Shona C. Fang

PM2.5 metal exposures and nocturnal heart rate variability: a panel study of boilermaker construction workers.

BackgroundTo better understand the mechanism(s) of particulate matter (PM) associated cardiovascular effects, research priorities include identifying the responsible PM characteristics. Evidence suggests that metals play a role in the cardiotoxicity of fine PM (PM2.5) and in exposure-related decreases in heart rate variability (HRV). We examined the association between daytime exposure to the metal content of PM2.5 and night HRV in a panel study of boilermaker construction workers exposed to metal-rich welding fumes.MethodsTwenty-six male workers were monitored by ambulatory electrocardiogram (ECG) on a workday while exposed to welding fume and a non-workday (baseline). From the ECG, rMSSD (square root of the mean squared differences of successive intervals) was summarized over the night (0:00–7:00). Workday, gravimetric PM2.5 samples were analyzed by x-ray fluorescence to determine metal content. We used linear mixed effects models to assess the associations between night rMSSD and PM2.5 metal exposures both with and without adjustment for total PM2.5. Matched ECG measurements from the non-workday were used to control for individual cardiac risk factors and models were also adjusted for smoking status. To address collinearity between PM2.5 and metal content, we used a two-step approach that treated the residuals from linear regression models of each metal on PM2.5 as surrogates for the differential effects of metal exposures in models for night rMSSD.ResultsThe median PM2.5 exposure was 650 μg/m3; median metal exposures for iron, manganese, aluminum, copper, zinc, chromium, lead, and nickel ranged from 226 μg/m3 to non-detectable. We found inverse linear associations in exposure-response models with increased metal exposures associated with decreased night rMSSD. A statistically significant association for manganese was observed, with a decline of 0.130 msec (95% CI: -0.162, -0.098) in night rMSSD for every 1 μg/m3 increase in manganese. However, even after adjusting for individual metals, increases in total PM2.5 exposures were associated with declines in night rMSSD.ConclusionThese results support the cardiotoxicity of PM2.5 metal exposures, specifically manganese. However the metal component alone did not account for the observed declines in night HRV. Therefore, results suggest the importance of other PM elemental components.

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.

Toenail, Blood, and Urine as Biomarkers of Manganese Exposure

Objective: This study examined the correlation between manganese exposure and manganese concentrations in different biomarkers. Methods: Air measurement data and work histories were used to determine manganese exposure over a work shift and cumulative exposure. Toenail samples (n = 49), as well as blood and urine before (n = 27) and after (urine, n = 26; blood, n = 24) a work shift were collected. Results: Toenail manganese, adjusted for age and dietary manganese, was significantly correlated with cumulative exposure in 7 to 9, 10 to 12, and 7 to 12 months before toenail clipping date, but not 1 to 6 months. Manganese exposure over a work shift was not correlated with changes in blood nor urine manganese. Conclusions: Toenails appeared to be a valid measure of cumulative manganese exposure 7 to 12 months earlier. Neither change in blood nor urine manganese appeared to be suitable indicators of exposure over a typical work shift.

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.CVD = cardiovascular disease; IL-6 = interleukin 6; CRP = C-reactive protein; sICAM-1 = soluble intercellular adhesion molecule 1; sVCAM-1 = soluble vascular cell adhesion molecule 1; sTNF-RII = soluble tumor necrosis factor receptor II; NAS = Normative Aging Study; BMI = body mass index; SBP = systolic blood pressure; DBP = diastolic blood pressure; LOT = Life Orientation Test; LOT-R = Revised Life Orientation Test; BSI = Brief Symptom Inventory; CI = confidence interval; SD = standard deviation; MESA = Multi-Ethnic Study of Atherosclerosis

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-1β, 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.

Urinary 8-hydroxy-2′-deoxyguanosine as a biomarker of oxidative DNA damage induced by ambient pollution in the Normative Aging Study

Background Studies show that exposure to air pollution damages human health, but the mechanisms are not fully understood. One suggested pathway is via oxidative stress. Objectives This study examines associations between exposure to air pollution and oxidative DNA damage, as indicated by urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentrations in ageing participants during 2006–2008. Methods We fit linear regression models to examine associations between air pollutants and 8-OHdG adjusting for potential confounders. Results 8-OHdG was significantly associated with ambient particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5), nitrogen dioxide (NO2), maximal 1 h ozone (O3), sulphate (SO42−) and organic carbon (OC), but not with black carbon (BC), carbon monoxide (CO), the number of particles (PN) or elemental carbon (EC). Effects were more apparent with multi-week averages of exposures. Per IQR increases in 21-day averages of PM2.5, PN, BC, EC, OC, CO, SO42−, NO2 and maximal 1 h O3 were associated with 30.8% (95% CI 9.3% to 52.2%), −13.1% (95% CI −41.7% to 15.5%), 3.0% (95% CI −19.8% to 25.8%), 5.3% (95% CI −23.6% to 34.2%), 24.4% (95% CI 1.8% to 47.1%), −2.0% (95% CI −12.4% to 8.3%), 29.8% (95% CI 6.3% to 53.3%), 32.2% (95% CI 7.4% to 56.9%) and 47.7% (95% CI 3.6% to 91.7%) changes in 8-OHdG, respectively. Conclusions This study suggests that ageing participants experienced an increased risk of developing oxidative DNA injury after exposure to secondary, but not primary, ambient pollutants.

Vascular Function, Inflammation, and Variations in Cardiac Autonomic Responses to Particulate Matter Among Welders

Patients with health conditions associated with impaired vascular function and inflammation may be more susceptible to the adverse health effects of fine particulate (particulate matter with a mass median aerodynamic diameter of </=2.5 mum (PM(2.5))) exposure. In 2006, the authors conducted a panel study to investigate directly whether vascular function and inflammation (assessed by C-reactive protein) modify PM(2.5)-associated reductions in heart rate variability among 23 young male workers (mean age, 40 years) from Massachusetts. Concurrent 24-hour ambulatory electrocardiogram and personal PM(2.5) exposure information was collected over a total of 36 person-days, including either or both welding and nonwelding days. Linear mixed models were used to examine the 5-minute standard deviation of normal-to-normal intervals (SDNN) in relation to the moving PM(2.5) averages in the preceding 1-4 hours. C-reactive protein levels and 3 measures of vascular function (augmentation index, mean arterial pressure, and pulse pressure) were determined at baseline. The authors observed an inverse association between the 1-hour PM(2.5) and 5-minute SDNN. Greater SDNN declines were observed among those with C-reactive protein (P(interaction) < 0.001) and augmentation index (P = 0.06) values at or above the 75th percentile and pulse pressure values below the 75th percentile (P < 0.001). Systemic inflammation and poorer vascular function appear to aggravate particle-related declines in heart rate variability among workers.

Acute changes in vascular function among welders exposed to metal-rich particulate matter.

Background: Although welding fume exposure is associated with adverse cardiovascular outcomes, the mechanisms remain unclear. To investigate the role of vascular function, we assessed levels of the augmentation index (a correlate of arterial stiffness) after short-term exposure to welding-derived fine particulate matter (PM2.5). Methods: In a panel study, we monitored 26 male welders over 24 hours on a welding day (n = 25), a nonwelding day (n = 15), or both (n = 14). Augmentation index (expressed as a percent) was obtained in the morning before exposure (baseline) and after exposure in the afternoon and the following morning. Personal PM2.5 exposure was measured over 6 hours of welding or an equivalent nonwelding period. We used linear mixed models adjusting for baseline augmentation index, smoking, age, and time to evaluate the effects of welding (binary) and PM2.5 (continuous) on augmentation index levels. We also assessed modification by welding exposure the day before monitoring (binary). Results: Welding was associated with a 2.8% increase in afternoon augmentation index (95% confidence interval = −1.4 to 7.0) and a 2.4% decrease (−6.9 to 2.2) in next-morning augmentation index. Additional exposure the day prior to monitoring was associated with a greater afternoon increase (5.1%; 0.8 to 9.5). Using PM2.5 concentration, a positive association was observed in the afternoon and an inverse association the next morning; results differed by previous days welding status after excluding outliers. Conclusions: Subsequent to welding fume exposure, there is an increase in afternoon augmentation index and a decrease in next-morning augmentation index, with greater changes after consecutive days of exposure. These results suggest that exposure to the PM2.5 component of welding fume elicits acute adverse vascular responses.

Time Course of Heart Rate Variability Decline Following Particulate Matter Exposures in an Occupational Cohort

Although research suggests that particles influence cardiac autonomic response as evidenced by decreases in heart rate variability (HRV), the time course of the response remains unclear. Using a crossover panel study, we monitored 36 male boilermaker welders, occupationally exposed to metal-rich particulate matter (PM) to investigate the temporal trend of hourly HRV subsequent to PM exposure. Ambulatory electrocardiograms were collected over work (exposure) and non-work (control) periods and the mean of the standard deviations of all normal-to-normal intervals for all 5-min segments (SDNNi) was calculated hourly for up to 14-hrs post-work. The exposure-response relationship was examined with linear mixed effects regression models to account for participants monitored over multiple occasions. Models were adjusted for non-work HRV to control for diurnal fluctuations and individual predictors of HRV. The mean (SD) work PM2. 5 concentration was 1.12 (0.76) mg/m3. Hourly SDNNi was consistently lower post-work as compared to the same time period on a non-work day. HRV was inversely associated with work PM2. 5 exposures in each of the 14-hrs post-work. The hourly associations suggested an early and later phase response, with the largest regression coefficients observed 2–3 hrs (β = −6.86 (95% CI: −11.91, −1.81) msec/1 mg/m3 at 3-hrs), and then 9–13 hrs (β = −8.60 (95% CI: −17.45, 0.24) msec/1 mg/m3 at 11-hrs), after adjusting for non-work HRV, smoking status, and age. This investigation demonstrates declines in HRV for up to 14 hours following PM exposure and a multiphase cardiovascular autonomic response with immediate (2 hrs) and delayed (9–13 hrs) responses.

Night heart rate variability and particulate exposures among boilermaker construction workers.

Background Although studies have documented the association between heart rate variability (HRV) and ambient particulate exposures, the association between HRV, especially at night, and metal-rich, occupational particulate exposures remains unclear. Objective Our goal in this study was to investigate the association between long-duration HRV, including nighttime HRV, and occupational PM2.5 exposures. Methods We used 24-hr ambulatory electrocardiograms (ECGs) to monitor 36 male boilermaker welders (mean age of 41 years) over a workday and nonworkday. ECGs were analyzed for HRV in the time domain; rMSSD (square root of the mean squared differences of successive intervals), SDNN (SD of normal-to-normal intervals over entire recording), and SDNNi (SDNN for all 5-min segments) were summarized over 24-hr, day (0730–2130 hours), and night (0000–0700 hours) periods. PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5 μm) exposures were monitored over the workday, and 8-hr time-weighted average concentrations were calculated. We used linear regression to assess the associations between HRV and workday particulate exposures. Matched measurements from a nonworkday were used to control for individual cardiac risk factors. Results Mean (± SD) PM2.5 exposure was 0.73 ± 0.50 mg/m3 and ranged from 0.04 to 2.70 mg/m3. We observed a consistent inverse exposure–response relationship, with a decrease in all HRV measures with increased PM2.5 exposure. However, the decrease was most pronounced at night, where a 1-mg/m3 increase in PM2.5 was associated with a change of −8.32 [95% confidence interval (CI), −16.29 to −0.35] msec nighttime rMSSD, −14.77 (95% CI, −31.52 to 1.97) msec nighttime SDNN, and −8.37 (95% CI, −17.93 to 1.20) msec nighttime SDNNi, after adjusting for nonworking nighttime HRV, age, and smoking. Conclusion Metal-rich particulate exposures were associated with decreased long-duration HRV, especially at night. Further research is needed to elucidate which particulate metal constituent is responsible for decreased HRV.