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  • 1. Belpomme, D.
    et al.
    Irigaray, P.
    Hardell, Lennart
    Örebro University, Department of Natural Sciences.
    Clapp, R.
    Montagnier, L.
    Epstein, S.
    Sasco, A. J.
    The multitude and diversity of environmental carcinogens2007In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 105, no 3, p. 414-429Article in journal (Refereed)
    Abstract [en]

    We have recently proposed that lifestyle-related factors, screening and aging cannot fully account for the present overall growing incidence of cancer. In order to propose the concept that in addition to lifestyle related factors, exogenous environmental factors may play a more important role in carcinogenesis than it is expected, and may therefore account for the growing incidence of cancer, we overview herein environmental factors, rated as certainly or potentially carcinogenic by the International Agency for Research on Cancer (IARC). We thus analyze the carcinogenic effect of microorganisms (including viruses), radiations (including radioactivity, UV and pulsed electromagnetic fields) and xenochemicals. Chemicals related to environmental pollution appear to be of critical importance, since they can induce occupational cancers as well as other cancers. Of major concerns are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children, and food pollution by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and cosmetics may be involved. Although the risk fraction attributable to environmental factors is still unknown, this long list of carcinogenic and especially mutagenic factors supports our working hypothesis according to which numerous cancers may in fact be caused by the recent modification of our environment. (C) 2007 Elsevier Inc. All rights reserved.

  • 2.
    Eriksson, Ulrika
    et al.
    Örebro University, School of Science and Technology.
    Roos, Anna
    Swedish Museum of Natural History, Stockholm, Sweden.
    Lind, Ylva
    Swedish Museum of Natural History, Stockholm, Sweden.
    Hope, Kjell
    Örebro University, School of Science and Technology.
    Ekblad, Alf
    Örebro University, School of Science and Technology.
    Kärrman, Anna
    Örebro University, School of Science and Technology.
    Comparison of PFASs contamination in the freshwater and terrestrial environments by analysis of eggs from osprey (Pandion haliaetus), tawny owl (Strix aluco), and common kestrel (Falco tinnunculus)2016In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 149, p. 40-47Article in journal (Refereed)
    Abstract [en]

    The level of PFAS (per- and polyfluorinated alkyl substances) contamination in freshwater and terrestrial Swedish environments in 2013/2014 was assessed by analyzing a range of perfluorinated alkyl acids, fluorotelomer acids, sulfonamides, sulfonamidoethanols and polyfluoralkyl phosphate diesters (diPAPs) in predator bird eggs. Stable isotopes ((13)C and (15)N) were analyzed to elucidate the dietary source. The tawny owl (Strix aluco, n=10) and common kestrel (Falco tinnunculus, n=40), two terrestrial species, and the osprey (Pandion haliaetus, n=30), a freshwater specie were included. In addition, a temporal trend (1997-2001, 2008-2009, 2013) in osprey was studied as well. The PFAS profile was dominated by perfluorooctane sulfonic acid (PFOS) in eggs from osprey and tawny owl, while for common kestrel perfluorinated carboxylic acids (∑PFCA) exceeded the level of PFOS. PFOS concentration in osprey eggs remained at the same level between 1997 and 2001 and 2013. For the long-chained PFCAs, there were a significant increase in concentrations in osprey eggs between 1997 and 2001 and 2008-2009. The levels of PFOS and PFCAs were about 10 and five times higher, respectively, in osprey compared to tawny owl and common kestrel. Evidence of direct exposure from PFCA precursor compounds to birds in both freshwater and terrestrial environment was observed. Low levels of diPAPs were detected in a few samples of osprey (<0.02-2.4ng/g) and common kestrel (<0.02-0.16ng/g) eggs, and 6:2 FTSA was detected in a majority of the osprey eggs (<6.3-52ng/g). One saturated telomer acid (7:3 FTCA), which is a transformation marker from precursor exposure, was detected in all species (<0.24-2.7ng/g). The (15)N data showed higher levels in osprey eggs compared to tawny owl and common kestrel, indicating that they feed on a 2-3 times higher trophic level. We conclude that ospreys are continuously exposed to PFAS at levels where adverse toxic effects have been observed in birds.

  • 3.
    Kumar, Jitender
    et al.
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Ingelsson, Erik
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Akademiska sjukhuset, Uppsala, Sweden.
    Persistent organic pollutants and liver dysfunction biomarkers in a population-based human sample of men and women2014In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 134, p. 251-256Article in journal (Refereed)
    Abstract [en]

    Background and objective: Persistent organic pollutants (POPs) are stable organic compounds generated through different industrial activities. Liver is involved in the metabolism of POPs, and hence exposure to POPs may interfere with liver function. Although a few studies have shown adverse effects of POPs on liver function, large-scale studies involving humans are lacking. We performed this large population-based cross-sectional study to assess the associations between different POPs and liver dysfunction biomarkers.

    Methods: A total of 992 individuals (all aged 70 years, 50% males) were recruited as part of Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. The total toxic equivalency (TEQ) value was calculated for seven mono-ortho and two non-ortho substituted polychlorinated biphenyls (PCBs) and octachloro-p-dibenzodioxin (OCDD) to assess their toxicological effects. The association of TEQ values, summary measures of 16 PCBs (sum of PCBs) and three organochlorine pesticides (sum of OC pesticides) with liver dysfunction biomarkers (bilirubin; alkaline phosphatase, ALP; alanine amino-transferase, ALT; and gamma-glutamyltransferase, GGT) was analyzed utilizing linear regression analysis.

    Results: The mono-ortho PCB TEQ values were found to be significantly positively associated with bilirubin (beta=0.71, P=0.008), while sum of OC pesticide concentrations was negatively associated with ALP (beta= -0.02, P=0.002) after adjusting for various potential confounders. When analyzed individually, a number of different POPs were associated with ALP, ALT and bilirubin. No such association with GGT was observed.

    Conclusion: Various POPs including PCBs, OCDD and pesticides were associated with the liver dysfunction biomarkers bilirubin, ALT and ALP, suggesting adverse effects on liver function from these environmental pollutants. (C) 2014 Elsevier Inc. All rights reserved.

  • 4.
    La Merrill, Michele A.
    et al.
    Department of Environmental Toxicology, University of California, Davis CA, USA.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Norwegian Institute for Water Research (NIVA), Oslo, Norway.
    van Bavel, Bert
    Örebro University, School of Science and Technology. Norwegian Institute for Water Research (NIVA), Oslo, Norway.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    The association between p,p'-DDE levels and left ventricular mass is mainly mediated by obesity2018In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 160, p. 541-546Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: The pesticide metabolite p,p'-DDE has been associated with left ventricular (LV) mass and known risk factors for LV hypertrophy in humans and in experimental models. We hypothesized that the associations of p,p'-DDE with LV hypertrophy risk factors, namely elevated glucose, adiposity and hypertension, mediate the association of p,p'-DDE with LV mass.

    METHODS: p,p'-DDE was measured in plasma from 70-year-old subjects (n = 988) of the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS). When these subjects were 70-, 75- and 80- years old, LV characteristics were measured by echocardiography, while fasting glucose, body mass index (BMI) and blood pressure were assessed with standard clinical techniques.

    RESULTS: We found that p,p'-DDE levels were associated with increased fasting glucose, BMI, hypertension and LV mass in separate models adjusted for sex. Structural equation modeling revealed that the association between p,p'-DDE and LV mass was almost entirely mediated by BMI (70%), and also by hypertension (19%).

    CONCLUSION: The obesogenic effect of p,p'-DDE is a major determinant responsible for the association of p,p'-DDE with LV mass.

  • 5.
    Lind, Lars
    et al.
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Penell, Johanna
    Dept Med Sci Occupat & Environm Med, Uppsala Univ, Uppsala, Sweden.
    Syvänen, Anne-Christine
    Dept Med Sci, Mol Med & Sci Life Lab, Uppsala Univ, Uppsala, Sweden.
    Axelsson, Tomas
    Dept Med Sci, Mol Med & Sci Life Lab, Uppsala Univ, Uppsala, Sweden.
    Ingelsson, Erik
    Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala Univ, Uppsala, Sweden; Wellcome Trust Ctr Human Genet, Univ Oxford, Oxford, England.
    Morris, Andrew P.
    Wellcome Trust Ctr Human Genet, Univ Oxford, Oxford, England.
    Lindgren, Cecilia
    Wellcome Trust Ctr Human Genet, Univ Oxford, Oxford, England.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, P. Monica
    Dept Med Sci Occupat & Environm Med, Uppsala Univ, Uppsala, Sweden.
    Genetic variation in the CYP1A1 gene is related to circulating PCB118 levels in a population-based sample2014In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 133, p. 135-140Article in journal (Refereed)
    Abstract [en]

    Several of the polychlorinated biphenyls (PCBs), i.e. the dioxin-like PCBs, are known to induce the P450 enzymes CYP1A1, CYP1A2 and CYP1B1 by activating the aryl hydrocarbon receptor (Ah)-receptor. We evaluated if circulating levels of PCBs in a population sample were related to genetic variation in the genes encoding these CYPs. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), 21 SNPs in the CYP1A1, CYP1A2 and CYP1B1 genes were genotyped. Sixteen PCB congeners were analysed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/ HRMS). Of the investigated relationships between SNPs in the CYP1A1, CYP1A2 and CYP1B1 and six PCBs (congeners 118, 126, 156, 169, 170 and 206) that captures > 80% of the variation of all PCBs measured, only the relationship between CYP1A1 rs2470893 was significantly related to PCB118 levels following strict adjustment for multiple testing (p=0.00011). However, there were several additional SNPs in the CYP1A2 and CYP1B1 that showed nominally significant associations with PCB118 levels (p-values in the 0.003-0.05 range). Further, several SNPs in the CYP1B1 gene were related to both PCB156 and PCB206 with p-values in the 0.005-0.05 range. Very few associations with p < 0.05 were seen for PCB126, PCB169 or PCB170. Genetic variation in the CYP1A1 was related to circulating PCB118 levels in the general elderly population. Genetic variation in CYP1A2 and CYP1B1 might also be associated with other PCBs.

  • 6.
    Lind, P. Monica
    et al.
    Dept Med Sci Occupat & Environm Med, Uppsala Univ, Uppsala, Sweden.
    Penell, Johanna
    Dept Med Sci Occupat & Environm Med, Uppsala Univ, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Circulating levels of p,p '-DDE are related to prevalent hypertension in the elderly2014In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 129, p. 27-31Article in journal (Refereed)
    Abstract [en]

    Background: Polychlorinated biphenyls (PCBs) and dioxin given to experimental animals increase the blood pressure. We therefore investigated if circulating levels of persistent organic pollutants (POPs) were related to hypertension in a population-based sample of men and women.

    Methods: One thousand and sixteen subjects aged 70 years were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Twenty-three POPs were analyzed using high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). Hypertension was defined as a systolic blood pressure >= 140 mmHg or a diastolic blood pressure >= 90 mmHg, and/or use of antihypertensive medication.

    Results: Seven hundred and thirty-two subjects (72%) showed hypertension. When the POPs were treated as continuous variables and adjusted for gender only, two PCBs with a low number of chlorine atoms (PCB 105 and 118) were related to prevalent hypertension. Also the OC pesticide p,p'-DDE was related to hypertension. The strongest of these associations was seen for p,p'-DDE (OR 135 for a 1 SD change, 95% CI 1.17-1.56, p < 0.0001). Following further adjustment also for BMI, smoking status, education level and exercise habits, only p,p'-DDE was still significantly related to hypertension (OR 1.23 for a 1 SD change, 95% CI 1.06-1.43, p=0.006).

    Conclusion: In this cross-sectional analysis of an elderly population, high levels of circulating levels of p,p'-DDE were associated with prevalent hypertension, further strengthening the experimental findings that POPs might influence blood pressure. (C) 2013 Elsevier Inc. All rights reserved.

  • 7.
    Lind, P. Monica
    et al.
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Circulating levels of perfluoroalkyl substances (PFASs) and carotid artery atherosclerosis2017In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 152, p. 157-164Article in journal (Refereed)
    Abstract [en]

    Background and objective: During recent years, some persistent organic pollutants (POPs) have been linked to atherosclerosis. One group of POPs, the poly- and perfluoroalkyl substances (PFASs) have not been investigated with regard to atherosclerotic plaques.

    Methods: Carotid artery atherosclerosis was assessed by ultrasound in 1016 subjects aged 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eight PFASs were detected in >75% of participants' plasma by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).

    Results: No significant linear associations were observed between the PFASs and intima-media thickness (IMT), or the echogenicity in the intima-media complex (IM-GSM, a marker of lipid infiltration in the artery) when men and women were analyzed together. Neither was occurrence of carotid plaques related to PFASs levels. However, highly significant interactions were observed between some PFASs and sex regarding both IM-GSM and plaque prevalence. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), were all related to IM-GSM in a positive fashion in women (p=0.002-0.003), while these relationships were negative in men. The levels of PFUnDA were significantly related to carotid plaque in women (OR 1.59, 95%CI 1.03-2.43, p=0.03), but not in men (OR 0.93, 95%CI 0.62-1.42, p=0.75).

    Conclusions: In this cross-sectional study, a pronounced gender difference was observed regarding associations between some PFASs, especially the long-chain PFUnDA, and markers of atherosclerosis, with more pronounced relationships found in women. These findings suggest a sex-specific role for PFASs in atherosclerosis.

  • 8.
    Ng, Esther
    et al.
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
    Salihovic, Samira
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Mahajan, Anubha
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
    Syvänen, Anne-Christine
    Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Axelsson, Tomas
    Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Ingelsson, Erik
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Lindgren, Cecilia M.
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Morris, Andrew P.
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample2015In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 140, p. 95-101Article in journal (Refereed)
    Abstract [en]

    Background: Polychlorinated biphenyls (PCBs) are a group of man-made environmental pollutants which accumulate in humans with adverse health effects. To date, very little effort has been devoted to the study of the metabolism of PCBs on a genome-wide level.

    Objectives: Here, we conducted a genome-wide association study (GWAS) to identify genomic regions involved in the metabolism of PCBs.

    Methods: Plasma levels of 16 PCBs ascertained in a cohort of elderly individuals from Sweden (n=1016) were measured using gas chromatography-high resolution mass spectrophotometry (GC-HRMS). DNA samples were genotyped on the Infinium Omni Express bead microarray, and imputed up to reference panels from the 1000 Genomes Project. Association testing was performed in a linear regression framework under an additive model.

    Results: Plasma levels of PCB-99 demonstrated genome-wide significant association with single nucleotide polymorphisms (SNPs) mapping to chromosome 19q13.2. The SNP with the strongest association was rs8109848 (p=3.7 x 10(-13)), mapping to an intronic region of CYP2B6. Moreover, when all PCBs were conditioned on PCB-99, further signals were revealed for PCBs -74, -105 and -118, mapping to the same genomic region. The lead SNPs were rs8109848 (p=3.8 x 10(-12)) for PCB-118, rs4802104 (p= 1.4 x 10(-9)) for PCB-74 and rs4803413 (p=2.5 x 10(-9)) for PCB-105, all of which map to CYP2B6.

    Conclusions: In our study, we found plasma levels of four lower-chlorinated PCBs to be significantly associated with the genetic region mapping to the CYP2B6 locus. These findings show that CYP2B6 is of importance for the metabolism of PCBs in humans, and may help to identify individuals who may be susceptible to PCB toxicity. (C) 2015 The Authors. Published by Elsevier Inc.

  • 9.
    Penell, Johanna
    et al.
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular epidemiology, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, R. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Persistent organic pollutants are related to the change in circulating lipid levels during a 5 year follow-up2014In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 134, p. 190-197Article in journal (Refereed)
    Abstract [en]

    When reporting circulating levels of persistent organic pollutants (POPs), usually lipid-normalized values are given. However, animal experiments and some human data indicate that exposure to POPs may change lipid values. The aim of the present study is to investigate if POP levels can predict future changes in levels of circulating lipids. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, lipids were measured at age 70 and at age 75 in 598 subjects without lipid-lowering medication. Twenty-three different POPs, including 16 polychlorinated biphenyls (PCBs), five organochlorine pesticides, one dioxin (OCDD) and one flame retardant brominated compound (BDE47) were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) at age 70. Strong relationships were seen among the baseline levels of the non-dioxin-like PCBs 194, 206 and 209 and the degree of increase in total serum cholesterol and LDL-cholesterol during the 5 year follow-up. These relationships were generally stronger when lipidnormalized levels were used compared to wet-weight based levels. On the contrary, for two of the pesticides, hexachlorobenzene and trans-nonachlordane, levels were inversely related to the change in LDL-cholesterol, with strongest associations found using wet-weight based levels. PCBs 194, 206 and 209 were inversely related to the change in HDL-cholesterol, in particular for wet-weight based levels. However, these relationships were only significant for wet-weight PCB 194 following adjustment for multiple testing. None of the POPs was related to the change in serum triglycerides. When investigating the association between the change in total serum cholesterol and LDL-cholesterol across different categories of change in BMI, we noted robust results especially in the group with stable BMI, suggesting that the observed relationships were not due to fluctuations in BMI over time. In conclusion, POPs are related to the change in lipids over time, especially LDL-cholesterol. This may explain why POP exposure previously has been linked to atherosclerosis and cardiovascular disease.

  • 10. Sjöberg Lind, Ylva
    et al.
    Lind, P. Monica
    Salihovic, Samira
    Örebro University, School of Science and Technology.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Circulating levels of persistent organic pollutants (POPs) are associated with left ventricular systolic and diastolic dysfunction in the elderly2013In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 123, p. 39-45Article in journal (Refereed)
    Abstract [en]

    Background and objective: Major risk factors for congestive heart failure (CHF) are myocardial infarction, hypertension, diabetes, atrial fibrillation, smoking, left ventricular hypertrophy (LVH) and obesity. However, since these risk factors only explain part of the risk of CHF, we investigated whether persistent organic pollutants (POPs) might also play a role.

    Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, left ventricular ejection fraction, (EF), E/A-ratio and isovolumic relaxation time (IVRT), were determined by echocardiography and serum samples of 21 POPs were analyzed in serum measured by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) in 998 subjects all aged 70 years.

    Results: In this cross-sectional analysis, high levels of several of the polychlorinated biphenyls (PCB congeners 99, 118, 105, 138, 153, and 180) and octachlorodibenzo-p-dioxin (OCDD) were significantly related to a decreased EF. Some POPs were also related to a decreased E/A-ratio (PCBs 206 and 209). All the results were adjusted for gender, hypertension, diabetes, smoking, LVH and BMI, and subjects with myocardial infarction or atrial fibrillation were excluded from the analysis.

    Conclusions: Circulating levels of POPs were related to impairments in both left ventricular systolic and diastolic function independently of major congestive heart failure risk factors, suggesting a possible role of POPs in heart failure. (C) 2013 Elsevier Inc. All rights reserved.

  • 11.
    Sjögren, Per
    et al.
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Montse, Rachel
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Lampa, Erik
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Circulating levels of perfluoroalkyl substances are associated with dietary patterns: A cross sectional study in elderly Swedish men and women2016In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 150, p. 59-65Article in journal (Refereed)
    Abstract [en]

    Background: In our daily life, we are exposed to perfluoroalkyl substances (PFAS) with possible health implications. The main exposure route for these substances is diet but comparative studies on how dietary habits influence exposure are lacking.

    Objectives: To examine the relations between blood levels of PFAS and adherence to three predefined dietary patterns (a WHO recommended diet, a Mediterranean-like diet, and a Low-Carbohydrate High-Protein (LCHP) diet) in an elderly Swedish population.

    Methods: Dietary data from 7-day food records and serum concentrations of PFAS were obtained from a 70-year-old Swedish population (n=844), the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The Healthy Diet Indicator score (based on WHO recommendations), the Mediterranean Diet Score and LCHP score were used to assess adherence. Multivariate linear regression was used to assess the associations between eight major PFAS and adherence to each dietary pattern.

    Results: The WHO recommended diet was positively associated with perfluorohexane sulfonic acid (PFHxS). The LCHP diet was positively related to four out of eight PFAS; namely, perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUnDA). The Mediterranean-like diet was positively associated with most PFAS; namely perfluorooctanoic acid (PFOA), perfluorooctane sulfonamide (PFOSA), PFHxS, PFNA, PFDA, and PFUnDA.

    Conclusions: All dietary patterns were positively associated with blood levels of PFAS. The highest body burden of PFAS was found in individuals with high adherence to a Mediterranean-like diet, whilst individuals who more closely followed the officially recommended diet displayed a lower body burden of these compounds.

  • 12.
    Stubleski, Jordan
    et al.
    Örebro University, School of Science and Technology.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Science and Technology. Department of Medical Sciences and Science for Life Laboratory, Molecular Epidemiology Unit, Uppsala University, Uppsala, Sweden.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Kärrman, Anna
    Örebro University, School of Science and Technology.
    Longitudinal changes in persistent organic pollutants (POPs) from 2001 to 2009 in a sample of elderly Swedish men and women2018In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 165, p. 193-200Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prospective cohort studies evaluating the temporal trends of background-level persistent organic pollutants (POPs) and their potential negative health effects in humans are needed.

    OBJECTIVE: The objectives of this study are to examine the five year longitudinal trend in chlorinated and brominated (Cl/Br) POP concentrations in a sample of elderly individuals and to investigate the relationship between gender, changes in body weight, plasma lipid levels and POP concentrations.

    METHODS: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, plasma samples were collected from the same individuals over a 5 year period. Originally 992 subjects (all aged 70) were sampled between 2001 and 2004 and 814 returning subjects (all aged 75) were sampled again from 2006 to 2009. Plasma concentrations of 16 polychlorinated biphenyls (PCBs), 5 organochlorine pesticides (OCPs), octachlorinated dibenzo-p-dioxin (OCDD), and one polybrominated diphenylether (BDE 47) were determined using high-throughput 96-well plate solid phase extraction and gas chromatography-high resolution mass spectrometry (GC-HRMS).

    RESULTS: During the 5-year follow-up, plasma concentrations of all POPs significantly decreased (p < 0.00001). Median reductions ranged from 4% (PCB105) to 45% (PCB 99), with most reductions being in the 30-40% range. For most POPs, a larger decline was seen in men than in women. The relationship between the weight change and change in POP concentrations was generally negative, but a positive relationship between lipid levels and POP concentrations when expressed as wet-weight was observed. In general, similar changes in POP concentrations and their relationships to body weight were observed regardless of using either wet-weight (pg/mL) or lipid-normalized (ng/g lipid) concentrations.

    CONCLUSION: In this longitudinal cohort study, gender and minor, but varying changes in body weight and lipid levels greatly influenced the individual-based changes in POP concentrations. In general, our findings suggest that men and women with larger decreases in body weight and greater increases in lipid levels have the slowest decline in body burden of POPs. Based on the results from this study, either wet-weight or lipid normalized concentrations can be used to determine the percent change in POP concentrations and their relationships to physiological changes and differences.

  • 13.
    Stubleski, Jordan
    et al.
    Örebro University, School of Science and Technology.
    Salihovic, Samira
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Lind, P. Monica
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Dunder, Linda
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    McCleaf, Philip
    Uppsala Vatten och Avfall AB, Uppsala, Sweden.
    Eurén, Karin
    Uppsala Vatten och Avfall AB, Uppsala, Sweden.
    Ahrens, Lutz
    Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
    Svartengren, Magnus
    Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.
    van Bavel, Bert
    Örebro University, School of Science and Technology. Norwegian Institute for Water Research (NIVA), Oslo, Norway.
    Kärrman, Anna
    Örebro University, School of Science and Technology.
    The effect of drinking water contaminated with perfluoroalkyl substances on a 10-year longitudinal trend of plasma levels in an elderly Uppsala cohort2017In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 159, p. 95-102Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In 2012, drinking water contaminated with per- and polyfluoroalkyl substances (PFASs), foremost perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) at levels over 20ng/L and 40ng/L, respectively, was confirmed in Uppsala, Sweden.

    OBJECTIVES: We assessed how a longitudinally sampled cohort's temporal trend in PFAS plasma concentration was influenced by their residential location and determined the plausible association or disparity between the PFASs detected in the drinking water and the trend in the study cohort.

    METHODS: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort provided plasma samples three times from 2001 to 2014. Individuals maintaining the same zip code throughout the study (n = 399) were divided into a reference (no known PFAS exposure), low, intermediate and high exposure area depending on the proportion of contaminated drinking water received. Eight PFASs detected in the majority (75%) of the cohort's plasma samples were evaluated for significant changes in temporal PFAS concentrations using a random effects (mixed) model.

    RESULTS: PFHxS plasma concentrations continued to significantly increase in individuals living in areas receiving the largest percentage of contaminated drinking water (p < 0.0001), while PFOS showed an overall decrease. The temporal trend of other PFAS plasma concentrations did not show an association to the quality of drinking water received.

    CONCLUSIONS: The distribution of contaminated drinking water had a direct effect on the trend in PFHxS plasma levels among the different exposure groups, resulting in increased concentrations over time, especially in the intermediate and high exposure areas. PFOS and the remaining PFASs did not show the same relationship, suggesting other sources of exposure influenced these PFAS plasma trends.

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