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Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been associated with earlier natural menopause; however, the underlying mechanisms are not well understood, particularly the extent to which this relationship is mediated by sex hormones. We analyzed data (1999–2017) on 1,120 premenopausal women from the Study of Women's Health Across the Nation (SWAN). Causal mediation analysis was applied to quantify the degree to which follicle-stimulating hormone (FSH) and estradiol levels could mediate the associations between PFAS and incident natural menopause. Participants with higher PFAS concentrations had shorter times to natural menopause, with a relative survival of 0.82 (95% confidence interval (CI): 0.69, 0.96) for linear perfluorooctane sulfonate (n-PFOS), 0.84 (95% CI: 0.69, 1.00) for sum of branched-chain perfluorooctane sulfonate (Sm-PFOS), 0.79 (95% CI: 0.66, 0.93) for linear-chain perfluorooctanoate (n-PFOA), and 0.84 (95% CI: 0.71, 0.97) for perfluorononanoate (PFNA), comparing the highest tertile of PFAS concentrations with the lowest. The proportion of the effect mediated through FSH was 8.5% (95% CI: −11.7, 24.0) for n-PFOS, 13.2% (95% CI: 0.0, 24.5) for Sm-PFOS, 26.9% (95% CI: 15.6, 38.4) for n-PFOA, and 21.7% (6.8, 37.0) for PFNA. No significant mediation by estradiol was observed. The effect of PFAS on natural menopause may be partially explained by variations in FSH concentrations. [ABSTRACT FROM AUTHOR]

Objective. To estimate the relationship between obesity (defined by both BMI and SAD) and various levels of depressive symptoms in women in the United States. Methods. This is a cross-sectional design. All data were collected from NHANES 2011-2012 and 2013-2014. The Patient Health Questionnaire (PHQ-9) was the primary variable used to index depressive symptoms. SAD was assessed using an abdominal caliper. We stratified participates into three groups according to SAD (trisection): T1: low (11.8-18.4 cm), T2: middle (18.5-22.8 cm), and T3: high (22.9-40.1 cm). Other data were collected following the NHANES protocols. We aimed to investigate the effects of obesity on the depression in the NHANES populations. Results. A total of 4477 women were enrolled in the final study population. Participants with a high SAD had the highest risk of clinical depression symptoms (OR = 1.2 , 95% CI: 1.1-1.4), which was, in particular, the case for moderate-severe depression (OR = 1.4 , 95% CI: 1.1-1.7) and severe depression (OR = 1.4 , 95% CI: 1.0-1.9). We also found a significant relationship between SAD and BMI (r = 0.836). We did, however, not find a significant relationship between BMI and severe depression. Conclusions. SAD had a better correlation with clinical depression symptoms than BMI, especially regarding severe depression symptoms. [ABSTRACT FROM AUTHOR]

Context: Previous epidemiologic studies of per- and polyfluoroalkyl substances (PFASs) and menopausal timing conducted in cross-sectional settings were limited by reverse causation because PFAS serum concentrations increase after menopause.Objectives: To investigate associations between perfluoroalkyl substances and incident natural menopause.Design and Setting: A prospective cohort of midlife women, the Study of Women's Health Across the Nation, 1999-2017.Participants: 1120 multiracial/ethnic premenopausal women aged 45-56 years.Methods: Serum concentrations of perfluoroalkyls were quantified by high-performance liquid chromatography isotope dilution tandem mass spectrometry. Natural menopause was defined as the bleeding episode prior to at least 12 months of amenorrhea not due to surgery or hormone use. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: Participants contributed 5466 person-years of follow-up, and 578 had incident natural menopause. Compared with the lowest tertile, women at the highest tertile of baseline serum concentrations had adjusted HR for natural menopause of 1.26 (95% CI: 1.02-1.57) for n-perfluorooctane sulfonic acid (n-PFOS) (Ptrend = .03), 1.27 (95% CI: 1.01-1.59) for branched-PFOS (Ptrend = .03), and 1.31 (95% CI: 1.04-1.65) for n-perfluorooctanoic acid (Ptrend = .01). Women were classified into four clusters based on their overall PFAS concentrations as mixtures: low, low-medium, medium-high, and high. Compared with the low cluster, the high cluster had a HR of 1.63 (95% CI: 1.08-2.45), which is equivalent to 2.0 years earlier median time to natural menopause.Conclusion: This study suggests that select PFAS serum concentrations are associated with earlier natural menopause, a risk factor for adverse health outcomes in later life. [ABSTRACT FROM AUTHOR]

Background: Feminine hygiene products (FHPs) are personal care products widely used by women. A few studies have detected some volatile organic compounds (VOCs) in FHPs, but no previous epidemiological studies have linked use of these products to human exposure to VOCs using biomarkers. Therefore, we evaluated whether the use of FHPs was associated with VOC exposures among reproductive-aged women in the United States. Materials and Methods: Data on 2432 women aged 20–49 years from National Health and Nutrition Examination Survey 2001–2004 were utilized. Self-reported use of feminine products (tampons, sanitary napkins, vaginal douches, sprays, powders, wipes/towelettes, and other products) was obtained from questionnaires. Survey-weighted linear regression models were used to estimate percent changes in VOC whole blood concentrations and 95% confidence intervals (CIs). Results: Black women had significantly more use of vaginal douching and significantly higher whole blood concentrations of 1,4-dichlorobenzene (DCB) (p < 0.0001). After adjusting for confounders, we observed a dose–response relationship between the frequency of vaginal douching in the past 6 months and 1,4-DCB concentrations. Compared with never users, women with occasional use (≤1 time/month) of vaginal douching had 18% (95% CI: −12% to 59%) higher concentrations, and those with frequent use (≥2 time/month) had 81% (95% CI: 2% to 221%) higher concentrations of 1,4-DCB (p for trend = 0.04). Use of feminine powder in the past month was significantly associated with 36% (95% CI: 0.4% to 83%) higher concentrations of ethylbenzene. Conclusions: Our findings suggest that differences in whole blood VOC concentrations might be explained by feminine hygiene practices. The presence of environmental chemicals in FHPs warrants further examination. [ABSTRACT FROM AUTHOR]

Rationale & Objective: Smoking is a modifiable risk factor for various adverse events. However, little is known about the association of smoking with the incidence of acute kidney injury (AKI) in the general population. This study investigated the association of cigarette smoking with the risk of AKI., Study Design: Prospective observational study., Setting & Participants: 14,571 participants (mean age 55±6 years, 55% women, and 25% Black participants) from the ARIC study visit 1 (1987-1989) followed through December 31, 2019., Exposure: Smoking parameters (status, duration, pack-years, intensity, and years since cessation)., Outcome: Incident hospitalization with AKI, defined by a hospital discharge with a diagnostic code relevant to AKI., Analytical Approach: Multivariable Cox regression models., Results: Over a median follow-up period of 26.3 years, 2,984 participants had an incident hospitalization with AKI. Current and former smokers had a significantly higher risk of AKI compared to never smokers after adjusting for potential confounders (HR, 2.22 [95% CI, 2.02-2.45] and 1.12 [1.02-1.23], respectively). A dose-response association was consistently seen for each of smoking duration, pack-years, and intensity with AKI (eg, HR, 1.19 [95% CI, 1.16-1.22] per 10 years of smoking). When years since cessation were considered as a time-varying exposure, the risk of AKI associated with smoking compared with current smokers began to decrease after 10 years, and became similar to never smokers at 30 years (HR for≥30 years, 1.07 [95% CI, 0.97-1.20] vs never smokers)., Limitations: Self-reported smoking measurements and missing outpatient AKI cases., Conclusions: In a community-based cohort, all smoking parameters were robustly associated with the risk of AKI. Smoking cessation was associated with decreased risk of AKI, although the excess risk lasted up to 30 years. Our study supports the importance of preventing smoking initiation and promoting smoking cessation for the risk of AKI., Plain-Language Summary: Smoking is a behavior that is associated with many negative health effects. It is not well understood how smoking relates to the occurrence of acute kidney injury (AKI) in the community. In this study, we looked at data from a group of 14,571 adults who were followed for 26 years to see how different aspects of smoking (such as whether someone smoked, how long they smoked for, how many cigarettes they smoked per day, and whether they quit smoking) were related to AKI. We found that smoking was strongly linked to an increased risk of AKI. This risk decreased after 5-10 years of quitting smoking, but the excess risk lasted up to 30 years. This study shows the importance of preventing people from starting smoking and to encourage smokers to quit to reduce their risk of AKI., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: There is a lack of understanding of how daily step counts differentially affect the risk of all-cause mortality in adult with congestive heart failure (CHF) by sex in the United States (US)., Objectives: To explore the relationship between daily step counts and all-cause mortality in patients with CHF by sex., Methods: This is a cohort analysis from the National Health and Nutrition Examination Survey from 2005 to 2006. Multiple Cox hazard regression was performed to explore the association of step counts and all-cause mortality in patients with CHF by sex., Results: In this study, 363 unweighted samples were enrolled from NHANES 2005-2006, representing about 8.4 million of the US population. Further, 46.28% were women, and the average age was 46 years. Patients with CHF in the more than 5581 steps/day group (HR, 0.31 [95% CI, 0.16-0.58]) had a significantly reduced risk of all-cause mortality compared with the patients in the less 5581 steps/day group after accounting for all covariates. In men, after accounting for all the covariates, there was a significant difference in more than 5581 steps/day group (HR, 0.33 [95% CI, 0.14-0.76]) on all-cause mortality in men with CHF compared with men in the less than 5581 steps/day group., Conclusions: Step count is associated with all-cause mortality in patients with CHF. Taking 5581 daily steps was associated with a decreased risk of all-cause mortality in patients with CHF., Competing Interests: Declaration of Competing Interest This manuscript is the original work of the authors and has not been submitted and is not under consideration for publication elsewhere. All the authors have reviewed the manuscript and approved it before submission. None of the authors has any conflict of interest in the publication of this manuscript. All authors participated in the manuscript preparation and contributed to the conception and design of the study. The specific contributions were as follows: XPC and ZYP was responsible for study conception and design and directed the analyses and writing of the manuscript. GFY, WP, and ND performed the data analyses and drafting of the manuscript. YZ conceived the study and participated in drafting of the manuscript. DSZ and HLZ conceived the study and participated in drafting of the manuscript. YZ carried out the data collection and data analyses and participated in drafting of the manuscript. This manuscript is the original work of the authors and has not been submitted and is not under consideration for publication elsewhere. All the authors have reviewed the manuscript and approved it before submission. None of the authors has any conflict of interest in the publication of this manuscript., (Copyright © 2023. Published by Elsevier Inc.)

Objective: The purpose of this study was to investigate the relationship between bedtime at night and the risk of diabetes in adults., Methods: We extracted data from 14,821 target subjects from the NHANES database for a cross-sectional study. The data on bedtime came from the question in the sleep questionnaire: "What time do you usually fall asleep on weekdays or workdays?". Diabetes was defined as fasting blood sugar ≥ 126mg/dL, or glycohemoglobin ≥ 6.5%, or 2-hour Oral Glucose Tolerance Test blood sugar ≥ 200mg/dL, or taking hypoglycemic agent and insulin, or self-reported diabetes mellitus. A weighted multivariate logistic regression analysis was conducted to explore the relationship between bedtime at night and diabetes in adults., Results: From 19:00 to 23:00, a significantly negative association can be found between bedtime and diabetes(OR, 0.91 [95%CI, 0.83, 0.99]). From 23:00 to 02:00, The relationship between the two was positive(OR, 1.07 [95%CI, 0.94, 1.22]), nevertheless, the P values was not statistically significant(p = 0.3524). In subgroup analysis, from 19:00-23:00, the relationship was negative across genders, and in males, the P-values were still statistically significant(p = 0.0414). From 23:00-02:00, the relationship was positive across genders., Conclusion: Earlier bedtime (before 23:00) increased the risk of developing diabetes. And this effect was not significantly different between male and female. For bedtime between 23:00-2:00, there was a trend of increasing the risk of diabetes as the bedtime was delayed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ouyang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Few studies have investigated the association of magnesium levels with incident peripheral artery disease (PAD) despite emerging evidence of magnesium contributing to vascular calcification. Moreover, no data are available on whether the magnesium-PAD relationship is independent of or modified by kidney function., Methods: A cohort of 11 839 participants free of PAD in the Atherosclerosis Risk in Communities Study at Visit 2 (1990-92) was studied. We investigated the association of serum magnesium and other bone-mineral metabolism markers [calcium, phosphorus, intact parathyroid hormone (iPTH) and intact fibroblast growth factor-23] with incident PAD using multivariable Cox proportional hazards regression., Results: Over a median of 23 years, there were 471 cases of incident PAD. The hazard ratio for incident PAD in Quartile 1 (<1.5 mEq/L) versus Quartile 4 (>1.7 mEq/L) of magnesium was 1.96 (95% confidence interval 1.40-2.74) after adjustment for potential confounders. Lower magnesium levels were associated with greater incidence of PAD, particularly in those with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 11 606). In contrast, the association was largely flat in those with eGFR <60 mL/min/1.73 m2 (n = 233) with P-for-interaction 0.03. Among bone-mineral metabolism markers, only higher iPTH showed an interaction with kidney function (P-for-interaction 0.01) and iPTH >65 pg/mL was significantly related to PAD only in those with eGFR <60 mL/min/1.73 m2., Conclusions: Lower magnesium was independently associated with incident PAD, but this association was significantly weaker in those with reduced kidney function. In contrast, higher iPTH levels were particularly related to PAD risk in this clinical population., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Objective: Inflammatory markers, such as hs-CRP (high-sensitivity C-reactive protein), have been reported to be related to peripheral artery disease (PAD). Galectin-3, a biomarker of fibrosis, has been linked to vascular remodeling and atherogenesis. However, its prospective association with incident PAD is unknown; as is the influence of inflammation on the association between galectin-3 and PAD. Approach and Results: In 9851 Atherosclerosis Risk in Communities Study participants free of PAD at baseline (1996-1998), we quantified the association of galactin-3 and hs-CRP with incident PAD (hospitalizations with PAD diagnosis [ International Classification of Diseases - Ninth Revision : 440.2-440.4] or leg revascularization [eg, International Classification of Diseases - Ninth Revision : 38.18]) as well as its severe form, critical limb ischemia (PAD cases with resting pain, ulcer, gangrene, or leg amputation) using Cox models. Over a median follow-up of 17.4 years, there were 316 cases of PAD including 119 critical limb ischemia cases. Log-transformed galectin-3 was associated with incident PAD (adjusted hazard ratio, 1.17 [1.05-1.31] per 1 SD increment) and critical limb ischemia (1.25 [1.05-1.49] per 1 SD increment). The association was slightly attenuated after further adjusting for hs-CRP (1.14 [1.02-1.27] and 1.22 [1.02-1.45], respectively). Log-transformed hs-CRP demonstrated robust associations with PAD and critical limb ischemia even after adjusting for galectin-3 (adjusted hazard ratio per 1 SD increment 1.34 [1.18-1.52] and 1.34 [1.09-1.65], respectively). The addition of galectin-3 and hs-CRP to traditional atherosclerotic predictors (C statistic of the base model 0.843 [0.815-0.871]) improved the risk prediction of PAD (ΔC statistics, 0.011 [0.002-0.020])., Conclusions: Galectin-3 and hs-CRP were independently associated with incident PAD in the general population, supporting the involvement of fibrosis and inflammation in the pathophysiology of PAD.

Background hs-cTnT (high-sensitivity cardiac troponin T), but not NT-proBNP (N-terminal pro-B natriuretic peptide), has been shown to predict bleeding in patients with atrial fibrillation. Whether these biomarkers are independently associated with bleeding in the general population is unknown. Methods and Results We used Cox proportional hazards models to examine the association of hs-cTnT and NT-proBNP with incident bleeding (defined by International Classification of Diseases, Ninth Revision [ ICD-9 ] codes) among 9550 middle-aged men and women without a history of cardiovascular disease or bleeding. There were 847 hospitalizations with bleeding (92% from gastrointestinal bleeding) during a median follow-up of 9.0 years. Serum levels of hs-cTnT were associated with bleeding in a graded fashion, with a hazard ratio of 1.28 (95% CI, 1.06-1.59) for 6 to <9 ng/L, 1.52 (1.21-1.91) for 9 to <14, and 2.05 (1.56-2.69) for ≥14 versus <3 ng/L. For NT-proBNP, the highest category (≥264 versus <42 pg/mL) showed a hazard ratio of 2.00 (1.59-2.61), and the remaining 3 categories had hazard ratios ranging from 1.2 to 1.3. Individuals in the highest category of both hs-cTnT and NT-proBNP had a hazard ratio of 3.03 (1.97-4.68) compared with those in the lowest categories. Conclusions In a community-based population, elevated hs-cTnT and NT-proBNP were associated with bleeding-related hospitalizations. These biomarkers may have a high utility in identifying people at high risk for bleeding. There is a need for research on the underlying mechanisms linking subclinical cardiac abnormalities and bleeding.

Background: Per- and poly-fluoroalkyl substances (PFAS) are public health concerns because of widespread exposure through contaminated foods/drinking water. Although some determinants of PFAS exposure have been suggested, the role of geographic location and race/ethnicity in PFAS exposure has not been well characterized., Objectives: We examined potential determinants of PFAS from the Study of Women's Health Across the Nation (SWAN)., Methods: This study includes 1302 women aged 45-56 years from 5 SWAN sites where white women and women from one minority group were recruited (black from Southeast Michigan, Pittsburgh, Boston; Chinese from Oakland; Japanese from Los Angeles). We determined concentrations of 11 PFAS in serum samples collected in 1999-2000 and examined 7 PFAS detected in most women (>97%). Linear regression with backward elimination was used to identify important determinants of PFAS serum concentrations among a set of pre-specified variables (age, body mass index, site, race/ethnicity, education, financial hardship, occupation, born outside the United States (US), parity, menstrual bleeding within the past year, smoking status, alcohol consumption, and consumption of fish, dairy, pizza, salty snack, and French fries)., Results: Site and race/ethnicity were two major determinants of PFAS. White women had higher concentrations of linear perfluorooctanoic acid (PFOA) compared with the Chinese in Oakland (p < 0.0001) and blacks in Pittsburgh (p = 0.048). Black women in Southeast Michigan and Boston (vs. white women) had higher concentrations of linear (p < 0.001 for Southeast Michigan; p < 0.0001 for Boston) and total perfluorooctane sulfonic acid (PFOS) (p < 0.001 for both Southeast Michigan and Boston) and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (p = 0.02 for Southeast Michigan; p < 0.001 for Boston). Chinese (Oakland) and Japanese (Los Angeles) women had higher concentrations of perfluorononanoic acid (PFNA) compared with white women in each site (p < 0.01 for both). Within white women, those in Pittsburgh had relatively higher concentrations of PFAS. Within Chinese and Japanese women, those who were born outside the US had significantly lower concentrations of most PFAS but significantly higher PFNA concentrations. Menstrual bleeding and parity were significantly associated with lower PFAS concentrations. Higher intake of salty snacks including popcorn was significantly associated with higher concentrations of linear PFOA, PFOS and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid., Discussion: Geographic locations and race/ethnicity play an important role in differential exposure to PFAS, with racial/ethnic burdens differing between PFOS, PFOA and PFNA. Menstruation and parity were also determinants of PFAS concentrations possibly as an elimination route., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Aims: Traditional glycemic markers, fasting glucose and hemoglobin A1c (HbA1c), predict incident peripheral artery disease (PAD). However, it is unknown whether nontraditional glycemic markers, fructosamine, glycated albumin, and 1,5-anhydroglucitol, are associated with PAD and whether these glycemic markers demonstrate particularly strong associations with severe PAD, critical limb ischemia (CLI)., Methods: We quantified the associations of these five glycemic markers with incident PAD (hospitalizations with PAD diagnosis or leg revascularization) in 11,634 ARIC participants using Cox regression models. Participants were categorized according to diabetes diagnosis and clinical cut-points of glycemic markers (nontraditional glycemic markers were categorized according to percentiles corresponding to the HbA1c cut-points)., Results: Over a median follow-up of 20.7 years, there were 392 cases of PAD (133 were CLI with tissue loss). HbA1c was more strongly associated with incident PAD than fasting glucose, with adjusted hazard ratios (HR) 6.00 (95% CI, 3.73-9.66) for diagnosed diabetes with HbA1c ≥ 7% and 3.53 (2.39-5.22) for no diagnosed diabetes with HbA1c ≥ 6.5% compared to no diagnosed diabetes with HbA1c <5.7%. Three nontraditional glycemic markers demonstrated risk gradients intermediate between HbA1c and fasting glucose and their risk gradients were substantially attenuated after adjusting for HbA1c. All glycemic markers consistently demonstrated stronger associations with CLI than PAD without CLI (p for difference <0.02 for all glycemic markers)., Conclusions: Nontraditional glycemic markers were associated with incident PAD independent of fasting glucose but not necessarily HbA1c. Our results also support the importance of glucose metabolism in the progression to CLI., (Copyright © 2018 Elsevier B.V. All rights reserved.)