Citrus Consumption and Risk of Cutaneous Malignant Melanoma

Purpose Citrus products are widely consumed foods that are rich in psoralens and furocoumarins, a group of naturally occurring chemicals with potential photocarcinogenic properties. We prospectively evaluated the risk of cutaneous malignant melanoma associated with citrus consumption. Methods A total of 63,810 women in the Nurses' Health Study (1984 to 2010) and 41,622 men in the Health Professionals Follow-Up Study (1986 to 2010) were included. Dietary information was repeatedly assessed every 2 to 4 years during follow-up. Incident melanoma cases were identified through self-report and confirmed by pathologic records. Results Over 24 to 26 years of follow-up, we documented 1,840 incident melanomas. After adjustment for other risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption < twice per week (reference), 1.10 (95% CI, 0.94 to 1.30) for two to four times per week, 1.26 (95% CI, 1.08 to 1.47) for five to six times per week, 1.27 (95% CI, 1.09 to 1.49) for once to 1.5 times per day, and 1.36 (95% CI, 1.14 to 1.63) for ≥ 1.6 times per day (Ptrend < .001). Among individual citrus products, grapefruit showed the most apparent association with risk of melanoma, which was independent of other lifestyle and dietary factors. The pooled multivariable hazard ratio for melanoma comparing the extreme consumption categories of grapefruit (≥ three times per week v never) was 1.41 (95% CI, 1.10 to 1.82; Ptrend < .001). Conclusion Citrus consumption was associated with an increased risk of malignant melanoma in two cohorts of women and men. Nevertheless, further investigation is needed to confirm our findings and explore related health implications.

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Farming tasks and the development of rheumatoid arthritis in the agricultural health study

Occupational and Environmental Medicine ◽

10.1136/oemed-2018-105361 ◽

2019 ◽

pp. oemed-2018-105361 ◽

Cited By ~ 4

Author(s):

Christine G Parks ◽

Armando Meyer ◽

Laura E Beane Freeman ◽

Jonathan Hofmann ◽

Dale P Sandler

Keyword(s):

Rheumatoid Arthritis ◽

Self Report ◽

Health Study ◽

Proportional Hazard ◽

Agricultural Health ◽

Cox Proportional Hazard ◽

Hazard Ratios ◽

Cox Proportional Hazard Models ◽

Agricultural Health Study

ObjectivesFarming has been associated with rheumatoid arthritis (RA). Some studies have evaluated the effects of pesticides, but other agricultural exposures may also affect immune response.MethodsWe investigated non-pesticide agricultural exposures in relation to RA in licensed pesticide applicators (n=27 175, mostly male farmers) and their spouses (n=22 231) in the Agricultural Health Study (AHS) cohort (1993–1997) who completed at least one follow-up survey through 2015. Incident RA cases (n=229 applicators and 249 spouses) were identified based on self-report confirmed by use of disease-modifying antirheumatic drugs or medical records. Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) were estimated by Cox proportional hazard models adjusting for applicator status, state, smoking, education and specific pesticide use, allowing estimates to vary by median age when hazards assumptions were not met.ResultsOverall, RA was associated with regularly applying chemical fertilisers (HR=1.50; 95% CI 1.11 to 2.02), using non-gasoline solvents (HR=1.40; 95% CI 1.09 to 1.80), and painting (HR=1.26; 95% CI 1.00 to 1.59). In older applicators (>62 years), RA was associated with driving combines (HR=2.46; 95% CI 1.05 to 5.78) and milking cows (HR=2.56; 95% CI 1.01 to 6.53). In younger participants (≤62 years), RA was inversely associated with raising animals as well as crops (HR=0.68; 95% CI 0.51 to 0.89 vs crops only). Associations with specific crops varied by age: some (eg, hay) were inversely associated with RA in younger participants, while others (eg, alfalfa) were associated with RA in older participants.ConclusionThese findings suggest several agricultural tasks and exposures may contribute to development of RA.

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Headache as a risk factor for dementia: A prospective population-based study

Cephalalgia ◽

10.1177/0333102413513181 ◽

2013 ◽

Vol 34 (5) ◽

pp. 327-335 ◽

Cited By ~ 22

Author(s):

Knut Hagen ◽

Eystein Stordal ◽

Mattias Linde ◽

Timothy J Steiner ◽

John-Anker Zwart ◽

...

Keyword(s):

Risk Factor ◽

Cohort Study ◽

Cox Regression ◽

Subsequent Development ◽

Population Based ◽

Health Study ◽

Cox Regression Analysis ◽

Hazard Ratios ◽

Increased Risk

Background Headache has not been established as a risk factor for dementia. The aim of this study was to determine whether any headache was associated with subsequent development of vascular dementia (VaD), Alzheimer’s disease (AD) or other types of dementia. Methods This prospective population-based cohort study used baseline data from the Nord-Trøndelag Health Study (HUNT 2) performed during 1995–1997 and, from the same Norwegian county, a register of cases diagnosed with dementia during 1997–2010. Participants aged ≥20 years who responded to headache questions in HUNT 2 were categorized (headache free; with any headache; with migraine; with nonmigrainous headache). Hazard ratios (HRs) for later inclusion in the dementia register were estimated using Cox regression analysis. Results Of 51,383 participants providing headache data in HUNT 2, 378 appeared in the dementia register during the follow-up period. Compared to those who were headache free, participants with any headache had increased risk of VaD ( n = 63) (multivariate-adjusted HR = 2.3, 95% CI 1.4–3.8, p = 0.002) and of mixed dementia (VaD and AD ( n = 52)) (adjusted HR = 2.0, 95% CI 1.1–3.5, p = 0.018). There was no association between any headache and later development of AD ( n = 180). Conclusion In this prospective population-based cohort study, any headache was a risk factor for development of VaD.

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Visual acuity and risk of overall, injury-related, and cardiovascular mortality: the Kangbuk Samsung Health Study

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab025 ◽

2021 ◽

Author(s):

So Young Han ◽

Yoosoo Chang ◽

Hocheol Shin ◽

Chul Young Choi ◽

Seungho Ryu

Keyword(s):

Visual Acuity ◽

Visual Impairment ◽

Cardiovascular Mortality ◽

Health Study ◽

Normal Vision ◽

Vital Status ◽

Hazard Ratios ◽

Risk Of Mortality ◽

Increased Risk

Abstract Aims The associations of visual impairment (VI) with cardio-metabolic risk factors have been reported but its association with cardiovascular mortality remains uncertain. Therefore, we evaluated the association of visual acuity (VA) with overall, injury-related, and cardiovascular mortality. Methods and results A cohort study was performed in 580 746 Korean adults (average age, 39.7 years) who were followed for a median of 8.1 years (maximum, 16 years). Presenting VA was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Visual acuity in the better vision eye was categorized as normal vision (≥0.8), lowered vision (0.5–0.8), mild visual impairment (VI) (0.3–0.5), or moderate to severe VI (<0.3). Vital status and cause of death were ascertained through linkage to national death records. During 4 632 892.2 person-years of follow-up, 6585 overall deaths, 974 cardiovascular deaths, and 1163 injury-related deaths were identified. After adjustment for possible confounders, the multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for overall mortality among participants with lowered vision, minimal VI, and moderate to severe VI were 1.21 (1.13–1.29), 1.26 (1.15–1.37), and 1.54 (1.40–1.68), respectively, compared with those with normal vision. The corresponding HRs (95% CIs) for injury-related mortality were 1.12 (0.96–1.32), 0.98 (0.76–1.26), and 1.36 (1.04–1.79), respectively, and the corresponding HRs (95% CIs) for cardiovascular mortality were 1.32 (1.12–1.57), 1.43 (1.15–1.77), and 2.41 (1.94–2.99). Conclusion In this large cohort of young and middle-aged individuals, VI was associated with increased risk of mortality especially due to cardiovascular disease.

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Abstract 018: Egg Consumption and Risk of Cardiovascular Disease: Findings from Three Large Prospective US Cohort Studies of Men and Women

Circulation ◽

10.1161/circ.127.suppl_12.a018 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Amanda L Sands ◽

Deirdre K Tobias ◽

Meir J Stampfer ◽

Walter C Willett ◽

Frank B Hu

Keyword(s):

Cardiovascular Disease ◽

Dietary Cholesterol ◽

Dietary Factors ◽

Self Report ◽

Health Study ◽

Processed Meat ◽

Cvd Risk ◽

Men And Women ◽

Increased Risk ◽

Incident Cases

Background: Limiting dietary cholesterol intake is widely recommended for prevention of cardiovascular disease (CVD). Eggs are a major source of dietary cholesterol, but they also contain a variety of other nutrients. Several recent studies have examined egg intake and CVD with conflicting findings. Objective: To prospectively evaluate the association between egg intake and CVD risk in three large cohorts. Methods: Women and men from the Nurses’ Health Study (1980-2010; N=84,537), Nurses’ Health Study II (1991-2010; N=92,588), and Health Professionals Follow-up Study (1986-2010; N=42,815) were included if they were free of CVD and cancer at baseline. Egg intake was assessed every 4 years via validated food frequency questionnaire and evaluated in the following categories for frequency of consuming 1 egg: <1/month (reference), 1-3/month, 1/week, 2-4/week, 5-6/week, 1+/day. Incident coronary heart disease (CHD) (nonfatal myocardial infarction (MI) and fatal coronary disease) and stroke cases were ascertained via self-report and confirmed with review of medical records. Relative risks (HR) and 95% confidence intervals (CI) for CVD risk across categories of egg intake were estimated using multivariate Cox proportional hazards models, adjusted for age, race, smoking, physical activity, BMI, family history of CVD, alcohol, red and processed meat, whole milk, and other dietary covariates. Individual cohort estimates were combined using fixed effects meta-analysis. Results: We identified 5,838 incident cases of CHD (nonfatal MI and fatal CHD) and 6,030 stroke cases. Consumption of up to 1+eggs/day was not significantly associated with risk of incident total CVD (CHD and stroke) after adjustment for several diet and lifestyle factors (HR (CI) by category: <1/month: 1(reference); 1-3/month: 0.95(0.88, 1.02); 1/week: 0.85(0.79, 0.91); 2-4/week: 0.88(0.81, 0.96); 5-6/week: 0.96(0.84, 1.09); 1+/day: 0.99 (0.87, 1.13) (p-trend=0.77). When incident stroke and CHD were evaluated individually, egg intake was not associated with either endpoint (p-trend=0.09 for CHD and 0.52 for stroke). Conclusions: After controlling for lifestyle and dietary factors, egg intake (up to 1+/day) was not associated with increased risk of CVD in three prospective cohorts of men and women.

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Abstract MP94: Consumption of Specific Fruits and Incidence of Type 2 Diabetes in Men and Women

Circulation ◽

10.1161/circ.127.suppl_12.amp94 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Isao Muraki ◽

Fumiaki Imamura ◽

Frank B Hu ◽

Walter C Willett ◽

Rob van Dam ◽

...

Keyword(s):

Type 2 Diabetes ◽

Lower Risk ◽

Fruit Juice ◽

Dietary Factors ◽

Health Study ◽

Significant Heterogeneity ◽

Men And Women ◽

Increased Risk

Background: Consumption of whole fruits, but not fruit juice, has been associated with lower risk of type 2 diabetes. However, individual fruits have different compositions of carbohydrate, phytochemicals and other nutrients, and may thus have different effects on diabetes risk. We examined whether consumption of specific fruits was prospectively associated with risk of type 2 diabetes in US men and women. In addition, we evaluated whether the associations of fruits with diabetes were determined by the glycemic load (GL) of fruits consumption. Methods: After excluding participants with chronic diseases at baseline, we evaluated 66,720 women from the Nurses' Health Study (1984-2008); 85,961 women from the Nurses’ Health Study II (1991-2009); and 26,149 men from the Health Professionals Follow-up Study (1986-2008). Validated semi-quantitative food frequency questionnaires were administered to assess habitual consumption of fruits and other foods every two to four years. Incidences of type 2 diabetes were identified using biennial self-reported questionnaires and confirmed using supplementary questionnaires. The associations were prospectively assessed in each cohort, using Cox proportional hazard regression. Sociodemographics, lifestyle, caloric intakes, intakes of other fruits, and other dietary factors were adjusted for to control for confounding. Cohort-specific estimates were pooled by a random-effects meta-analysis. Results: During 3,447,866 person-years of follow-up, 11,521 participants were newly diagnosed with type 2 diabetes. The pooled multivariable-adjusted hazard ratios (HRs) for type 2 diabetes (for every 3 servings/week increase of fruit intake) were 0.74 [95% confidence interval (CI): 0.66, 0.83] for blueberries; 0.86 (0.80, 0.93) for grapes or raisins; 0.86 (0.75, 0.99) for prunes; 0.91 (0.81, 1.03) for bananas; 0.93 (0.88, 0.97) for apples or pears; 0.95 (0.91, 1.00) for grapefruits; 0.96 (0.90, 1.02) for peaches, plums or apricots; 1.01 (0.97, 1.05) for oranges; 1.06 (0.96, 1.19) for strawberries; and 1.11 (1.03, 1.20) for cantaloupe. No significant heterogeneity was found among the three cohorts, except associations with banana consumption. In contrast, each drink per day of fruit juice was associated with a HR (95% CI) of 1.07 (1.00, 1.14). The HRs for type 2 diabetes were 0.81 (0.69, 0.96) per 1 serving/day of high GL fruits, 0.96 (0.86, 1.07) for moderate GL fruits, and 1.05 (0.92, 1.19) for low GL fruits. Conclusion: Our data suggest that intakes of certain whole fruits, including grapes or raisins, prunes, apples or pears, grapefruits, and blueberries, are associated with lower risk of type 2 diabetes, whereas high consumption of fruit juice may lead to increased risk. Future research is needed to confirm our findings and elucidate mechanism underlying the associations for individual fruits.

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Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

Journal of Clinical Medicine ◽

10.3390/jcm10071514 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1514

Author(s):

Hilde Espnes ◽

Jocasta Ball ◽

Maja-Lisa Løchen ◽

Tom Wilsgaard ◽

Inger Njølstad ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Pressure Management ◽

Reference Models ◽

Proportional Hazards Regression ◽

Hazard Ratios ◽

Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

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Association of oral contraceptives and tubal ligation with risk of early natural menopause

Human Reproduction ◽

10.1093/humrep/deab054 ◽

2021 ◽

Author(s):

C R Langton ◽

B W Whitcomb ◽

A C Purdue-Smithe ◽

L L Sievert ◽

S E Hankinson ◽

...

Keyword(s):

Oral Contraceptives ◽

Proportional Hazards ◽

Reproductive Factors ◽

Cox Proportional Hazards ◽

Tubal Ligation ◽

Health Study ◽

Early Menopause ◽

Natural Menopause ◽

Increased Risk

Abstract STUDY QUESTION What is the association of oral contraceptives (OCs) and tubal ligation (TL) with early natural menopause? SUMMARY ANSWER We did not observe an association of OC use with risk of early natural menopause; however, TL was associated with a modestly higher risk. WHAT IS KNOWN ALREADY OCs manipulate hormone levels, prevent ovulation, and may modify the rate of follicular atresia, while TL may disrupt the blood supply to the ovaries. These mechanisms may be associated with risk of early menopause, a condition associated with increased risk of cardiovascular disease and other adverse health outcomes. STUDY DESIGN, SIZE, DURATION We examined the association of OC use and TL with natural menopause before the age of 45 years in a population-based study within the prospective Nurses’ Health Study II (NHSII) cohort. Participants were followed from 1989 to 2017 and response rates were 85-90% for each cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants included 106 633 NHSII members who were premenopausal and aged 25-42 years at baseline. Use, duration and type of OC, and TL were measured at baseline and every 2 years. Menopause status and age were assessed every 2 years. Follow-up continued until early menopause, age 45 years, hysterectomy, oophorectomy, death, cancer diagnosis, or loss to follow-up. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs adjusted for lifestyle, dietary, and reproductive factors. MAIN RESULTS AND THE ROLE OF CHANCE Over 1.6 million person-years, 2579 members of the analytic cohort experienced early natural menopause. In multivariable models, the duration, timing, and type of OC use were not associated with risk of early menopause. For example, compared with women who never used OCs, those reporting 120+ months of OC use had an HR for early menopause of 1.01 (95% CI, 0.87-1.17; P for trend=0.71). TL was associated with increased risk of early menopause (HR = 1.17, 95% CI, 1.06-1.28). LIMITATIONS, REASONS FOR CAUTION Our study population is homogenous with respect to race and ethnicity. Additional evaluation of these relations in more diverse populations is important. WIDER IMPLICATIONS OF THE FINDINGS To our knowledge, this is the largest study examining the association of OC use and TL with early natural menopause to date. While TL was associated with a modest higher risk of early menopause, our findings do not support any material hazard or benefit for the use of OCs. STUDY FUNDING/COMPETING INTEREST(S) The study was sponsored by UO1CA176726 and R01HD078517 from the National Institutes of Health and Department of Health and Human Services. The work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have no competing interests to report. TRIAL REGISTRATION NUMBER N/A

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Consumption of flavonoid-rich fruits, flavonoids from fruits, and stroke risk: a prospective cohort study

British Journal Of Nutrition ◽

10.1017/s0007114521000404 ◽

2021 ◽

pp. 1-26

Author(s):

Qi Gao ◽

Jia-Yi Dong ◽

Renzhe Cui ◽

Isao Muraki ◽

Kazumasa Yamagishi ◽

...

Keyword(s):

Lower Risk ◽

Stroke Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Dietary Factors ◽

Citrus Fruits ◽

Proportional Hazards Regression ◽

Hazard Ratios ◽

Index Study

Abstract We sought to examine the prospective associations of specific fruit consumption, in particular flavonoid-rich fruit (FRF) consumption, with the risk of stroke and subtypes of stroke in a Japanese population. A study followed a total of 39,843 men and 47,334 women aged 44-76 years, and free of cardiovascular disease, diabetes, and cancer at baseline since 1995 and 1998 to the end of 2009 and 2012, respectively. Data on total and specific FRF consumption for each participant were obtained using a self-administrated food frequency questionnaire. The hazard ratios (HRs) of stroke in relation to total and specific FRF consumption were estimated through Cox proportional hazards regression models. During a median follow-up of 13.1 years, 4092 incident stroke cases (2557 cerebral infarctions and 1516 hemorrhagic strokes) were documented. After adjustment for age, body mass index, study area, lifestyles, dietary factors, and other risk factors, it was found that total FRF consumption was associated with a significantly lower risk of stroke in women (HR= 0.70; 95% CI, 0.58-0.84), while the association in men was not significant (HR= 0.93; 95% CI, 0.79-1.09). As for specific FRFs, consumptions of citrus fruits, strawberries, and grapes were found associated with a lower stroke risk in women. Higher consumptions of FRFs, in particular citrus fruits, strawberries, and grapes, were associated with a lower risk of developing stroke in Japanese women.

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Association between Oral Contraceptives and cutaneous melanoma: a systematic review and metanalysis

European Journal of Public Health ◽

10.1093/eurpub/ckaa166.1093 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

I Giacchetta ◽

M Chiavarini ◽

G Naldini ◽

R Fabiani

Keyword(s):

Systematic Review ◽

Malignant Melanoma ◽

Publication Bias ◽

Oral Contraceptives ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Cutaneous Malignant Melanoma ◽

Hormonal Factors ◽

Increased Risk

Abstract Background The probability of developing invasive cutaneous malignant melanoma (CMM) is higher in women than in men up until the age of 49. Several studies investigated the association between hormonal factors and CMM. The aim of this systematic review and meta-analysis is to summarize the evidence on the association between Oral Contraceptives (OC) and the risk of CMM. Methods This review and meta-analysis follow the PRISMA guidelines. A systematic literature search was conducted on Medline and Web of Science until December 2019. Studies were eligible if reported a risk estimate for the association between OC and CMM. Heterogeneity testing was performed using Cochran's Q and I2 statistics. Publication bias was assessed by Egger's test and Begg's test. Meta-analysis was performed using random effect model. Results The results of the pooled analysis of all 32 studies showed no significant association between OC and the risk of CMM (OR 1.02; 95% CI 0.94-1.11; I2=39.32%, p = 0.013). The stratified analyses by study design found no significant association between OC and the risk of CMM neither in the 18 case-control studies (OR 1.02; 95% CI 0.87-1.21; I2=56.91%, p = 0.002) nor in the 14 cohort studies (OR 1.04; 95% CI 0.98-1.11; I2=0.00%, p = 0.557). No significant publication bias could be detected by Egger's test or Begg's test. Conclusions This meta-analysis of available literature suggests no significant association between OC and the risk of developing CMM. Further investigations are needed to evaluate the possible relationship of OC use and other hormonal factors potentially contributing to the increased risk of CMM in women during their reproductive years. Key messages Oral contraceptives (OC) do not significantly contribute to the risk of Cutaneous Malignant Melanoma (CMM). Further studies are needed to investigate the potential role of other hormonal factors in the increased probability of developing CMM in women during their reproductive years.

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Self-reported and cotinine-verified smoking and increased risk of incident hearing loss

Scientific Reports ◽

10.1038/s41598-021-87531-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Woncheol Lee ◽

Yoosoo Chang ◽

Hocheol Shin ◽

Seungho Ryu

Keyword(s):

Smoking Status ◽

Objective Measure ◽

Self Report ◽

Urinary Cotinine ◽

Increased Risk ◽

Former Smokers ◽

Never Smokers ◽

Time Varying Covariates ◽

New Onset

AbstractWe examined the associations of smoking status and urinary cotinine levels, an objective measure of smoking, with the development of new-onset HL. This cohort study was performed in 293,991 Korean adults free of HL who underwent a comprehensive screening examination and were followed for up to 8.8 years. HL was defined as a pure-tone average of thresholds at 0.5, 1.0, and 2.0 kHz ≥ 25 dB in both ears. During a median follow-up of 4.9 years, 2286 participants developed new-onset bilateral HL. Self-reported smoking status was associated with an increased risk of new-onset bilateral HL. Multivariable-adjusted HRs (95% CIs) for incident HL comparing former smokers and current smokers to never-smokers were 1.14 (1.004–1.30) and 1.40 (1.21–1.61), respectively. Number of cigarettes, pack-years, and urinary cotinine levels were consistently associated with incident HL. These associations were similarly observed when introducing changes in smoking status, urinary cotinine, and other confounders during follow-up as time-varying covariates. In this large cohort of young and middle-aged men and women, smoking status based on both self-report and urinary cotinine level were independently associated with an increased incidence of bilateral HL. Our findings indicate smoking is an independent risk factor for HL.

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