Toxic Metals and Subclinical Atherosclerosis in Carotid, Femoral, and Coronary Vascular Territories: The Aragon Workers Health Study.

OBJECTIVE: Studies evaluating the association of metals with subclinical atherosclerosis are mostly limited to carotid arteries. We assessed individual and joint associations of nonessential metals exposure with subclinical atherosclerosis in 3 vascular territories. Approach and Results: One thousand eight hundred seventy-three Aragon Workers Health Study participants had urinary determinations of inorganic arsenic species, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten. Plaque presence in carotid and femoral arteries was determined by ultrasound. Coronary Agatston calcium score ≥1 was determined by computed tomography scan. Median arsenic, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten levels were 1.83, 1.98, 0.27, 1.18, 0.05, 9.8, 0.03, 0.66, and 0.23 µg/g creatinine, respectively. The adjusted odds ratio (95% CI) for subclinical atherosclerosis presence in at least one territory was 1.25 (1.03-1.51) for arsenic, 1.67 (1.22-2.29) for cadmium, and 1.26 (1.04-1.52) for titanium. These associations were driven by arsenic and cadmium in carotid, cadmium and titanium in femoral, and titanium in coronary territories and mostly remained after additional adjustment for the other relevant metals. Titanium, cadmium, and antimony also showed positive associations with alternative definitions of increased coronary calcium. Bayesian Kernel Machine Regression analysis simultaneously evaluating metal associations suggested an interaction between arsenic and the joint cadmium-titanium exposure. CONCLUSIONS: Our results support arsenic and cadmium and identify titanium and potentially antimony as atherosclerosis risk factors. Exposure reduction and mitigation interventions of these metals may decrease cardiovascular risk in individuals without clinical disease.

Three Dimensional Carotid and Femoral Ultrasound is not Superior to Two Dimensional Ultrasound as a Predictor of Coronary Atherosclerosis Among Men With Intermediate Cardiovascular Risk.

BACKGROUND: Current cardiovascular disease (CVD) risk stratification scales, drawn up from traditional risk factors, have important limitations. The detection of subclinical atherosclerosis, by a non-invasive technique such as peripheral arteries ultrasound (US) may improve cardiovascular risk (CVR) stratification, especially in intermediate risk population. Our aim was to compare the predictive power of atherosclerotic plaques detected in carotid and femoral arteries by 2-dimensional (2D) vs. 3-dimensional (3D) US for positive coronary artery calcium score (CACS), used as a proxy for CVD, in a middle-aged sample with intermediate 10-year CVR (7.5-20%). METHODS: To detect atherosclerotic plaques by 2D vs. 3D US scan of carotid and femoral arteries and comparison of their association with CACS obtained by computed tomography (CT) of subjects with intermediate CVR belonging to the Aragon Workers' Health Study. RESULTS: 120 men were included, with a 10.4% average 10 years CVR. Forty-one (34.2%) participants had CACS ≥ 1. 90 participants (75%) had at least one plaque detected by 2D scan while 85 participants (70.8%) had at least a plaque detected by 3D US. Conventional CVR estimates c-statistic for CACS was .590. Although the variables most predicted of CACS ≥ 1 were those measured by 3D US (total plaque volume and mean of plaque density, c-statistics: .743 and .750 respectively), their predictive capacity was not statistically significantly different from the number of territories with plaque, measured either by 2D and 3D US (c-statistics .728 to .740 respectively). CONCLUSION: Subclinical atherosclerosis measured by 2D and 3D US were better predictors of CACS ≥ 1 than CVR estimated by conventional guidelines. In our sample, 3D US did not show any significant advantages with respect to 2D US for the prediction of coronary atherosclerosis.

Assessing the Performance of RGB-D Sensors for 3D Fruit Crop Canopy Characterization under Different Operating and Lighting Conditions.

The use of 3D sensors combined with appropriate data processing and analysis has provided tools to optimise agricultural management through the application of precision agriculture. The recent development of low-cost RGB-Depth cameras has presented an opportunity to introduce 3D sensors into the agricultural community. However, due to the sensitivity of these sensors to highly illuminated environments, it is necessary to know under which conditions RGB-D sensors are capable of operating. This work presents a methodology to evaluate the performance of RGB-D sensors under different lighting and distance conditions, considering both geometrical and spectral (colour and NIR) features. The methodology was applied to evaluate the performance of the Microsoft Kinect v2 sensor in an apple orchard. The results show that sensor resolution and precision decreased significantly under middle to high ambient illuminance (>2000 lx). However, this effect was minimised when measurements were conducted closer to the target. In contrast, illuminance levels below 50 lx affected the quality of colour data and may require the use of artificial lighting. The methodology was useful for characterizing sensor performance throughout the full range of ambient conditions in commercial orchards. Although Kinect v2 was originally developed for indoor conditions, it performed well under a range of outdoor conditions.

Mapping Vineyard Leaf Area Using Mobile Terrestrial Laser Scanners: Should Rows be Scanned On-the-Go or Discontinuously Sampled?

The leaf area index (LAI) is defined as the one-side leaf area per unit ground area, and is probably the most widely used index to characterize grapevine vigor. However, LAI varies spatially within vineyard plots. Mapping and quantifying this variability is very important for improving management decisions and agricultural practices. In this study, a mobile terrestrial laser scanner (MTLS) was used to map the LAI of a vineyard, and then to examine how different scanning methods (on-the-go or discontinuous systematic sampling) may affect the reliability of the resulting raster maps. The use of the MTLS allows calculating the enveloping vegetative area of the canopy, which is the sum of the leaf wall areas for both sides of the row (excluding gaps) and the projected upper area. Obtaining the enveloping areas requires scanning from both sides one meter length section along the row at each systematic sampling point. By converting the enveloping areas into LAI values, a raster map of the latter can be obtained by spatial interpolation (kriging). However, the user can opt for scanning on-the-go in a continuous way and compute 1-m LAI values along the rows, or instead, perform the scanning at discontinuous systematic sampling within the plot. An analysis of correlation between maps indicated that MTLS can be used discontinuously in specific sampling sections separated by up to 15 m along the rows. This capability significantly reduces the amount of data to be acquired at field level, the data storage capacity and the processing power of computers.

Design and development of an instrument to measure overall lifestyle habits for epidemiological research: the Mediterranean Lifestyle (MEDLIFE) index.

OBJECTIVE: To design and develop a questionnaire that can account for an individual's adherence to a Mediterranean lifestyle including the assessment of diet and physical activity patterns, as well as social interaction. DESIGN: The Mediterranean Lifestyle (MEDLIFE) index was created based on the current Spanish Mediterranean food guide pyramid. MEDLIFE is a twenty-eight-item derived index consisting of questions about food consumption (fifteen items), traditional Mediterranean dietary habits (seven items) and physical activity, rest and social interaction habits (six items). Linear regression models and Spearman rank correlation were fitted to assess content validity and internal consistency. SETTING: A subset of participants in the Aragon Workers' Health Study cohort (Zaragoza, Spain) provided the data for development of MEDLIFE. SUBJECTS: Participants (n 988) of the Aragon Workers' Health Study cohort in Spain. RESULTS: Mean MEDLIFE score was 11·3 (sd 2·6; range: 0-28), and the quintile distribution of MEDLIFE score showed a significant association with each of the individual items as well as with specific nutrients and lifestyle indicators (intra-validity). We also quantified MEDLIFE correspondence with previously reported diet quality indices and found significant correlations (ρ range: 0·44-0·53; P<0·001) for the Alternate Healthy Eating Index, the Alternate Mediterranean Diet Index and Mediterranean Diet Adherence Screener. CONCLUSIONS: MEDLIFE is the first index to include an overall assessment of lifestyle habits. It is expected to be a more holistic tool to measure adherence to the Mediterranean lifestyle in epidemiological studies.

Aragon workers' health study--design and cohort description.

BACKGROUND: Spain, a Mediterranean country with relatively low rates of coronary heart disease, has a high prevalence of traditional cardiovascular risk factors and is experiencing a severe epidemic of overweight/obesity. We designed the Aragon Workers' Health Study (AWHS) to characterize the factors associated with metabolic abnormalities and subclinical atherosclerosis in a middle aged population in Spain free of clinical cardiovascular disease. The objective of this paper is to describe the study design, aims and baseline characteristics of participants in the AWHS. METHODS/DESIGN: Longitudinal cohort study based on the annual health exams of 5,400 workers of a car assembly plant in Figueruelas (Zaragoza, Spain). Study participants were recruited during a standardized clinical exam in 2009-2010 (participation rate 95.6%). Study participants will undergo annual clinical exams and laboratory assays, and baseline and triennial collection of biological materials for biobanking and cardiovascular imaging exams (carotid, femoral and abdominal ultrasonography, coronary calcium score, and ankle-arm blood pressure index). Participants will be followed-up for 10 years. RESULTS: The average (SD) age, body mass index, and waist circumference were 49.3 (8.7) years, 27.7 (3.6) kg/m² and 97.2 (9.9) cm, respectively, among males (N = 5,048), and 40.8 (11.6) years, 24.4 (3.8) kg/m², and 81.9 (9.9) cm, among females (N = 351). The prevalence of overweight, obesity, current smoking, hypertension, hypercholesterolemia, and diabetes were 55.0, 23.1, 37.1, 40.3, 75.0, and 7.4%, respectively, among males, and 23.7, 8.3, 45.0, 12.1, 59.5, and 0.6%, respectively, among females. In the initial 587 study participants who completed all imaging exams (94.5% male), the prevalence of carotid plaque, femoral plaque, coronary calcium score >1 to 100, and coronary calcium score >100 was 30.3, 56.9, 27.0, and 8.8%, respectively. 67.7% of study participants had at least one plaque in the carotid or femoral arteries. DISCUSSION: Baseline data from the AWHS show a high prevalence of cardiovascular risk factors and of sublinical atherosclerosis. Follow-up of this cohort will allow the assessment of subclinical atherosclerosis progression and the link of disease progression to traditional and emergent risk factors.

Cardiorespiratory fitness decreases the odds for subclinical carotid plaques in apolipoprotein e4 homozygotes.

Some studies suggest that being an apolipoprotein e4 (APOE e4) carrier increases the risk of atherosclerosis, and others suggest that cardiorespiratory fitness (CRF) could play a key role in atherosclerotic prevention. Our aim was to analyze the association of APOE e4 with carotid atherosclerosis and the association of CRF with atherosclerosis in APOE e4 carriers. A cross-sectional analysis based on a subsample of 90 participants in the Aragon Workers' Health Study was carried out. Ultrasonography was used to assess the presence of plaques in carotid territory; the submaximal Chester Step Test was used to assess CRF; and behavioral, demographic, anthropometric, and clinical data were obtained by trained personnel during annual medical examinations. APOE e4e4 participants were categorized into Low-CRF (VO2max < 35 mL/kg/min) and High-CRF (VO2max ≥ 35 mL/kg/min) groups. After adjusting for several confounders, compared with APOE e3e3, those participants genotyped as APOE e3e4 and APOE e4e4 showed an OR = 1.60 (95% CI 0.45, 5.71) and OR = 4.29 (95% CI 1.16, 15.91), respectively, for carotid atherosclerosis. Compared to Low-CRF APOE e4e4 carriers, the odds of carotid plaque detection were 0.09 (95% CI 0.008, 0.98) times lower among High-CRF APOE e4e4 carriers. The APOE e4e4 genotype was associated with increased carotid atherosclerosis. However, CRF is a modifiable factor that may be targeted by APOE e4e4 to decrease the elevation of atherosclerotic risk due to this genetic condition.

Hillslope terracing effects on the spatial variability of plant development as assessed by NDVI in vineyards of the Priorat region (NE Spain).

The availability of heavy machinery and the vineyard restructuring and conversion plans of the European Union Common Agricultural Policy (Commission Regulation EC no. 1227/2000 of 31 May 2000) have encouraged the restructuring of many vineyards on hillslopes of Mediterranean Europe, through the creation of terraces to favor the mechanization of agricultural work. Terrace construction requires cutting and filling operations that create soil spatial variability, which affects soil properties and plant development. In the present paper, we study the effects of hillslope terracing on the spatial variability of the normalized difference vegetation index (NDVI) in fields of the Priorat region (NE Spain) during 2004, 2005, and 2006. This index was computed from high-resolution remote sensing data (Quickbird-2). Detailed digital terrain models before and after terrace construction were used to assess the earth movements. The results indicate that terracing by heavy machinery induced high variability on the NDVI values over the years, showing significant differences as effect of the cut and fill operations.

Gender differences in obesity related cardiovascular risk factors in Spain.

BACKGROUND: Obesity and overweight are increasing progressively leading to an increase in cardiovascular risk factors and cardiovascular events. METHODS: The MESYAS Registry (Metabolic Syndrome in Active Subjects) recruited active workers from their annual health examinations in Spain through 2003. Body mass index was used to diagnose overweight and obesity. Metabolic syndrome (MS) and risk factors were assessed according to the ATP-III definitions. RESULTS: 19,041 subjects were included (80% males), mean age 42.2 (10.7). The prevalence of overweight was 44.6% (44.0-45.2), obesity 17.3% (17.0-17.5) and MS 12.0% (11.8-12.2). Women had lower prevalence of all cardiovascular risk factors. Multivariate analysis showed independent associations between overweight (OR: 2.4; 95% CI 2.2-2.6) or obesity (OR: 5.3; 95% CI 4.7-5.9) and any other two MS criteria. Overweight and obesity were independently associated with all cardiovascular risk factors, except low high-density lipoproteins in women. Significantly higher association was found in women between obesity and diabetes (OR: 13.6; 95% CI 3.8-48.6), MS (OR: 10.6; 7.6-14.8), hypertriglyceridemia (OR: 8.6; 95% CI 5.6-13.1), and impaired fasting glucose (OR: 3.7; 95% CI 2.7-5.3). CONCLUSIONS: Overweight and obesity are strongly related to classical cardiovascular risk factors, atherogenic dyslipidaemia and MS. Obesity has higher association to insulin-resistance related risk factors in women.

Comparison of serum lipid values in subjects with and without the metabolic syndrome.

Insulin resistance is supposed to be the basis of metabolic syndrome (MS), although it is difficult to measure. The ratio of triglyceride (TG) to high-density lipoprotein (HDL) has been proposed as a surrogate marker of insulin resistance in overweight subjects. The aim of the present study was to assess the accuracy of the TG/HDL ratio for the diagnosis of MS. Data of 18,778 active workers (77.6% men) enrolled in 3 insurance companies in Spain were collected from their annual health examinations. Mean age was 42.2 +/- 10.7 years. MS was assessed according to modified Adult Treatment Panel III criteria. Prevalences of MS were 18.8% in men and 6.1% in women. Mean value of the TG/HDL ratio was 2.50 +/- 2.2 and increased in parallel to the number of MS components present. Subjects with MS had a ratio that was 2 times higher compared with those without (5.10 vs 2.03, p <0.001). Receiver operating characteristic curves were performed to assess the capability of the TG/HDL ratio to contribute to a diagnosis of MS and 80% sensitivity and 78% specificity were obtained for values >2.75 in men and >1.65 in women. In conclusion, the TG/HDL ratio is a feasible and accurate measurement for assessment of MS in healthy subjects. We propose cut-off values of 2.75 for men and 1.65 for women for a diagnosis of MS.

Spatial variability in orchards after land transformation: Consequences for precision agriculture practices.

The change from traditional to a more mechanized and technical agriculture has involved, in many cases, land transformations. This has supposed alteration of landforms and soils, with significant consequences. The effects of induced soil variability and the subsequent implications in site-specific crop management have not been sufficiently studied. The present work investigated the application of a resistivity soil sensor (Veris 3100), to map the apparent electrical conductivity (ECa), and detailed multispectral airborne images to analyse soil and crop spatial variability to assist in site-specific orchard management. The study was carried out in a peach orchard (Prunus persica (L.) Stokes), in an area transformed in the 1980 decade to change from rainfed arable crops to irrigated orchards. A total of 40 soil samples at two depths (0-30cm and 30-60cm) were analysed and compared to ECa and the normalised difference vegetation index (NDVI). Two types of statistical analysis were performed between ECa or NDVI classes with soil properties: a linear correlation analysis and multivariate analysis of variance (MANOVA). The results showed that the land transformation altered the spatial distribution and continuity of soil properties. Although a relationship between ECa and peach tree vigour could be expected, it was not found, even in the case of trees planted in soils with salts content above the tolerance threshold. Two types of management zones were proposed: a) zones delineated according to ECa classes to leach salts in the high ECa zones, and b) zones delineated according to NDVI classes to regulate tree vigour and yield. These strategies respond to the alteration of the original soil functions due to the land transformation carried out in previous years.

Sleep duration and subclinical atherosclerosis: The Aragon Workers' Health Study.

BACKGROUND AND AIMS: Few studies have evaluated the association of sleep duration with subclinical atherosclerosis, and with heterogeneous findings. We evaluated the association of sleep duration with the presence of coronary, carotid, and femoral subclinical atherosclerosis in healthy middle-age men with low prevalence of clinical comorbidities. METHODS: We performed a cross-sectional analysis of 1968 men, 40-60 years of age, participating in the Aragon Workers' Health Study (AWHS). Duration of sleep during a typical work week was assessed by questionnaire. Coronary artery calcium scores (CACS) was assessed by computed tomography and the presence of carotid plaque and femoral plaque by ultrasound. RESULTS: In fully adjusted models, the odds ratios (95% CI) for CACS >0 comparing sleep durations of ≤5, 6, and ≥8 h with 7 h were 1.34 (0.98-1.85), 1.35 (1.08-1.69) and 1.21 (0.90-1.62), respectively (p = 0.04). A similar U-shaped association was observed for CACS ≥100 and for CACS. The corresponding odds ratios for the presence of at least one carotid plaque were ≤5, 6, and ≥8 h with 7 h were 1.23 (0.88-1.72), 1.09 (0.86-1.38), and 0.86 (0.63-1.17), respectively (p = 0.31), and for the presence of at least one femoral plaque were 1.25 (0.87-1.80), 1.19 (0.93-1.51) and 1.17 (0.86-1.61), respectively (p = 0.39). CONCLUSIONS: Middle-aged men reporting 7 h of sleep duration had the lowest prevalence of subclinical coronary atherosclerosis as assessed by CACs. Our results support that men with very short or very long sleep durations are at increased risk of atherosclerosis.

In silico epigenetics of metal exposure and subclinical atherosclerosis in middle aged men: pilot results from the Aragon Workers Health Study.

We explored the association of metal levels with subclinical atherosclerosis and epigenetic changes in relevant biological pathways. Whole blood DNA Infinium Methylation 450 K data were obtained from 23 of 73 middle age men without clinically evident cardiovascular disease (CVD) who participated in the Aragon Workers Health Study in 2009 (baseline visit) and had available baseline urinary metals and subclinical atherosclerosis measures obtained in 2010-2013 (follow-up visit). The median metal levels were 7.36 µg g-1, 0.33 µg g-1, 0.11 µg g-1 and 0.07 µg g-1, for arsenic (sum of inorganic and methylated species), cadmium, antimony and tungsten, respectively. Urine cadmium and tungsten were associated with femoral and carotid intima-media thickness, respectively (Pearson's r = 0.27; p = 0.03 in both cases). Among nearest genes to identified differentially methylated regions (DMRs), 46% of metal-DMR genes overlapped with atherosclerosis-DMR genes (p < 0.001). Pathway enrichment analysis of atherosclerosis-DMR genes showed a role in inflammatory, metabolic and transport pathways. In in silico protein-to-protein interaction networks among proteins encoded by 162 and 108 genes attributed to atherosclerosis- and metal-DMRs, respectively, with proteins known to have a role in atherosclerosis pathways, we observed hub proteins in the network associated with both atherosclerosis and metal-DMRs (e.g. SMAD3 and NOP56), and also hub proteins associated with metal-DMRs only but with relevant connections with atherosclerosis effectors (e.g. SSTR5, HDAC4, AP2A2, CXCL12 and SSTR4). Our integrative in silico analysis demonstrates the feasibility of identifying epigenomic regions linked to environmental exposures and potentially involved in relevant pathways for human diseases. While our results support the hypothesis that metal exposures can influence health due to epigenetic changes, larger studies are needed to confirm our pilot results.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.

Arsenic exposure, diabetes-related genes and diabetes prevalence in a general population from Spain.

Inorganic arsenic exposure may be associated with diabetes, but the evidence at low-moderate levels is not sufficient. Polymorphisms in diabetes-related genes have been involved in diabetes risk. We evaluated the association of inorganic arsenic exposure on diabetes in the Hortega Study, a representative sample of a general population from Valladolid, Spain. Total urine arsenic was measured in 1451 adults. Urine arsenic speciation was available in 295 randomly selected participants. To account for the confounding introduced by non-toxic seafood arsenicals, we designed a multiple imputation model to predict the missing arsenobetaine levels. The prevalence of diabetes was 8.3%. The geometric mean of total arsenic was 66.0 µg/g. The adjusted odds ratios (95% confidence interval) for diabetes comparing the highest with the lowest tertile of total arsenic were 1.76 (1.01, 3.09) and 2.14 (1.47, 3.11) before and after arsenobetaine adjustment, respectively. Polymorphisms in several genes including IL8RA, TXN, NR3C2, COX5A and GCLC showed suggestive differential associations of urine total arsenic with diabetes. The findings support the role of arsenic on diabetes and the importance of controlling for seafood arsenicals in populations with high seafood intake. Suggestive arsenic-gene interactions require confirmation in larger studies.

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.

Adherence to a Mediterranean diet is associated with the presence and extension of atherosclerotic plaques in middle-aged asymptomatic adults: The Aragon Workers' Health Study.

BACKGROUND: The Mediterranean diet (MeDi) is known to prevent cardiovascular events but the mechanisms mediating this association are not fully understood. OBJECTIVE: The objective of the study was to examine the association between MeDi adherence and the presence and extent of atherosclerotic plaques in carotid, femoral, and aorta territories and its relationship with risk factors in asymptomatic middle-aged adults. METHODS: Cross-sectional analysis of the Aragon Workers' Health Study, a cohort of 2588 subjects (94.9% men aged 51.3 ± 3.89 years) without previous cardiovascular history. Participants underwent carotid, femoral, and aorta ultrasound for the quantification of number and thickness of plaques and intima-media thickness. To estimate the participant's adherence to MeDi, we computed the Alternative MEDiterranean index (aMED). RESULTS: The overall aMED score was 4.19 ± 1.70, representing a moderate adherence to MeDi. aMED score was associated with the presence of plaque in femoral arteries (odds ratio highest vs lowest aMED score quartile: 0.63; 95% confidence interval: 0.48-0.83; P trend = .045) independently of risk factors and mediators. The strongest association between aMED quartiles and presence of plaque was found among smokers, both in femoral (0.39 [0.22-0.69]; P trend = .001) and in any territory (0.33 [0.14-0.79], P trend = .008). aMED was inversely associated with the number of plaques in all territories except for carotids. CONCLUSION: MeDi adherence showed a dose-dependent protective association with the presence, number, and thickness of plaques independent of other risk factors. The association was strongest for femoral arteries and among smokers.

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.

Prehypertension is associated with insulin resistance state and not with an initial renal function impairment. A Metabolic Syndrome in Active Subjects in Spain (MESYAS) Registry substudy.

BACKGROUND: The aim of this study was to assess the prevalence of metabolic syndrome (MS) and other surrogate markers of insulin resistance, and whether these markers are better for defining the prehypertensive state than is renal dysfunction. METHODS: Data from 19,041 healthy active workers, mean age 42.2 (10.7) years, from three health insurance companies, were prospectively collected. Presence of MS, assessed according to the modified criteria of the National Cholesterol Education Program Third Adult Treatment Panel, and the ratio of triglycerides to high-density lipoprotein were considered as surrogate markers of insulin resistance. Renal function was assessed by the Modification of Diet in Renal Disease Study equation. Blood pressure was classified as normotension (NT), prehypertension (PHT), or hypertension (HT) according to the guidelines of the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. RESULTS: The global presence of MS was 11.8% The higher prevalence was found in subjects with hypertension (30%), followed by those with PHT (9.6%). The prevalence in normotensive subjects was very low (0.9%). The presence of MS and hypertension increased in parallel with age. Metabolic syndrome (odds ratio [OR] 4.3), obesity (OR 2.2), overweight (OR 1.7), impaired fasting glucose (OR 1.3), and elevated triglycerides to HDL ratio (OR 1.2), but no degree of renal dysfunction, were independent risk factors for the progression from NT to PHT. CONCLUSIONS: Prehypertension is associated with markers of insulin resistance, assessed by the presence of MS and other surrogate markers, and not with an initial renal dysfunction. In this study, MS was found to be present in almost one third of hypertensive but asymptomatic and otherwise healthy workers.

Femoral and Carotid Subclinical Atherosclerosis Association With Risk Factors and Coronary Calcium: The AWHS Study.

BACKGROUND: Early subclinical atherosclerosis has been mainly researched in carotid arteries. The potential value of femoral arteries for improving the predictive capacity of traditional risk factors is an understudied area. OBJECTIVES: This study sought to evaluate the association of subclinical carotid and femoral plaques with risk factors and coronary artery calcium score (CACS) in middle-aged men. METHODS: Participants (n = 1,423) of the AWHS (Aragon Workers' Health Study), a study designed to assess cardiovascular risk and subclinical atherosclerosis in a cohort of middle-aged men (40 to 59 years of age), underwent carotid and femoral ultrasound plus noncontrast coronary computed tomography. Subclinical atherosclerosis was defined as the presence of any plaque in carotid or femoral arteries and/or CACS ≥1. Logistic regression models were used to estimate the prevalence of atherosclerosis adjusted for risk factors and age, to evaluate the association of atherosclerosis with risk factors, and to calculate areas under the receiver-operating characteristic curves for the presence of positive CACS. RESULTS: Subclinical atherosclerosis was found in 72% of participants. Plaques were most common in femoral arteries (54%), followed by coronary calcification (38%) and carotid plaques (34%). Association of atherosclerosis with risk factors was stronger in femoral arteries than carotid or coronary arteries. The area under the receiver-operating characteristic curve for prediction of positive CACS increased from 0.665 when considering only risk factors (dyslipidemia, current smoking, hypertension, diabetes, and age) to 0.719 when adding femoral and carotid plaques (p < 0.001). In this model, the femoral odds ratio (2.58) exceeded the carotid odds ratio (1.80) for prediction of positive CACS. CONCLUSIONS: Subclinical atherosclerosis was highly prevalent in this middle-aged male cohort. Association with risk factors and positive CACS was stronger in femoral than carotid arteries. Screening for femoral plaques may be an appealing strategy for improving cardiovascular risk scales and predicting coronary disease.

[Prevalence of metabolic syndrome in the Spanish working population: MESYAS registry]. / Prevalencia del síndrome metabólico en población laboral española: registro MESYAS.

INTRODUCTION AND OBJECTIVES: To assess the prevalence of metabolic syndrome in the active Spanish working population and to describe differences related to work type. SUBJECTS AND METHOD: Data were collected on 7256 individuals [82.4% male; mean age (SD), 45.4 (9.8) years] actively employed in a large car factory and a department store. Metabolic syndrome was diagnosed according to modified ATP-III criteria (using body mass index instead of waist circumference). RESULTS: Overall, the prevalence of metabolic syndrome was 10.2%. When data were adjusted to match the age and gender of the general population (age range, 20-60 years), the prevalence was 5.8% (95% CI, 4.1%-7.6%). Moreover, it was significantly higher in men than women, at 8.7% (95% CI, 7.3%-10.0%) vs 3.0% (95% CI, 0.8%-5.1%), respectively. All the components of the metabolic syndrome were significantly more common in males, except a low HDL-cholesterol level. Prevalence increased with age and male gender (OR=1.7), obesity (OR=9.6), hypertension (OR=3.4), and diabetes (OR=15.4). The prevalence was highest in manual workers (11.8%), and lower in office workers (9.3%) and managers (7.7%), which indicates an inverse relationship with social class. The likelihood of presenting with metabolic syndrome, irrespective of age or gender, was highest in manual workers (OR=1.3). This phenomenon seemed to depend on the serum triglyceride level. CONCLUSIONS: One in ten active workers had metabolic syndrome. The prevalence rose with age, male gender, and blood pressure, and was greatly increased by obesity and diabetes. Manual workers had the highest prevalence, whereas managers had a more favorable profile.