs/week, median (range)
      1989 values are presented to be representative, however, physical activity was updated in the analyses.
      1.9 (<4.0)6.5 (4.0-9.6)13.6 (9.7-18.9)25.4 (19.0-36.5)56.7 (36.6+)
      Cases22642233227820361923
      Age-adjusted RR (95% CI)1.00 (ref)0.96 (0.90-1.01)0.95 (0.90-1.01)0.85 (0.80-0.90)0.83 (0.78-0.88)<.001
      Multivariate-adjusted
      Adjusted for: age, race, smoking, alcohol intake, intake of B12, magnesium, potassium, vitamin A, and folate, baseline hypertension, baseline diabetes, acetaminophen use, and ibuprofen use.
      RR (95% CI) (without BMI)
      1.00 (ref)0.95 (0.90-1.01)0.95 (0.90-1.01)0.86 (0.81-0.91)0.83 (0.78-0.88)<.001
      Multivariate-adjusted
      Adjusted for all of the above as well as for body mass index (BMI).
      RR (95% CI) (with BMI)
      1.00 (ref)0.96 (0.91-1.02)0.97 (0.91-1.03)0.88 (0.83-0.93)0.86 (0.81-0.92)<.001
      CI = confidence interval; RR = relative risk.
      Information on waist circumference was first obtained in 1993. Information on analgesic use was first obtained in 1995.
      1989 values are presented to be representative, however, physical activity was updated in the analyses.
      Adjusted for: age, race, smoking, alcohol intake, intake of B12, magnesium, potassium, vitamin A, and folate, baseline hypertension, baseline diabetes, acetaminophen use, and ibuprofen use.
      Adjusted for all of the above as well as for body mass index (BMI).
      Walking was the most common form of physical activity; therefore, we examined the relation between walking and risk of hearing loss. After multivariate adjustment, walking 2 or more hours/week was associated with lower risk of hearing loss (P-trend <.001) (Table 5). For example, compared with women who walked <1 h/week, the multivariate-adjusted RR of hearing loss for women who walked 4 or more hours per week was 0.85 (95% CI, 0.80-0.91).
      Table 5Walking and Risk of Self-reported Hearing Loss among Women in the Nurses' Health Study II (1989-2009)
      Walking (h/week)P-Trend
      <11-1.52-34+
      Cases4672255118391305
      Multivariate-adjusted
      Adjusted for: age, race, smoking, alcohol intake, intake of B12, magnesium, potassium, vitamin A, and folate, baseline hypertension, baseline diabetes, acetaminophen use, and ibuprofen use.
      RR (95% CI) (without BMI)
      1.00 (ref)0.98 (0.94-1.03)0.90 (0.85-0.95)0.85 (0.80-0.91)<.001
      Multivariate-adjusted
      Adjusted for all of the above as well as for body mass index (BMI).
      RR (95% CI) (with BMI)
      1.00 (ref)0.99 (0.94-1.03)0.92 (0.87-0.97)0.87 (0.81-0.92)<.001
      CI = confidence interval; RR = relative risk.
      Information on waist circumference was first obtained in 1993. Information on analgesic use was first obtained in 1995.
      Adjusted for: age, race, smoking, alcohol intake, intake of B12, magnesium, potassium, vitamin A, and folate, baseline hypertension, baseline diabetes, acetaminophen use, and ibuprofen use.
      Adjusted for all of the above as well as for body mass index (BMI).
      We examined the relation between strenuous physical activity, moderate physical activity, walking, and risk of hearing loss. We did not observe additional reduction in risk with more strenuous exercise. Similarly, when we examined the relation between walking, jogging, and running and risk of hearing loss, there was no additional reduction in risk with jogging or running (data not shown).
      The observed relations between BMI, waist circumference, physical activity, and hearing loss did not vary by age (P-interaction >.20 for global interaction with age for each exposure). In addition, the results were materially unchanged when relevant covariates were included as continuous rather than categorical (data not shown). We also performed analyses that did not exclude women with tinnitus and the results were not materially changed (data not shown).

      Discussion

      In this large prospective study of women, higher BMI and larger waist circumference were associated independently with an increased risk of hearing loss. The risk decreased with increasing level of physical activity; even walking 2 hours or more per week was associated with a lower risk. These findings may provide insight into potential mechanisms that underlie acquired hearing loss and suggest possible strategies for prevention.
      This prospective study confirms previous cross-sectional findings of an association between obesity and increased prevalence of hearing loss. Higher BMI was associated with poorer hearing sensitivities in a multinational European study
      • Fransen E.
      • Topsakal V.
      • Hendrickx J.J.
      • et al.
      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.
      and the Health ABC Study.
      • Helzner E.P.
      • Patel A.S.
      • Pratt S.
      • et al.
      Hearing sensitivity in older adults: associations with cardiovascular risk factors in the health, aging and body composition study.
      Moreover, our findings that larger waist circumference was associated independently with increased risk of hearing loss even after adjusting for BMI, similar to previous cross-sectional findings,
      • Hwang J.H.
      • Wu C.C.
      • Hsu C.J.
      • Liu T.C.
      • Yang W.S.
      Association of central obesity with the severity and audiometric configurations of age-related hearing impairment.
      suggest that waist circumference provides additional information about risk beyond BMI and that central adiposity may itself be a risk factor for hearing loss.
      This study also provides prospective evidence consistent with cross-sectional studies that reported higher levels of cardiorespiratory fitness associated with better hearing sensitivities.
      • Hutchinson K.M.
      • Alessio H.
      • Baiduc R.R.
      Association between cardiovascular health and hearing function: pure-tone and distortion product otoacoustic emission measures.
      Our findings suggest that walking 2 hours or more per week may reduce risk of hearing loss. Adjustment for BMI and waist circumference only modestly attenuated the association, suggesting the association is not primarily mediated through effects of physical activity on adiposity.
      Mechanisms that may underlie the relation between obesity, physical activity, and hearing function include hypoxia and ischemic damage, oxidative stress, and formation of reactive species, and resultant death of cochlear and spiral ganglion cells that leads to hearing loss. The Beaver Dam Offspring Study found cross-sectional associations between larger central retinal venular equivalent, an indicator of microvascular inflammation and endothelial dysfunction, and carotid intima media thickness, a subclinical measure of macrovascular atherosclerotic disease, and poorer hearing thresholds.
      • Nash S.D.
      • Cruickshanks K.J.
      • Klein R.
      • et al.
      The prevalence of hearing impairment and associated risk factors: the Beaver Dam Offspring Study.
      Obesity-related atherosclerosis may lead to stiffening and constriction of the internal auditory artery and reduction in cochlear blood flow.
      • Makishima K.
      Arteriolar sclerosis as a cause of presbycusis.
      Reduced blood supply to the cochlea, whether due to microvascular or macrovascular compromise, can lead to capillary constriction within the stria vascularis, cell death, and poorer hearing sensitivity.
      • Torre 3rd, P.
      • Cruickshanks K.J.
      • Klein B.E.
      • Klein R.
      • Nondahl D.M.
      The association between cardiovascular disease and cochlear function in older adults.
      • Gates G.A.
      • Cobb J.L.
      • D'Agostino R.B.
      • Wolf P.A.
      The relation of hearing in the elderly to the presence of cardiovascular disease and cardiovascular risk factors.
      • Liew G.
      • Wong T.Y.
      • Mitchell P.
      • Newall P.
      • Smith W.
      • Wang J.J.
      Retinal microvascular abnormalities and age-related hearing loss: the Blue Mountains hearing study.
      • Seidman M.D.
      • Quirk W.S.
      • Shirwany N.A.
      Mechanisms of alterations in the microcirculation of the cochlea.
      Oxidative stress also has been implicated in acquired hearing loss.
      • Poirrier A.L.
      • Pincemail J.
      • Van Den Ackerveken P.
      • Lefebvre P.P.
      • Malgrange B.
      Oxidative stress in the cochlea: an update.
      • Seidman M.D.
      • Ahmad N.
      • Joshi D.
      • Seidman J.
      • Thawani S.
      • Quirk W.S.
      Age-related hearing loss and its association with reactive oxygen species and mitochondrial DNA damage.
      Antioxidants may prevent hearing loss due to exposure to ototoxic drugs or noise.
      • Hight N.G.
      • McFadden S.L.
      • Henderson D.
      • Burkard R.F.
      • Nicotera T.
      Noise-induced hearing loss in chinchillas pre-treated with glutathione monoethylester and R-PIA.
      Animal studies of cochlear changes that accompany age-related hearing loss demonstrate decreased antioxidant activity
      • Menardo J.
      • Tang Y.
      • Ladrech S.
      • et al.
      Oxidative stress, inflammation, and autophagic stress as the key mechanisms of premature age-related hearing loss in SAMP8 mouse Cochlea.
      and a decline in the ability to protect against free radical damage. Obesity-related oxidative stress and resultant damage to the auditory epithelia due to accumulation of reactive oxidative species may contribute to hearing loss.
      • Loffredo L.
      • Martino F.
      • Carnevale R.
      • et al.
      Obesity and hypercholesterolemia are associated with NOX2 generated oxidative stress and arterial dysfunction.
      Our findings suggest that larger waist circumference, a marker of central adiposity,
      • Ketel I.J.
      • Volman M.N.
      • Seidell J.C.
      • Stehouwer C.D.
      • Twisk J.W.
      • Lambalk C.B.
      Superiority of skinfold measurements and waist over waist-to-hip ratio for determination of body fat distribution in a population-based cohort of Caucasian Dutch adults.
      may increase the risk of hearing loss, beyond higher BMI. Greater central fat mass is associated with dyslipidemia, hypertension, and hypercoagulability.
      • Pou K.M.
      • Massaro J.M.
      • Hoffmann U.
      • et al.
      Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: the Framingham Heart Study.
      Low adiponectin plasma concentrations related to larger waist circumference may increase risk of hearing loss.
      • Hwang J.H.
      • Hsu C.J.
      • Liu T.C.
      • Yang W.S.
      Association of plasma adiponectin levels with hearing thresholds in adults.
      Higher levels of physical activity or better cardiorespiratory fitness may protect against hearing loss by improving vascular supply to the cochlea,
      • Gielen S.
      • Schuler G.
      • Adams V.
      Cardiovascular effects of exercise training: molecular mechanisms.
      preventing auditory neurodegeneration and neurotransmitter loss,
      • Kramer A.F.
      • Hahn S.
      • Cohen N.J.
      • et al.
      Ageing, fitness and neurocognitive function.
      and possibly moderating noise-induced damage.
      • Manson J.
      • Alessio H.M.
      • Cristell M.
      • Hutchinson K.M.
      Does cardiovascular health mediate hearing ability?.
      Higher levels of physical activity also are related inversely to a number of purported risk factors for hearing loss, including diabetes, vascular dysfunction, and cardiovascular disease.
      • Hu F.B.
      • Sigal R.J.
      • Rich-Edwards J.W.
      • et al.
      Walking compared with vigorous physical activity and risk of type 2 diabetes in women: a prospective study.
      • Manson J.E.
      • Hu F.B.
      • Rich-Edwards J.W.
      • et al.
      A prospective study of walking as compared with vigorous exercise in the prevention of coronary heart disease in women.
      • Hambrecht R.
      • Wolf A.
      • Gielen S.
      • et al.
      Effect of exercise on coronary endothelial function in patients with coronary artery disease.
      Physical activity may improve endothelial function, leading to endothelium-mediated arterial vasodilation and enhanced blood flow to the stria vascularis.
      • Gielen S.
      • Schuler G.
      • Adams V.
      Cardiovascular effects of exercise training: molecular mechanisms.
      Physical activity increases endothelial nitric oxide formation and improves endothelium-dependent vasodilation of cardiac and renal vasculature
      • Hambrecht R.
      • Wolf A.
      • Gielen S.
      • et al.
      Effect of exercise on coronary endothelial function in patients with coronary artery disease.
      • Robinson E.S.
      • Fisher N.D.
      • Forman J.P.
      • Curhan G.C.
      Physical activity and albuminuria.
      and could have similar protective effects on cochlear vasculature. Even moderate levels of physical activity can improve cardiorespiratory fitness.
      • Stofan J.R.
      • DiPietro L.
      • Davis D.
      • Kohl 3rd, H.W.
      • Blair S.N.
      Physical activity patterns associated with cardiorespiratory fitness and reduced mortality: the Aerobics Center Longitudinal Study.
      Higher cardiorespiratory fitness may be associated with protection against hypertension in the internal auditory artery and neuroprotective effects in the central nervous system, such as preservation of central auditory processing, attenuation of aging-related neurotransmitter loss, increased brain-derived neurotrophic factor expression, and increased resistance to auditory neurodegeneration.
      • Seifert T.
      • Brassard P.
      • Wissenberg M.
      • et al.
      Endurance training enhances BDNF release from the human brain.
      Higher levels of physical activity and cardiorespiratory fitness also may enhance resistance to noise-induced auditory damage.
      • Manson J.
      • Alessio H.M.
      • Cristell M.
      • Hutchinson K.M.
      Does cardiovascular health mediate hearing ability?.
      • Kolkhorst F.W.
      • Smaldino J.J.
      • Wolf S.C.
      • et al.
      Influence of fitness on susceptibility to noise-induced temporary threshold shift.
      Strengths of this study include its prospective design, large sample size, high follow-up rate, and validated methods to quantify BMI, waist circumference, and physical activity. The study population was relatively homogeneous with respect to education and occupation, reducing variability in those factors.
      • Cruickshanks K.J.
      • Nondahl D.M.
      • Tweed T.S.
      • et al.
      Education, occupation, noise exposure history and the 10-yr cumulative incidence of hearing impairment in older adults.
      Limitations include assessment of hearing loss based on self-report. Although sudden sensorineural hearing loss occurs, hearing loss is commonly insidious in onset, thus, imprecision in the assessment of date of onset exists. We defined incident hearing loss as when a hearing problem was first noticed by the participant. Standard pure-tone audiometry is the gold standard measure for evaluation of hearing loss; however, assessment of hearing loss based on self-report has been found to be reasonably reliable.
      • Gomez M.I.
      • Hwang S.A.
      • Sobotova L.
      • Stark A.D.
      • May J.J.
      A comparison of self-reported hearing loss and audiometry in a cohort of New York farmers.
      • Schow R.L.
      • Gatehouse S.
      Fundamental issues in self-assessment of hearing.
      • Ferrite S.
      • Santana V.S.
      • Marshall S.W.
      Validity of self-reported hearing loss in adults: performance of three single questions.
      • Coren S.
      • Hakstian A.R.
      The development and cross-validation of a self-report inventory to assess pure-tone threshold hearing sensitivity.
      Assessment of hearing loss was based on participant report in 2009 regarding date of onset. All information on exposures and covariates was collected before reported date of hearing loss onset; therefore, the relations were examined prospectively. We did not have information on hearing loss severity at the time of onset, thus, severity of hearing loss could not be considered. Although some participants were lost to follow-up since the inception of this cohort or did not answer the 2009 questionnaire, the baseline characteristics of participants who did and did not answer the 2009 questionnaire did not appreciably differ. Our study was limited to predominantly non-Hispanic white women, thus, further research in additional populations is warranted.

      Conclusion

      Higher body mass index and larger waist circumference are associated with an increased risk, and higher level of physical activity is associated with a decreased risk of hearing loss in women.

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