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Background: Heart failure (HF) is increasing in the United States, and awareness is needed for prevention. Hypertension is the leading cause of HF, and adherence to antihypertensive medication is critical for reducing HF risk. Self-efficacy positively influences health-promoting behaviors. Objectives: Assess HF awareness, test associations with antihypertensive medication adherence, and self-efficacy for managing chronic conditions. Design: We conducted a cross-sectional, observational survey research study. Methods: We leveraged data from participants enrolled in the American Heart Association's Research Goes Red™ registry, an online platform powered by Verily. Three surveys ascertained HF awareness, blood pressure management, and self-efficacy. Chi-squared and Wilcoxon rank sum determined associations between survey domains and participant characteristics. Results: Two thousand three hundred twenty women took the HF awareness survey, 678 the blood pressure management survey, and 755 the self-efficacy survey (response rates: 12%, 78%, and 76%, respectively). Participants were predominantly non-Hispanic White (78%), with a median age of 51 (interquartile range (IQR): 39, 62). Median HF awareness score was 4/5 (IQR: 4, 5). Participants with high HF awareness versus low were more likely to be older (p < 0.001), non-Hispanic White (p < 0.001), and less likely to smoke (p < 0.001) or have depression (p = 0.004). Nearly 90% of hypertensive participants reported medication adherence, which was not associated with HF awareness or self-efficacy. Participants with greater self-efficacy versus less were more likely to have higher HF awareness (p = 0.01), be older (p = 0.01), and less likely to have depression (p < 0.001). Conclusion: Women's awareness of HF and adherence to antihypertensive medication in this cohort was high. Depression and younger age may be important factors affecting women's HF awareness and confidence in managing chronic disease medication plans. Plain language summary: Awareness of heart failure, blood pressure management and self-efficacy in the Research Goes Red for Women Registry The following study investigated heart failure (HF) awareness, antihypertensive medication adherence, and self-efficacy among women from the American Heart Association's Research Goes Red for Women Registry. We found high levels of HF awareness and medication adherence among these women. However, younger age and depression were associated with lower HF awareness and self-efficacy. These findings emphasize the importance of targeting education and support interventions, especially for younger women and those dealing with depression, to improve HF prevention strategies and medication management. [ABSTRACT FROM AUTHOR]

Proteomics offers great promise in improving risk prediction of patients with heart failure. In this community-based cohort study, 7289 plasma proteins were measured in 1351 patients to derive a protein risk score to predict mortality. The study showed that the protein score outperformed clinical risk tools in predicting mortality. Studies to further validate the score and determine risk thresholds for intervention now seem necessary. Visual Abstract. Development and Validation of a Protein Risk Score for Mortality in Heart Failure: Proteomics offers great promise in improving risk prediction of patients with heart failure. In this community-based cohort study, 7289 plasma proteins were measured in 1351 patients to derive a protein risk score to predict mortality. The study showed that the protein score outperformed clinical risk tools in predicting mortality. Studies to further validate the score and determine risk thresholds for intervention now seem necessary. Background: Heart failure (HF) is a complex clinical syndrome with high mortality. Current risk stratification approaches lack precision. High-throughput proteomics could improve risk prediction. Its use in clinical practice to guide the management of patients with HF depends on validation and evidence of clinical benefit. Objective: To develop and validate a protein risk score for mortality in patients with HF. Design: Community-based cohort. Setting: Southeast Minnesota. Participants: Patients with HF enrolled between 2003 and 2012 and followed through 2021. Measurements: A total of 7289 plasma proteins in 1351 patients with HF were measured using the SomaScan Assay (SomaLogic). A protein risk score was derived using least absolute shrinkage and selection operator regression and temporal validation in patients enrolled between 2003 and 2007 (development cohort) and 2008 and 2012 (validation cohort). Multivariable Cox regression was used to examine the association between the protein risk score and mortality. The performance of the protein risk score to predict 5-year mortality risk was assessed using calibration plots, decision curves, and relative utility analyses and compared with a clinical model, including the Meta‐Analysis Global Group in Chronic Heart Failure mortality risk score and N -terminal pro–B-type natriuretic peptide. Results: The development (n = 855; median age, 78 years; 50% women; 29% with ejection fraction <40%) and validation cohorts (n = 496; median age, 76 years; 45% women; 33% with ejection fraction <40%) were mostly similar. In the development cohort, 38 unique proteins were selected for the protein risk score. Independent of ejection fraction, the protein risk score demonstrated good calibration, reclassified mortality risk particularly at the extremes of the risk distribution, and showed greater clinical utility compared with the clinical model. Limitation: Participants were predominantly of European ancestry, potentially limiting the generalizability of the findings to different patient populations. Conclusion: Validation of the protein risk score demonstrated good calibration and evidence of predicted benefits to stratify the risk for death in HF superior to that of clinical methods. Further studies are needed to prospectively evaluate the score's performance in diverse populations and determine risk thresholds for interventions. Primary Funding Source: Division of Intramural Research at the National Heart, Lung, and Blood Institute of the National Institutes of Health. [ABSTRACT FROM AUTHOR]

Introduction The incidence of renal cell carcinoma (RCC), the most common form of kidney cancer, has been steadily increasing in the United States for several decades (Noone et al. 2018; [...], BACKGROUND: Agricultural work and occupational pesticide use have been associated with increased risk of renal cell carcinoma (RCC), the most common form of kidney cancer. However, few prospective studies have investigated links to specific pesticides. OBJECTIVE: We evaluated the lifetime use of individual pesticides and the incidence of RCC. METHODS: We evaluated the associations between intensity-weighted lifetime days (IWDs) of 38 pesticides and incident RCC in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. Among 55,873 applicators, 308 cases were diagnosed between enrollment (1993-1997) and the end of follow-up (2014-2015). We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounding factors, with lagged and unlagged pesticide exposures. RESULTS: There was a statistically significant increased risk of RCC among the highest users of 2,4,5-T compared with never users [unlagged R[R.sub.IWD Tertile 3] = 2.92 (95% CI: 1.65, 5.17; [p.sub.trend] = 0.001)], with similar risk estimates for lagged exposure [20-y lag R[R.sub.IWD Tertile 3] = 3.37 (95% CI: 1.83, 6.22; [p.sub.trend] = 0.001)]. In 20-y lagged analyses, we also found exposure--response associations with chlorpyrifos [R[R.sub.IWD Quartile 4] = 1.68 (95% CI: 1.05, 2.70; [p.sub.trend] = 0.01)], chlordane [R[R.sub.IWD Tertile 3] = 2.06 (95% CI: 1.10, 3.87; [p.sub.trend] = 0.02)], atrazine [R[R.sub.IWD Quartile 4] = 1.43 (95% CI: 1.00, 2.03; [p.sub.trend] = 0.02)], cyanazine [R[R.sub.IWD Quartile 4] = 1.61 (95% CI: 1.03, 2.50; [p.sub.trend] = 0.02)], and paraquat [R[R.sub.IWD >Median] = 1.95 (95% CI: 1.03,3.70; [p.sub.trend] = 0.04)]. CONCLUSIONS: This is, to our knowledge, the first prospective study to evaluate RCC risk in relation to various pesticides. We found evidence of associations with RCC for four herbicides (2,4,5-T, atrazine, cyanazine, and paraquat) and two insecticides (chlorpyrifos and chlordane). Our findings provide insights into specific chemicals that may influence RCC risk among pesticide applicators. Confirmation of these findings and investigations of the biologic plausibility and potential mechanisms underlying the observed associations are warranted. https://doi.org/10.1289/EHP6334

Introduction An excess in the incidence of multiple myeloma (MM), an aggressive plasma cell malignancy, has been consistently observed in studies of farmers and other agricultural workers conducted over the [...], Background: Farmers have a higher incidence of multiple myeloma, and there is suggestive evidence of an elevated prevalence of its precursor, monoclonal gammopathy of undetermined significance (MGUS), relative to the general population. Pesticide exposures are suspected to play a role; however, the biologic plausibility for associations with multiple myeloma remains unclear. Objectives: Our objectives were to examine the prevalence of MGUS and evaluate associations with a wide range of pesticides in a large sample of farmers. Methods: We obtained sera and assessed MGUS among 1,638 male farmers [greater than or equal to] 50 years of age in the Agricultural Health Study (AHS), a prospective cohort in Iowa and North Carolina. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to estimate associations with MGUS for recent use (within the 12 months before phlebotomy) and cumulative intensity-weighted lifetime days of use of specific pesticides. Results: The age-standardized MGUS prevalence was significantly elevated among AHS farmers (7.7%) compared with demographically similar men in the National Health and Nutrition Examination Survey (2.8%) or Olmsted County, Minnesota (3.8%; p < 0.001). Recent use of permethrin was associated with MGUS [recent use vs. no recent use, OR = 1.82 (95% CI: 1.06, 3.13)], especially among those who had also used it in the past [recent and past use vs. never use, OR = 2.49 (95% CI: 1.32, 4.69)]. High intensity-weighted lifetime use of the organochlorine insecticides aldrin and dieldrin was associated with MGUS relative to those who never used either of these pesticides [OR = 2.42 (95% CI: 1.29, 4.54); ptiend = 0.006]. We also observed a positive association with high lifetime use of petroleum oil/distillates as an herbicide, as well as an inverse association with fonofos use. Discussion: This is the largest investigation of MGUS in farmers and the first to identify an association with MGUS for permethrin, a pyrethroid insecticide previously associated with multiple myeloma. Given the continued widespread use of permethrin in various residential and commercial settings, our findings may have important implications for exposed individuals in the general population. https://doi.org/10.1289/EHP6960

Introduction Inorganic arsenic (iAs) is a ubiquitously distributed environmental toxicant that is classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC) (IARC 2012). The [...], Background: The tumor microenvironment plays an important role in the progression of cancer by mediating stromal--epithelial paracrine signaling, which can aberrantly modulate cellular proliferation and tumorigenesis. Exposure to environmental toxicants, such as inorganic arsenic (iAs), has also been implicated in the progression of prostate cancer. OBJECTIVE: The role of iAs exposure in stromal signaling in the tumor microenvironment has been largely unexplored. Our objective was to elucidate molecular mechanisms of iAs-induced changes to stromal signaling by an enriched prostate tumor microenvironment cell population, adipose-derived mesenchymal stem/stromal cells (ASCs). RESULTS: ASC-conditioned media (CM) collected after 1 week of iAs exposure increased prostate cancer cell viability, whereas CM from ASCs that received no iAs exposure decreased cell viability. Cytokine array analysis suggested changes to cytokine signaling associated with iAs exposure. Subsequent proteomic analysis suggested a concentration-dependent alteration to the HMOX1/THBS1/TGFβ signaling pathway by iAs. These results were validated by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting, confirming a concentration-dependent increase in HMOX1 and a decrease in THBS1 expression in ASC following iAs exposure. Subsequently, we used a TGFβ pathway reporter construct to confirm a decrease in stromal TGFβ signaling in ASC following iAs exposure. CONCLUSIONS: Our results suggest a concentration-dependent alteration of stromal signaling: specifically, attenuation of stromal-mediated TGFβ signaling following exposure to iAs. Our results indicate iAs may enhance prostate cancer cell viability through a previously unreported stromal-based mechanism. These findings indicate that the stroma may mediate the effects of iAs in tumor progression, which may have future therapeutic implications. http://dx.doi.org/10.1289/ehp.1510090

Background: Per- and polyfluoroalkyl substances (PFAS) are highly persistent chemicals that have been detected in the serum of over 98% of the US population. Studies among highly exposed individuals suggest an association with perfluorooctanoic acid (PFOA) exposure and kidney cancer. It remains unclear whether PFOA or other PFAS are renal carcinogens or if they influence risk of renal cell carcinoma (RCC) at concentrations observed in the general population.Methods: We measured prediagnostic serum concentrations of PFOA and 7 additional PFAS in 324 RCC cases and 324 individually matched controls within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) relating serum PFAS concentrations and RCC risk. Individual PFAS were modeled continuously (log2-transformed) and categorically, with adjustment for kidney function and additional potential confounders. All statistical tests were 2-sided.Results: We observed a positive association with RCC risk for PFOA (doubling in serum concentration, ORcontinuous = 1.71, 95% CI = 1.23 to 2.37, P = .002) and a greater than twofold increased risk among those in the highest quartile vs the lowest (OR = 2.63, 95% CI = 1.33 to 5.20, Ptrend = .007). The association with PFOA was similar after adjustment for other PFAS (ORcontinuous = 1.68, 95% CI = 1.07 to 2.63, P = .02) and remained apparent in analyses restricted to individuals without evidence of diminished kidney function and in cases diagnosed 8 or more years after phlebotomy.Conclusions: Our findings add substantially to the weight of evidence that PFOA is a renal carcinogen and may have important public health implications for the many individuals exposed to this ubiquitous and highly persistent chemical. [ABSTRACT FROM AUTHOR]

Background Experimental and clinical studies have implicated certain chemokines and angiogenic cytokines in multiple myeloma (MM) pathogenesis. To investigate whether systemic concentrations of these markers are associated with future MM risk and progression from its precursor, monoclonal gammopathy of undetermined significance (MGUS), we conducted a prospective study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Methods We measured concentrations of 45 immunologic and pro-angiogenic markers in sera from 241 MM case patients, 441 participants with nonprogressing MGUS, and 258 MGUS-free control participants using Luminex-based multiplex assays and enzyme-linked immunosorbent assays. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. We also evaluated absolute risk of progression using weighted Kaplan-Meier estimates. All statistical tests were two-sided. Results Prediagnostic levels of six markers were statistically significantly elevated among MM case patients compared with MGUS-free control participants using a false discovery rate of 10% (EGF, HGF, Ang-2, CXCL12, CCL8, and BMP-9). Of these, three angiogenesis markers were associated with future progression from MGUS to MM: EGF (fourth vs first quartile: OR = 3.01, 95% CI = 1.61 to 5.63, P trend =.00028), HGF (OR = 2.59, 95% CI = 1.33 to 5.03, P trend =.015), and Ang-2 (OR = 2.14, 95% CI = 1.15 to 3.98, P trend =.07). A composite angiogenesis biomarker score substantially stratified risk of MGUS progression to MM beyond established risk factors for progression, particularly during the first 5 years of follow-up (areas under the curve of 0.71 and 0.64 with and without the angiogenesis marker score, respectively). Conclusions Our prospective findings provide new insights into mechanisms involved in MM development and suggest that systemic angiogenesis markers could potentially improve risk stratification models for MGUS patients. [ABSTRACT FROM AUTHOR]

Objectives: The American Heart Association (AHA) recently defined cardiovascular-kidney-metabolic (CKM) syndrome to better characterize the associations among cardiovascular, kidney, and metabolic diseases. Although about 9 in 10 U.S. adults have at least 1 risk factor for CKM syndrome, its prevalence in other populations is less understood. To fill this gap, we examined the prevalence of CKM syndrome in South Korea and its association with demographic and socioeconomic status (SES)., Methods: Using data from the Korean National Health and Nutrition Examination Survey between 2011 and 2021, we calculated the prevalence of CKM syndrome across the following stages: stage 0 (no risk factors), stage 1 (excess or dysfunctional adiposity), stage 2 (other metabolic risk factors or chronic kidney disease), and stages 3-4 (subclinical/clinical cardiovascular diseases) among adults aged ≥20 years. Weighted analyses were used to estimate prevalence and 95% confidence intervals (CIs) for each CKM syndrome stage, stratified by age, sex, and SES factors., Results: Among 54,994 Korean adults, the prevalence of CKM syndrome was as follows: stage 0 (25.2%; 95% CI, 24.7%-25.8%), stage 1 (19.3%; 95% CI, 18.9%-19.7%), stage 2 (51.6%; 95% CI, 51.1%-52.2%), and stages 3-4 (3.9%; 95% CI, 3.7%-4.0%). The prevalence of stages 2 and 3-4 was higher in men than in women. In addition, stages 3-4 were more prevalent among rural residents and those with lower education or income., Conclusion: About 3 out of 4 South Koreans are at risk for CKM syndrome. These findings highlight that CKM syndrome is a global health problem and that interventions are urgently needed to prevent further progression.

Background: Cardiovascular-Kidney-Metabolic syndrome reflects the complex interplay between metabolic risk factors, cardiovascular and chronic kidney disease. Differences in disease burden by demographics, social determinants of health, and mortality are not well characterized., Methods: Data from adults who completed the National Health and Nutrition Examination Survey between 2011-2018 were used to estimate age-adjusted prevalence and 95% confidence intervals (CI) for Cardiovascular-Kidney-Metabolic syndrome stages. Joinpoint regression was used to identify linear trends. Kaplan-Meier curves were used to examine all-cause mortality risk by stages., Results: Among 8,474 adults in the study, the median age was 46.8 years, 49.1% were male, and 65.0% were non-Hispanic White. Age-adjusted prevalence of stages 0-4 were 11.2%, 28.1%, 47.4%, 5.3%, and 8.1%, respectively. The highest proportion of stage 4 was among adults aged ≥60 years, males, and non-Hispanic Black individuals. The advanced stages 3-4 was associated with lower educational attainment, income, and employment and higher mortality with a crude death rate of 188.8 per 1,000 person-years., Conclusion: Approximately 13% of adults were in advanced stages, which disproportionately affects non-Hispanic Black adults and increased over time. These results provide a roadmap for targeted intervention strategies., Competing Interests: Declaration of competing interest All authors (Ji-Eun Kim, Jungnam Joo, Kayode O. Kuku, Carolina Downie, Maryam Hashemian, Tiffany M. Powell-Wiley, Joseph J. Shearer, and Véronique L. Roger) declare that there are no conflicts of interest related to this work., (Copyright © 2025. Published by Elsevier Inc.)

Background: Heart failure is heterogeneous syndrome with persistently high mortality. Nuclear magnetic resonance spectroscopy enables high-throughput metabolomics, suitable for precision phenotyping. We aimed to use targeted metabolomics to derive a metabolic risk score (MRS) that improved mortality risk stratification in heart failure., Methods: Nuclear magnetic resonance was used to measure 21 metabolites (lipoprotein subspecies, branched-chain amino acids, alanine, GlycA (glycoprotein acetylation), ketone bodies, glucose, and citrate) in plasma collected from a heart failure community cohort. The MRS was derived using least absolute shrinkage and selection operator penalized Cox regression and temporal validation. The association between the MRS and mortality and whether risk stratification was improved over the Meta-Analysis Global Group in Chronic Heart Failure clinical risk score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels were assessed., Results: The study included 1382 patients (median age, 78 years, 52% men, 43% reduced ejection fraction) with a 5-year survival rate of 48% (95% CI, 46%-51%). The MRS included 9 metabolites measured. In the validation data set, a 1 standard deviation increase in the MRS was associated with a large increased rate of death (hazard ratio, 2.2 [95% CI, 1.9-2.5]) that remained after adjustment for Meta-Analysis Global Group in Chronic Heart Failure score and NT-proBNP (hazard ratio, 1.6 [95% CI, 1.3-1.9]). These associations did not differ by ejection fraction. The integrated discrimination and net reclassification indices, and Uno's C statistic, indicated that the addition of the MRS improved discrimination over Meta-Analysis Global Group in Chronic Heart Failure and NT-proBNP., Conclusions: This MRS developed in a heart failure community cohort was associated with a large excess risk of death and improved risk stratification beyond an established risk score and clinical markers., Competing Interests: Disclosures Dr Connelly is an employee of and holds stock in Labcorp. Dr Otvos is a consultant, stockholder, and former employee of Labcorp. The other authors report no conflicts.

Background: Glyphosate is the most widely applied herbicide worldwide, and its use has been associated with increased risks of certain hematopoietic cancers in epidemiologic studies. Animal and in vitro experiments suggest that glyphosate may induce oxidative stress, a key characteristic of carcinogens; however, evidence in human populations remains scarce. We investigated associations between glyphosate exposure and urinary oxidative stress biomarkers in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiologic subcohort in the Agricultural Health Study., Methods: This analysis included 268 male farmers selected based on self-reported recent and lifetime occupational glyphosate use and 100 age- and geography-matched male nonfarmers. Concentrations of glyphosate and oxidative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-iso-prostaglandin-F2α, and malondialdehyde [MDA]) were quantified in first-morning-void urine. We performed multivariable linear regression to evaluate associations of urinary glyphosate and self-reported glyphosate use with each oxidative stress biomarker., Results: Urinary glyphosate concentrations were positively associated with levels of 8-OHdG (highest vs lowest glyphosate quartile; geometric mean ratio = 1.15, 95% confidence interval = 1.03 to 1.28; Ptrend = .02) and MDA (geometric mean ratio = 1.20, 95% confidence interval = 1.03 to 1.40; Ptrend = .06) overall. Among farmers reporting recent glyphosate use (last 7 days), use in the previous day was also associated with statistically significantly increased 8-OHdG and MDA levels. Compared with nonfarmers, we observed elevated 8-iso-prostaglandin-F2α levels among farmers with recent, high past 12-month, or high lifetime glyphosate use., Conclusions: Our findings contribute to the weight of evidence supporting an association between glyphosate exposure and oxidative stress in humans and may inform evaluations of the carcinogenic potential of this herbicide., (© The Author(s) 2023. Published by Oxford University Press.)