Arsenic exposure and human blood DNA methylation and hydroxymethylation profiles in two diverse populations from Bangladesh and Spain.

BACKGROUND: Associations of arsenic (As) with the sum of 5-mC and 5-hmC levels have been reported; however, As exposure-related differences of the separated 5-mC and 5-hmC markers have rarely been studied. METHODS: In this study, we evaluated the association of arsenic exposure biomarkers and 5-mC and 5-hmC in 30 healthy men (43-55 years) from the Aragon Workers Health Study (AWHS) (Spain) and 31 healthy men (31-50 years) from the Folic Acid and Creatinine Trial (FACT) (Bangladesh). We conducted 5-mC and 5-hmC profiling using Infinium MethylationEPIC arrays, on paired standard and modified (ox-BS in AWHS and TAB in FACT) bisulfite converted blood DNA samples. RESULTS: The median for the sum of urine inorganic and methylated As species (ΣAs) (µg/L) was 12.5 for AWHS and 89.6 for FACT. The median of blood As (µg/L) was 8.8 for AWHS and 10.2 for FACT. At a statistical significance p-value cut-off of 0.01, the differentially methylated (DMP) and hydroxymethylated (DHP) positions were mostly located in different genomic sites. Several DMPs and DHPs were consistently found in AWHS and FACT both for urine ΣAs and blood models, being of special interest those attributed to the DIP2C gene. Three DMPs (annotated to CLEC12A) for AWHS and one DHP (annotated to NPLOC4) for FACT remained statistically significant after false discovery rate (FDR) correction. Pathways related to chronic diseases including cardiovascular, cancer and neurological were enriched. CONCLUSIONS: While we identified common 5-hmC and 5-mC signatures in two populations exposed to varying levels of inorganic As, differences in As-related epigenetic sites across the study populations may additionally reflect low and high As-specific associations. This work contributes a deeper understanding of potential epigenetic dysregulations of As. However, further research is needed to confirm biological consequences associated with DIP2C epigenetic regulation and to investigate the role of 5-hmC and 5-mC separately in As-induced health disorders at different exposure levels.

Work Shift, Lifestyle Factors, and Subclinical Atherosclerosis in Spanish Male Workers: A Mediation Analysis.

(1) Background: Working night shifts has been associated with altered circadian rhythms, lifestyle habits, and cardiometabolic risks. No information on the potential association of working shift and the presence of atherosclerosis is available. The aim of this study was to quantify the association between different work shifts and the presence of subclinical atherosclerosis objectively measured by imaging. (2) Methods: Analyses were conducted on the baseline data of the Aragon Workers Health Study (AWHS) cohort, including information on 2459 middle-aged men. Categories of shift work included central day shift, rotating morning-evening or morning-evening-night shift, and night shift. The presence of atherosclerotic plaques was assessed by 2D ultrasound in the carotid and femoral vascular territories. Multivariable logistic models and mediation analysis were conducted to characterize and quantify the association between study variables. (3) Results: Participants working night or rotating shifts presented an overall worse cardiometabolic risk profile, as well as more detrimental lifestyle habits. Workers in the most intense (morning-evening-night) rotating shift presented higher odds of subclinical atherosclerosis (odds ratio: 1.6; 95% confidence interval: 1.12 to 2.27) compared to workers in the central shift, independently of the presence of lifestyle and metabolic risk factors. A considerable (21%) proportion of this association was found to be mediated by smoking, indicating that altered sleep-wake cycles have a direct relationship with the early presence of atherosclerotic lesions. (4) Conclusions: Work shifts should be factored in during workers health examinations, and when developing effective workplace wellness programs.

The additive effect of adherence to multiple healthy lifestyles on subclinical atherosclerosis: Insights from the AWHS.

BACKGROUND: Public health strategies targeting multiple healthy behaviors, rather than individual factors, have been proposed as more efficient strategies to promote cardiovascular health. However, the additive effect of multiple targets on primary prevention has not been fully characterized. OBJECTIVE: To examine how adherence to multiple healthy behaviors is associated with the presence of subclinical atherosclerosis, a measure of early cardiovascular disease. METHODS: Analysis of a baseline data from 1798 middle-aged men from the Aragon Workers Health Study conducted between 2009 and 2010. Healthy behaviors were defined according to American Heart Association recommendations, aligned with Spanish Nutritional recommendations and included moderate alcohol consumption, smoking abstinence, no abdominal adiposity, decreased sedentarism, and adherence to Alternate Mediterranean Dietary Index. Presence of coronary artery calcium and plaques in femoral and carotid was quantified by a 16-slice computed tomography scanner and 2D ultrasound. RESULTS: Moderate alcohol consumption, as well as adherence to Mediterranean diet is independently associated with a 6% lower risk of having subclinical atherosclerosis. Smoking abstinence is associated with a 11% lower risk of subclinical atherosclerosis. Those who follow 3 lifestyle behaviors (Mediterranean diet, nonsmoking, and moderate alcohol intake) have 18% lower odds of presenting subclinical atherosclerosis compared with those who do not follow these protective lifestyle habits. CONCLUSION: Adoption of multiple healthy lifestyle behaviors early in life could be a key strategy to tackle the onset of atherosclerosis and reduce cardiovascular disease burden.

Influence of cardiovascular condition on retinal and retinal nerve fiber layer measurements.

OBJECTIVE: To assess changes in the retinal nerve fiber layer (RNFL) and macula in subjects with cardiovascular risk factors or subclinical ischemia. DESIGN: Prospective and observational study. METHODS: A total of 152 healthy men underwent cardiovascular examination, including quantification of subclinical atheroma plaques by artery ultrasound scans, blood analysis, and a complete ophthalmic evaluation, including spectral-domain optical coherence tomography. The variables registered in cardiovascular examination were quantification of classic major risk factors, subclinical atheroma plaques by artery ultrasound scans, and analytical records. The ophthalmic evaluation registered RNFL and macular thickness. RESULTS: Mean subject age was 51.27±3.71 years. The 40 subjects without classic cardiovascular risk factors did not show differences in RNFL and macular thicknesses compared with the 112 subjects with at least one risk factor (except in sector 9 that showed higher thicknesses in subjects with ≥1 risk factor). Comparison between the group of subjects with and without atheroma plaques revealed no differences in RNFL and macular thicknesses. The sub-analysis of subjects with subclinical atheroma plaques in the common carotid artery revealed a significant reduction in central macular thickness in the left eye compared with the right eye (p = 0.016), RNFL in the superior quadrant (p = 0.007), and the 11 o'clock sector (p = 0.020). Comparison between smokers and nonsmokers revealed that smokers had significant thinning of the central macular thickness (p = 0.034), the nasal RNFL quadrant (p = 0.006), and the 3 and 5 o'clock sectors (p = 0.016 and 0.009). CONCLUSIONS: Classic cardiovascular risk factors do not cause RNFL or macular thickness reduction, but tobacco smoking habit reduces nasal RNFL thickness. Subclinical atherosclerosis in the common carotid artery associates a reduction in central macular and nasal RNFL quadrant thicknesses in the left eye compared with the right eye.

Identification of differentially methylated BRCA1 and CRISP2 DNA regions as blood surrogate markers for cardiovascular disease.

Genome-wide Illumina InfiniumMethylation 450 K DNA methylation analysis was performed on blood samples from clinical atherosclerosis patients (n = 8) and healthy donors (n = 8) in the LVAD study (NCT02174133, NCT01799005). Multiple differentially methylated regions (DMR) could be identified in atherosclerosis patients, related to epigenetic control of cell adhesion, chemotaxis, cytoskeletal reorganisations, cell proliferation, cell death, estrogen receptor pathways and phagocytic immune responses. Furthermore, a subset of 34 DMRs related to impaired oxidative stress, DNA repair, and inflammatory pathways could be replicated in an independent cohort study of donor-matched healthy and atherosclerotic human aorta tissue (n = 15) and human carotid plaque samples (n = 19). Upon integrated network analysis, BRCA1 and CRISP2 DMRs were identified as most central disease-associated DNA methylation biomarkers. Differentially methylated BRCA1 and CRISP2 regions were verified by MassARRAY Epityper and pyrosequencing assays and could be further replicated in blood, aorta tissue and carotid plaque material of atherosclerosis patients. Moreover, methylation changes at BRCA1 and CRISP2 specific CpG sites were consistently associated with subclinical atherosclerosis measures (coronary calcium score and carotid intima media thickness) in an independent sample cohort of middle-aged men with subclinical cardiovascular disease in the Aragon Workers' Health Study (n = 24). Altogether, BRCA1 and CRISP2 DMRs hold promise as novel blood surrogate markers for early risk stratification and CVD prevention.

[Compliance with Physical Activity Recommendations and Associated Factors in a Cohort of Spanish Adult Workers]. / Factores asociados al cumplimiento de las recomendaciones sobre actividad física en población trabajadora de entre 40 y 55 años de edad.

BACKGROUND: Physical inactivity remains a public health problem worldwide. The purpose of this study was to determine compliance with physical activity (PA) recommendations developed by the World Health Organization (WHO) and to analyze the association with different cardiovascular risk factors (CVRF) and sociodemographic and lifestyle determinants in a sample of Spanish workers. METHODS: A cross sectional analysis was carried out in a sample of 2.651 individuals (2.428 men and 133 women, aged 40-55 years old) from the Aragon Workers' Health Study (AWHS). Sample was divided into two groups depending on whether they met PA recommendations during the last year, including transportation, leisure and occupational PA. Sociodemographic, anthropometric, clinical, pharmacological and lifestyle data were collected during the years 2011-2014. Median and interquartile range for quantitative variables and frequency distribution for categorical variables were used. Crude and adjusted binary logistic regression models were carried out to study the likelihood of meeting with PA recommendations based on the number of CVRF (hypertension, dyslipidemia, diabetes, obesity and smoking) present. RESULTS: 47.0% of workers complied with WHO recommendations for PA. Lower prevalence of compliance was found among those participants presenting some CVRF (39.7% in hypertensive, 38.7% in dyslipidemic and 32.7% in diabetic). Of the total study sample, 51.3% reported not performing PA or practice a light PA, 20.2% moderate and 28.5% vigorous or very vigorous PA. The likelihood of compliance with PA recommendations decreased with increasing the number of CVRF: 1 CVRF (OR: 0.62; 95%IC: 0.49-0.78), 2 CVRF (OR: 0.49; 95% IC: 0.38-0.62), 3 CVRF (OR: 0.34; 95% IC: 0.25-0.46), 4 CVRF (OR: 0.19; 95% IC: 0.11-0.32). CONCLUSIONS: Compliance with recommendations of PA in our population remains insufficient, moreover in those with increased cardiovascular risk.

[Cardiovascular risk factor progression in young males at 15-year follow-up in the General Military Academy of Zaragoza (AGEMZA) Study]. / Evolución de los factores de riesgo cardiovascular en jóvenes varones tras 15 años de seguimiento en el estudio Academia General Militar de Zaragoza (AGEMZA).

INTRODUCTION AND OBJECTIVES: The AGEMZA cohort comprises military men whose risk factors were studied in 1985 when they were 20 years old. As these men reached the age of 35 years, we investigated the stability of or changes in anthropometric measures, lipid levels and arterial pressure, and looked for interrelationships between any changes. METHODS: In 2000, we collected new data (by cross-sectional study) on body mass index (BMI), cholesterol, cholesterol fractions, triglycerides and blood pressure, which could be compared with the original data. Persistence or tracking was evaluated using standardized regression coefficients and odds for persistence within the same quintile. Current data were modelled using multivariate regression models. RESULTS: In the 250 subjects studied, significant changes were observed in the following variables: weight +12.1 kg, BMI +3.9 kg/m(2), cholesterol +68.0 mg/dL, HDL cholesterol -5.2 mg/dL, LDL cholesterol +57.9 mg/dL, and triglycerides +76.3 mg/dL. The degree of persistence was high for all variables, except for diastolic blood pressure. Persistence was most pronounced for BMI, cholesterol, and LDL cholesterol. The changes observed indicate an increase in cardiovascular risk that adds to the effect of aging. The change in lipid profile was mainly influenced by the increase in BMI experienced, whereas blood pressure was mainly influenced by the final BMI attained. In addition, being a current smoker was associated with worse cholesterol fractions and triglyceride levels. CONCLUSIONS: Cardiovascular risk factors increase during the third decade of the life. Early evaluation (after adolescence) enables the identification of individuals who will later be at an increased risk. Modifiable risk factors were identified, such as weight increase and smoking. Preventive measures should be designed for these groups.