50 research outputs found
Systemic inflammation and lung function decline in a repeated measure study on an elderly cohort
No full textRATIONALE
Decreased lung function has been linked to increased inflammation and oxidative stress. Higher C-reactive protein (CRP) levels have been associated with lower lung function in cross-sectional studies. Whether CRP, as a marker of systemic inflammation, is related with lung function decline is unresolved.
METHODS
We investigated the association of CRP levels on lung function decline on 2,014 lung function measurements on 803 elderly men from the Eastern Massachusetts Normative Aging Study, whose lung function (forced vital capacity [FVC] and forced expiratory volume in one second [FEV1]) was measured 2-4 times between 1995-2005. Subjects were categorized according to the median CRP level (1.61 mg/L). We used mixed linear models to estimate FVC or FEV1 decline by CRP category, adjusting for potential confounders.
RESULTS
FVC decline was 22.1 mL/yr (95% CI 16.7-27.4) in subjects with CRP>1.61 mg/L, while subjects with CRP1.61 mg/L, while those with CRP>1.61 mg/L had a FEV1 decline of 11.3 mL/yr (95% CI 7.5-15.0). The effect of CRP on FEV decline was also was significant (p=0.01).
CONCLUSIONS
Our results indicate that higher CRP levels are associated with a decline in lung function in the elderly
Ozone exposure, antioxidant genes, and lung function in an elderly cohort : VA normative aging study
No full textBackground: Ozone (O3) exposure is known to cause oxidative stress. This study investigated the acute effects of O3 on lung function in the elderly, a suspected risk group. It then investigated whether genetic polymorphisms of antioxidant genes (heme oxygenase-1 (HMOX1) and glutathione 5-transferase pi (GSTP1)] modified these associations. Methods: 1100 elderly men from the Normative Aging Study were examined whose lung function (forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1)) was measured every 3 years from 1995 to 2005. The study genotyped the GSTP1 lle105Val and Ala114Val polymorphisms and the (GT)n repeat polymorphism in the HMOX1 promoter, classifying repeats as short (n<25) or long (n≥25). Ambient O3 was measured continuously at locations in the Greater Boston area. Mixed linear models were used, adjusting for known confounders. Results: A 15 ppb increase in O3 during the previous 48 h was associated with a 1.25% decrease in FEV1 (95% CI: -1.96% to -0.54%). This estimated effect was worsened with either the presence of a long (GT)n repeat in HMOX1 (-1.38%, 95% CI: -2.11% to -0.65%) or the presence of an allele coding for Val105 in GSTP1 (-1.69%, 95% CI: -2.63% to -0.75%). A stronger estimated effect of O3 on FEV1 was found in subjects carrying both the GSTP1 105Val variant and the HMOX1 long (GT)n repeat (-1.94%, 95% CI: -2.89% to -0.98%). Similar associations were also found between FVC and O3 exposure. Conclusions: Our results suggest that O3 has an acute effect on lung function in the elderly, and the effects may be modified by the presence of specific polymorphisms in antioxidant genes
Ambient pollutants, polymorphisms associated with microRNA processing and adhesion molecules: the Normative Aging Study
No full textAbstract Background Particulate air pollution has been associated with cardiovascular morbidity and mortality, but it remains unclear which time windows and pollutant sources are most critical. MicroRNA (miRNA) is thought to be involved in cardiovascular regulation. However, little is known about whether polymorphisms in genes that process microRNAs influence response to pollutant exposure. We hypothesized that averaging times longer than routinely measured one or two day moving averages are associated with higher soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) levels, and that stationary and mobile sources contribute differently to these effects. We also investigated whether single nucleotide polymorphisms (SNPs) in miRNA-processing genes modify these associations. Methods sICAM-1 and sVCAM-1 were measured from 1999-2008 and matched to air pollution monitoring for fine particulate matter (PM2.5) black carbon, and sulfates (SO42-). We selected 17 SNPs in five miRNA-processing genes. Mixed-effects models were used to assess effects of pollutants, SNPs, and interactions under recessive inheritance models using repeated measures. Results 723 participants with 1652 observations and 1-5 visits were included in our analyses for black carbon and PM2.5. Sulfate data was available for 672 participants with 1390 observations. An interquartile range change in seven day moving average of PM2.5 (4.27 μg/m3) was associated with 3.1% (95%CI: 1.6, 4.6) and 2.5% (95%CI: 0.6, 4.5) higher sICAM-1 and sVCAM-1. Interquartile range changes in sulfates (1.39 μg/m3) were associated with 1.4% higher (95%CI: 0.04, 2.7) and 1.6% (95%CI: -0.4, 3.7) higher sICAM-1 and sVCAM-1 respectively. No significant associations were observed for black carbon. In interaction models with PM2.5, both sICAM-1 and sVCAM-1 levels were lower in rs1062923 homozygous carriers. These interactions remained significant after multiple comparisons adjustment. Conclusions PM2.5 seven day moving averages are associated with higher sICAM-1 and sVCAM-1 levels. SO4-2 seven day moving averages are associated with higher sICAM-1 and a suggestive association was observed with sVCAM-1 in aging men. SNPs in miRNA-processing genes may modify associations between ambient pollution and sICAM-1 and sVCAM-1, which are correlates of atherosclerosis and cardiovascular disease.</p
Gene environment interactions and postural blood pressure in community exposed elderly men : the VA normative aging study
No full textBackground:
Evidence has shown a positive association between environmental air pollution and blood pressure (BP) change, a marker of autonomic function and a predictor of cardiovascular outcomes. We investigated the associations between postural changes in systolic and diastolic BP and fine particulate matter (PM2.5), single nucleotide polymorphisms (SNPs), and SNP-by-PM2.5 interactions.
Methods:
Systolic and diastolic BP measurements were obtained from men in the Normative Aging Study who lived in the Boston area and visited the study center every 3-5 years. Postural BP change was defined as the difference between standing and supine measurements for systolic and diastolic BP. PM2.5 was measured continuously with exposures averaged over 48 hours prior to study visit for analyses. Blood samples were analyzed for 975 SNPs in 62 candidate genes and included haplotype tag SNPs and known or suspected functional SNPs. Data were stratified into a screening cohort and testing cohort. In the screening cohort, the relationship between postural change in BP and SNP, PM2.5, and SNP-by-PM2.5 interactions was analyzed using linear mixed effect models with random intercepts for each subject to account for repeated BP measurements within the study period. Models were adjusted for age and body mass index (BMI). A positive outcome in the screening cohort was defined as a P-value < 0.1 for the interaction term. SNPs meeting these criteria were subsequently analyzed in the testing cohort. SNPs were confirmed as significant predictors if they also met criteria of P < 0.05 in the testing cohort with an association in the same direction as in the screening cohort. All confirmed associations were analyzed within the full cohort data in models adjusted for age, BMI, smoking status and use of hypertension medications.
Results:
930 participants with a mean (±SD) age of 72 (±7) provided information on exposure, outcomes and covariates of interest. Average systolic BP was 132.97 (±17.9) mmHg with a postural change in pressure of 2.4 (±12.7) mmHg. Average diastolic BP was 78.11 (±10.4) mmHg with -0.5 (±6.5) mmHg change. SNP-by-PM2.5 interactions in ITPR2 and MMP1 decreased the magnitude of change in systolic BP and a polymorphism in the PHF11 gene suppressed postural change in diastolic pressure. For example, the main effect of the minor allele of rs9568232 in PHF11 was associated with greater postural change in diastolic BP (β = 2.5, P = .001) and the interaction was associated with a suppression in diastolic BP change (β = -2.4, P = .001) for an increase of 10 μg/m3 PM2.5. The effect of PM2.5 in subjects with the major variant was non-significant (β = 0.3, P = .23).
Conclusions:
We observed SNPs associated with decreases in magnitude of postural change in BP and found different candidate genes to be associated with differences in postural change in diastolic and systolic blood pressure. Our findings also suggest that considering gene main effects alone may overlook relationships modified by environmental exposures such as PM2.5
Association between blood pressure and DNA methylation of retrotransposons and pro-inflammatory genes
No full textBackground Methylation of deoxyribonucleic acid (DNA) is an epigenetic regulator of gene expression that changes with age, but its contribution to aging-related disorders, including high blood pressure (BP), is still largely unknown. We examined the relation of BP to the methylation of retrotransposon sequences of DNA and of selected candidate genes. Methods This investigation included 789 elderly participants in the Normative Aging Study, ranging in age from 55 to 100 years, who had longitudinal measurements of DNA methylation. In these subjects DNA we measured the proportion of methylated sites in retrotransposable sequences and in pro-inflammatory genes, expressed as the percent of 5-methylated cytosines (5mC) among all cytosines. From one to four methylation measurements were made for each subject between 1999 and 2009. We fit mixed-effects models, using repeated measures of BP as the outcome and DNA methylation as the explanatory variable, adjusting for confounding variables. We also fit a Bayesian mixed-effects structural equation model to account for heterogeneity in the effects of methylation sites within each gene. Results An increase in inter-quartile range (IQR) in the methylation of Alu elements was associated with an increase of 0.97 mm Hg in diastolic blood pressure (DBP) (95 CI 0.32-1.57), but no such association was observed for long interspersed nuclear element-1 (LINE-1). We also found positive associations between DBP and methylation of the genes for toll-like receptor 2 (TLR2) and inducible nitric oxide synthase (iNOS), and a negative association between DBP and methylation of the gene for interferon-γ (IFN-γ). Associations between methylation and systolic blood pressure (SBP) were weaker than those between methylation and DBP. Bayesian mixed-effects structural equation model results were similar for both DBP and SBP models. Conclusions The results of our study suggest that changes in DNA methylation of some pro-inflammatory genes and retrotransposable elements are related to small changes in BP. Published by Oxford University Press on behalf of the International Epidemiological Associatio
Traffic-related air pollution in relation to cognitive function in older adults.
No full textBACKGROUND: Few epidemiologic studies have investigated associations of air pollution with cognition in older adults, and none has specifically compared associations across particle sources. We investigated whether exposure to particulate air pollution, characterized by size and source, was associated with cognitive function and decline in cognitive function. METHODS: We included participants of the Whitehall II cohort who were residents of greater London and who attended the medical examination in study wave 2007-2009 (n = 2867). Annual average concentrations of particulate matter (PM) (PM10 and PM2.5 from all sources and from traffic exhaust) were modeled at resolution of 20 × 20 m for 2003-2009. We investigated the relationship between exposure to particles and a cognitive battery composed of tests of reasoning, memory, and phonemic and semantic fluency. We also investigated exposure in relation to decline in these tests over 5 years. RESULTS: Mean age of participants was 66 (standard deviation = 6) years. All particle metrics were associated with lower scores in reasoning and memory measured in the 2007-2009 wave but not with lower verbal fluency. Higher PM2.5 of 1.1 μg/m (lag 4) was associated with a 0.03 (95% confidence interval = -0.06 to 0.002) 5-year decline in standardized memory score and a 0.04 (-0.07 to -0.01) decline when restricted to participants remaining in London between study waves. CONCLUSIONS: This study provides support for an association between particulate air pollution and some measures of cognitive function, as well as decline over time in cognition; however, it does not support the hypothesis that traffic-related particles are more strongly associated with cognitive function than particles from all sources
Pesticide and Environmental Toxicology Branch
No full textUnder the Calderon-Sher California Safe Drinking Water Act of 1996, the Office of Environmental Health Hazard Assessment (OEHHA) develops public health goals (PHGs) for regulated chemicals in drinking water and reviews and updates the risk assessments every five years (Health and Safety Code Section 116365(e)(1). This memorandum represents an update of the literature review and reevaluation of the existing PHG for 1,3-dichloropropene, also known as Telone II ® (OEHHA, 1999). Our re-evaluation supports the previous PHG derivation in 1999. We conclude that the PHG for 1,3-dichloropropene should remain at 0.2 parts per billion (ppb). Summary of Review We have surveyed the scientific literature for recently published research studies to determine if there are new toxicity studies that would warrant revising the PHG of 0.2 ppb or making substantive changes to the PHG support document. We also searched for new risk assessments of 1,3-dichloropropene since the publication of the PHG document in 1999, including U.S. EPA reviews, and new risk assessment methods that might be applied to evaluation of 1,3-dichloropropene. California Environmental Protection Agency The energy challenge facing California is real. Every Californian needs to take immediate action to reduce energy consumption. Printed on Recycled PaperJoan E. Denton, Ph.D
Prevalence and predictors of delayed clinical diagnosis of Type 2 diabetes: a longitudinal cohort study
No full textParticulate Air Pollution and Risk of Cardiovascular Events Among Adults With a History of Stroke or Acute Myocardial Infarction
No full textBackground Previous studies have found associations between fine particulate matter <2.5 µm in diameter (PM2.5) and increased risk of cardiovascular disease (CVD) among populations with no CVD history. Less is understood about susceptibility of adults with a history of CVD and subsequent PM2.5‐related CVD events and whether current regulation levels for PM2.5 are protective for this population. Methods and Results This retrospective cohort study included 96 582 Kaiser Permanente Northern California adults with a history of stroke or acute myocardial infarction. Outcome, covariate, and address data obtained from electronic health records were linked to time‐varying 1‐year mean PM2.5 exposure estimates based on residential locations. Cox proportional hazard models estimated risks of stroke, acute myocardial infarction, and cardiovascular mortality associated with PM2.5 exposure, adjusting for multiple covariates. Secondary analyses estimated risks below federal and state regulation levels (12 µg/m3 for 1‐year mean PM2.5). A 10‐µg/m3 increase in 1‐year mean PM2.5 exposure was associated with an increase in risk of cardiovascular mortality (hazard ratio [HR], 1.20; 95% CI, 1.11–1.30), but no increase in risk of stroke or acute myocardial infarction. Analyses of <12 µg/m3 showed increased risk for CVD mortality (HR, 2.31; 95% CI, 1.96–2.71), stroke (HR, 1.41; 95% CI, 1.09–1.83]), and acute myocardial infarction (HR, 1.51; 95% CI, 1.21–1.89) per 10‐µg/m3 increase in 1‐year mean PM2.5. Conclusions Adults with a history of CVD are susceptible to the effects of PM2.5 exposure, particularly on CVD mortality. Increased risks observed at exposure levels <12 µg/m3 highlight that current PM2.5 regulation levels may not be protective for this susceptible population
