Person:

Mehta, A

Background: Occupational exposure to endotoxin is associated with decrements in pulmonary function, but how much variation in this association is explained by genetic variants is not well understood. Objective: We aimed to identify single nucleotide polymorphisms (SNPs) that are associated with the rate of forced expiratory volume in one second (FEV1) decline by a large scale genetic association study in newly-hired healthy young female cotton textile workers. Methods: DNA samples were genotyped using the Illumina Human CVD BeadChip. Change rate in FEV1 was modeled as a function of each SNP genotype in linear regression model with covariate adjustment. We controlled the type 1 error in study-wide level by permutation method. The false discovery rate (FDR) and the family-wise error rate (FWER) were set to be 0.10 and 0.15 respectively. Results: Two SNPs were found to be significant (P<6.29×(10^{−5})), including rs1910047 (P = 3.07×(10^{−5}), FDR = 0.0778) and rs9469089 (P = 6.19×(10^{−5}), FDR = 0.0967), as well as other eight suggestive (P<5×(10^{−4})) associated SNPs. Gene-gene and gene-environment interactions were also observed, such as rs1910047 and rs1049970 (P = 0.0418, FDR = 0.0895); rs9469089 and age (P = 0.0161, FDR = 0.0264). Genetic risk score analysis showed that the more risk loci the subjects carried, the larger the rate of FEV1 decline occurred (Ptrend = 3.01×(10^{−18})). However, the association was different among age subgroups (P = 7.11×(10^{−6})) and endotoxin subgroups (P = 1.08×(10^{−2})). Functional network analysis illustrates potential biological connections of all interacted genes. Conclusions: Genetic variants together with environmental factors interact to affect the rate of FEV1 decline in cotton textile workers.

Background: Household cleaning products are associated with adverse respiratory health outcomes, but the cardiovascular health effects are largely unknown. Objective: We determined if long-term use of household sprays and scented products at home was associated with reduced heart rate variability (HRV), a marker of autonomic cardiac dysfunction. Methods: We recorded 24-hr electrocardiograms in a cross-sectional survey of 581 Swiss adults, ≥ 50 years of age, who answered a detailed questionnaire regarding their use of household cleaning products in their homes. The adjusted average percent changes in standard deviation of all normal-to-normal intervals in 24 hr (24-hr SDNN) and total power (TP) were estimated in multiple linear regression in association with frequency [< 1, 1–3, or 4–7 days/week, unexposed (reference)] of using cleaning sprays, air freshening sprays, and scented products. Results: Decreases in 24-hr SDNN and TP were observed with frequent use of all product types, but the strongest reductions were associated with air freshening sprays. Compared with unexposed participants, we found that using air freshening sprays 4–7 days/week was associated with 11% [95% confidence interval (CI): –20%, –2%] and 29% (95% CI: –46%, –8%) decreases in 24-hr SDNN and TP, respectively. Inverse associations of 24-SDNN and TP with increased use of cleaning sprays, air freshening sprays, and scented products were observed mainly in participants with obstructive lung disease (p < 0.05 for interactions). Conclusions: In predominantly older adult women, long-term frequent use of household spray and scented products was associated with reduced HRV, which suggests an increased risk of cardiovascular health hazards. People with preexisting pulmonary conditions may be more susceptible.

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-1(\beta) and tumor necrosis factor-(\alpha)). 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.

Background: The underlying mechanisms of the association between ambient temperature and cardiovascular morbidity and mortality are not well understood, particularly for daily temperature variability. We evaluated if daily mean temperature and standard deviation of temperature was associated with heart rate-corrected QT interval (QTc) duration, a marker of ventricular repolarization in a prospective cohort of older men. Methods: This longitudinal analysis included 487 older men participating in the VA Normative Aging Study with up to three visits between 2000–2008 (n = 743). We analyzed associations between QTc and moving averages (1–7, 14, 21, and 28 days) of the 24-hour mean and standard deviation of temperature as measured from a local weather monitor, and the 24-hour mean temperature estimated from a spatiotemporal prediction model, in time-varying linear mixed-effect regression. Effect modification by season, diabetes, coronary heart disease, obesity, and age was also evaluated. Results: Higher mean temperature as measured from the local monitor, and estimated from the prediction model, was associated with longer QTc at moving averages of 21 and 28 days. Increased 24-hr standard deviation of temperature was associated with longer QTc at moving averages from 4 and up to 28 days; a 1.9°C interquartile range increase in 4-day moving average standard deviation of temperature was associated with a 2.8 msec (95%CI: 0.4, 5.2) longer QTc. Associations between 24-hr standard deviation of temperature and QTc were stronger in colder months, and in participants with diabetes and coronary heart disease. Conclusion/Significance In this sample of older men, elevated mean temperature was associated with longer QTc, and increased variability of temperature was associated with longer QTc, particularly during colder months and among individuals with diabetes and coronary heart disease. These findings may offer insight of an important underlying mechanism of temperature-related cardiovascular morbidity and mortality in an older population.

Background: It is unknown if ambient fine particulate matter (PM2.5) is associated with lower renal function, a cardiovascular risk factor. Objective: We investigated whether long-term PM2.5 exposure was associated with estimated glomerular filtration rate (eGFR) in a cohort of older men living in the Boston Metropolitan area. Methods: This longitudinal analysis included 669 participants from the Veterans Administration Normative Aging Study with up to four visits between 2000 and 2011 (n = 1,715 visits). Serum creatinine was measured at each visit, and eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration equation. One-year exposure to PM2.5 prior to each visit was assessed using a validated spatiotemporal model that utilized satellite remote-sensing aerosol optical depth data. eGFR was modeled in a time-varying linear mixed-effects regression model as a continuous function of 1-year PM2.5, adjusting for important covariates. Results: One-year PM2.5 exposure was associated with lower eGFRs; a 2.1-μg/m3 interquartile range higher 1-year PM2.5 was associated with a 1.87 mL/min/1.73 m2 lower eGFR [95% confidence interval (CI): –2.99, –0.76]. A 2.1 μg/m3-higher 1-year PM2.5 was also associated with an additional annual decrease in eGFR of 0.60 mL/min/1.73 m2 per year (95% CI: –0.79, –0.40). Conclusions: In this longitudinal sample of older men, the findings supported the hypothesis that long-term PM2.5 exposure negatively affects renal function and increases renal function decline. Citation: Mehta AJ, Zanobetti A, Bind MC, Kloog I, Koutrakis P, Sparrow D, Vokonas PS, Schwartz JD. 2016. Long-term exposure to ambient fine particulate matter and renal function in older men: the VA Normative Aging Study. Environ Health Perspect 124:1353–1360; http://dx.doi.org/10.1289/ehp.1510269

Background: Short‐term fine particles (PM2.5) exposure is associated with reduced heart rate variability, a strong predictor of cardiac mortality among older people. Identifying modifiable factors that confer susceptibility is essential for intervention. We evaluated whether Toll‐like receptor 2 (TLR2) methylation, a reversible immune‐epigenetic process, and its dietary modulation by flavonoids and methyl nutrients, modify susceptibility to heart rate variability effects following PM2.5 exposure. Methods and Results: We measured heart rate variability and PM2.5 repeatedly over 11 years (1275 total observations) among 573 elderly men from the Normative Aging Study. Blood TLR2 methylation was analyzed using pyrosequencing. Daily flavonoid and methyl nutrients intakes were assessed through the Food Frequency Questionnaire (FFQ). Every 10 μg/m3 increase in 48‐hour PM2.5 moving average was associated with 7.74% (95% CI: −1.21% to 15.90%; P=0.09), 7.46% (95% CI: 0.99% to 13.50%; P=0.02), 14.18% (95% CI: 1.14% to 25.49%; P=0.03), and 12.94% (95% CI: −2.36% to 25.96%; P=0.09) reductions in root mean square of successive differences, standard deviation of normal‐to‐normal intervals, low‐frequency power, and high‐frequency power, respectively. Higher TLR2 methylation exacerbated the root mean square of successive differences, standard deviation of normal‐to‐normal intervals, low‐frequency, and high‐frequency reductions associated with heightened PM2.5 (Pinteraction=0.006, 0.03, 0.05, 0.04, respectively). Every interquartile‐range increase in flavonoid intake was associated with 5.09% reduction in mean TLR2 methylation (95% CI: 0.12% to 10.06%; P=0.05) and counteracted the effects of PM2.5 on low frequency (Pinteraction=0.05). No significant effect of methyl nutrients on TLR2 methylation was observed. Conclusions: Higher TLR2 methylation may confer susceptibility to adverse cardiac autonomic effects of PM2.5 exposure in older individuals. Higher flavonoid intake may attenuate these effects, possibly by decreasing TLR2 methylation.

Background: It is unknown whether habitual intake of dietary flavonoids, known for their antioxidative and anti-inflammatory properties, affects longitudinal change in lung function. Objective: We investigated whether different flavonoid subclasses present in the habitual diet were associated with beneficial changes in lung function over time in the elderly. Design: This longitudinal analysis included 839 participants from the VA (Veterans Affairs) Normative Aging Study whose lung function [forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] was measured at 2 and up to 5 visits between 1992 and 2008 (n = 2623 measurements). Yearly average intake of major flavonoid subclasses (anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polymers) was calculated from food-frequency questionnaires at each visit. We estimated adjusted differences in annual change in lung function associated with each flavonoid subclass, categorized into quartiles, in linear mixed-effects regression models after adjustment for lifestyle and dietary confounders. Results: Strong inverse associations were found between anthocyanin intake and age-related decline in lung function. Independent of dietary and nondietary risk factors, slower rates of FEV1 and FVC decline by 23.6 (95% CI: 16.6, 30.7) and 37.3 (95% CI: 27.8, 46.8) mL/y, respectively, were observed in participants in the fourth quartile of intake compared with participants in the first quartile (P-trend < 0.0001). The protective associations observed for anthocyanin intake were present in both current/former and never smokers. Compared with no or very low intakes, an intake of ≥2 servings of anthocyanin-rich blueberries/wk was associated with slower decline in FEV1 and FVC by 22.5 (95% CI: 10.8, 34.2) and 37.9 (95% CI: 22.1, 53.7) mL/y, respectively. To a lesser extent, higher flavan-3-ol intake was also associated with slower lung function decline. Conclusions: An attenuation of age-related lung function decline was associated with higher dietary anthocyanin intake in this longitudinal sample of predominantly elderly men. Further prospective studies are needed to confirm these novel associations.

Background: There is mixed evidence suggesting that air pollution may be associated with increased risk of developing psychiatric disorders. We aimed to investigate the association between air pollution and non-specific perceived stress, often a precursor to development of affective psychiatric disorders. Methods: This longitudinal analysis consisted of 987 older men participating in at least one visit for the Veterans Administration Normative Aging Study between 1995 and 2007 (n = 2,244 visits). At each visit, participants were administered the 14-item Perceived Stress Scale (PSS), which quantifies stress experienced in the previous week. Scores ranged from 0–56 with higher scores indicating increased stress. Differences in PSS score per interquartile range increase in moving average (1, 2, and 4-weeks) of air pollution exposures were estimated using linear mixed-effects regression after adjustment for age, race, education, physical activity, anti-depressant medication use, seasonality, meteorology, and day of week. We also evaluated effect modification by season (April-September and March-October for warm and cold season, respectively). Results: Fine particles (PM2.5), black carbon (BC), nitrogen dioxide, and particle number counts (PNC) at moving averages of 1, 2, and 4-weeks were associated with higher perceived stress ratings. The strongest associations were observed for PNC; for example, a 15,997 counts/cm3 interquartile range increase in 1-week average PNC was associated with a 3.2 point (95%CI: 2.1-4.3) increase in PSS score. Season modified the associations for specific pollutants; higher PSS scores in association with PM2.5, BC, and sulfate were observed mainly in colder months. Conclusions: Air pollution was associated with higher levels of perceived stress in this sample of older men, particularly in colder months for specific pollutants. Electronic supplementary material The online version of this article (doi:10.1186/1476-069X-14-10) contains supplementary material, which is available to authorized users.