Log Unit Increase Research Articles

Oxidized LDL, insulin sensitivity and beta-cell function in newborns

IntroductionOxidized low-density lipoprotein (OxLDL), a biomarker of oxidative stress, itself possesses proatherogenic and proinflammatory effects. Elevated circulating OxLDL levels have been consistently associated with insulin resistance and diabetes in adults....

Soluble Angiotensin-Converting Enzyme 2, Cardiac Biomarkers, Structure, and Function, and Cardiovascular Events (from the Atherosclerosis Risk in Communities Study)

Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin-angiotensin-aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels were associated with significantly higher biomarkers of cardiac injury (high-sensitivity cardiac troponin I and T, N-terminal pro-B-type natriuretic peptide), greater left ventricular mass index, and impaired diastolic function in linear regression analyses, and with increased risk for heart failure hospitalization (adjusted hazard ratio per natural log unit increase [HR] 1.32, 95% confidence interval [CI] 1.10 to 1.58), CVD events (HR 1.34, 95% CI 1.13 to 1.60), and all-cause death (HR 1.26, 95% CI 1.01 to 1.57). In an elderly biracial cohort, sACE2 was positively associated with biomarkers reflecting myocardial injury and neurohormonal activation, left ventricular mass index, impaired diastolic function, CVD, events and all-cause death.

Plasma Soluble Suppression of Tumorigenicity-2 Associates with Ventilator Liberation in Acute Hypoxemic Respiratory Failure.

Rationale: Standard physiologic assessments of extubation readiness in patients with acute hypoxemic respiratory failure (AHRF) may not reflect lung injury resolution and could adversely affect clinical decision-making and patient outcomes. Objectives: We hypothesized that elevations in inflammatory plasma biomarkers sST2 (soluble suppression of tumorigenicity-2) and IL-6 indicate ongoing lung injury in AHRF and better inform patient outcomes compared with standard clinical assessments. Methods: We measured daily plasma biomarkers and physiologic variables in 200 patients with AHRF for up to 9 days after intubation. We tested the associations of baseline values with the primary outcome of unassisted breathing at Day 29. We analyzed the ability of serial biomarker measurements to inform successful ventilator liberation. Measurements and Main Results: Baseline sST2 concentrations were higher in patients dead or mechanically ventilated versus breathing unassisted at Day 29 (491.7 ng/ml [interquartile range (IQR), 294.5-670.1 ng/ml] vs. 314.4 ng/ml [IQR, 127.5-550.1 ng/ml]; P = 0.0003). Higher sST2 concentrations over time were associated with a decreased probability of ventilator liberation (hazard ratio, 0.80 per log-unit increase; 95% confidence interval [CI], 0.75-0.83; P = 0.03). Patients with higher sST2 concentrations on the day of liberation were more likely to fail liberation compared with patients who remained successfully liberated (320.9 ng/ml [IQR, 181.1- 495.6 ng/ml] vs. 161.6 ng/ml [IQR, 95.8-292.5 ng/ml]; P = 0.002). Elevated sST2 concentrations on the day of liberation decreased the odds of successful liberation when adjusted for standard physiologic parameters (odds ratio, 0.325; 95% CI, 0.119-0.885; P = 0.03). IL-6 concentrations did not associate with outcomes. Conclusions: Using sST2 concentrations to guide ventilator management may more accurately reflect underlying lung injury and outperform traditional measures of readiness for ventilator liberation.

Sex Differences in the Risk of Coronary Heart Disease Associated With Type 2 Diabetes: A Mendelian Randomization Analysis.

OBJECTIVEObservational studies have demonstrated that type 2 diabetes is a stronger risk factor for coronary heart disease (CHD) in women compared with men. However, it is not clear whether this reflects a sex differential in the causal effect of diabetes on CHD risk or results from sex-specific residual confounding.RESEARCH DESIGN AND METHODSUsing 270 single nucleotide polymorphisms (SNPs) for type 2 diabetes identified in a type 2 diabetes genome-wide association study, we performed a sex-stratified Mendelian randomization (MR) study of type 2 diabetes and CHD using individual participant data in UK Biobank (251,420 women and 212,049 men). Weighted median, MR-Egger, MR-pleiotropy residual sum and outlier, and radial MR from summary-level analyses were used for pleiotropy assessment.RESULTSMR analyses showed that genetic risk of type 2 diabetes increased the odds of CHD for women (odds ratio 1.13 [95% CI 1.08–1.18] per 1-log unit increase in odds of type 2 diabetes) and men (1.21 [1.17–1.26] per 1-log unit increase in odds of type 2 diabetes). Sensitivity analyses showed some evidence of directional pleiotropy; however, results were similar after correction for outlier SNPs.CONCLUSIONSThis MR analysis supports a causal effect of genetic liability to type 2 diabetes on risk of CHD that is not stronger for women than men. Assuming a lack of bias, these findings suggest that the prevention and management of type 2 diabetes for CHD risk reduction is of equal priority in both sexes.

Standing activity as assessed by seismic accelerometers and cognitive function in community‐dwelling older adults: The MIND trial

AbstractBackgroundFew older adults are able to achieve recommended levels of moderate‐vigorous physical activity despite known cognitive benefits. Alternatively, small movements, such as increasing movement while standing during usual tasks, can easily be integrated into daily routines by older adults. However, standing activity is best assessed with specific devices (i.e., seismic accelerometers). No existing study of older adults has examined the impact of device‐measured standing activity on cognition. Therefore, the purpose of this secondary analysis is to examine the association between standing activity (as measured by a seismic accelerometer) and cognition in cognitively healthy older adults.MethodParticipants were 98 cognitively healthy adult participants aged 65 years or older with family history of dementia from the ongoing MIND trial (NCT02817074), which tests the effects of a 3‐year diet intervention on cognitive decline. Exclusion criteria included diagnosis or symptoms of mild cognitive impairment or dementia. Linear regression analyses tested cross‐sectional associations between standing intensity and cognition. Standing activities were mean intensity of standing and static activities (sum of standing and shuffling) assessed by the MoveMonitor+ accelerometer/gyroscope. Cognition was composed of 4 cognitive domains constructed from 12 cognitive performance tests.ResultParticipants were on average 69.7 years old (SD=3.7), 69.4% women, and 73.5% had a college degree or higher. Both higher mean intensity of standing activity and static activity were significantly associated with higher levels of executive functioning and perceptual speed in models adjusted for age, gender, and education. Each log unit increase in standing activity intensity was associated with 0.77 units higher of executive function (p=.041), and 0.85 units higher of perceptual speed (p=.032). For static activities, significant log unit increases were 0.86 (p=.009) for executive function and 0.96 (p=.006) for perceptual speed. When we additionally adjusted for time spent in moderate‐vigorous physical activity and cognitive activity, the positive associations between higher intensity of standing and static activity and perceptual speed remained.ConclusionThese findings suggest the importance of considering intensity of standing activity in cognition. The relationships should be further explored in longitudinal analyses and interventions that incorporate small changes to daily routines in addition to promoting moderate‐vigorous physical activity.

Abstract 13514: Gender-Stratified Difference in the Association Between Coronary Artery Calcium and Incident Peripheral Artery Disease: The Multi-Ethnic Study of Atherosclerosis

Introduction: Coronary artery calcium score (CACs) measured by non-contrast cardiac CT has a strong correlation with coronary atherosclerotic burden. Although CACs predicts incident coronary heart disease, its gender-specific association with incident peripheral artery disease (PAD) is not clear. Methods: The multi-ethnic study of atherosclerosis (MESA) is a prospective population-based cohort consisting of 6814 men and female free of overt cardiovascular disease at enrollment. In this study we included MESA participants with baseline CACs and at least one ankle brachial index (ABI) measured at follow up exams. We excluded participants with baseline ABI≤ 0.9 or> 1.4. Incident PAD was defined as a follow up ABI≤ 0.9 and decline of ≥15%. Multivariable logistic regression models were deployed to evaluate the association between baseline CACs and incident PAD in female and male. Results: The mean age (SD) was 61.29 (9.96) years and 52.6% (3013/5725) were female. Female had lower baseline ABI [1.10 (0.08) vs 1.15 (0.09); p < 0.001]. Over a median (IQR) of 9.23 (8.22-9.60) years, 113(4%) female and 85(3%) male developed PAD. Every one unit increase in log (CACs+1) was associated with 1.11-fold higher odds of incident PAD in male (p=0.001). This association remained significant after adjustment for demographics, traditional cardiovascular risk factor and baseline ABI. Male participants with CACs>300 showed 1.94-fold higher odds of incident PAD compared to participant with CACs=0 (p=0.005). In female there was no statistically significant association between CACs and incident PAD in multivariable analysis. Conclusions: Baseline CACs is associated with future PAD independent of traditional cardiovascular risk factors in male participants of a multi-ethnic cohort. Disclaimer statement: The views expressed in this abstract are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.

Abstract 14093: High-Sensitivity C-reactive Protein Modifies the Effect of Lipoprotein (a) on Cardiovascular Risk: The Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Lipoprotein (a) (Lp(a)) and inflammation, as represented by elevated high-sensitivity C-reactive protein (hsCRP) concentration, are both considered as risk-enhancers in the 2018 AHA/ACC Cholesterol guidelines. However, little is known as to whether the association of Lp(a) with atherosclerotic cardiovascular disease (ASCVD) risk is modified by inflammation. Objective: We assessed whether hsCRP modifies the association of Lp(a) with ASCVD risk. Methods: MESA participants with baseline hsCRP and Lp(a) levels were included. Incident ASCVD events were ascertained from baseline through 2017. Time to incident ASCVD was analyzed using Kaplan Meir curves. Cox proportional hazards models were used to assess the association between Lp(a), hsCRP, and time to ASCVD events adjusting for covariates. Results: The study included 4,654 participants with mean age of 62 and 52.5% females (1,702 Caucasians, 557 Chinese Americans, 1,336 African Americans and 1,059 Hispanics). With a mean 13.6-year follow-up, 676 ASCVD events occurred among 4,609 participants (Figure 1). In participants with hsCRP <2mg/L, the association of Lp(a) (per 1 Log unit increase) and risk for ASCVD as represented by hazard ratio (HR) and 95%CI was 1.01 (0.79, 1.28). In subjects with hsCRP ≥2mg/L, the risk increased to 1.26 (1.01, 1.58). When compared to the reference group with Lp(a) <50mg/dL and hsCRP <2mg/L, the risk for ASCVD in participants with Lp(a) ≥50mg/dL and hsCRP <2mg/L was 1.13 (0.85, 1.50) and in those with Lp(a) <50mg/dL and hsCRP ≥2mg/L was 1.09 (0.92, 1.31). The risk increased significantly to 1.62 (1.26, 2.07) in participants with Lp(a) ≥50mg/dL and hsCRP ≥2mg/L. Conclusions: Lp(a)-related ASCVD risk is modified by hsCRP levels. The findings of this analysis suggest that Lp(a) may serve as a risk enhancing factor in individuals with hsCRP level ≥2mg/L. Future studies are needed to determine whether Lp(a) is associated with risk of ASCVD in the absence of subclinical inflammation.

Abstract 14054: Soluble ACE2, Cardiac Biomarkers, Structure, Function and Events: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Membrane-bound angiotensin-converting enzyme 2 (ACE2) has been identified to a have prominent role in SARS-COV-2 infection and is an important counter-regulator of renin-angiotensin system. But the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) remains unclear. We sought to identify the association of sACE2 with cardiac biomarkers, structure, function and events in the Atherosclerosis Risk in Communities (ARIC) Study. Methods: sACE2 was measured in a subset of 497 patients from a case-control study of incident heart failure (HF) at visit 5 (2011-2013), mean age 78 (SD 5.4), 53% men and 27% black. We used linear regression to evaluate the associations of sACE2 with cardiac biomarkers (hs-cTnI, hs-cTnT, NT-proBNP) and echocardiographic parameters. We used Cox regression to evaluate associations of sACE2 with risk of HF hospitalization, global CVD events (CHD, ischemic stroke or HF hospitalization) and all-cause death. Results: Over a median follow up of 6.1 (4.6, 6.8) years, 282 global CVD events and 190 all-cause deaths occurred. sACE2 levels were higher in men, blacks, those with prevalent CVD, diabetes and hypertension. Higher sACE2 levels were associated with significantly higher hs-cTnI, hs-cTnT, NT-proBNP levels, greater left ventricular (LV) mass index, impaired diastolic function ( Table ) and increased risk for HF hospitalization (adjusted HR 1.32 per log unit increase, 95% CI 1.10-1.58), global CVD events (HR 1.34, 95% CI 1.13-1.60) and all-cause death (HR 1.26, 95% CI 1.01-1.57). Conclusions: In an elderly biracial cohort, sACE2 was positively associated with biomarkers reflecting myocardial injury and neurohormonal activation, LV mass index, impaired diastolic function, CVD events and all-cause death. Future research is needed to elucidate the significance of sACE2 in development of CVD, not only in patients with SAR—COV2 infection, but the general population

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and birth outcomes: A longitudinal cohort with repeated measurements

BackgroundPrevious studies on perfluoroalkyl and polyfluoroalkyl substances (PFAS) showed inconsistent results when biological samples were collected in different time of pregnancy. ObjectivesTo describe the change of PFAS concentration during pregnancy and to identify a sensitive window for adverse effects of PFAS on the fetus. MethodsA total of 255 pregnant women were selected from the Shanghai Birth Cohort (SBC). We quantified 10 PFAS with high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) in maternal plasma at three trimesters and cord blood at delivery. Multiple linear regression analyses were used to analyze the association between PFAS and birth outcomes, including birth weight, birth length, and head circumference. ResultsThe concentrations of most PFAS declined substantially during pregnancy. PFOS, PFNA, PFDA, PFUA and PFDoA were negatively related to birth length only in the first trimester. The coefficients and 95% confidence intervals (CI) of birth length change with a log-unit increase in PFOS, PFNA, PFDA, PFUS and PFDoA concentrations were −0.27 cm (−0.51, −0.02), −0.34 cm (−0.65, −0.03), −0.27 cm (−0.53, −0.01), −0.29 cm (−0.58, −0.01), and −0.54 cm (−1.00, −0.08), respectively. The effects were only observed for female fetuses. No association between PFAS and birth weight or head circumference was observed. ConclusionThe concentrations of most PFAS in the maternal circulation declined during pregnancy. There were negative associations between several PFAS and birth length. The sensitive window of exposure appeared to be the first trimester. The association was stronger for female fetuses.

Urinary parabens and their mixture in relation to fecundability among a cohort of women with prior pregnancy loss

Background/Aim: Parabens are antimicrobial preservatives with widespread exposure, and may affect endocrine function. Few studies have evaluated their influence on fecundability. Our aim was to determine the association between parabens and fecundability among a cohort of women with one or two prior pregnancy losses who were trying to conceive. Methods: The EAGeR trial followed women who were trying to conceive for up to 6 cycles. Six parabens (benzyl, butyl, ethyl, heptyl, methyl, propyl) and four paraben metabolites (OH-methyl, OH-ethyl, 4-hydroxybenzoic acid [4-HB] and 3,4-dihydroxybenzoic acid [3,4-DHB]) were measured as pools combining three consecutive days of spot urine samples, at baseline, from 1185 women. Urinary creatinine was measured on day 1 of the pool. Fecundability, defined as time to pregnancy, was measured as number of menstrual cycles to achieve hCG positive pregnancy. Fecundability odds ratios (FORs) were determined by discrete-time survival analysis to model the association between fecundability and each chemical, adjusting for age, race/ethnicity, body mass index, creatinine, nulliparity and smoking, and accounting for left truncation (time trying prior to study enrollment). Quantile g-computation was used to estimate the effect of increasing all parabens by one quantile, in relation to fecundability. Results: Parabens were weakly (ethyl:heptyl rho -0.04) to highly (propyl:methyl rho 0.82) correlated with each other. Results were largely null in single chemical models, for example, butyl paraben FOR=0.99, 95% CI 0.95-1.03, per 1-log unit increase. Propyl paraben was marginally associated with reduced fecundability (FOR=0.96, 95% CI 0.92-1.01) and heptyl paraben with increased fecundability (FOR=1.15, 95% CI 1.00-1.33). Together as a mixture, parabens were not associated with fecundability (FOR=0.91, 95% CI 0.77-1.08).Conclusion: In single chemical models and as a mixture, most parabens were not associated with fecundability. While this is reassuring, given the high exposure prevalence, future studies should consider mixtures across endocrine disrupting chemical classes.

Phthalate Exposure and Respiratory Diseases Among Adults and Children: the US NHANES 2007-2016

Background/Aim: Phthalates are used as plasticizers in many consumer products. Although they have associations with multiple adverse health outcomes, studies on phthalate exposure and respiratory outcomes are limited. The objective of our study was to examine the association between phthalate exposure and respiratory diseases in the US population. Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016, we analyzed the data on twelve urinary metabolites and current respiratory diseases (asthma, bronchitis, and emphysema) among adults (≥ 20 years of age) and children and adolescents (6-19 years of age). The logistic regression was conducted to estimate the odds ratios (ORs) per one log10 unit increase in the concentration of urinary phthalate metabolites, and age, gender, race, waist/height ratio, urinary creatinine, serum cotinine level, and poverty index ratio were included in the model for adjustment. Analyses were conducted separately on children and adults to investigate the difference by age. Results: In adults, mono-benzyl phthalate (MBzP) was positively associated with asthma and chronic bronchitis (OR 1.34; 95% CI 1.11-1.61 and OR 1.39; 95% CI 1.02-1.91). Mono-(3-carboxypropyl) phthalate and mono-(carboxynonyl) phthalate also showed the significant associations with chronic bronchitis (OR 1.38; 95% CI 1.04-1.84 and OR 1.44; 95% 1.03-2.02). Although there was a trend with elevated risk between low-molecular-weight phthalates and emphysema, it was not significant (OR 1.26; 95% CI 0.98-1.62 for mono-ethyl phthalate, and OR 1.28; 95% CI 0.80-2.04 for mono-isobutyl phthalate). In children and adolescents, no evidence of associations between phthalates and asthma was found. Conclusion: Our cross-sectional study advocates for the positive associations of high-molecular -weight phthalate metabolites with respiratory diseases among adults. However, in children, the evidence of such association was absent, for which further analysis and research are recommended.

Methods for accounting for urine dilution in arsenic analyses: comparisons to blood arsenic

Background. Arsenic (As) exposure remains ubiquitous affecting hundreds of millions of people worldwide. Urinary As (uAs) is an established biomarker of As exposure; urinary creatinine (uCr), a breakdown product of creatine phosphate in muscle, is excreted constantly via urine and commonly used to correct uAs for urine dilution. However, uCr levels are influenced by meat intake, muscle mass, and other factors that may also be related to As elimination. Alternative methods utilize specific gravity, which has limitations in individuals with kidney damage and diabetes. We compared uAs corrected for uCr and specific gravity vs. blood As (bAs), an increasingly used biomarker of As exposure that is unaffected by hydration status. Methods. We examined 539 participants from the Folic Acid and Creatine Trial (FACT) study to analyze the relationship between log-transformed total bAs and log-transformed uAs with adjustments for age, sex, and BMI, with further adjustments for uCr or specific gravity in separate models. Results. Median (IQR) uAs and bAs were 112.8 (133.6) and 8.41 (5.88) µg/L, respectively. Urinary creatinine and specific gravity were highly correlated with each other (Spearman correlation = 0.86, p < 0.001). Regression models revealed that a log 10-unit increase in total bAs concentrations was related to 0.69, 0.72, and 0.57 increases in log-10 uAs when unadjusted for dilution factors, adjusted for uCr, and adjusted for specific gravity, respectively (p < 0.001). Conclusions. We compared uAs to bAs to identify which strategy for urine dilution adjustment is appropriate in epidemiologic research and found that uCr outperforms specific gravity in predicting bAs in a Bangladeshi population exposed to high As levels in drinking water. More studies are needed in populations with different sociodemographic characteristics and levels of As exposure to evaluate the consistency of the findings and the optimization of urine dilution adjustment methods in As-related research.

Prenatal organophosphate flame retardant exposure and the odds of small- and large-for-gestational age births

Background: Deviations in normal fetal growth trajectories may predispose infants to adverse outcomes later in life, such as cardio-metabolic disorders and decreased intellectual performance during childhood. Environmental exposures, including commonly used organophosphate flame retardants (OPFRs), have the ability to disturb normal hormonal and metabolic processes during pregnancy; however, associations with fetal growth have been minimally examined in human populations. Methods: Using a pilot case-control study, we investigated the association between 9 OPFRs and the odds of small-for (SGA) and large-for-gestational age (LGA) births. Concentrations of OPFRs were measured in maternal urine collected from three study visits during pregnancy using high performance liquid chromatography-tandem mass spectrometry. SGA (<10th percentile birth weight-for-gestational age, n = 30), LGA (>90th percentile, n = 30), and control (10th - 90th percentile, n = 30) births were selected from the LIFECODES birth cohort study. Odds ratios (OR) and 95% confidence intervals (95% CI) for associations between average OPFR concentrations over pregnancy and SGA and LGA were estimated using multinomial logistic regression. Results: Among the 9 urinary OPFRs measured, only bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate (DPHP) were detected in at least 85% of the participants at each study visit. After adjusting for potential confounders, we observed inverse associations between BDCPP and DPHP concentrations and odds of delivering an LGA baby. For example, a log-unit increase in BDCPP was associated with an OR (95% CI) of 0.37 (0.16, 0.84). All associations between OPFR concentrations and SGA were null. Conclusions: In a pilot study of prenatal OPFR exposure and fetal growth, urinary OPFR concentrations were associated with reduced odds of delivering LGA. While no associations with the SGA group were observed, these findings are consistent with previous observations that OPFRs are associated with lower measures of fetal growth and warrant additional investigation in future work.

Associations between bisphenols, benzophenones, and chlorophenols with fecundability modified by dietary phenols

Background/Aim: Antioxidant dietary phenols, which are abundant in vegetables, fruits, and herbs, may ameliorate adverse associations between environmental phenols (found in food packaging, UV filters, herbicides, and disinfectants) and reproductive outcomes as they exert protective effects. We therefore evaluated whether dietary phenols modified the relationship between environmental phenols and fecundability.Methods: In a prospective cohort study following 1,228 women for up to 6 menstrual cycles while trying to conceive (United States, 2007-2011), concentrations of dietary phenols, bisphenols, benzophenones, and chlorophenols were measured in urine at baseline. Pregnancy was assessed using urine hCG. We used discrete Cox regression to examine how low-to-moderate (<75th percentile) versus high (≥75th percentile) levels of dietary phenols modified associations between environmental phenols and fecundability, adjusting for potential confounders.Results: Bisphenol-S was associated with reduced fecundability (fecundability odds ratio [FOR] 0.95, 95% confidence interval [CI] 0.90, 1.00, per log-unit increase), independent of dietary phenols, though other phenols were not associated with fecundability. Selected environmental phenols were associated with reduced fecundability in women with low-to-moderate dietary phenols but not in women with higher dietary phenols. Specifically, bisphenol-A was associated with reduced fecundability in women with low-to-moderate gallic acid (FOR 0.90, 95% CI 0.81, 1.01). 4-hydroxybenzophenone was associated with reduced fecundability in women with low-to-moderate versus high 3,4-dihydroxyphenylacetic acid (FOR 0.90, 95% CI 0.83, 0.97 versus FOR 0.87, 95% CI 0.69, 1.11, respectively) and caffeic acid (FOR 0.88, 95% CI 0.82, 0.96 versus FOR 1.18, 95% CI 0.94, 1.48, respectively). For pentachlorophenol, reduced fecundability was observed in women with low-to-moderate 3-hydroxybenzoic acid (FOR 0.90, 95% CI 0.81, 1.00) and gallic acid (FOR 0.89, 95% CI 0.81, 0.99).Conclusions: Consumption of dietary phenols may help mitigate the adverse effect of selected environmental phenols on fecundability, highlighting the potential interplay between diet and environmental exposures among women attempting pregnancy.

Prenatal exposure to organophosphate pesticides and executive function in the Norwegian Mother, Father and Child Cohort

Organophosphate pesticides (OPP) cause acute toxicity by inhibiting acetylcholinesterase, however neurodevelopmental effects have been found at relatively low exposure concentrations. Contamination of conventionally-grown produce with OPPs remains an important exposure route for the general population due to agricultural spraying. Previous research suggests a relationship between prenatal exposure and executive functions (EF), but no studies have performed a detailed assessment inclusive of rater and performance-based measures. Methods: We used data from the preschool ADHD sub-substudy of the Norwegian Mother, Father, and Child Cohort Study. 262 preschool children with clinical or subclinical ADHD symptoms and 78 typically developing children underwent an on-site evaluation including the Stanford-Binet nonverbal and verbal working memory (WM), the NEPSY-II statue test, and the cookie delay task. Rating-based assessments were the parent-rated Child Behavior Questionnaire (CBQ) and the parent- and preschool teacher-rated Behavior Rating Inventory of Executive Function (BRIEF). Non-specific OPP exposure was estimated by measuring total diethyl (∑DEP) and dimethylphosphate (∑DMP) metabolites in urine collected at 17-18 weeks’ gestation. Change in EF z-score (β) and 95% confidence intervals (CI) per log-unit increase in specific gravity standardized exposure was estimated using multivariable linear regression with adjustment for dietary factors and other covariates. Results: There was no consistent pattern of association between log-∑DEP or ∑DMP and performance-based assessments and parent CBQ and BRIEF measures. However, log-∑DMP was associated with more adverse scores on teacher BRIEF scales among preschool children with symptoms of ADHD (emotional control: β=-0.27, 95% CI: -0.53, 0.00; inhibition: β=-0.21, 95% CI: -0.48, 0.05; WM: β=-0.14, 95% CI: -0.41, 0.13) and typically developing children (emotional control: β=-0.27, 95% CI: -0.63, 0.10; inhibition: β=-0.31, 95% CI: -0.68, 0.06; WM: β=-0.34, 95% CI: -0.68, 0.00). Conclusion: We found some evidence that prenatal log-∑DMP was associated with more adverse EF in a population experiencing primarily dietary exposure.

Indoor endotoxin, proximity to a major roadway, and severe asthma exacerbations among children in Puerto Rico

BackgroundFew studies have examined concurrent exposure to household endotoxin and traffic-related air pollution in relation to childhood asthma, yet both factors are associated with asthma outcomes. ObjectiveTo examine whether proximity to a major roadway (a traffic-related air pollution proxy) modifies the estimated effects of indoor endotoxin on asthma outcomes in children. MethodsCross-sectional study of 200 children with asthma (ages, 6-14 years) living in Puerto Rico. Residential distance to a major roadway was calculated as the distance from the participant’s residential US census block centroid to the nearest major road. The outcomes of interest were severe asthma exacerbations, missed school days for asthma, atopy, lung function, and bronchodilator response (BDR). Logistic, linear, or negative binomial regression was used for the multivariable analysis. ResultsIn the multivariable analysis, there was an interaction between indoor endotoxin and residential distance to a roadway on severe asthma exacerbations (P = .02) and BDR (P = .07). In an analysis stratified by distance to a roadway, each log10-unit increase in endotoxin was associated with 4.21 times increased odds of severe asthma exacerbations among children living within 499 m (the lower 3 quartiles of residential distance) to a road (95% confidence interval, 1.5-12.0). Among subjects living further than 499 m away from a roadway, each log10-unit increase in endotoxin was associated with reduced odds of severe asthma exacerbations (odds ratio, 0.03; 95% confidence interval, 0.001-0.67). Similar but less substantial findings were observed for BDR. ConclusionOur findings suggest that residential proximity to a major road modifies the estimated effect of endotoxin on severe asthma exacerbations in children.

Prognostic utility of triglyceride-rich lipoprotein-related markers in patients with coronary artery disease

TG-rich lipoprotein (TRL)-related biomarkers, including TRL-cholesterol (TRL-C), remnant-like lipoprotein particle-cholesterol (RLP-C), and apoC-III have been associated with atherosclerosis. However, their prognostic values have not been fully determined, especially in patients with previous CAD. This study aimed to examine the associations of TRL-C, RLP-C, and apoC-III with incident cardiovascular events (CVEs) in the setting of secondary prevention of CAD. Plasma TRL-C, RLP-C, and total apoC-III were directly measured. A total of 4,355 participants with angiographically confirmed CAD were followed up for the occurrence of CVEs. During a median follow-up period of 5.1 years (interquartile range: 3.9-6.4 years), 543 (12.5%) events occurred. Patients with incident CVEs had significantly higher levels of TRL-C, RLP-C, and apoC-III than those without events. Multivariable Cox analysis indicated that a log unit increase in TRL-C, RLP-C, and apoC-III increased the risk of CVEs by 49% (95% CI: 1.16-1.93), 21% (95% CI: 1.09-1.35), and 40% (95% CI: 1.11-1.77), respectively. High TRL-C, RLP-C, and apoC-III were also independent predictors of CVEs in individuals with LDL-C levels ≤1.8 mmol/l (n = 1,068). The addition of RLP-C level to a prediction model resulted in a significant increase in discrimination, and all three TRL biomarkers improved risk reclassification. Thus, TRL-C, RLP-C, and apoC-III levels were independently associated with incident CVEs in Chinese CAD patients undergoing statin therapy.

Concentrations of perfluoroalkyl and polyfluoroalkyl substances and blood glucose in pregnant women

BackgroundEvidence on the association between exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) and blood glucose concentrations in pregnant women is inconsistent. This study aimed to examine the association between PFAS exposure and the concentrations of fasting plasma glucose (FPG) and one-hour plasma glucose (1 h-PG) after a 50-g oral glucose tolerance test in pregnant women.MethodsThe study was based on the Shanghai-Minhang Birth Cohort, in which 1292 pregnant women were recruited. Among them, 981 women provided blood samples (at 12–16 gestational weeks) for PFAS measurement. FPG data collected from 856 women at 12–20 GW and 1 h-PG data collected from 705 women at 20–28 GW were obtained through medical records from the routine prenatal care system. High FPG or 1 h-PG was defined as ≥90th percentile of FPG or 1 h-PG. The analysis of eight PFASs was conducted in this study: perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), and perfluorotridecanoic acid (PFTrDA). The odds ratios (ORs) and associated 95% confidence intervals (CIs) were estimated to determine the associations of each PFAS compound with high FPG and 1 h-PG from a logistic regression model.ResultsAfter adjustment for potential confounders, most PFASs were positively associated with high 1 h-PG concentrations. The OR for high 1 h-PG concentrations was 1.87 (95% CI: 1.15–3.05) with a one log unit increase of PFOS; similar associations were observed for PFNA (OR: 2.15, 95% CI: 1.24–3.74), PFDA (OR: 1.61, 95% CI: 1.10–2.44), PFUdA (OR: 1.71, 95% CI: 1.12–2.62), and PFDoA (OR: 1.34, 95% CI: 1.00–1.81). When the PFAS concentrations were categorized into three groups by tertiles, the highest tertiles of PFOS, PFOA, PFNA, PFDA, PFDoA, and PFTrDA had a statistically significant increase in the risk of high 1 h-PG concentrations compared with the lowest tertiles. No statistically significant association was observed between PFAS exposure and high FPG.ConclusionPFAS exposure was associated with an increased risk of high 1 h-PG among pregnant women, but no such association was observed for FPG.

Association between prenatal bisphenol a exposure and promoter hypermethylation of CAPS2, TNFRSF25, and HKR1 genes in cord blood

In utero exposure to bisphenol A (BPA) in early stages of development has been reported to exert adverse health effects on offspring later in life. Epigenetic alterations, particularly DNA methylation, may be one plausible biological mechanism involved. We examined the association between maternal BPA exposure and DNA methylation in cord blood. We randomly selected 96 paired samples of maternal urine and infant cord blood collected from the Shanghai-Minhang Birth Cohort. BPA levels in maternal urine were measured using high-performance liquid chromatography (HPLC). Three cord blood samples with maternal BPA levels >2.0 μg/g Cr and three samples with undetected BPA were randomly selected for genome-wide methylation analysis using methylated DNA binding domain sequencing (MBD-Seq). The genes with hypermethylated promoter regions were chosen for validation using quantitative methylation-specific polymerase chain reaction (Q-MSP). Based on MBD-seq results, we observed that maternal BPA exposure was primarily associated with hypermethylation of genes involved in signal transduction in the nervous system. Using Q-MSP, we further validated the association between maternal BPA exposure and promoter hypermethylation of three genes in multiple linear regression models: a log unit increase in BPA was associated with 12.63% (95%CI: 7.99, 17.26), 11.17%, (95%CI: 3.31, 19.02), and 16.57% (95% CI: 10.59, 22.56) increase in promoter of CAPS2, TNFRSF25, and HKR1 methylation, respectively. Our findings provide evidence that in utero exposure to BPA could alter the offspring's epigenome by altering DNA methylation pattern.

Exposures to phthalates and bisphenols in pregnancy and postpartum weight gain in a population-based longitudinal birth cohort

BackgroundExperimental evidence suggests that exposures to phthalates and bisphenols may interfere with processes related to glucose and lipid metabolism, insulin sensitivity, and body weight. Few studies have considered the possible influence of chemical exposures during pregnancy on maternal weight gain or metabolic health outcomes postpartum. ObjectiveTo examine the associations of early and mid-pregnancy bisphenol and phthalate urine concentrations with maternal weight gain 6 years postpartum. MethodsWe analyzed urine samples for bisphenol, phthalate and creatinine concentrations from early and mid-pregnancy in 1192 women in a large, population-based birth cohort in Rotterdam, the Netherlands, and examined postpartum weight gain using maternal anthropometrics before pregnancy and 6 years postpartum. We have used covariate-adjusted linear regressions to evaluate associations of early and mid-pregnancy bisphenols and phthalate metabolites with weight change. Mediator and interaction models have been used to assess the role of gestational weight gain and breastfeeding, respectively. Sensitivity analysis is performed among women without subsequent pregnancies. ResultsAmong all 1192 mothers included in the analysis, each log unit increase in the average bisphenol A and all assessed phthalate groupings were associated with increased maternal weight gain. As a proxy for phthalate exposure, each log unit increase in averaged phthalic acid was associated with 734 g weight gain (95% CI 273–1196 g) between pre-pregnancy and 6 years postpartum. Mediation by gestational weight gain was not present. Breastfeeding and ethnicity did not modify the effects. Stratification revealed these associations to be strongest among overweight and obese women. Among women without subsequent pregnancies (n = 373) associations of bisphenols, HMW phthalate metabolites and di-2-ethylhexylphthalate metabolites attenuated. For phthalic acid, LMW phthalate metabolites and di-n-octylphthalate metabolites associations increased. Similarly to the whole group, stratification yielded significant results among overweight and obese women. DiscussionIn a large population-based birth cohort, early and mid-pregnancy phthalate exposures are associated with weight gain 6 years postpartum, particularly among overweight and obese women. These data support ongoing action to replace phthalates with safer alternatives.