Risk of gynecomastia and breast cancer associated with the use of 5-alpha reductase inhibitors for benign prostatic hyperplasia.

BACKGROUND: Clinical trial results suggest that 5-alpha reductase inhibitors (5ARIs) for the treatment of benign prostatic hyperplasia (BPH) may increase the risk of gynecomastia and male breast cancer, but epidemiological studies have been limited. PATIENTS AND METHODS: We conducted a cohort study with nested case-control analyses using the UK Clinical Practice Research Datalink. We identified men diagnosed with BPH who were free from Klinefelter syndrome, prostate, genital or urinary cancer, prostatectomy or orchiectomy, or evidence of gynecomastia or breast cancer. Patients entered the cohort at age ≥40 years and at least 3 years after the start of their electronic medical record. We classified exposure as 5ARIs (alone or in combination with alpha blockers [ABs]), AB only, or unexposed to 5ARIs and ABs. Cases were men who had a first-time diagnosis of gynecomastia or breast cancer. Incidence rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) in the gynecomastia analysis and crude and adjusted odds ratios (ORs) with 95% CIs in both analyses were calculated. RESULTS: Compared to no exposure, gynecomastia risk was elevated for users of 5ARIs (alone or in combination with ABs) in both the cohort (IRR=3.55, 95% CI 3.05-4.14) and case-control analyses (OR=3.31, 95% CI 2.66-4.10), whereas the risk was null for users of AB only. The increased risk of gynecomastia with the use of 5ARIs persisted regardless of the number of prescriptions, exposure timing, and presence or absence of concomitant prescriptions for drugs known to be associated with gynecomastia. The risk was higher for dutasteride than for finasteride. 5ARI users did not have an increased risk of breast cancer compared to unexposed men (OR=1.52, 95% CI 0.61-3.80). CONCLUSION: In men with BPH, 5ARIs significantly increased the risk of gynecomastia, but not breast cancer, compared to AB use and no exposure.

Validity of Self-Reported Tobacco Smoke Exposure among Non-Smoking Adult Public Housing Residents.

INTRODUCTION: Tobacco smoke exposure (TSE) in public multi-unit housing (MUH) is of concern. However, the validity of self-reports for determining TSE among non-smoking residents in such housing is unclear. METHODS: We analyzed data from 285 non-smoking public MUH residents living in non-smoking households in the Boston area. Participants were interviewed about personal TSE in various locations in the past 7 days and completed a diary of home TSE for 7 days. Self-reported TSE was validated against measurable saliva cotinine (lower limit of detection (LOD) 0.02 ng/ml) and airborne apartment nicotine (LOD 5 ng). Correlations, estimates of inter-measure agreement, and logistic regression assessed associations between self-reported TSE items and measurable cotinine and nicotine. RESULTS: Cotinine and nicotine levels were low in this sample (median = 0.026 ng/ml and 0.022 µg/m(3), respectively). Prevalence of detectable personal TSE was 66.3% via self-report and 57.0% via measurable cotinine (median concentration among those with cotinine>LOD: 0.057 ng/ml), with poor agreement (kappa = 0.06; sensitivity = 68.9%; specificity = 37.1%). TSE in the home, car, and other peoples' homes was weakly associated with cotinine levels (Spearman correlations rs = 0.15-0.25), while TSE in public places was not associated with cotinine. Among those with airborne nicotine and daily diary data (n = 161), a smaller proportion had household TSE via self-report (41.6%) compared with measurable airborne nicotine (53.4%) (median concentration among those with nicotine>LOD: 0.04 µg/m(3)) (kappa = 0.09, sensitivity = 46.5%, specificity = 62.7%). CONCLUSIONS: Self-report alone was not adequate to identify individuals with TSE, as 31% with measurable cotinine and 53% with measurable nicotine did not report TSE. Self-report of TSE in private indoor spaces outside the home was most associated with measurable cotinine in this low-income non-smoking population.

Environmental and occupational particulate matter exposures and ectopic heart beats in welders.

OBJECTIVES: Links between arrhythmias and particulate matter exposures have been found among sensitive populations. We examined the relationship between personal particulate matter ≤2.5 µm aerodynamic diameter (PM2.5) exposures and ectopy in a panel study of healthy welders. METHODS: Simultaneous ambulatory ECG and personal PM2.5 exposure monitoring with DustTrak Aerosol Monitor was performed on 72 males during work and non-work periods for 5-90 h (median 40 h). ECGs were summarised hourly for supraventricular ectopy (SVE) and ventricular ectopy (VE). PM2.5 exposures both work and non-work periods were averaged hourly with lags from 0 to 7 h. Generalised linear mixed-effects models with a random participant intercept were used to examine the relationship between PM2.5 exposure and the odds of SVE or VE. Sensitivity analyses were performed to assess whether relationships differed by work period and among current smokers. RESULTS: Participants had a mean (SD) age of 38 (11) years and were monitored over 2993 person-hours. The number of hourly ectopic events was highly skewed with mean (SD) of 14 (69) VE and 1 (4) SVE. We found marginally significant increases in VE with PM2.5 exposures in the sixth and seventh hour lags, yet no association with SVE. For every 100 µg/m(3) increase in sixth hour lagged PM2.5, the adjusted OR (95% CI) for VE was 1.03 (1.00 to 1.05). Results persisted in work or non-work exposure periods and non-smokers had increased odds of VE associated with PM2.5 as compared with smokers. CONCLUSIONS: A small increase in the odds of VE with short-term PM2.5 exposure was observed among relatively healthy men with environmental and occupational exposures.

Are the Associations of Cardiac Acceleration and Deceleration Capacities With Fine Metal Particulate in Welders Mediated by Inflammation?

OBJECTIVE: The aim of this study was to investigate whether associations of acceleration capacity (AC) and deceleration capacity (DC) with metal-PM2.5 are mediated by inflammation. METHODS: We obtained PM2.5, C-reactive protein, interleukin (IL)-6, 8, and 10, and electrocardiograms to compute AC and DC, from 45 male welders. Mediation analyses were performed using linear mixed models to assess associations between PM2.5 exposure, inflammatory mediator, and AC or DC, controlling for covariates. RESULTS: The proportion of total effect of PM2.5 on AC or DC (indirect effect) mediated through IL-6 on AC was 4% at most. Controlling for IL-6 (direct effect), a 1 mg/m increase of PM2.5 was associated with a decrease of 2.16 (95% confidence interval -0.36 to 4.69) msec in AC and a decrease of 2.51 (95% confidence interval -0.90 to 5.93) msec in DC. CONCLUSION: IL-6 may be mediating the effect of metal particulates on AC.

Assessment of Residents' Attitudes and Satisfaction Before and After Implementation of a Smoke-Free Policy in Boston Multiunit Housing.

INTRODUCTION: In 2012, the Boston Housing Authority (BHA) in Massachusetts implemented a smoke-free policy prohibiting smoking within its residences. We sought to characterize BHA resident experiences before and after the smoke-free policy implementation, and compare them to that of nearby residents of the Cambridge Housing Authority, which had no such policy. METHODS: We recruited a convenience sample of nonsmoking residents from the BHA and Cambridge Housing Authority. We measured residents' awareness and support of their local smoking policies before and 9-12 months after the BHA's policy implementation, as well as BHA respondents' attitudes towards the smoke-free policy. We assessed tobacco smoke exposure via saliva cotinine, airborne apartment nicotine, and self-reported number of days smelling smoke in the home. We evaluated predictors of general satisfaction at follow-up using linear regression. RESULTS: At follow-up, 91% of BHA respondents knew that smoking was not allowed in apartments and 82% were supportive of such a policy in their building. BHA residents believed enforcement of the smoke-free policy was low. Fifty-one percent of BHA respondents indicated that other residents "never" or "rarely" followed the new smoke-free rule and 41% of respondents were dissatisfied with policy enforcement. Dissatisfaction with enforcement was the strongest predictor of general housing satisfaction, while objective and self-reported measures of tobacco smoke exposure were not predictive of satisfaction. At follow-up, 24% of BHA participants had complained to someone in charge about policy violations. CONCLUSIONS: Resident support for smoke-free policies is high. However, lack of enforcement of smoke-free policies may cause frustration and resentment among residents, potentially leading to a decrease in housing satisfaction. IMPLICATIONS: Smoke-free housing laws are becoming increasingly prevalent, yet little is known about satisfaction and compliance with such policies post-implementation. We evaluated nonsmoking residents' attitudes about smoke-free rules and their satisfaction with enforcement 1 year after the BHA implemented its comprehensive smoke-free policy. We found that while residents were supportive of the policy, they believed enforcement was low, a perception that was associated with a drop in housing satisfaction. Our findings point to a desire for smoke-free housing among public housing residents, and the importance of establishing systems and guidelines to help landlords monitor and enforce these policies effectively.

Short-term metal particulate exposures decrease cardiac acceleration and deceleration capacities in welders: a repeated-measures panel study.

OBJECTIVE: Acceleration (AC) and deceleration (DC) capacities measure heart rate variability during speeding up and slowing down of the heart, respectively. We investigated associations between AC and DC with occupational short-term metal PM2.5 exposures. METHODS: A panel of 48 male welders had particulate matter less than 2.5 microns in diameter (PM2.5) exposure measurements over 4-6 h repeated over 5 sampling periods between January 2010 and June 2012. We simultaneously obtained continuous recordings of digital ECG using a Holter monitor. We analysed ECG data in the time domain to obtain hourly AC and DC. Linear mixed models were used to assess the associations between hourly PM2.5 exposure and each of hourly AC and DC, controlling for age, smoking status, active smoking, exposure to secondhand smoke, season/time of day when ECG reading was obtained and baseline AC or DC. We also ran lagged exposure response models for each successive hour up to 3 h after onset of exposure. RESULTS: Mean (SD) shift PM2.5 exposure during welding was 0.47 (0.43) mg/m(3). Significant exposure-response associations were found for AC and DC with increased PM2.5 exposure. In our adjusted models without any lag between exposure and response, a 1 mg/m(3) increase of PM2.5 was associated with a decrease of 1.46 (95% CI 1.00 to 1.92) ms in AC and a decrease of 1.00 (95% CI 0.53 to 1.46) ms in DC. The effect of PM2.5 on AC and DC was maximal immediately postexposure and lasted 1 h following exposure. CONCLUSIONS: There are short-term effects of metal particulates on AC and DC.

Changes in Tobacco Smoke Exposure following the Institution of a Smoke-Free Policy in the Boston Housing Authority.

INTRODUCTION: To protect residents from tobacco smoke exposure (TSE), the Boston Housing Authority (BHA) prohibited smoking in BHA-owned apartments beginning in 2012. Our goal was to determine if the smoke-free policy reduced TSE for non-smoking BHA residents. METHODS: We compared TSE before the smoke-free policy (2012) and one year later among BHA residents as well as residents of the neighboring Cambridge Housing Authority (CHA) where no such policy was in place. Participants were a convenience sample of adult non-smoking BHA and CHA residents cohabitating with only non-smokers. Main outcomes were 7-day airborne nicotine in participants' apartments; residents' saliva cotinine; and residents' self-reported TSE. RESULTS: We enrolled 287 confirmed non-smokers (192 BHA, 95 CHA). Seventy-nine percent (229) were assessed at follow-up. At baseline, apartment and resident TSE were high in both housing authorities (detectable airborne nicotine: 46% BHA, 48% CHA; detectable saliva cotinine: 49% BHA, 70% CHA). At follow-up there were significant but similar declines in nicotine in both sites (detectable: -33% BHA, -39% CHA, p = 0.40). Detectable cotinine rose among BHA residents while declining among CHA participants (+17% BHA vs. -13% CHA, p = 0.002). Resident self-reported TSE within and outside of the housing environment decreased similarly for both BHA and CHA residents. CONCLUSIONS: Apartment air nicotine decreased after the introduction of the smoke-free policy, though the decline may not have resulted from the policy. The BHA policy did not result in reduced individual-level TSE. Unmeasured sources of non-residential TSE may have contributed to BHA residents' cotinine levels.

The relationship between occupational metal exposure and arterial compliance.

BACKGROUND: The objective of this study was to evaluate the relationship between cumulative occupational exposure to various metals and arterial compliance in welders. METHODS: The observational follow-up study consisted of 25 subjects. Levels of nickel (Ni), lead, cadmium, manganese, and arsenic from toenails were assessed using mass spectrometry. Arterial compliance as reflected by augmentation index (AIx) was measured using SphygmoCor Px Pulse Wave Analysis System. Linear regression models were used to assess the associations. RESULTS: For every 1 unit increase in log-transformed toenail Ni, there was a statistically significant 5.68 (95% confidence interval, 1.38 to 9.98; P = 0.01) unit increase in AIx. No significant associations were found between AIx and lead, cadmium, manganese, and arsenic. CONCLUSIONS: Cumulative Ni exposure is associated with increased arterial stiffness in welders and may increase risk of adverse cardiovascular outcomes.

Traffic-related air pollution and sleep in the Boston Area Community Health Survey.

Little is known about environmental determinants of sleep. We investigated the association between black carbon (BC), a marker of traffic-related air pollution, and sleep measures among participants of the Boston Area Community Health Survey. We also sought to assess the impact of sociodemographic factors, health conditions, and season on associations. Residential 24-h BC was estimated from a validated land-use regression model for 3821 participants and averaged over 1-6 months and 1 year. Sleep measures included questionnaire-assessed sleep duration, sleep latency, and sleep apnea. Linear and logistic regression models controlling for confounders estimated the association between sleep measures and BC. Effect modification was tested with interaction terms. Main effects were not observed between BC and sleep measures. However, in stratified models, males experienced 0.23 h less sleep (95% CI: -0.42, -0.03) and those with low SES 0.25 h less sleep (95% CI: -0.48, -0.01) per IQR increase in annual BC (0.21 µg/m(3)). In blacks, sleep duration increased with annual BC (ß=0.34 per IQR; 95% CI: 0.12, 0.57). Similar findings were observed for short sleep (≤5 h). BC was not associated with sleep apnea or sleep latency, however, long-term exposure may be associated with shorter sleep duration, particularly in men and those with low SES, and longer sleep duration in blacks.

Heart rate variability and DNA methylation levels are altered after short-term metal fume exposure among occupational welders: a repeated-measures panel study.

BACKGROUND: In occupational settings, boilermakers are exposed to high levels of metallic fine particulate matter (PM2.5) generated during the welding process. The effect of welding PM2.5 on heart rate variability (HRV) has been described, but the relationship between PM2.5, DNA methylation, and HRV is not known. METHODS: In this repeated-measures panel study, we recorded resting HRV and measured DNA methylation levels in transposable elements Alu and long interspersed nuclear element-1 (LINE-1) in peripheral blood leukocytes under ambient conditions (pre-shift) and right after a welding task (post-shift) among 66 welders. We also monitored personal PM2.5 level in the ambient environment and during the welding procedure. RESULTS: The concentration of welding PM2.5 was significantly higher than background levels in the union hall (0.43 mg/m3 vs. 0.11 mg/m3, p < 0.0001). The natural log of transformed power in the high frequency range (ln HF) had a significantly negative association with PM2.5 exposure (ß = -0.76, p = 0.035). pNN10 and pNN20 also had a negative association with PM2.5 exposure (ß = -0.16%, p = 0.006 and ß = -0.13%, p = 0.030, respectively). PM2.5 was positively associated with LINE-1 methylation [ß = 0.79%, 5-methylcytosince (%mC), p = 0.013]; adjusted for covariates. LINE-1 methylation did not show an independent association with HRV. CONCLUSIONS: Acute decline of HRV was observed following exposure to welding PM2.5 and evidence for an epigenetic response of transposable elements to short-term exposure to high-level metal-rich particulates was reported.

The relationship between inflammatory biomarkers and telomere length in an occupational prospective cohort study.

BACKGROUND: Chronic inflammation from recurring trauma is an underlying pathophysiological basis of numerous diseases. Furthermore, it may result in cell death, scarring, fibrosis, and loss of tissue function. In states of inflammation, subsequent increases in oxidative stress and cellular division may lead to the accelerated erosion of telomeres, crucial genomic structures which protect chromosomes from decay. However, the association between plasma inflammatory marker concentrations and telomere length has been inconsistent in previous studies. OBJECTIVE: The purpose of this study was to determine the longitudinal association between telomere length and plasma inflammatory biomarker concentrations including: CRP, SAA, sICAM-1, sVCAM-1, VEGF, TNF-α, IL-1ß, IL-2, IL-6, IL-8, and IL-10. METHODS: The longitudinal study population consisted of 87 subjects. The follow-up period was approximately 2 years. Plasma inflammatory biomarker concentrations were assessed using highly sensitive electrochemiluminescent assays. Leukocyte relative telomere length was assessed using Real-Time qPCR. Linear mixed effects regression models were used to analyze the association between repeated-measurements of relative telomere length as the outcome and each inflammatory biomarker concentration as continuous exposures separately. The analyses controlled for major potential confounders and white blood cell differentials. RESULTS: At any follow-up time, each incremental ng/mL increase in plasma CRP concentration was associated with a decrease in telomere length of -2.6×10⁻² (95%CI: -4.3×10⁻², -8.2×10⁻³, p = 0.004) units. Similarly, the estimate for the negative linear association between SAA and telomere length was -2.6×10⁻² (95%CI:-4.5×10⁻², -6.1×10⁻³, p = 0.011). No statistically significant associations were observed between telomere length and plasma concentrations of pro-inflammatory interleukins, TNF-α, and VEGF. CONCLUSIONS: Findings from this study suggest that increased systemic inflammation, consistent with vascular injury, is associated with decreased leukocyte telomere length.

Toenail metal concentration as a biomarker of occupational welding fume exposure.

In populations exposed to heavy metals, there are few biomarkers that capture intermediate exposure windows. We sought to determine the correlation between toenail metal concentrations and prior 12-month work activity in welders with variable, metal-rich, welding fume exposures. Forty-eight participants, recruited through a local union, provided 69 sets of toenail clippings. Union-supplied and worker-verified personal work histories were used to quantify hours welded and respirator use. Toenail samples were digested and analyzed for lead (Pb), manganese (Mn), cadmium (Cd), nickel (Ni), and arsenic (As) using ICP-MS. Spearman correlation coefficients were used to examine the correlation between toenail metal concentrations. Using mixed models to account for multiple participation times, we divided hours welded into three-month intervals and examined how weld hours correlated with log-transformed toenail Pb, Mn, Cd, Ni, and As concentrations. Highest concentrations were found for Ni, followed by Mn, Pb and As, and Cd. All the metals were significantly correlated with one another (rho range = 0.28-0.51), with the exception of Ni and As (rho = 0.20, p = 0.17). Using mixed models adjusted for age, respirator use, smoking status, and BMI, we found that Mn was associated with weld hours 7-9 months prior to clipping (p = 0.003), Pb was associated with weld hours 10-12 months prior to clipping (p = 0.03) and over the entire year (p = 0.04). Cd was associated with weld hours 10-12 months prior to clipping (p = 0.05), and also with the previous year's total hours welded (p = 0.02). The association between Ni and weld hours 7-9 months prior to clipping approached significance (p = 0.06). Toenail metal concentrations were not associated with the long-term exposure metric, years as a welder. Results suggest Mn, Pb, and Cd may have particular windows of relevant exposure that reflect work activity. In a population with variable exposure, toenails may serve as useful biomarkers for occupational metal fume exposures to Mn, Pb, and Cd during distinct periods over the year prior to sample collection.

Secondhand tobacco smoke exposure and heart rate variability and inflammation among non-smoking construction workers: a repeated measures study.

BACKGROUND: Although it has been well recognized that exposure to secondhand tobacco smoke (SHS) is associated with cardiovascular mortality, the mechanisms and time course by which SHS exposure may lead to cardiovascular effects are still being explored. METHODS: Non-smoking workers were recruited from a local union and monitored inside a union hall while exposed to SHS over approximately 6 hours. Participants were fitted with a continuous electrocardiographic monitor upon enrollment which was removed at the end of a 24-hr monitoring period. A repeated measures study design was used where resting ECGs and blood samples were taken from individuals before SHS exposure (baseline), immediately following SHS exposure (post) and the morning following SHS exposure (next-morning).Inflammatory markers, including high sensitivity C-reactive protein (CRP) and white blood cell count (WBC) were analyzed. Heart rate variability (HRV) was analyzed from the ECG recordings in time (SDNN, rMSSD) and frequency (LF, HF) domain parameters over 5-minute periods. SHS exposure was quantified using a personal fine particulate matter (PM2.5) monitor.Linear mixed effects regression models were used to examine within-person changes in inflammatory and HRV parameters across the 3 time periods. Exposure-response relationships with PM2.5 were examined using mixed effects models. All models were adjusted for age, BMI and circadian variation. RESULTS: A total of 32 male non-smokers were monitored between June 2010 and June 2012. The mean PM2.5 from SHS exposure was 132 µg/m3. Immediately following SHS exposure, a 100 µg/m3 increase in PM2.5 was associated with declines in HRV (7.8% [standard error (SE) =3%] SDNN, 8.0% (SE = 3.9%) rMSSD, 17.2% (SE = 6.3%) LF, 29.0% (SE = 10.1%) HF) and increases in WBC count 0.42 (SE = 0.14) k/µl. Eighteen hours following SHS exposure, a 100 µg/m3 increase in PM2.5 was associated with 24.2% higher CRP levels. CONCLUSIONS: Our study suggest that short-term SHS exposure is associated with significantly lower HRV and higher levels of inflammatory markers. Exposure-associated declines in HRV were observed immediately following exposure while higher levels of CRP were not observed until 18 hours following exposure. Cardiovascular autonomic and inflammation responses may contribute to the pathophysiologic pathways that link SHS exposure with adverse cardiovascular outcomes.

A panel study of occupational exposure to fine particulate matter and changes in DNA methylation over a single workday and years worked in boilermaker welders.

BACKGROUND: Exposure to pollutants including metals and particulate air pollution can alter DNA methylation. Yet little is known about intra-individual changes in DNA methylation over time in relationship to environmental exposures. Therefore, we evaluated the effects of acute- and chronic metal-rich PM2.5 exposures on DNA methylation. METHODS: Thirty-eight male boilermaker welders participated in a panel study for a total of 54 person days. Whole blood was collected prior to any welding activities (pre-shift) and immediately after the exposure period (post-shift). The percentage of methylated cytosines (%mC) in LINE-1, Alu, and inducible nitric oxide synthase gene (iNOS) were quantified using pyrosequencing. Personal PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 µm) was measured over the work-shift. A questionnaire assessed job history and years worked as a boilermaker. Linear mixed models with repeated measures evaluated associations between DNA methylation, PM2.5 concentration (acute exposure), and years worked as a boilermaker (chronic exposure). RESULTS: PM2.5 exposure was associated with increased methylation in the promoter region of the iNOS gene (ß = 0.25, SE: 0.11, p-value = 0.04). Additionally, the number of years worked as a boilermaker was associated with increased iNOS methylation (ß = 0.03, SE: 0.01, p-value = 0.03). No associations were observed for Alu or LINE-1. CONCLUSIONS: Acute and chronic exposure to PM2.5 generated from welding activities was associated with a modest change in DNA methylation of the iNOS gene. Future studies are needed to confirm this association and determine if the observed small increase in iNOS methylation are associated with changes in NO production or any adverse health effect.

Residential black carbon exposure and circulating markers of systemic inflammation in elderly males: the normative aging study.

BACKGROUND: Traffic-related particles (TRPs) are associated with adverse cardiovascular events. The exact mechanisms are unclear, but systemic inflammatory responses likely play a role. OBJECTIVES: We conducted a repeated measures study among male participants of the Normative Aging Study in the greater Boston, Massachusetts, area to determine whether individual-level residential black carbon (BC), a marker of TRPs, is associated with systemic inflammation and whether coronary heart disease (CHD), diabetes, and obesity modify associations. METHODS: We quantified markers of inflammation in 1,163 serum samples from 580 men. Exposure to BC up to 4 weeks prior was predicted from a validated spatiotemporal land-use regression model. Linear mixed effects models estimated the effects of BC on each marker while adjusting for potential confounders. RESULTS: Associations between BC and blood markers were not observed in main effects models or when stratified by obesity status. However, BC was positively associated with markers of inflammation in men with CHD (particularly vascular endothelial growth factor) and in men with diabetes (particularly interleukin-1ß and tumor necrosis factor-α). Significant exposure time windows varied by marker, although in general the strongest associations were observed with moving averages of 2-7 days after a lag of several days. CONCLUSIONS: In an elderly male population, estimated BC exposures were positively associated with markers of systemic inflammation but only in men with CHD or diabetes.

Lead concentrations in relation to multiple biomarkers of cardiovascular disease: the Normative Aging Study.

BACKGROUND: Lead exposure has been associated with cardiovascular disease (CVD) in animal and human studies. However, the mechanisms of action have not been fully elucidated. We therefore examined the relationship between lead and multiple biomarkers of CVD. METHODS: Participants were older men from the Normative Aging Study without preexisting coronary heart disease, diabetes, or active infection at baseline (n = 426). Serum biomarkers included lipid profile [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides] and inflammatory markers [C-reactive protein, intercellular adhesion molecule-1, interleukin-6, and tumor necrosis factor receptor-2 (TNF-R2)]. We measured lead in blood and in bone by K-shell X-ray fluorescence. In this sample, 194 men (44.3%) had two or more repeated measures, resulting in 636 observations for analysis. We conducted analyses using mixed effects models with random subject intercepts. RESULTS: Lead levels were associated with several CVD biomarkers, including levels of TNF-R2 and lipid markers. Specifically, in multivariable models, a 50% increase in blood lead level was associated with 26% increased odds of high TNF-R2 levels (> 5.52 ng/mL; odds ratio = 1.26; 95% confidence interval: 1.09, 1.45). There were positive associations of blood lead level with total cholesterol and HDL levels, and these associations were more evident when modeled as continuous outcomes than when categorized using clinically relevant cut points. In addition, longitudinal analyses indicated a significant increase in TNF-R2 levels over time to be associated with high blood lead level at the preceding visit. CONCLUSIONS: Blood lead level may be related with CVD in healthy older men through its association with TNF-R2 levels. In addition, the magnitude of the association of blood lead level with TNF-R2 level increased with age in the study population.

Optimism in relation to inflammation and endothelial dysfunction in older men: the VA Normative Aging Study.

BACKGROUND: Recent research suggests that optimism may reduce the risk of incident cardiovascular disease, but the mechanisms have not been determined. This study examines the association of optimism with change in inflammation and endothelial function over time in men. METHODS: Longitudinal data were obtained from the Normative Aging Study excluding men with preexisting coronary heart disease or active infection at the time optimism was assessed (n = 340; mean [standard deviation] age = 70.9 [6.7] years). The Life Orientation Test was used to measure optimism, and serum markers were used to measure inflammation and endothelial dysfunction and were obtained repeatedly during the course of the study (1999-2008). These markers included high-sensitivity C-reactive protein, interleukin 6, soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and soluble tumor necrosis factor receptor II. Within this sample, 243 men (71%) had two or more repeated measures of each outcome, resulting in a total of 746 observations for analysis. Linear mixed-effects models with a random subject intercept were used to estimate associations. RESULTS: Higher overall optimism scores were associated with lower levels of interleukin 6 and soluble intercellular adhesion molecule 1 pooled across multiple time points in multivariable models but were not associated with rate of change in these markers over time. Analyses considering separate effects of optimism and pessimism subscales with each outcome indicated stronger effects of a pessimistic orientation versus an optimistic orientation. CONCLUSIONS: Higher overall optimism scores were associated with lower levels of inflammation and endothelial dysfunction in older men free of coronary heart disease.

Acute decrease in HDL cholesterol associated with exposure to welding fumes.

OBJECTIVE: To investigate acute changes in circulating lipids after exposure to relatively high levels of particulate matter through welding. METHODS: Using a repeated measures panel study, lipid levels before and after welding and personal exposures to fine particulate matter (PM2.5) were measured in 36 male welders over 63 exposure and/or control days. RESULTS: There was a trend toward decrease in HDL (-2.3 mg/dL, P = 0.08) 18 hours after welding. This effect became significant (-2.6 mg/dL, P = 0.05) after adjustment for possible confounders. The effect was strongest (-4.3 mg/dL, P = 0.02) among welders who did not weld the day before the study. There were no significant changes in other lipids associated with welding or PM2.5 exposure. CONCLUSION: Welding exposure was associated with an acute decrease in circulating HDL, which may relate to the inflammatory and proatherosclerotic effects of fine particle exposure.

A systematic review of occupational exposure to particulate matter and cardiovascular disease.

Exposure to ambient particulate air pollution is a recognized risk factor for cardiovascular disease; however the link between occupational particulate exposures and adverse cardiovascular events is less clear. We conducted a systematic review, including meta-analysis where appropriate, of the epidemiologic association between occupational exposure to particulate matter and cardiovascular disease. Out of 697 articles meeting our initial criteria, 37 articles published from January 1990 to April 2009 (12 mortality; 5 morbidity; and 20 intermediate cardiovascular endpoints) were included. Results suggest a possible association between occupational particulate exposures and ischemic heart disease (IHD) mortality as well as non-fatal myocardial infarction (MI), and stronger evidence of associations with heart rate variability and systemic inflammation, potential intermediates between occupational PM exposure and IHD. In meta-analysis of mortality studies, a significant increase in IHD was observed (meta-IRR = 1.16; 95% CI: 1.06-1.26), however these data were limited by lack of adequate control for smoking and other potential confounders. Further research is needed to better clarify the magnitude of the potential risk of the development and aggravation of IHD associated with short and long-term occupational particulate exposures and to clarify the clinical significance of acute and chronic changes in intermediate cardiovascular outcomes.

Assessment of occupational exposure to manganese and other metals in welding fumes by portable X-ray fluorescence spectrometer.

Elemental analysis of welding fume samples can be done using several laboratory-based techniques. However, portable measurement techniques could offer several advantages. In this study, we sought to determine whether the portable X-ray fluorescence spectrometer (XRF) is suitable for analysis of five metals (manganese, iron, zinc, copper, and chromium) on 37-mm polytetrafluoroethylene filters. Using this filter fitted on a cyclone in line with a personal pump, gravimetric samples were collected from a group of boilermakers exposed to welding fumes. We assessed the assumption of uniform deposition of these metals on the filters, and the relationships between measurement results of each metal obtained from traditional laboratory-based XRF and the portable XRF. For all five metals of interest, repeated measurements with the portable XRF at the same filter area showed good consistency (reliability ratios are equal or close to 1.0 for almost all metals). The portable XRF readings taken from three different areas of each filter were not significantly different (p-values = 0.77 to 0.98). This suggested that the metal rich PM(2.5) deposits uniformly on the samples collected using this gravimetric method. For comparison of the two XRFs, the results from the portable XRF were well correlated and highly predictive of those from the laboratory XRF. The Spearman correlation coefficients were from 0.325 for chromium, to 0.995 for manganese and 0.998 for iron. The mean differences as a percent of the mean laboratory XRF readings were also small (<5%) for manganese, iron, and copper. The differences were greater for zinc and chromium, which were present at very low amounts in our samples and below the limits of detection of the portable XRF for many of the samples. These five metals were moderately to strongly correlated with the total fine particle fraction on filters (Spearman rho = 0.41 for zinc to 0.97 for iron). Such strong correlations and comparable results suggested that the portable XRF could be used as an effective and reliable tool for exposure assessment in many studies.