Blood Levels of Organochlorine Contaminants Mixtures and Cardiovascular Disease

The study was supported by the Swedish Research Council (No. 2017-00822). We acknowledge the Swedish Infrastructure for Medical Population-based Life-course and Environmental Research for providing facilities and experimental support (Swedish Research Council No. 2017-00644). The computations were performed on resources provided by Swedish National Infrastructure for Computing Sensitive Personal Data through the Uppsala Multidisciplinary Center for Advanced Computational Science under project SIMP2019015. Dr Arrebola is under contract within the Ramón y Cajal Program, Ministerio de Economía, Industria y Competitividad, Madrid, Spain.Importance: Cardiovascular toxic effects derived from high exposures to individual organochlorine compounds are well documented. However, there is no evidence on low but continuous exposure to combined organochlorine compounds in the general population. Objective: To evaluate the association of combined exposure to several organochlorine compounds, including organochlorine pesticides and polychlorinated biphenyls, with incident cardiovascular disease (CVD) in the general population. Design, Setting, and Participants: This prospective nested case-control study included data from 2 cohorts: the Swedish Mammography Cohort-Clinical (SMC-C) and the Cohort of 60-Year-Olds (60YO), with matched case-control pairs based on age, sex, and sample date. Baseline blood sampling occurred from November 2003 to September 2009 (SMC-C) and from August 1997 to March 1999 (60YO), with follow-up through December 2017 (SMC-C) and December 2014 (60YO). Participants with myocardial infarction or ischemic stroke were matched with controls for composite CVD evaluation. Data were analyzed from September 2020 to May 2023. Exposures: A total of 25 organochlorine compounds were measured in blood at baseline by gas chromatography-triple quadrupole mass spectrometry. For 7 compounds, more than 75% of the samples were lower than the limit of detection and not included. Main Outcomes and Measures: Incident cases of primary myocardial infarction and ischemic stroke were ascertained via linkage to the National Patient Register (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes I21 and I63). The quantile-based g-computation method was used to estimate the association between the combined exposure to several organochlorine compounds and composite CVD. Results: Of 1528 included participants, 1024 (67.0%) were female, and the mean (SD) age was 72 (7.0) years in the SMC-C and 61 (0.1) years in the 60YO. The odds ratio of composite CVD was 1.71 (95% CI, 1.11-2.64) per 1-quartile increment of total organochlorine compounds mixture. Organochlorinated pesticides were the largest contributors, and β-hexachlorocyclohexane and transnonachlor had the highest impact. Most of the outcome was not explained by disturbances in the main cardiometabolic risk factors, ie, high body mass index, hypertension, lipid alteration, or diabetes. Conclusions and Relevance: In this prospective nested case-control study, participants with higher exposures to organochlorines had an increased probability of experiencing a cardiovascular event, the major cause of death worldwide. Measures may be required to reduce these exposures.Swedish Research Council 2017-00822, 2017-00644Uppsala Multidisciplinary Center for Advanced Computational Science SIMP2019015Ramón y Cajal Program, Ministerio de Economía, Industria y Competitividad, Madrid, Spai

Exposure to drinking water chlorination by-products and fetal growth and prematurity: A nation wide register-based prospective study

Background: Chlorination is globally used to produce of safe drinking water. Chlorination by-products are easily formed, and there are indications that these are associated with adverse reproductive outcomes. Objectives: We conducted a nationwide register-based prospective study to assess whether gestational exposure to the four most common chlorination by-products [total trihalomethanes (TTHMs)] via tap water was associated with risk of small for gestational age (SGA), preterm delivery, and very preterm delivery. To date, this is one of the largest studies assessing drinking water TTHM-associated adverse reproductive outcomes. Methods: We included all singleton births 2005–2015 (live and stillbirths) of mothers residing in Swedish localities having >10,000 inhabitants, ≤2 operating waterworks, adequate information on chlorination treatment, and a sufficient number of routine TTHM measurements in tap water. Individual maternal second and third trimester exposure was obtained by linking TTHM measurements to residential history, categorized into no chlorination, 15μg TTHM/L. Outcomes and covariates were obtained via the linkage to Swedish health and administrative registers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression using inverse probability weighting. We stratified the analyses by chlorination treatment (chloramine, hypochlorite). Results: Based on approximately 500,000 births, we observed a TTHM dose-dependent association with increased risk of SGA, confined to treatment with hypochlorite, corresponding to a multivariable-adjusted OR=1.20 (95% CI: 1.08, 1.33) comparing drinking water TTHM >15μg to the unexposed. Similar results were obtained when, instead of unexposed, the lowest exposure category (<5μg/L TTHM) was used as reference. No clear associations were observed for preterm delivery and very preterm delivery. Discussion: Chlorination by-products exposure via drinking water was associated with increased risk of SGA in areas with hypochlorite treatment. https://doi.org/10.1289/EHP6012This study was funded by the Swedish Research Council Formas (grant 942-2015-425

Consumir alcohol en la adolescencia aumenta el riesgo de cáncer de mama a lo largo de la vida

Artículo de divulgación publicado en The Conversation España el día 03/03/2022.Durante la adolescencia, las glándulas mamarias se están desarrollando y es cuando son particularmente susceptibles a exposiciones carcinógenas.N

Exposure to dietary polychlorinated biphenyls and dioxins, and its relationship with subclinical coronary atherosclerosis: The Aragon workers' health study

Background: Experimental evidence has revealed that exposure to polychlorinated biphenyls (PCBs) and dioxins directly impairs endothelial function and induces atherosclerosis progression. In the general population, despite a small number of recent studies finding a link between PCBs, and stroke and myocardial infraction, the association with early coronary atherosclerosis has not been examined yet. Objective: To examine whether dietary exposure to PCBs and dioxins is associated with subclinical coronary atherosclerosis in a middle-aged men. Design: Cross-sectional analysis comprising 1844 men in their 50 s and free of cardiovascular disease, who participated in the Aragon Workers' Health Study (AWHS). Individual dietary exposures to PCBs and dioxins were estimated by the contaminant’s concentration in food coupled with the corresponding consumption and then participants were classified into quartiles of consumption. Coronary artery calcium score (CACS) was assessed by computerized tomography. We conducted ordered logistic regressions to estimate the odds ratio (OR) and 95% confidence intervals (CIs) for progression to the categories of more coronary artery calcium, adjusting for potential confounders. Results: Among the participants, coronary calcium was not shown in 60.1% (n=1108), 29.8% had a CACS > 0 and<100 (n=550), and the remaining 10.1% (n=186) had a CACS≥100. Compared with those in the first quartile of PCBs exposure, those in the fourth one had an increased odds for having coronary calcium (OR 2.02, 95% CI [1.18, 3.47], p trend 0.019) and for having progressed to categories of more intense calcification (OR 2.03, 95% CI [1.21, 3.40], p trend 0.012). However, no association was found between dietary dioxins exposure and prevalent coronary artery calcium. Conclusions: In this general male population, dietary exposure to PCBs, but not to dioxins, was associated with a higher prevalence of coronary calcium and to more intense subclinical coronary atherosclerosis. PCBs exposure seems to increase the risk of coronary disease in men from the very early stagesThis work was supported by the Instituto Aragonés de Ciencias de la Salud (I+CS) of the regional Government of Aragón, the National Center for Cardiovascular Research (CNIC) of the Instituto de Salud Carlos III, and Opel Spain. This study was also partially supported by grants: PI17/1709 (State Secretary of R+D and FEDER/FSE), and Excellence Integrated Projects in Health Research Institutes PIE16/ 00022 (State Secretary of R+D and FEDER/FSE), the ATHLOS project (EU H2020-Project ID: 635316), CIBERCV and CIBERESP from the Instituto de Salud Carlos III. Madrid, Spain. We also acknowledge the Juan de la Cierva-formación (Spanish State Research Agency) for funding grant to Carolina Donat-Varga

Associations of serum phthalate metabolites with thyroid hormones in GraMo cohort, Southern Spain

These results would not have been achieved without the selfless collaboration of the staff from Santa Ana and San Cecilio Hospitals and the participants who took part in the study. Dr. JP Arrebola is under contract within the Ramon y Cajal Program (RYC-2016-20155, Ministerio de Economia, Industria y Competitividad, Spain) and Dr. C Donat-Vargas is under contract within the Atraccion de Talento (from the community of Madrid, Spain) . This study was supported by research grants from Instituto de Salud Carlos III (PI20/01568, PI16/01858) .The general population is continuously exposed to phthalates via various consumer products. Epidemiological research relating phthalate exposure to thyroid function during non-developmental periods is limited. This study aimed to investigate the associations between specific serum phthalate metabolites and indicators of thyroid function in adults. We measured 10 serum phthalate metabolites and thyroid hormones - total triiodothymnine (TT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) - in a subsample of 207 adults from the GraMo cohort. This subsample was made up of men and women (in equal proportions) of middle age (49 +/- 17 years) and from Southern Spain (province of Granada). Data on age, sex, body mass index, residence area, tobacco use, alcohol consumption and attained education were obtained from a questionnaire. Phthalate metabolites were log-transformed and categorized into tertiles. Cross-sectional associations of each metabolite with thyroid hormones were analyzed using multivariable-adjusted linear regression models. The mixture effect of metabolite phthalates was assessed using weighted quantile sum regression. After multivariable-adjustment, the following phthalate metabolites were significantly associated with TT3 in a dose-response manner: MMP (beta = 0.90: 95% confidence interval 0.68,1.12), MEP (beta = 0.67: 0.44, 0.90), MiBP (beta = 0.49: 0.21, 0.77), MiDP (beta = 0.27: 0.03, 0.52), MBzP (beta = 0.51: 0.28, 0.73), MEHP (beta = -0.59: -0.82, -0.35) and MiNP (beta = -0.43: -0.71, -0.14), when comparing highest vs. lowest exposed. The sum of all metabolites was also linked to FT4 levels. No significant associations were observed for TSH except for MiNP. Although phthalate metabolites with different molecular weight showed opposite associations, overall metabolite concentrations seem to associate with increased TT3 and FT4 serum levels. The cross-sectional nature of this analysis limits causal inference.Ramon y Cajal Program (Ministerio de Economia, Industria y Competitividad, Spain) RYC-2016-20155Instituto de Salud Carlos III European Commission PI20/01568 PI16/0185

High consumption of ultra-processed food may double the risk of subclinical coronary atherosclerosis: The Aragon Workers' Health Study (AWHS)

Background: Ultra-processed food (UPF) consumption, which is increasing worldwide, has recently been associated with an increased risk of death and cardiovascular disease. We aimed to assess whether consumption of UPF is directly associated with subclinical coronary atherosclerosis in middle-aged men. Methods: A computed tomography scan was performed on 1876 men from the Aragon Workers' Health Study, recruited from January 2011 to December 2014, to assess coronary calcium. All participants were free of coronary heart disease. Dietary intake was collected by a validated 136-item semi-quantitative food frequency questionnaire. UPF was defined according to the NOVA classification. Associations between consumption of total energy-adjusted UPF and Coronary Calcium Agatston Score (CACS) - categorized into CACS of 0, > 0 and 0 and < 100). The fully adjusted ORs (95% CI) of having a CACS ≥ 100 across quartiles of energy-adjusted UPF consumption (approximately 100 g/day in the lowest quartile (ref.) and 500 g/day in the highest) were 1.00 (ref.), 1.50 (0.93, 2.42), 1.56 (0.96, 2.52), and 2.00 (1.26, 3.16), p trend.005. Conclusion: In this middle-aged worker's sample, approximately 500 g/day of UPF consumption was associated with a 2-fold greater prevalence of subclinical coronary atherosclerosis than consuming only 100 g/day, independently of total energy intake and other well-established cardiovascular risk factorsAWHS was funded through a collaboration agreement between the Aragonese Institute of Health Sciences (I+CS) of the Regional Government of Aragon, the National Cardiovascular Research Centre (CNIC) of the Carlos III Health Institute, and Opel Spain. This study was also partially supported by grants: PI17/1709 (Secretary of State for R&D and ERDF/ESF), and Integrated Projects of Excellence in Health Research Institutes PIE16/00022 (Secretary of State for R&D and ERDF/ESF), the ATHLOS Project (EU H2020-ID project: 635316), CIBERCV and CIBERESP of the Carlos III Health Institute, Madrid, Spai

Only virgin type of olive oil consumption reduces the risk of mortality. Results from a Mediterranean population-based cohort

Evidence on the association between virgin olive oil (OO) and mortality is limited since no attempt has previously been made to discern about main OO varieties. We examined the association between OO consumption (differentiating by common and virgin varieties) and total as well as cause-specific long-term mortality. 12,161 individuals, representative of the Spanish population ≥18 years old, were recruited between 2008 and 2010 and followed up through 2019. Habitual food consumption was collected at baseline with a validated computerized dietary history. The association between tertiles of OO main varieties and all-cause, cardiovascular and cancer mortality were analyzed using Cox models. After a mean follow-up of 10.7 years (129,272 person-years), 143 cardiovascular deaths, and 146 cancer deaths occurred. The hazard ratio (HR) (95% confidence interval) for all-cause mortality in the highest tertile of common and virgin OO consumption were 0.96 (0.75–1.23; P-trend 0.891) and 0.66 (0.49–0.90; P-trend 0.040). The HR for all-cause mortality per a 10 g/day increase in virgin OO was 0.91 (0.83–1.00). Virgin OO consumption was also inversely associated with cardiovascular mortality, with a HR of 0.43 (0.20–0.91; P-trend 0.017), but common OO was not, with a HR of 0.88 (0.49–1.60; P-trend 0.242). No variety of OO was associated with cancer mortality. Daily moderate consumption of virgin OO (1 and 1/2 tablespoons) was associated with a one-third lower risk of allcause as well as half the risk of cardiovascular mortality. These effects were not seen for common OO. These findings may be useful to reappraise dietary guideline

Association of a healthy beverage score with total mortality in the adult population of Spain: a nationwide cohort study

Despite the substantial evidence of the relationship between diet and mortality, the role of beverage consumption patterns is not well known. The aim of this study was to assess the association of the adherence to a Healthy Beverage Score (HBS) and all-cause mortality in a representative sample of the Spanish adult population. We conducted an observational cohort study using data from the Study on Nutrition and Cardiovascular Risk in Spain (ENRICA), which included 12,161 community-dwelling individuals aged ≥18 years recruited in 2008 to 2010 and followed until January 2022. At baseline, food consumption was collected using a validated diet history. The HBS consists of 7 items, each of which is scored from 1 to 4 (highest adherence). The HBS ranges from 7 to 28 points with a higher score representing a healthier pattern. Adherence was assigned as a higher consumption of low-fat milk, and coffee and tea, a lower consumption of whole-fat milk, no consumption of fruit juice, artificially sweetened beverages, or sugar-sweetened beverages, and no or moderate consumption of alcohol. Total mortality was ascertained by linkage to the Spanish National Death Index. Statistical analyses were performed with Cox models and adjusted for the main confounders, including sociodemographic, lifestyle, dietary variables, and morbidity. After a mean follow-up of 12.5 years (SD: 1.7; range: 0.5 to 12.9), a total of 967 deaths occurred. For all-cause mortality, the fully adjusted hazard ratio (HR) for the highest versus lowest sex-specific quartiles of HBS was 0.72 (95% confidence interval [0.57, 0.91], p linear- trend = 0.015), corresponding to an 8.3% reduction in the absolute risk of death. A linear relationship between the risk of death and the adherence to the HBS was observed using restricted cubic splines. The results were robust to sensitivity analyses. The main limitation was that repeated measurements on beverage consumption were not available and beverage consumption could have changed during follow-up. In this study, we observed that higher adherence to the HBS was associated with lower total mortality. Adherence to a healthy beverage pattern could play a role in the prevention of premature mortalityThis work was supported by FIS grants 17/1709, and 20/144 from the Carlos III Health Institute, the Secretary of R+D+I, and the European Regional Development Fund/European Social Fund (to P.G-C); by the National Plan on Drugs grant 2020/17, Spanish Ministry of Health, Spain (to F.RA); by the FACINGLCOVID-CM project, Comunidad de Madrid and European Regional Development Fund (ERDF), European Union (to F.R-A); and by the REACT EU Program, Comunidad de Madrid and European Regional Development Fund (ERDF), European Union (to F.R-A). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

The inflammatory potential of diet and pain incidence: a cohort study in older adults

This article has been accepted for publication in The Journals of Gerontology: Series A Published by Oxford University PressBackground: Pain is a highly prevalent and on-the-rise symptom with heavy associated healthcare and social burdens among older adults, yet evidence regarding its prevention is inadequate. The growing knowledge on how diet regulates inflammation may be utilized for pain prevention. Objective: To examine the association of 3-year changes in the inflammatory potential of diet (2008-2010 to 2012) with pain incidence over the subsequent 3 years (2012 to 2014-2015) among older adults. Methods: We used data from 820 individuals aged ≥60 years and free of pain in 2012, drawn from the Seniors-ENRICA cohort study in Spain. Food consumption was collected with a validated diet history, and the inflammatory potential of diet was estimated via the a priori empirical dietary inflammatory index (EDII) and the a posteriori dietary inflammatory index (DII). The frequency, severity (impact on daily activities), and number of locations of incident pain were combined into a scale that classified subjects as suffering from no pain, intermediate pain, and highest pain. The associations were summarized with relative risk ratios (RRR) and their 95% confidence interval (CI), estimated with multinomial logistic regression, and adjusted for potential sociodemographic, lifestyle, and morbidity confounders. Results: Shifting the diet towards a higher inflammatory potential was associated with a subsequent increased risk of intermediate pain [fully adjusted RRR (95% CI) per 1-point increment in the EDII=1.30 (1.03,1.65)] and highest pain [DII=1.14 (1.03,1.26)]. The three components of the pain scale followed similar trends, the most consistent one being with moderate-to-severe pain [EDII=1.26 (1.04,1.54); DII=1.12 (1.01,1.24)]. The association of increasing DII with highest incident pain was only apparent among the least physically active subjects [1.35 (1.17,1.56) vs 0.96 (0.83,1.10); p for interaction <0.001]. Conclusions: An increase in the inflammatory potential of diet was associated with higher pain incidence over the following years. Future studies in older adults should assess the efficacy of pain prevention interventions targeting the inflammatory potential of dietThe present study was supported by Instituto de Salud Carlos III, State Secretary of R+D+I and FEDER/FSE (FIS grants 16/1512, 18/287, and 19/319

Urinary phosphate is associated with cardiovascular disease incidence

Elevated phosphate (P) in urine may reflect a high intake of inorganic P salts from food additives. Elevated P in plasma is linked to vascular dysfunction and calcification. Objective, To explore associations between P in urine as well as in plasma and questionnaire-estimated P intake, and incidence of cardiovascular disease (CVD). Methods, We used the Swedish Mammography Cohort-Clinical, a population-based cohort study. At baseline (2004–2009), P was measured in urine and plasma in 1625 women. Dietary P was estimated via a food-frequency questionnaire. Incident CVD was ascertained via register-linkage. Associations were assessed using Cox proportional hazards regression. Results, After a median follow-up of 9.4 years, 164 composite CVD cases occurred (63 myocardial infarctions [MIs] and 101 strokes). Median P (percentiles 5–95) in urine and plasma were 2.4 (1.40–3.79) mmol/mmol creatinine and 1.13 (0.92–1.36) mmol/L, respectively, whereas dietary P intake was 1510 (1148–1918) mg/day. No correlations were observed between urinary and plasma P (r = −0.07) or dietary P (r = 0.10). Urinary P was associated with composite CVD and MI. The hazard ratio of CVD comparing extreme tertiles was 1.57 (95% confidence interval 1.05, 2.35; P trend 0.037)—independently of sodium excretion, the estimated glomerular filtration rate, both P and calcium in plasma, and diuretic use. Association with CVD for plasma P was 1.41 (0.96, 2.07; P trend 0.077). Conclusion, Higher level of urinary P, likely reflecting a high consumption of highly processed foods, was linked to CVD. Further investigation is needed to evaluate the potential cardiovascular toxicity associated with excessive intake of P beyond nutritional requirement