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  • Sjöberg Lind, Ylva, et al. (författare)
  • Circulating levels of persistent organic pollutants (POPs) are associated with left ventricular systolic and diastolic dysfunction in the elderly
  • 2013
  • Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 123, s. 39-45
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
  • Sjöberg Lind, Ylva, et al. (författare)
  • Persistent organic pollutants and abnormal geometry of the left ventricle in the elderly
  • 2013
  • Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 31:8, s. 1547-1553
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:Established risk factors for left ventricular hypertrophy (LVH) are hypertension, diabetes, and obesity. However, as these risk factors explain only part of the variation in left ventricular mass, we investigated whether persistent organic pollutants (POPs) might also play a role in LVH, because exposure to polychlorinated biphenyl 126 induced cardiac growth in rats.Methods:In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), left ventricular mass index (LVMI), relative wall thickness (RWT), and geometric groups of LVH, were determined by echocardiography and 21 POPs were measured by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) in 1016 individuals aged 70 years. All individuals with a history of myocardial infarction were excluded from analysis (n=72).Results:Several of the POPs were related to abnormal left ventricular geometry before adjustment for established risk factors, but lost in significance following adjustment. However, the pesticide hexachlorobenzene (HCB) levels were significantly related to RWT, and concentric left ventricular remodeling, also following adjustment for sex, blood pressure, antihypertensive treatment, diabetes, and BMI (Pandlt;0.0001).Conclusion:In this cross-sectional study, circulating levels of HCB were related to increased wall thickness of the left ventricle and concentric left ventricular remodeling, independently of LVH risk factors, suggesting a role of this environmental contaminant in abnormal growth of the left ventricle.
  • Ax, Erika, et al. (författare)
  • Circulating levels of environmental contaminants are associated with dietary patterns in older adults
  • 2015
  • Ingår i: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 75, s. 93-102
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Food intake contributes substantially to our exposure to environmental contaminants. Still, little is known about our dietary habits' contribution to exposure variability.Objective: The aim of this study was to assess circulating levels of environmental contaminants in relation to predefined dietary patterns in an elderly Swedish population.Methods: Dietary data and serum concentrations of environmental contaminants were obtained from 844 70-year-old Swedish subjects (50% women) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Dietary data from 7-day food records was used to assess adherence to a Mediterranean-like diet, a low carbohydrate-high protein diet and the WHO dietary recommendations. Circulating levels of 6 polychlorinated biphenyl markers, 3 organochlorine pesticides, 1 dioxin and 1 polybrominated diphenyl ether, the metals cadmium, lead, mercury and aluminum and serum levels of bisphenol A and 4 phthalate metabolites were investigated in relation to dietary patterns in multivariate linear regression models.Results: A Mediterranean-like diet was positively associated with levels of several polychlorinated biphenyls (118, 126, 153, and 209), trans-nonachlor and mercury. A low carbohydrate-high protein diet was positively associated with polychlorinated biphenyls 118 and 153, trans-nonachlor, hexachlorobenzene and p, p'-dichlorodiphenyldichloroethylene, mercury and lead. The WHO recommended diet was negatively related to levels of dioxin and lead, and borderline positively to polychlorinated biphenyl 118 and trans-nonachlor.Conclusion: Dietary patterns were associated in diverse manners with circulating levels of environmental contaminants in this elderly Swedish population. Following the WHO dietary recommendations seems to be associated with a lower burden of environmental contaminants.
  • Ferreira, Daniel, et al. (författare)
  • The interactive effect of demographic and clinical factors on hippocampal volume : A multicohort study on 1958 cognitively normal individuals
  • 2017
  • Ingår i: Hippocampus. - : John Wiley and Sons. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.
  • Joshi, Peter K, et al. (författare)
  • Directional dominance on stature and cognition in diverse human populations
  • 2015
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
  • Tidskriftsartikel (refereegranskat)abstract
    • Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
  • Lind, Lars, et al. (författare)
  • Global DNA hypermethylation is associated with high serum levels of persistent organic pollutants in an elderly population
  • 2013
  • Ingår i: Environment International. - 0160-4120 .- 1873-6750. ; 59, s. 456-461
  • Tidskriftsartikel (refereegranskat)abstract
    • Dioxin exposure has experimentally been associated with changes in DNA methylation, an epigenetic change that is associated with disease. The present study aims to investigate if serum levels of dioxin and other persistent environmental pollutants are related to global DNA methylation in a human sample. In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (all aged 70), global DNA methylation was measured by the Luminometric Methylation Assay in 524 subjects. Twenty-three different POPs, including 16 PCBs, five pesticides, one dioxin (OCDD) and one brominated flame retardant (BDE47) were analysed by HRGC/HRMS. Ten single nucleotide polymorphisms (SNPs) in the Aryl hydrocarbon (Ah)-receptor were analysed by mini-sequencing. High levels of toxic equivalency (TEQ) for PCBs and dioxin were associated with DNA hypermethylation (p = 0.030). This was mainly attributed to coplanar non-ortho PCBs. While no significant associations were found between DNA methylation and SNPs in the Ah-receptor, an interaction was found between the SNP rs2237297 and TEQ so that TEQ was associated with hypermethylation (p = 0.009) only in subjects with one G-allele (n = 103). Also high levels of the PCB126 congener, the OCDD, and the pesticide metabolite p,p'-DDE were related to DNA hypermethylation (p = 0.01, 0.03 and 0.003, respectively). In conclusion, in a sample of elderly subjects, high TEQ including PCBs and the dioxin OCDD and high serum levels of PCB126, OCDD, and p,p'-DDE were related to global DNA hypermethylation in a cross-sectional analysis. (C) 2013 Elsevier Ltd. All rights reserved.
  • Murray, Christopher J. L., et al. (författare)
  • Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition
  • 2015
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 386:10009, s. 2145-2191
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6.2 years (95% UI 5.6-6.6), from 65.3 years (65.0-65.6) in 1990 to 71.5 years (71.0-71.9) in 2013, HALE at birth rose by 5.4 years (4.9-5.8), from 56.9 years (54.5-59.1) to 62.3 years (59.7-64.8), total DALYs fell by 3.6% (0.3-7.4), and age-standardised DALY rates per 100 000 people fell by 26.7% (24.6-29.1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition-in which increasing sociodemographic status brings structured change in disease burden-is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.
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