Long-term noise exposures and cardiovascular diseases mortality: A study in 5 U.S. states.

BACKGROUND: Previous studies have linked noise exposure with adverse cardiovascular events. However, evidence remains inconsistent, and most previous studies only focused on traffic noise, excluding other anthropogenic sources like constructions, industrial process and commercial activities. Additionally, few studies have been conducted in the U.S. or evaluated the non-linear exposure-response relationships. METHODS: We conducted a relative incidence analysis study using all cardiovascular diseases mortality as cases (n = 936,019) and external causes mortality (n = 232,491) as contrast outcomes. Mortality records geocoded at residential addresses were obtained from five U.S. states (Indiana, 2007; Kansas, 2007-2009, Missouri, 2010-2019, Ohio, 2007-2013, Texas, 2007-2016). Time-invariant long-term noise exposure was obtained from a validated model developed based on acoustical measurements across 2000-2014. Noises from both natural sources (natural activities, including animals, insects, winds, water flows, thunder, etc.) and anthropogenic sources (human activities, including transportation, industrial activities, community facilities & infrastructures, commercial activities, entertainments, etc.) were included. We used daytime and nighttime total anthropogenic noise & day-night average sound pressure level combining natural and anthropogenic sources as exposures. Logistic regression models were fit controlling for Census tract-level & individual-level characteristics. We examined potential modification by sex by interaction terms and potential non-linear associations by thin plate spline terms. RESULTS: We observed positive associations for daytime anthropogenic L50 (sound level exceeded 50% of time) noise (10-dBA OR = 1.047, 95%CI 1.025-1.069), nighttime anthropogenic L50 noise (10-dBA OR = 1.061, 95%CI 1.033-1.091) in a two-exposure-term model, and overall Ldn (day-night average) sound pressure level (10-dBA OR = 1.064, 95%CI 1.040-1.089) in single-exposure-term model. Females were more susceptible to all three exposures. All exposures showed monotonic positive associations with cardiovascular mortality up to certain thresholds around 45-55 dBA, with a generally flattened or decreasing trend beyond those thresholds. CONCLUSIONS: Both daytime anthropogenic and nighttime anthropogenic noises were associated with cardiovascular disease mortality, and associations were stronger in females.

Modification of the PM2.5- and extreme heat-mortality relationships by historical redlining: a case-crossover study in thirteen U.S. states.

BACKGROUND: Redlining has been associated with worse health outcomes and various environmental disparities, separately, but little is known of the interaction between these two factors, if any. We aimed to estimate whether living in a historically-redlined area modifies the effects of exposures to ambient PM2.5 and extreme heat on mortality by non-external causes. METHODS: We merged 8,884,733 adult mortality records from thirteen state departments of public health with scanned and georeferenced Home Owners Loan Corporation (HOLC) maps from the University of Richmond, daily average PM2.5 from a sophisticated prediction model on a 1-km grid, and daily temperature and vapor pressure from the Daymet V4 1-km grid. A case-crossover approach was used to assess modification of the effects of ambient PM2.5 and extreme heat exposures by redlining and control for all fixed and slow-varying factors by design. Multiple moving averages of PM2.5 and duration-aware analyses of extreme heat were used to assess the most vulnerable time windows. RESULTS: We found significant statistical interactions between living in a redlined area and exposures to both ambient PM2.5 and extreme heat. Individuals who lived in redlined areas had an interaction odds ratio for mortality of 1.0093 (95% confidence interval [CI]: 1.0084, 1.0101) for each 10 µg m-3 increase in same-day ambient PM2.5 compared to individuals who did not live in redlined areas. For extreme heat, the interaction odds ratio was 1.0218 (95% CI 1.0031, 1.0408). CONCLUSIONS: Living in areas that were historically-redlined in the 1930's increases the effects of exposures to both PM2.5 and extreme heat on mortality by non-external causes, suggesting that interventions to reduce environmental health disparities can be more effective by also considering the social context of an area and how to reduce disparities there. Further study is required to ascertain the specific pathways through which this effect modification operates and to develop interventions that can contribute to health equity for individuals living in these areas.

Intermediate and long-term exposure to air pollution and temperature and the extracellular microRNA profile of participants in the normative aging study (NAS).

BACKGROUND: The molecular effects of intermediate and long-term exposure to air pollution and temperature, such as those on extracellular microRNA (ex-miRNA) are not well understood but may have clinical consequences. OBJECTIVES: To assess the association between exposure to ambient air pollution and temperature and ex-miRNA profiles. METHODS: Our study population consisted of 734 participants in the Normative Aging Study (NAS) between 1999 and 2015. We used high-resolution models to estimate four-week, eight-week, twelve-week, six-month, and one-year moving averages of PM2.5, O3, NO2, and ambient temperature based on geo-coded residential addresses. The outcome of interest was the extracellular microRNA (ex-miRNA) profile of each participant over time. We used a longitudinal quantile regression approach to estimate the association between the exposures and each ex-miRNA. Results were corrected for multiple comparisons and ex-miRNAs that were still significantly associated with the exposures were further analyzed using KEGG pathway analysis and Ingenuity Pathway Analysis. RESULTS: We found 151 significant associations between levels of PM2.5, O3, NO2, and ambient temperature and 82 unique ex-miRNAs across multiple quantiles. Most of the significant results were associations with intermediate-term exposure to O3, long-term exposure to PM2.5, and both intermediate and long-term exposure to ambient temperature. The exposures were most often associated with the 75th and 90th percentile of the outcomes. Pathway analyses of significant ex-miRNAs revealed their involvement in biological pathways involving cell function and communication as well as clinical diseases such as cardiovascular disease, respiratory disease, and neurological disease. CONCLUSION: Our results show that intermediate and long-term exposure to all our exposures of interest were associated with changes in the ex-miRNA profile of study participants. Further studies on environmental risk factors and ex-miRNAs are warranted.

Epigenome-wide DNA methylation in leukocytes and toenail metals: The normative aging study.

BACKGROUND: Environmental metal exposures have been associated with multiple deleterious health endpoints. DNA methylation (DNAm) may provide insight into the mechanisms underlying these relationships. Toenail metals are non-invasive biomarkers, reflecting a medium-term time exposure window. OBJECTIVES: This study examined variation in leukocyte DNAm and toenail arsenic (As), cadmium (Cd), lead (Pb), manganese (Mn), and mercury (Hg) among elderly men in the Normative Aging Study, a longitudinal cohort. METHODS: We repeatedly collected samples of blood and toenail clippings. We measured DNAm in leukocytes with the Illumina HumanMethylation450 K BeadChip. We first performed median regression to evaluate the effects of each individual toenail metal on DNAm at three levels: individual cytosine-phosphate-guanine (CpG) sites, regions, and pathways. Then, we applied a Bayesian kernel machine regression (BKMR) to assess the joint and individual effects of metal mixtures on DNAm. Significant CpGs were identified using a multiple testing correction based on the independent degrees of freedom approach for correlated outcomes. The approach considers the effective degrees of freedom in the DNAm data using the principal components that explain >95% variation of the data. RESULTS: We included 564 subjects (754 visits) between 1999 and 2013. The numbers of significantly differentially methylated CpG sites, regions, and pathways varied by metals. For example, we found six significant pathways for As, three for Cd, and one for Mn. The As-associated pathways were associated with cancer (e.g., skin cancer) and cardiovascular disease, whereas the Cd-associated pathways were related to lung cancer. Metal mixtures were also associated with 47 significant CpG sites, as well as pathways, mainly related to cancer and cardiovascular disease. CONCLUSIONS: This study provides an approach to understanding the potential epigenetic mechanisms underlying observed relations between toenail metals and adverse health endpoints.

Long-term exposure to ambient fine particulate components and leukocyte epigenome-wide DNA Methylation in older men: the Normative Aging Study.

BACKGROUND: Epigenome-wide association studies of ambient fine particulate matter (PM2.5) have been reported. However, few have examined PM2.5 components (PMCs) and sources or included repeated measures. The lack of high-resolution exposure measurements is the key limitation. We hypothesized that significant changes in DNA methylation might vary by PMCs and the sources. METHODS: We predicted the annual average of 14 PMCs using novel high-resolution exposure models across the contiguous U.S., between 2000-2018. The resolution was 50 m × 50 m in the Greater Boston Area. We also identified PM2.5 sources using positive matrix factorization. We repeatedly collected blood samples and measured leukocyte DNAm with the Illumina HumanMethylation450K BeadChip in the Normative Aging Study. We then used median regression with subject-specific intercepts to estimate the associations between long-term (one-year) exposure to PMCs / PM2.5 sources and DNA methylation at individual cytosine-phosphate-guanine CpG sites. Significant probes were identified by the number of independent degrees of freedom approach, using the number of principal components explaining > 95% of the variation of the DNA methylation data. We also performed regional and pathway analyses to identify significant regions and pathways. RESULTS: We included 669 men with 1,178 visits between 2000-2013. The subjects had a mean age of 75 years. The identified probes, regions, and pathways varied by PMCs and their sources. For example, iron was associated with 6 probes and 6 regions, whereas nitrate was associated with 15 probes and 3 regions. The identified pathways from biomass burning, coal burning, and heavy fuel oil combustion sources were associated with cancer, inflammation, and cardiovascular diseases, whereas there were no pathways associated with all traffic. CONCLUSIONS: Our findings showed that the effects of PM2.5 on DNAm varied by its PMCs and sources.

Maternal exposure to black carbon and nitrogen dioxide during pregnancy and birth weight: Using machine-learning methods to achieve balance in inverse-probability weights.

BACKGROUND: Low birth weight is associated with increased risks of health problems in infancy and later life. Among the epidemiological analyses suggesting an association between air pollution and birth weight, few have estimated the effects of black carbon (BC) or together with nitrogen dioxide (NO2), and even fewer studies have used causal modelling. METHODS: We examined 1,119,011 birth records between 2001/01/01 and 2015/12/31 from the Massachusetts Birth Registry to investigate causal associations between prenatal exposure to BC and NO2 and birth weight. We calculated mean residential BC and NO2 exposures 0-30, and 31-280 days prior to birth from validated spatial-temporal models. We fit generalized propensity score models with gradient boosting tuned by a new algorithm to achieve covariate balance, then fit marginal structural models with stabilized inverse-probability weights. RESULTS: Throughout pregnancy, the average birth weight would drop by 17.0 g (95% CI: 15.4, 18.6) for an IQR increase of 0.14 µg/m3 in BC and would independently drop by 19.9 g (95% CI: 18.6, 21.3) for an IQR increase of 9.8 ppb in NO2. Most of the negative effects of BC on birth weight are from 0 to 30 days before the delivery date. The estimated odds ratio of low birth weight for every IQR increase during the entire pregnancy was 1.131 (95% CI: 1.106, 1.156) for BC and 1.082 (95% CI: 1.062, 1.103) for NO2. CONCLUSIONS: We found that prenatal exposures to both BC and NO2 were associated with lower birth weight.

Short term exposure to air pollution and mortality in the US: a double negative control analysis.

RATIONALE: Studies examining the association of short-term air pollution exposure and daily deaths have typically been limited to cities and used citywide average exposures, with few using causal models. OBJECTIVES: To estimate the associations between short-term exposures to fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) and all-cause and cause-specific mortality in multiple US states using census tract or address exposure and including rural areas, using a double negative control analysis. METHODS: We conducted a time-stratified case-crossover study examining the entire population of seven US states from 2000-2015, with over 3 million non-accidental deaths. Daily predictions of PM2.5, O3, and NO2 at 1x1 km grid cells were linked to mortality based on census track or residential address. For each pollutant, we used conditional logistic regression to quantify the association between exposure and the relative risk of mortality conditioning on meteorological variables, other pollutants, and using double negative controls. RESULTS: A 10 µg/m3 increase in PM2.5 exposure at the moving average of lag 0-2 day was significantly associated with a 0.67% (95%CI: 0.34-1.01%) increase in all-cause mortality. 10 ppb increases in NO2 or O3 exposure at lag 0-2 day were marginally associated with and 0.19% (95%CI: -0.01-0.38%) and 0.20 (95% CI-0.01, 0.40), respectively. The adverse effects of PM2.5 persisted when pollution levels were restricted to below the current global air pollution standards. Negative control models indicated little likelihood of omitted confounders for PM2.5, and mixed results for the gases. PM2.5 was also significantly associated with respiratory mortality and cardiovascular mortality. CONCLUSIONS: Short-term exposure to PM2.5 and possibly O3 and NO2 are associated with increased risks for all-cause mortality. Our findings delivered evidence that risks of death persisted at levels below currently permissible.

Associations between long-term exposures to airborne PM2.5 components and mortality in Massachusetts: mixture analysis exploration.

BACKGROUND: Numerous studies have documented PM2.5's links with adverse health outcomes. Comparatively fewer studies have evaluated specific PM2.5 components. The lack of exposure measurements and high correlation among different PM2.5 components are two limitations. METHODS: We applied a novel exposure prediction model to obtain annual Census tract-level concentrations of 15 PM2.5 components (Zn, V, Si, Pb, Ni, K, Fe, Cu, Ca, Br, SO42-, NO3-, NH4+, OC, EC) in Massachusetts from 2000 to 2015, to which we matched geocoded deaths. All non-accidental mortality, cardiovascular mortality, and respiratory mortality were examined for the population aged 18 or over. Weighted quantile sum (WQS) regression models were used to examine the cumulative associations between PM2.5 components mixture and outcomes and each component's contributions to the cumulative associations. We have fit WQS models on 15 PM2.5 components and a priori identified source groups (heavy fuel oil combustion, biomass burning, crustal matter, non-tailpipe traffic source, tailpipe traffic source, secondary particles from power plants, secondary particles from agriculture, unclear source) for the 15 PM2.5 components. Total PM2.5 mass analysis and single component associations were also conducted through quasi-Poisson regression models. RESULTS: Positive cumulative associations between the components mixture and all three outcomes were observed from the WQS models. Components with large contribution to the cumulative associations included K, OC, and Fe. Biomass burning, traffic emissions, and secondary particles from power plants were identified as important source contributing to the cumulative associations. Mortality rate ratios for cardiovascular mortality were of greater magnitude than all non-accidental mortality and respiratory mortality, which is also observed in cumulative associations estimated from WQS, total PM2.5 mass analysis, and single component associations. CONCLUSION: We have found positive associations between the mixture of 15 PM2.5 components and all non-accidental mortality, cardiovascular mortality, and respiratory mortality. Among these components, Fe, K, and OC have been identified as having important contribution to the cumulative associations. The WQS results also suggests potential source effects from biomass burning, traffic emissions, and secondary particles from power plants.

PRACTICAL ASPECTS AND RESULTS OF COGNITIVE THERAPY IN THE EARLY RECOVERY PERIOD OF ISCHEMIC STROKE.

OBJECTIVE: The aim: To determine the impact of cognitive training on the degree of cognitive functions recovery and quality of life in the early recovery period of ischemic stroke. PATIENTS AND METHODS: Materials and methods: 108 patients with cerebral infarction were examined outpatiently, follow-up from 1 to 3 months from the onset of the disease. Basic assessment methods: screening index of cognitive disorders according to the Montreal Cognitive Assessment Scale (MoCA), SF-36 questionnaire. RESULTS: Results and Conclusions: Comprehensive rehabilitation measures for the early recovery period of ischemic stroke achieve improvement of the cognitive sphere: a significant increase in the average score on the Montreal scale of cognitive functions assessment (MoCA scale) in both observation groups.

Metabolomic signatures of the long-term exposure to air pollution and temperature.

BACKGROUND: Long-term exposures to air pollution has been reported to be associated with inflammation and oxidative stress. However, the underlying metabolic mechanisms remain poorly understood. OBJECTIVES: We aimed to determine the changes in the blood metabolome and thus the metabolic pathways associated with long-term exposure to outdoor air pollution and ambient temperature. METHODS: We quantified metabolites using mass-spectrometry based global untargeted metabolomic profiling of plasma samples among men from the Normative Aging Study (NAS). We estimated the association between long-term exposure to PM2.5, NO2, O3, and temperature (annual average of central site monitors) with metabolites and their associated metabolic pathways. We used multivariable linear mixed-effect regression models (LMEM) while simultaneously adjusting for the four exposures and potential confounding and correcting for multiple testing. As a reduction method for the intercorrelated metabolites (outcome), we further used an independent component analysis (ICA) and conducted LMEM with the same exposures. RESULTS: Men (N = 456) provided 648 blood samples between 2000 and 2016 in which 1158 metabolites were quantified. On average, men were 75.0 years and had an average body mass index of 27.7 kg/m2. Almost all men (97%) were not current smokers. The adjusted analysis showed statistically significant associations with several metabolites (58 metabolites with PM2.5, 15 metabolites with NO2, and 6 metabolites with temperature) while no metabolites were associated with O3. One out of five ICA factors (factor 2) was significantly associated with PM2.5. We identified eight perturbed metabolic pathways with long-term exposure to PM2.5 and temperature: glycerophospholipid, sphingolipid, glutathione, beta-alanine, propanoate, and purine metabolism, biosynthesis of unsaturated fatty acids, and taurine and hypotaurine metabolism. These pathways are related to inflammation, oxidative stress, immunity, and nucleic acid damage and repair. CONCLUSIONS: Using a global untargeted metabolomic approach, we identified several significant metabolites and metabolic pathways associated with long-term exposure to PM2.5, NO2 and temperature. This study is the largest metabolomics study of long-term air pollution, to date, the first study to report a metabolomic signature of long-term temperature exposure, and the first to use ICA in the analysis of both.

Fine Particulate Air Pollution and Birthweight: Differences in Associations Along the Birthweight Distribution.

BACKGROUND: Maternal exposure to fine particulate air pollution (PM2.5) during pregnancy is associated with lower newborn birthweight, which is a risk factor for chronic disease. Existing studies typically report the average association related with PM2.5 increase, which does not offer information about potentially varying associations at different points of the birthweight distribution. METHODS: We retrieved all birth records in Massachusetts between 2001 and 2013 then restricted our analysis to full-term live singletons (n = 775,768). Using the birthdate, gestational age, and residential address reported at time of birth, we estimated the average maternal PM2.5 exposure during pregnancy of each birth. PM2.5 predictions came from a model that incorporates satellite, land use, and meteorologic data. We applied quantile regression to quantify the association between PM2.5 and birthweight at each decile of birthweight, adjusted for individual and neighborhood covariates. We considered effect modification by indicators of individual and neighborhood socioeconomic status (SES). RESULTS: PM2.5 was negatively associated with birthweight. An interquartile range increase in PM2.5 was associated with a 16 g [95% confidence interval (CI) = 13, 19] lower birthweight on average, 19 g (95% CI = 15, 23) lower birthweight at the lowest decile of birthweight, and 14 g (95% CI = 9, 19) lower birthweight at the highest decile. In general, the magnitudes of negative associations were larger at lower deciles. We did not find evidence of effect modification by individual or neighborhood SES. CONCLUSIONS: In full-term live births, PM2.5 and birthweight were negatively associated with more severe associations at lower quantiles of birthweight.

Associations of Annual Ambient Fine Particulate Matter Mass and Components with Mitochondrial DNA Abundance.

BACKGROUND: Fine particulate matter (PM2.5) represents a mixture of components with potentially different toxicities. However, little is known about the relative effects of PM2.5 mass and PM2.5 components on mitochondrial DNA (mtDNA) abundance, which may lie on the pathway of PM2.5-associated disease. METHODS: We studied 646 elderly male participants in the Normative Aging Study from Greater Boston to investigate associations of long-term exposure to PM2.5 mass and PM2.5 components with mtDNA abundance. We estimated concentrations of pollutants for the 365-day preceding examination at each participant's address using spatial- and temporal-resolved chemical transport models. We measured blood mtDNA abundance using RT-PCR. We applied a shrinkage and selection method (adaptive LASSO) to identify components most predictive of mtDNA abundance, and fit multipollutant linear mixed-effects models with subject-specific intercept to estimate the relative effects of individual PM component. RESULTS: MtDNA abundance was negatively associated with PM2.5 mass in the previous year and-after adjusting for PM2.5 mass-several PM2.5 components, including organic carbon, sulfate (marginally), and nitrate. In multipollutant models including as independent variables PM2.5 mass and PM2.5 components selected by LASSO, nitrate was associated with mtDNA abundance. An SD increase in annual PM2.5-associated nitrate was associated with a 0.12 SD (95% confidence intervals [CI] = -0.18, -0.07) decrease in mtDNA abundance. Analyses restricted to PM2.5 annual concentration below the current 1-year U.S. Environmental Protection Agency standard produced similar results. CONCLUSIONS: Long-term exposures to PM2.5-associated nitrate were related to decreased mtDNA abundance independent of PM2.5 mass. Mass alone may not fully capture the potential of PM2.5 to oxidize the mitochondrial genome.See video abstract at, http://links.lww.com/EDE/B274.

Development of a realtime RT-PCR assay for the rapid detection of influenza A(H2) viruses.

Influenza and other acute respiratory infections are of great concern for public health, causing excessive morbidity and mortality throughout the world. Influenza virus A(H2N2), which caused a pandemic of so called "Asian flu" in 1957 was expelled from the human population by the new pandemic virus subtype H3N2 in 1968, however, influenza A(H2) viruses continue to circulate in wild birds and poultry. The lack of immunity in human population and the continued circulation of influenza A(H2) among animals makes emergence of a new pandemic virus possible. One of the basic techniques of molecular diagnostics of infectious diseases is the realtime polymerase chain reaction (PCR). The aim of this work was to design oligonucleotide primers and probes for the rapid detection of influenza A virus subtype H2 by realtime reverse transcription - polymerase chain reaction (rRT-PCR). Analysis of 539 sequences of influenza A(H2N2) virus hemagglutinin gene from GISAID EpiFlu database revealed conservative regions suitable for use as binding sites for primers and probes. 191 probes were designed and 2 sets of primers and probes (H2-1 and H2-2) were selected for further experimental evaluation. Detection limit of RT-PCR system was 50 copies of DNA per 25 µl reaction when 10-fold dilutions of pCI-neo-H2 plasmid used as template. Analytical specificity of selected sets of primers and probes were tested on wide range of influenza strains and non-influenza respiratory viruses. H2-2 set found to have insufficient specificity detecting seasonal influenza A(H1N1) viruses and was excluded from further analysis. Analytical sensitivity was further tested on vaccine strain A/17/California/66/395 (H2N2) and A/Japan/305/1957 (H2N2), limit of detection for primers-probe set H2-1 was 3.2 (CI95%: 3.07-3.48) lg EID50/ml. Designed primers and probes for the realtime RT-PCR universal detection of influenza A(H2) viruses could be used in clinical trials of vaccines against influenza A(H2) and screening for H2 in cases of unsubtypeable influenza A in humans.

Estimating daily air temperature across the Southeastern United States using high-resolution satellite data: A statistical modeling study.

Accurate estimates of spatio-temporal resolved near-surface air temperature (Ta) are crucial for environmental epidemiological studies. However, values of Ta are conventionally obtained from weather stations, which have limited spatial coverage. Satellite surface temperature (Ts) measurements offer the possibility of local exposure estimates across large domains. The Southeastern United States has different climatic conditions, more small water bodies and wetlands, and greater humidity in contrast to other regions, which add to the challenge of modeling air temperature. In this study, we incorporated satellite Ts to estimate high resolution (1km×1km) daily Ta across the southeastern USA for 2000-2014. We calibrated Ts-Ta measurements using mixed linear models, land use, and separate slopes for each day. A high out-of-sample cross-validated R(2) of 0.952 indicated excellent model performance. When satellite Ts were unavailable, linear regression on nearby monitors and spatio-temporal smoothing was used to estimate Ta. The daily Ta estimations were compared to the NASA's Modern-Era Retrospective Analysis for Research and Applications (MERRA) model. A good agreement with an R(2) of 0.969 and a mean squared prediction error (RMSPE) of 1.376°C was achieved. Our results demonstrate that Ta can be reliably predicted using this Ts-based prediction model, even in a large geographical area with topography and weather patterns varying considerably.

Heat stroke admissions during heat waves in 1,916 US counties for the period from 1999 to 2010 and their effect modifiers.

BACKGROUND: Heat stroke is a serious heat-related illness, especially among older adults. However, little is known regarding the spatiotemporal variation of heat stroke admissions during heat waves and what factors modify the adverse effects. METHODS: We conducted a large-scale national study among 23.5 million Medicare fee-for-service beneficiaries per year residing in 1,916 US counties during 1999-2010. Heat wave days, defined as a period of at least two consecutive days with temperatures exceeding the 97th percentile of that county's temperatures, were matched to non-heat wave days by county and week. We fitted random-effects Poisson regression models to estimate the relative risk (RR) of heat stroke admissions on a heat wave day as compared to a matched non-heat wave day. A variety of effect modifiers were tested including individual-level covariates, community-level covariates, meteorological conditions, and the intensity and duration of the heat wave event. RESULTS: The RR declined substantially from 71.0 (21.3-236.2) in 1999 to 3.5 (1.9-6.5) in 2010, and was highest in the northeast and lowest in the west north central regions of the US. We found a lower RR among counties with higher central air conditioning (AC) prevalence. More severe and longer-lasting heat waves had higher RRs. CONCLUSIONS: Heat stroke hospitalizations associated with heat waves declined dramatically over time, indicating increased resilience to extreme heat among older adults. Considerable risks, however, still remain through 2010, which could be addressed through public health interventions at a regional scale to further increase central AC and monitoring heat waves.

Age at menarche: 50-year socioeconomic trends among US-born black and white women.

OBJECTIVES: We investigated 50-year US trends in age at menarche by socioeconomic position (SEP) and race/ethnicity because data are scant and contradictory. METHODS: We analyzed data by income and education for US-born non-Hispanic Black and White women aged 25 to 74 years in the National Health Examination Survey (NHES) I (1959-1962), National Health Examination and Nutrition Surveys (NHANES) I-III (1971-1994), and NHANES 1999-2008. RESULTS: In NHES I, average age at menarche among White women in the 20th (lowest) versus 80th (highest) income percentiles was 0.26 years higher (95% confidence interval [CI] = -0.09, 0.61), but by NHANES 2005-2008 it had reversed and was -0.33 years lower (95% CI = -0.54, -0.11); no socioeconomic gradients occurred among Black women. The proportion with onset at younger than 11 years increased only among women with low SEP, among Blacks and Whites (P for trend < .05), and high rates of change occurred solely among Black women (all SEP strata) and low-income White women who underwent menarche before 1960. CONCLUSIONS: Trends in US age at menarche vary by SEP and race/ethnicity in ways that pose challenges to several leading clinical, public health, and social explanations for early age at menarche and that underscore why analyses must jointly include data on race/ethnicity and socioeconomic position. Future research is needed to explain these trends.

Does the association between depressive symptoms and cardiovascular mortality risk vary by race? Evidence from the Health and Retirement Study.

OBJECTIVE: To test whether the association between depressive symptoms and cardiovascular disease (CVD) mortality is stronger among Blacks than Whites. DESIGN, SETTING AND PARTICIPANTS: 2,638 Black and 15,132 White participants from a prospective, observational study of community-dwelling Health and Retirement Study participants (a nationally representative sample of U.S. adults aged > or = 50). Average follow-up was 9.2 years. OUTCOME MEASURE: Cause of death (per ICD codes) and month of death were identified from National Death Index linkages. METHODS: The associations between elevated depressive symptoms and mortality from stroke, ischemic heart disease (IHD), or total CVD were assessed using Cox proportional hazards models to estimate adjusted hazard ratios (HRs). We used interaction terms for race by depressive symptoms to assess effect modification (multiplicative scale). RESULTS: For both Whites and Blacks, depressive symptoms were associated with a significantly elevated hazard of total CVD mortality (Whites: HR=1.46; 95% CI: 1.33, 1.61; Blacks: HR=1.42, 95% CI: 1.10, 1.83). Adjusting for health and socioeconomic covariates, Whites with elevated depressive symptoms had a 13% excess hazard of CVD mortality (HR=1.13, 95% CI: 1.03, 1.25) compared to Whites without elevated depressive symptoms. The HR in Blacks was similar, although the confidence interval included the null (HR=1.12, 95% CI: .86, 1.46). The hazard associated with elevated depressive symptoms did not differ significantly by race (P>.15 for all comparisons). Patterns were similar in analyses restricted to respondents age > or =65. CONCLUSION: Clinicians should consider the depressive state of either Black or White patients as a potential CVD mortality risk factor.

Short-term air pollution and temperature exposure and changes in the extracellular microRNA profile of Normative Aging Study (NAS) participants.

BACKGROUND: While the health effects of air pollution and temperature are widely studied, the molecular effects are poorly understood. Extracellular microRNAs (ex-miRNAs) have the potential to serve as diagnostic or prognostic biomarkers and/or to act as intercellular signaling molecules that mediate the effects of environmental exposures on health outcomes. METHODS: We examined the relationship between short-term exposure to air pollution and ambient temperature and the ex-miRNA profiles of participants in the Normative Aging Study (NAS) from 1999 to 2015. Our exposures were defined as same-day, two-day, three-day, one-week, two-week, and three-week moving averages of PM2.5, NO2, O3, and temperature which were derived from high-resolution spatio-temporal models. The ex-miRNA profiles of the subjects were obtained during follow-up visits. We analyzed the data using a longitudinal quantile regression model adjusted for individual covariates, batch effects, and time trends. We adjusted for multiple comparisons using a false discovery rate (FDR) correction. Ex-miRNAs that were significantly associated with exposures were further investigated using pathway analyses. RESULTS: We found that all the examined exposures were associated with changes in ex-miRNA profiles in our study, particularly PM2.5 which was responsible for most of the statistically significant results. We found 110 statistically significant exposure-outcome relationships that revealed associations with the levels of 52 unique ex-miRNAs. Pathway analyses showed these ex-miRNAs have been linked to target mRNAs, genes, and biological mechanisms that could affect virtually every organ system, and as such may be linked to multiple clinical disease presentations such as cardiovascular disease, respiratory disease, and neurological disease. CONCLUSIONS: Air pollution and temperature exposures were significantly associated with alterations in the ex-miRNA profiles of NAS subjects with possible biological consequences.

Psychological Stress and Epigenetic Aging in Older Men: The VA Normative Aging Study.

Psychological stress remains an important risk factor for morbidity and mortality throughout the life course. However, there have been counterintuitive findings reported in previous studies of older persons that examine the relationships of perceived psychological stress with DNA methylation-based markers of aging, which also serve as predictors of morbidity and mortality (epigenetic age/clocks). We aimed to replicate and expand findings from existing work by examining relationships of self-reported stress with nine epigenetic clocks: Hannum, Horvath, Intrinsic, Extrinsic, SkinBloodClock, PhenoAge, GrimAge, DNAm Telomere Length, and Pace of Aging. We analyzed data from 607 male participants (mean age 73.2 years) of the VA Normative Aging Study with one to two study visits from 1999 to 2007 (observations = 956). Stress was assessed via the 14-item Perceived Stress Scale (PSS). Epigenetic age was calculated from DNA methylation measured in leukocytes with the HumanMethylation450 BeadChip. In linear mixed effects models adjusted for demographic/lifestyle/health factors, a standard deviation (sd) increase in PSS was associated with Horvath (ß = -0.35-years, 95%CI: -0.61, -0.09, P=0.008) and Intrinsic (ß = -0.40-years, 95%CI: -0.67, -0.13, P=0.004) epigenetic age deceleration. However, in models limited to participants with the highest levels of stress (≥ 75th-percentile), Horvath (ß = 2.29-years, 95%CI: 0.16, 4.41, P=0.04) and Intrinsic (ß = 2.06-years, 95%CI: -0.17, 4.28, P=0.07) age acceleration associations were observed. Our results reinforce the complexity of psychological stress and epigenetic aging relationships and lay a foundation for future studies that explore longitudinal relationships with other adult stress metrics and factors that can influence stress such as resilience measures.