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Hearing difficulty (HD) is a major health burden in older adults. While ageing-related changes in the peripheral auditory system play an important role, genetic variation associated with brain structure and function could also be involved in HD predisposition. We analysed a large-scale HD genome-wide association study (GWAS; ntotal = 501 825, 56% females) and GWAS data related to 3935 brain imaging-derived phenotypes (IDPs) assessed in up to 33 224 individuals (52% females) using multiple MRI modalities. To investigate HD pleiotropy with brain structure and function, we conducted genetic correlation, latent causal variable, Mendelian randomization and multivariable generalized linear regression analyses. Additionally, we performed local genetic correlation and multi-trait co-localization analyses to identify genomic regions and loci implicated in the pleiotropic mechanisms shared between HD and brain IDPs. We observed a widespread genetic correlation of HD with 120 IDPs in females, 89 in males and 171 in the sex-combined analysis. The latent causal variable analysis showed that some of these genetic correlations could be due to cause-effect relationships. For seven of them, the causal effects were also confirmed by the Mendelian randomization approach: vessel volume→HD in the sex-combined analysis; hippocampus volume→HD, cerebellum grey matter volume→HD, primary visual cortex volume→HD and HD→fluctuation amplitudes of node 46 in resting-state functional MRI dimensionality 100 in females; global mean thickness→HD and HD→mean orientation dispersion index in superior corona radiata in males. The local genetic correlation analysis identified 13 pleiotropic regions between HD and these seven IDPs. We also observed a co-localization signal for the rs13026575 variant between HD, primary visual cortex volume and SPTBN1 transcriptomic regulation in females. Brain structure and function may have a role in the sex differences in HD predisposition via possible cause-effect relationships and shared regulatory mechanisms., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Men are at higher risk of developing stones compared with women; however, recent data suggest a changing epidemiology, with women being relatively more affected than before., Methods: To estimate the proportion of excess risk among men, we analysed data from large cohorts (Health Professionals Follow-up Study and Nurses' Health Study I and II). Kidney stone incidence rates were computed and hazard ratios (HRs) and 95% confidence intervals (CIs) generated with age-adjusted Cox proportional regression models. Mediation analysis estimated the excess risk for men explained by risk factors, including waist circumference, high blood pressure, diabetes, use of thiazides and dietary intake. The 24-h urine composition was also examined., Results: The analysis included 268 553 participants, contributing 5 872 249 person-years of follow-up. A total of 10 302 incident stones were confirmed and the overall incidence rate was 271 and 159 per 100 000 person-years for men and women, respectively. The age-adjusted HR was 2.32 (95% CI 2.20, 2.45) and the risk of stones was consistently higher across categories of age (HRs ranging from 2.02 to 2.76) for men compared with women. The risk remained higher among men, but tended to decrease over time (48.1%), while it increased among women. Urine supersaturations for calcium oxalate and uric acid were higher among men, primarily because of higher oxalate (26.3%), uric acid (16.3%), phosphate (23.5%) and lower pH., Conclusions: The risk of kidney stones is higher among men and this difference is only partly explained by lifestyle risk factors; differences in urine chemistries explain a substantial fraction of the excess risk., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: One limitation of the use of 24-hour collection is impracticality. We analysed the performance of spot urine measurements to estimate 24-hour excretion in patients with kidney stones., Methods: A total of 74 adult patients from two centres performed a 24-hour urine collection. A sample of the last micturition was sent for spot urine analysis. Twenty patients were asked to collect two additional spot urine samples, one before dinner and the other after dinner. Urinary concentrations of creatinine, calcium, oxalate, uric acid, citrate and magnesium were measured in the 24-hour and each of the spot urine samples. Four approaches were used to estimate 24-hour urinary excretion, multiplying the ratio of the spot urinary analyte to creatinine concentration by (i) measured 24-hour urinary creatinine excretion (Prediction 1), (ii) estimated 24-hour urinary creatinine excretion (Prediction 2), (iii) assumed 1-g 24-hour urinary creatinine excretion (Prediction 3) or (iv) assumed 1.5-g 24-hour urinary creatinine excretion (Prediction 4). For each parameter we computed Lin's concordance correlation coefficients (CCCs), Bland-Altman plots and 95% limits of agreement., Results: The performance of estimates obtained with Prediction 1 and Prediction 2 was similar, except for citrate and uric acid, for which Prediction 2 performed worse. Both approaches performed moderately well: citrate CCC {0.82 [95% confidence interval (CI) 0.75-0.90]}, oxalate [0.66 (95% CI 0.55-0.78)], magnesium [0.66 (95% CI 0.54-0.77)], calcium [0.63 (95% CI 0.50-0.75)] and uric acid [0.52 (95% CI 0.36-0.68)]. The performance of Predictions 3 and 4 was worse., Conclusions: Although spot urine samples may hold promise for clinical and population-based research, at present they have limited utility in clinical practice. Measuring or estimating 24-hour creatinine, rather than assuming a given creatinine excretion, will be necessary in future studies of spot urine samples., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Context: Chronic hypoparathyroidism (HypoPT) is conventionally managed with oral calcium and active vitamin D. Recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) is a therapy targeting the pathophysiology of HypoPT by replacing parathyroid hormone., Objective: To compare changes in the estimated glomerular filtration rate (eGFR) in patients with chronic HypoPT receiving or not receiving rhPTH(1-84) during a 5-year period., Design/setting: A retrospective analysis of patients with chronic HypoPT treated with or without rhPTH(1-84)., Patients: Sixty-nine patients with chronic HypoPT from 4 open-label, long-term trials (NCT00732615, NCT01268098, NCT01297309, and NCT02910466) composed the rhPTH(1-84) cohort and 53 patients with chronic HypoPT not receiving rhPTH(1-84) from the Geisinger Healthcare Database (01/2004-06/2016) composed the historical control cohort., Interventions: The rhPTH(1-84) cohort (N = 69) received rhPTH(1-84) therapy; the historical control cohort (N = 53) did not receive rhPTH(1-84)., Main Outcome Measures: Changes in eGFR from baseline during a 5-year follow-up were examined in multivariate regression analyses., Results: At baseline, demographic characteristics and eGFR were similar between cohorts, though the proportions with diabetes and cardiac disorders were lower in the rhPTH(1-84) cohort. At the end of follow-up, mean eGFR increased by 2.8 mL/min/1.73 m2 in the rhPTH(1-84) cohort, while mean eGFR fell by 8.0 mL/min/1.73 m2 in the control cohort. In the adjusted model, the difference in the annual eGFR change between the rhPTH(1-84) cohort and the control cohort was 1.7 mL/min/1.73 m2 per year (P = 0.009)., Conclusions: Estimated glomerular filtration rate was preserved for over 5 years among patients with chronic HypoPT receiving rhPTH(1-84) treatment, contrasting with an eGFR decline among those not receiving rhPTH(1-84)., (© Endocrine Society 2020.)

Background: Whether calcium oxalate (CaOx) deposition in kidney allografts following transplantation (Tx) adversely affects patient outcomes is uncertain, as are its associated risk factors., Methods: We performed a retrospective cohort study of patients who had kidney allograft biopsies performed within 3 months of Tx at Brigham and Women's Hospital and examined the association of CaOx deposition with the composite outcome of death or graft failure within 5 years., Results: Biopsies from 67 of 346 patients (19.4%) had CaOx deposition. In a multivariable logistic regression model, higher serum creatinine [odds ratio (OR) = 1.28 per mg/dL, 95% confidence interval (CI) 1.15-1.43], longer time on dialysis (OR = 1.11 per additional year, 95% CI 1.01-1.23) and diabetes (OR = 2.26, 95% CI 1.09-4.66) were found to be independently associated with CaOx deposition. CaOx deposition was strongly associated with delayed graft function (DGF; OR = 11.31, 95% CI 5.97-21.40), and with increased hazard of the composite outcome after adjusting for black recipient race, donor type, time on dialysis before Tx, diabetes and borderline or acute rejection (hazard ratio 1.90, 95% CI 1.13-3.20)., Conclusions: CaOx deposition is common in allografts with poor function and portends worse outcomes up to 5 years after Tx. The extent to which CaOx deposition may contribute to versus result from DGF, however, cannot be determined based on our retrospective and observational data. Future studies should examine whether reducing plasma and urine oxalate prevents CaOx deposition in the newly transplanted kidney and whether this has an effect on clinical outcomes., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

We conducted a prospective study of dietary patterns and longitudinal change in audiometric hearing thresholds among 3,135 women (mean age = 59 years) in the Nurses' Health Study II (2012-2018). Diet adherence scores for the Dietary Approaches to Stop Hypertension (DASH) and Alternate Mediterranean (AMED) diets and the Alternate Healthy Eating Index 2010 (AHEI-2010) were calculated using validated food-frequency questionnaires. Baseline and 3-year follow-up hearing sensitivities were assessed by pure-tone audiometry at 19 US sites. We used multivariable-adjusted logistic regression models to examine independent associations between diet adherence scores and risk of ≥5 dB elevation in the pure-tone average (PTA) of low-frequency (LPTA0.5,1,2 kHz), mid-frequency (MPTA3,4 kHz), and high-frequency (HPTA6,8 kHz) hearing thresholds. Higher adherence scores were associated with lower risk of hearing loss. Compared with the lowest quintile of DASH score, the multivariable-adjusted odds ratios for mid-frequency and high-frequency threshold elevation in the highest quintile were 0.71 (95% confidence interval (CI): 0.55, 0.92; P for trend = 0.003) and 0.75 (95% CI: 0.59, 0.96; P for trend = 0.02); for AMED and AHEI scores, for mid-frequency threshold elevation, they were 0.77 (95% CI: 0.60, 0.99; P for trend = 0.02) and 0.72 (95% CI: 0.57, 0.92; P for trend = 0.002). Nonsignificant inverse associations were observed for high-frequency threshold elevation. There were no significant associations between adherence scores and low-frequency threshold elevation. Our findings indicate that eating a healthy diet might reduce the risk of acquired hearing loss., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite established sex differences and longstanding hypotheses of sex hormone influence in the etiology of obstructive sleep apnea (OSA), we have found no studies that evaluated type of menopause and age at menopause, which affect postmenopausal hormonal milieu, in relation to OSA risk in women. We followed 50,473 postmenopausal women from the Nurses' Health Study during 2002-2012 and 53,827 postmenopausal women from the Nurses' Health Study II during 1995-2013, with 1,712 and 2,560 incident OSA diagnoses, respectively. Compared with natural menopause, the pooled hazard ratio for OSA was 1.27 (95% confidence interval (CI): 1.17, 1.38) for surgical menopause by hysterectomy/oophorectomy. The association remained the same after further accounting for age at menopause (hazard ratio = 1.26, 95% CI: 1.15, 1.38). The risk associated with surgical menopause was higher among women who were not obese as well as among women who never used hormone therapy (P for interaction < 0.05). Earlier menopause was associated with higher OSA risk prior to adjustment for type of menopause (comparing those aged <40 years versus those aged 50-54 years, hazard ratio = 1.21, 95% CI: 1.08, 1.35; P for trend = 0.008), although no association was observed after the adjustment. Surgical as compared with natural menopause was independently associated with higher OSA risk in postmenopausal women. Our results provide additional evidence for a role for sex hormones, particularly abrupt hormonal changes, in modulating OSA risk.

Background: High blood pressure (HBP) is a major cardiovascular disease (CVD) risk factor. Clinical trials including Dietary Approaches to Stop Hypertension (DASH) have demonstrated beneficial effects of dairy consumption on risks of HBP and CVD. Yogurt, a fermented dairy product, may independently be related to CVD risk., Objective: To evaluate the association between yogurt consumption and CVD risk among hypertensive individuals in 2 large cohorts and to determine whether the association differs among those whose eating pattern more closely resembles the DASH diet., Methods: Overall, 55,898 female Nurses' Health Study (NHS) and 18,232 male Health Professionals Follow-Up Study (HPFS) participants with prevalent HBP were included. Cumulative average estimates of yogurt intake from validated food frequency questionnaires were related to verified self-reported CVD outcomes using Cox proportional hazards models. Hazard ratios and 95% confidence intervals (CI) were adjusted for CVD risk factors, medications, and diet covariates., Results: Yogurt intake was inversely associated with CVD risk (myocardial infarction and stroke) among hypertensive participants (P <0.01 in both cohorts). Among participants consuming ≥2 servings/week of yogurt, NHS women had a 17% (95% CI: 0.74-0.92) lower risk while HPFS men experienced a 21% (95% CI: 0.66-0.96) lower CVD risk compared to those who consumed <1 serving/month. Regular yogurt consumers with higher DASH diet scores had 16% (95% CI: 0.73-0.96) and 30% (95% CI: 0.57-0.85) CVD risk reductions in the 2 cohorts, respectively., Conclusion: Hypertensive men and women who consumed ≥2 servings/week of yogurt, especially in the context of a healthy diet, were at lower risk for developing CVD.

Black individuals have a lower risk of hearing loss than do whites, possibly because of differences in cochlear melanocytes. Previous studies have suggested that darker-skinned individuals tend to have more inner ear melanin, and cochlear melanocytes are important in generating the endocochlear potential. We investigated the relationship between self-reported hearing loss and skin pigmentation by using hair color, skin tanning ability, and skin reaction to prolonged sun exposure as surrogate measures of pigmentation among 49,323 white women in the Nurses' Health Study. Cox proportional hazards regression models were used to adjust for potential confounders. During 1,190,170 person-years of follow-up (1982-2012), there was no association between risk of hearing loss and hair color (for black hair vs. red or blonde hair, multivariable-adjusted relative risk (RR) = 0.99, 95% confidence interval (CI): 0.90, 1.09), skin tanning ability (for dark tan vs. no tan, multivariable-adjusted RR = 0.98, 95% CI: 0.92, 1.05), skin reaction to prolonged sun exposure (for painful burn with blisters vs. practically no reaction, multivariable-adjusted RR = 1.01, 95% CI: 0.93, 1.08), or Fitzpatrick skin phototype (for type IV vs. type I, multivariable-adjusted RR = 0.99, 95% CI: 0.92, 1.05). In our cohort of white women, surrogates for skin pigmentation were not associated with risk of hearing loss., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In nonhypertensive individuals, lower levels of 25-hydroxyvitamin D (25[OH]D) have been associated with an increased risk of hypertension, and vitamin D deficiency has been associated with endothelial dysfunction in such individuals. However, the effect of vitamin D supplementation on endothelial dysfunction in nonhypertensive individuals has not been examined in a rigorous fashion., Methods: In this randomized, double-blind, placebo-controlled trial of nonhypertensive, nondiabetic overweight, or obese individuals with vitamin D deficiency (body mass index ≥25 and 25[OH]D ≤ 20 ng/ml), we assigned subjects to receive either ergocalciferol (50,000 units) or matching placebo, once a week for 8 weeks. Our primary outcome was endothelial-dependent vasodilation (EDV) measured by brachial artery ultrasound at baseline and 8 weeks postrandomization., Results: By the end of the trial, 46 and 47 participants were allocated to receive ergocalciferol and placebo, respectively. Mean 25(OH)D levels increased from 14.9 to 30.3 in the vitamin D group and 14.4 to 17.4 in the placebo. EDV did not change significantly with either vitamin D repletion (from 6.3 ± 3.6% at baseline to 6.1 ± 4.6% at 8 weeks; P value = 0.78) or placebo (7.9 ± 4.7% to 6.8 ± 4.7%; P = 0.17). The treatment effect P value (comparing the 8-week change with ergocalciferol to the change with placebo) was 0.35., Conclusions: In this randomized, double-blind, placebo-controlled trial, there was no improvement in endothelial function (measured as EDV) after repletion of vitamin D in overweight/obese nonhypertensive individuals., (© American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aspirin, nonsteroidal antiinflammatory drugs (NSAID), and acetaminophen are commonly used. Frequent use of analgesics has been associated with a higher risk of hearing loss. However, the association between duration of analgesic use and the risk of hearing loss is unclear. We investigated the relationship between duration of analgesic use and self-reported hearing loss among 55,850 women in the Nurses' Health Study. Cox proportional hazards regression was used to adjust for potential confounders. During 873,376 person-years of follow-up (1990-2012), longer durations of NSAID use (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.10, 95% confidence interval: 1.06, 1.15; P for trend < 0.001) and acetaminophen use (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.09, 95% confidence interval: 1.04, 1.14; P for trend < 0.001) were associated with higher risks of hearing loss. Duration of aspirin use was not associated with hearing loss (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.01, 95% confidence interval: 0.97, 1.05; P for trend = 0.35). In this cohort of women, longer durations of NSAID and acetaminophen use were associated with slightly higher risks of hearing loss, but duration of aspirin use was not. Considering the high prevalence of analgesic use, this may be an important modifiable contributor to hearing loss., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Primary hyperparathyroidism (P-HPTH) is relatively common and predominantly affects women. Prior studies have shown that physical activity (PA) can lower PTH levels., Objective: Our objective was to evaluate the hypothesis that lower PA is a risk factor for developing P-HPTH., Design, Setting, and Participants: This prospective cohort study included 69 621 female participants in the Nurses' Health Study I followed for 22 years., Exposures: PA and other dietary and demographic exposures were quantified via detailed, and validated, biennial questionnaires., Outcomes: Incident P-HPTH was confirmed by medical record review after initial assessment by questionnaire. Adjusted Cox proportional hazards models were used to evaluate whether PA was an independent risk factor for developing P-HPTH. We also evaluated the risk of developing P-HPTH when combining low PA (<16 metabolic equivalent hours/week) with a previously identified independent risk factor for developing P-HPTH: low calcium intake (<800 mg/day). The relation between PA and PTH levels was evaluated in 625 participants., Results: We confirmed 302 incident cases of P-HPTH during 1 474 993 person-years of follow-up. Participants in the highest quintile (Q) of PA had a 50% lower risk of developing P-HPTH: age-adjusted relative risks and 95% confidence intervals for incident P-HPTH by lowest to highest of PA were Q1 = 1.0 (reference); Q2 = 0.83 (0.60–1.15); Q3 = 0.84 (0.61–1.15); Q4 = 0.50 (0.34–0.74); Q5 = 0.50 (0.35–0.73); P for trend <.001. Extensive multivariable adjustments did not materially change these findings. The adjusted relative risk for developing P-HPTH among participants with the combination lower PA and lower calcium intake was 2.37-fold (1.60–3.51) higher than in participants with higher PA and higher calcium intake. PA was inversely correlated with serum PTH (ρ = −0.09, P = .03); the mean adjusted serum PTH in Q 2–5 of PA was lower than in Q 1 (36.3 vs 39.1 pg/mL, P = .02)., Conclusion: Low physical activity may be a modifiable risk factor for developing P-HPTH in women.

Context: Hypertension is associated with higher PTH levels, and specific antihypertensive medications may modulate PTH. Whether hypertension or the use of specific antihypertensive medications influences the risk of developing incident primary hyperparathyroidism (P-HPTH) is not known., Objective: The purpose of this study was to investigate whether a history of hypertension and the use of specific antihypertensive medications determine the risk for developing P-HPTH in a large prospective study., Design/participants: A longitudinal prospective cohort of female nurses in the Nurses' Health Study I (n = 75 600), who did not have P-HPTH at baseline and completed a questionnaire assessment of lifetime history of P-HPTH were followed from 1986 to 2008. Most participants were white and postmenopausal., Setting: The study was a nationwide cohort study., Main Outcome Measure: Incident P-HPTH was assessed initially via questionnaire and then was confirmed by medical record review. Cox proportional hazards models were used to adjust for potential confounders., Results: We documented 347 incident cases of P-HPTH during 1 719 416 person-years of follow-up. The age-adjusted relative risk (RR) for incident P-HPTH associated with hypertension was 1.80 (95% confidence interval [CI], 1.43-2.26), and the multivariate-adjusted RR was 1.45 (95% CI, 1.10-1.91). Among participants with a history of hypertension, the use of furosemide, when compared with the use of other antihypertensive medications, was associated with increased risk for developing P-HPTH; age-adjusted RR for incident P-HPTH was 1.79 (95% CI, 1.15-2.79) and multivariate-adjusted RR was 1.71 (95% CI, 1.08-2.71)., Conclusions: In a large longitudinal prospective cohort study of mostly older white women, a history of hypertension and use of furosemide were associated with a significantly higher risk of developing P-HPTH.

Background: Several biomarkers of metabolic acidosis, including lower plasma bicarbonate, have been associated with prevalent hypertension in cross-sectional studies. We sought to examine prospectively whether lower plasma bicarbonate is associated with incident hypertension., Methods: We conducted a prospective case-control study nested within the Nurses' Health Study II. Plasma bicarbonate was measured in 695 nonobese women without hypertension at time of blood draw who subsequently developed hypertension during 6 years of follow-up. Control subjects were matched to case subjects according to age, race, time and day of blood draw, and day of menstrual cycle. We used unconditional logistic regression to generate odds ratios (ORs) for development of hypertension by quintile of baseline plasma bicarbonate., Results: After adjusting for matching factors, body mass index, family history of hypertension, plasma creatinine, and dietary and lifestyle factors, higher plasma bicarbonate was associated with lower odds of developing hypertension across quintiles (P for linear trend = 0.04). Those in the highest compared with the lowest quintile of plasma bicarbonate had 31% lower odds of developing hypertension (OR = 0.69; 95% confidence interval = 0.48-0.99). Further adjustment for diet-estimated net endogenous acid production, plasma insulin, 25-hydroxyvitamin D, and uric acid did not alter these findings., Conclusions: Our case-control study is consistent with a modest association between higher plasma bicarbonate and reduced odds of developing hypertension among nonobese women, although our findings are of borderline statistical significance. Further research is required to confirm this finding as part of a larger prospective cohort study and to elucidate the mechanism for this relation.

Exogenous melatonin ameliorates insulin resistance in animals, while among humans, polymorphisms in the melatonin receptor gene are associated with insulin resistance. We aimed to investigate the association of endogenous nocturnal melatonin secretion with insulin resistance in humans. We analyzed the association between endogenous nocturnal melatonin secretion, estimated by measuring the main melatonin metabolite, 6-sulfatoxymelatonin, from the first morning urinary void, and the prevalence of insulin resistance based on fasting blood samples collected in a cross-sectional study of 1,075 US women (1997-1999) without diabetes, hypertension, or malignancy. Urinary 6-sulfatoxymelatonin level was standardized to urinary creatinine level; insulin resistance was defined as an insulin sensitivity index value (using the McAuley formula) less than 7.85. Logistic regression models included adjustment for age, body mass index, smoking, physical activity, alcohol intake, dietary glycemic index, family history of diabetes mellitus, blood pressure, plasma total cholesterol, uric acid, and estimated glomerular filtration rate. Higher nocturnal melatonin secretion was inversely associated with insulin levels and insulin resistance. In fully adjusted models, the odds ratio for insulin resistance was 0.45 (95% confidence interval: 0.28, 0.74) among women in the highest quartile of urinary 6-sulfatoxymelatonin:creatinine ratio compared with women in the lowest quartile. Nocturnal melatonin secretion is independently and inversely associated with insulin resistance.

Context: Studies examining the association between subclinical hypothyroidism and mortality have yielded conflicting results. Emerging data suggest these associations may depend upon underlying congestive heart failure (CHF) and/or race, but this has not been empirically determined., Objective: Our objective was to examine the association between subclinical hypothyroidism and hypothyroidism overall with mortality according to pre-existing CHF and race., Design and Participants: We examined the associations of subclinical hypothyroidism (TSH higher than assay upper limit of normal; total T4 within reference) and hypothyroidism overall (TSH higher than assay upper limit of normal; total T4 below lower limit of normal or within reference) with all-cause mortality among Third National Health and Nutrition Examination Survey participants stratified by CHF and race using multivariable Cox models. To confirm whether differences between strata were statistically significant, we tested for interaction on the basis of CHF (separately) and race by likelihood ratio testing., Results: There were 14 130 (95.0%) euthyroid controls and 749 (5.0%) participants with hypothyroidism, 691 (4.6%) of whom had subclinical disease. Subclinical hypothyroidism vs euthyroidism was associated with greater mortality in those with CHF but not in those without: adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) = 1.44 (1.01-2.06) and 0.97 (0.85-1.11), respectively (P interaction = .03). Similar findings were observed for hypothyroidism overall. Hypothyroidism overall vs euthyroidism was associated with greater mortality in Black participants (HR = 1.44 [95% CI = 1.03-2.03]) but not in non-Blacks (HR = 0.95 [95% CI = 0.83-1.08]) (P interaction = .03)., Conclusion: Among participants with CHF, subclinical hypothyroidism and hypothyroidism overall are associated with greater death risk. Additional studies are needed to confirm findings and explore possible mechanisms for the differential hypothyroidism-mortality association across race.

Use of analgesics is common and is associated with increased risk of hearing loss in men; however, the relation has not been examined prospectively in women. The authors prospectively examined the relation between frequency of aspirin, ibuprofen, and acetaminophen use and risk of hearing loss among 62,261 women aged 31-48 years at baseline (1995) in Nurses' Health Study II. The outcome was self-reported hearing loss (n = 10,012), and the follow-up period was 1995-2009. Cox proportional hazards regression was used to adjust for potential confounders. During 764,247 person-years of follow-up, ibuprofen use and acetaminophen use were independently associated with increased risk of hearing loss, but aspirin use was not. For ibuprofen, the multivariate-adjusted relative risk of hearing loss was 1.13 (95% confidence interval (CI): 1.06, 1.19) for use 2-3 days/week, 1.21 (95% CI: 1.11, 1.32) for use 4-5 days/week, and 1.24 (95% CI: 1.14, 1.35) for use ≥6 days/week (P-trend < 0.0001), compared with use less than once per week. For acetaminophen, the corresponding relative risks were 1.11 (95% CI: 1.02, 1.19), 1.21 (95% CI: 1.07, 1.37), and 1.08 (95% CI: 0.95, 1.22), respectively (P-trend = 0.0007). In this study, use of ibuprofen or acetaminophen (but not aspirin) 2 or more days per week was associated with an increased risk of hearing loss in women.

Background: Recent studies suggest a possible association between periodontal disease and hypertension; however, prospective evidence is limited., Methods: The study population consisted of 31,543 participants of the Health Professionals' Follow-Up Study (HPFS) prospective cohort who were 40-75 years old at baseline, had no prior hypertension history and had complete baseline information on oral health. Information on periodontal disease, hypertension and potential confounders was updated biennially. We used Cox proportional hazards models to study the relation between periodontal disease at baseline, during follow-up, periodontal bone loss severity, baseline number of teeth, and tooth loss during follow-up, and the risk of developing hypertension. Multivariate models included age, calendar time, race, comprehensive smoking index (CSI), diabetes, alcohol consumption, family history of hypertension, dental profession, body mass index (BMI), physical activity, fruit and vegetable intake, multivitamin use, calcium, vitamin D and vitamin E intake., Results: We identified 10,828 cases of incident hypertension over 20 years of follow-up. After adjusting for potential confounders, we did not observe significant associations between incident hypertension and periodontal disease at baseline (relative risk (RR) = 1.04; 95% confidence interval (CI): 0.98-1.10), periodontitis during follow-up (RR = 1.01; 95% CI: 0.96-1.05), tooth loss during follow-up (RR = 1.03; 95% CI: 0.98-1.09), or when comparing men with 0-10 teeth to men with ≥ 25 teeth at baseline (RR = 1.05; 95% CI: 0.91-1.21). Participants reporting severe periodontal bone loss had a RR for incident hypertension of 1.02 compared to those without bone loss (95% CI: 0.77-1.35)., Conclusions: We did not observe an association between periodontal disease measures and incident hypertension in this cohort of middle-aged men.

Background: Psoriasis has been linked to cardiovascular comorbidities in cross-sectional studies, but evidence regarding the association between psoriasis and incident cardiovascular disease (CVD) is limited., Objectives: To make a prospective evaluation of the association between psoriasis and risk of incident nonfatal CVD., Methods: Participants (n = 96, 008) were included from the Nurses' Health Study II, and followed for 18 years. Information on physician-diagnosed psoriasis was obtained by self-report and diagnosis was confirmed by supplementary questionnaires. We included 2463 individuals with self-reported psoriasis and a subsample of 1242 with validated psoriasis. The main outcome was incident nonfatal CVD events [nonfatal myocardial infarction (MI) and nonfatal stroke], ascertained by biennial questionnaires and confirmed., Results: During 1 709 069 person-years of follow-up, 713 incident nonfatal CVD events were confirmed. Psoriasis was associated with a significantly increased multivariate-adjusted hazard ratio (HR) of nonfatal CVD, 1·55 [95% confidence interval (CI): 1·04-2·31]. HRs for nonfatal MI and stroke were 1·70 (95% CI: 1·01-2·84) and 1·45 (95% CI: 0·80-2·65), respectively. The association remained consistent in a sensitivity analysis of confirmed psoriasis (HR: 2·06, 95% CI: 1·31-3·26). For individuals with concomitant psoriatic arthritis, the risk of nonfatal CVD was even higher (HR: 3·47; 95% CI: 1·85-6·51). Women diagnosed with psoriasis at < 40 years of age or with duration of psoriasis ≥ 9 years had substantial elevations in CVD risk: HR: 3·26 (95% CI: 1·21-8·75) and 3·09 (95% CI: 1·15-8·29), respectively., Conclusions: Psoriasis is an independent predictor for nonfatal CVD among women, with particularly high risk for those with longer duration of psoriasis and concomitant psoriatic arthritis., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Higher urinary albumin excretion predicts future cardiovascular disease, hypertension, and chronic kidney disease. Physical activity improves endothelial function so activity may reduce albuminuria. Among diabetics, physical activity decreases albuminuria. In nondiabetics, prior studies have shown no association. The authors explored the cross-sectional association between physical activity and albuminuria in 3,587 nondiabetic women in 2 US cohorts, the Nurses' Health Study I in 2000 and the Nurses' Health Study II in 1997. Physical activity was expressed as metabolic equivalents per week. The outcome was the top albumin/creatinine ratio (ACR) decile. Multivariate logistic regression was used. Secondary analyses explored the ACR association with strenuous activity and walking. The mean age was 58.6 years. Compared with women in the lowest physical activity quintile, those in the highest quintile had a multivariate-adjusted odds ratio for the top ACR decile of 0.65 (95% confidence interval (CI): 0.46, 0.93). The multivariate-adjusted odds ratio for the top ACR decile for those with greater than 210 minutes per week of strenuous activity compared with no strenuous activity was 0.61 (95% CI: 0.37, 0.99), and for those in the highest quintile of walking compared with the lowest quintile, it was 0.69 (95% CI: 0.47, 1.02). Greater physical activity is associated with a lower ACR in nondiabetic women.

Background: Higher levels of urinary albumin excretion predict future hypertension and chronic kidney disease. Post-menopausal hormone use may influence the renin-angiotensin system and renal endothelial function, impacting albumin excretion. The association between post-menopausal hormone use and albuminuria is not well defined., Methods: We explored the cross-sectional association between duration of PMH use and albuminuria in 2445 post-menopausal, non-diabetic women from the Nurses' Health Study. Women were categorized as hormone non-users, past users or current users grouped by 3-year intervals of duration of use, from < or =3 years to >15 years. The outcome was the top decile of urine albumin/creatinine ratio (ACR). Multivariate logistic regression was used to assess the association between duration of PMH use and risk of being in the top decile., Results: The mean age was 66.8 years, and 57% were currently using PMH. The median ACR was 2.9 mg/g, and the 90th percentile was 9.2 mg/g. Compared with women with no history of PMH use, the odds ratio for being in the top ACR decile was lower for women with use of >6-9 years, >9-12 years, >12-15 years and >15 years, but there was no dose-response. The overall odds ratio was 0.55 (95% CI: 0.39-0.77) among women with >6 years of current PMH use compared with non-users. Current hormone use of shorter duration and past hormone use were not associated with albumin excretion., Conclusions: Current PMH use of >6 years is associated with a lower urinary ACR in non-diabetic women.

Background: Urinary excretion of albumin indicates kidney damage and is recognized as a risk factor for progression of kidney disease and cardiovascular disease. The role of urinary albumin measurements has focused attention on the clinical need for accurate and clearly reported results. The National Kidney Disease Education Program and the IFCC convened a conference to assess the current state of preanalytical, analytical, and postanalytical issues affecting urine albumin measurements and to identify areas needing improvement., Content: The chemistry of albumin in urine is incompletely understood. Current guidelines recommend the use of the albumin/creatinine ratio (ACR) as a surrogate for the error-prone collection of timed urine samples. Although ACR results are affected by patient preparation and time of day of sample collection, neither is standardized. Considerable intermethod differences have been reported for both albumin and creatinine measurement, but trueness is unknown because there are no reference measurement procedures for albumin and no reference materials for either analyte in urine. The recommended reference intervals for the ACR do not take into account the large intergroup differences in creatinine excretion (e.g., related to differences in age, sex, and ethnicity) nor the continuous increase in risk related to albumin excretion., Discussion: Clinical needs have been identified for standardization of (a) urine collection methods, (b) urine albumin and creatinine measurements based on a complete reference system, (c) reporting of test results, and (d) reference intervals for the ACR.

Background: Cross-sectional analyses of kidney function and physical function have identified profound quality of life impairments in people with advanced kidney dysfunction. No data are currently available, however, on how kidney function decline may be associated with physical function., Methods: We undertook a study of kidney function decline and physical function in 2544 women participating in the Nurses' Health Study. Glomerular filtration rates (GFR) were estimated using the four-variable MDRD equation from plasma creatinine measured in blood collected in 1989 and 2000. Physical function was assessed by the Physical Function Sub-Scale (PFS) score of the Short Form 36 (SF-36) in a questionnaire administered in the year 2000. PFS scores have been shown to correlate well with direct measures of physical function., Results: In the year 2000, the median age was 67 years, median body mass index (BMI) was 25.6 kg/m(2), 48.5% had hypertension and 5.8% had diabetes. There were 427 women (16.8%) who experienced an >/=25% decline in eGFR between 1989 and 2000. Median PFS in 2000 for those with an eGFR decline of >/=25% was 80 compared to a PFS score of 85 for those without (P < 0.001). In fully adjusted models, the presence of an eGFR decline of >/=25% was independently associated with a 3.5-point lower PFS score (95% CI -5.4 to -1.5). Also, an eGFR decline of >/=25% was independently associated with an increased odds ratio of being in the lowest quartile of PFS score (OR 1.37; 95% CI 1.04-1.81)., Conclusions: We conclude that an eGFR decline of >/=25% over 11 years is independently associated with lower physical function in women.

Background: The impact of moderate alcohol consumption on renal function has important public health implications given the high prevalence of alcohol use. Experimentally, alcohol may adversely affect renal function, but clinical data are limited and no large, prospective studies have examined this issue., Methods: In a prospective study of 1658 nurses enrolled in the Nurses' Health Study, we sought to determine if there was an association between moderate alcohol consumption and rate of decline in renal function. Daily alcohol intake was measured in 1990, 1994 and 1998 using a detailed questionnaire. Maximum daily alcohol intake was measured in 1988. Creatinine, measured from blood samples provided in 1989 and 2000, was used to estimate glomerular filtration rate (GFR) and creatinine clearance (CCr)., Results: Compared to individuals with no alcohol intake, the odds ratios (ORs) for developing a >or=25% estimated GFR decline were: 0.98 (95% CI: 0.72-1.32) for 0.1-4.9 g/day, 0.83 (95% CI: 0.56-1.21) for 5-14.9 g/day and 0.81 (95% CI: 0.50-1.31) for 15-59.9 g/day. For women with hypertension (n = 726), the ORs for a >or=25% estimated GFR decline were: 0.98 (95% CI: 0.53-1.21) for 0.1-4.9 g/day, 0.62 (95% CI: 0.34-1.12) for 5-14.9 g/day and 0.53 (95% CI: 0.25-1.12) for 15-59.9 g/day., Conclusions: Moderate alcohol consumption had no substantial adverse effect on renal function in women over an 11 year follow-up period.

Background: Hypertension treatment is important in managing chronic renal insufficiency (CRI). Little is known, however, about the blood pressure (BP) control achieved or the pattern of antihypertensive drug prescription among CRI patients., Methods: Using computerized medical records, we studied 3,089 adult hypertensive subjects treated at Brigham and Women's Hospital (Boston, MA) from 1990 through 1998. All subjects had at least two serum creatinine measurements 2 years apart, at least two BP readings, and online weight (to estimate Cockcroft-Gault creatinine clearance [CrCl])., Results: The average mean arterial pressure over time (mean MAP) was 103 +/- 9 mm Hg among those with CrCI >60 mL/min, 102 t 9 mm Hg among those with CrCl 41 to 60 mL/min. and 101 +/- 9 mm Hg among those with CrCl 21 to 40 mL/min. There were no significant differences in mean MAP among the different categories of renal function in the multivariate analysis (P = .26 for trend). The proportion of patients with final systolic BP < 160 mm Hg and diastolic BP <90 mm Hg was 68% and did not vary with renal function (P = .68 for trend). The proportion of subjects who were prescribed ACE inhibitors was 38% among those with CrCl >60 mL/min, 36% among those with CrCI 41 to 60 mL/min, and only 27% among those with CrCl 21 to 40 mL/min (P = .003 for trend)., Conclusions: The BP control achieved among hypertensive CRI subjects, although no worse than that among those without CRI, was found to be suboptimal. Patients with CrCl 21 to 40 mL/min were less likely to be prescribed ACE inhibitors than were those with CrCl >60 mL/min. Improvement is needed in the clinical management of these factors that can influence the progression of CRI.

The authors retrospectively evaluated the relation between birth weight and prostate cancer (1986-1994) among 21,140 men of the Health Professionals Follow-up Study who reported in 1994 their weight at birth. No relation between birth weight and prostate cancer (n=545) was observed in multivariate logistic models. For high stage/grade tumors (n=213), compared with birth weights <7.0 lbs (<3,175 g), the relative risks were 1.20 (95% confidence interval (CI) 0.79-1.83) for 8.5-9.9 lbs (3,855.6-4,490.6 g) and 1.30 (95% CI 0.80-2.10) for > or = 10 lbs (> or = 4,536 g). These findings do not support an overall association between birth weight and prostate cancer incidence, but the possibility of a modest positive association between birth weight and high stage/grade prostatic cancer cannot be excluded.

A positive association between nephrolithiasis and blood pressure has been suggested in previous studies. However, controversy remains, due to methodological problems in some of the previous studies and absence of prospective data. We evaluated the relationship between nephrolithiasis and the risk of hypertension in a cohort of 51,529 men followed prospectively for 8 years. Information was obtained by biennial mailed questionnaires. At baseline in 1986, 4111 (8.0%) subjects reported a history of nephrolithiasis and 11,623 (22.6%) a diagnosis of hypertension. A positive association was found between the two disorders (age adjusted odds ratio [OR]: 1.31; 95% confidence interval [CI]: 1.30 to 1.32). Among men who reported both disorders, 79.5% reported that the occurrence of nephrolithiasis was prior to or concomitant with the diagnosis of hypertension. Among men without hypertension at baseline, the odds ratio for incident hypertension in men with a history of nephrolithiasis compared with those without was 1.29 (95% CI: 1.12 to 1.41; adjusted for age, body mass index, and intake of calcium, sodium, potassium, magnesium, and alcohol). The occurrence of incident nephrolithiasis during follow-up was similar in men with hypertension at baseline compared with that in men without (adjusted OR: 0.99, 95% CI: 0.82 to 1.21). These data support the hypothesis that prior occurrence of nephrolithiasis increases the risk of subsequent hypertension.

Patients with kidney stones are routinely advised to increase their fluid intake to decrease the risk of stone recurrence. However, there has been no detailed examination to determine whether the effect on recurrence varies by the type of beverage consumed. The authors conducted a prospective study of the relation between the intake of 21 different beverages and the risk of symptomatic kidney stones in a cohort of 45,289 men, 40-75 years of age, who had no history of kidney stones. Beverage use and other dietary information was measured by means of a semiquantitative food frequency questionnaire in 1986. During 6 years of follow-up (242,100 person-years), 753 incident cases of kidney stones were documented. After adjusting simultaneously for age, dietary intake of calcium, animal protein and potassium, thiazide use, geographic region, profession, and total fluid intake, consumption of specific beverages significantly added to the prediction of kidney stone risk (p < 0.001). After mutually adjusting for the intake of other beverages, the risk of stone formation decreased by the following amount for each 240-ml (8-oz) serving consumed daily: caffeinated coffee, 10% (95% confidence interval 4-15%); decaffeinated coffee, 10% (3-16%); tea, 14% (5-22%); beer, 21% (12-30%); and wine, 39% (10-58%). For each 240-ml serving consumed daily, the risk of stone formation increased by 35% (4-75%) for apple juice and 37% (1-85%) for grapefruit juice. The authors conclude that beverage type may have an effect on stone formation that involves more than additional fluid intake alone.