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Sökning: WFRF:(Carlsson Axel)

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1.
  • Alsharari, Zayed, et al. (författare)
  • Association between carbohydrate intake and fatty acids in the de novo lipogenic pathway in serum phospholipids and adipose tissue in a population of Swedish men
  • 2020
  • Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 59:5, s. 2089-2097
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Fatty acid composition in blood and adipose tissue (AT) is a useful biomarker of dietary fat quality. However, circulating saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) have been proposed to also reflect carbohydrate-induced de novo lipogenesis (DNL) and stearoyl-CoA desaturase (SCD) activity. We aimed to test the hypothesis that high carbohydrate intake is related to SFA and MUFA in serum or AT in a Swedish population. Methods Fatty acid composition was measured in serum phospholipids (PL) and AT by gas chromatography in 63-year-old men (n = 299). Carbohydrate and alcohol intake was assessed (validated 7-day food records) in relation to total SFA, 16:0 (palmitate), 16:1 (palmitoleate), and estimated SCD activity (16:1n-7/16:0-ratio) in serum PL and in AT, respectively. Results Total carbohydrate intake was inversely associated with 16:0 in PL (P = 0.005), independently of BMI. Disaccharides were non-linearly (restricted cubic splines) and weakly associated with 16:1 and SCD activity in PL (nonlinear trend,P <= 0.02) but not AT. Carbohydrate intake and SCD expression were not associated (P >= 0.08,n = 81). Alcohol intake was, however, linearly associated with 16:0 in PL (P < 0.001), and with 16:1 (P < 0.001) and SCD activity (P <= 0.005) in both PL and AT. Conclusions Higher carbohydrate intake from sugar-rich foods or beverages was not clearly reflected by higher SFA or SCD activity in serum PL or AT. Alcohol was, however, associated with higher SFA and MUFA.
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2.
  • Alsharari, Zayed, et al. (författare)
  • Association between carbohydrate intake and fatty acids in the de novo lipogenic pathwayin serum phospholipids and adipose tissue among 63-year old men
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • AbstractBackground: Fatty acid composition in blood and adipose tissue is useful to reflect dietary fatquality, although the utility of even-chain saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) has been debated. Since SFA also can be produced via de novo lipogenesis (DNL), and desaturated to MUFA, it has been proposed that these fatty acids may reflect carbohydrate-induced DNL. We aimed to test the hypothesis that high carbohydrate intake, especially sugars, is related to SFA and MUFA in serum and adipose tissue.Methods: Validated 7-day food records were collected and fatty acid composition in serum phospholipids (PL) and adipose tissue (AT) were measured in 63-year-old men (n=299). Stearoyl-CoA desaturate (SCD) activities in AT and PL were estimated by the palmitoleic acid (16:1) to palmitic acid (16:0) ratio. Associations of dietary carbohydrate, disaccharides,  monosaccharides, carbohydrate-to-fiber ratio, and alcohol with the sum of even-chain SFA, 16:0, 16:1, and SCD activity were assessed using linear regression models with and without adjustment for BMI. Non-linear trends were evaluated using restricted cubic splines. In a subsample (n=81) with RNA measured in AT biopsies, associations of dietary carbohydrate and alcohol with SCD gene expression were assessed using linear regression models.Results: In BMI-adjusted models, intake of carbohydrates was inversely associated with palmitic acid in PL (P=0.005). Disaccharide intake was non-linearly associated with 16:1 and SCD activity in PL (P for nonlinear trend ≤0.02), with the lowest values observed in the mid tertile. Alcohol intake was linearly associated with 16:0 in PL (P<0.001) and with 16:1 (P<0.001) and SCD activity (P ≤0.005) in AT. Alcohol intake was non-linear associated (P≤0.02) with 16:1 and SCD activity in PL; with initially stable levels at lower intakes that rapidly increased at intakes above median. In the subsample, we found no associations between carbohydrate intake and SCD gene expression (P ≥0.08).Conclusion: In this Swedish population, we found no evidence to suggest that higher carbohydrate intake or sugar-rich foods or beverages is reflected by higher SFA in PL and AT.Instead, alcohol was consistently associated with higher SFA and MUFA.
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3.
  • Alsharari, Zayed, et al. (författare)
  • Serum Fatty Acids, Desaturase Activities and Abdominal Obesity - A Population-Based Study of 60-Year Old Men and Women
  • 2017
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Abdominal obesity is a key contributor of metabolic disease. Recent trials suggest that dietary fat quality affects abdominal fat content, where palmitic acid and linoleic acid influence abdominal obesity differently, while effects of n-3 polyunsaturated fatty acids are less studied. Also, fatty acid desaturation may be altered in abdominal obesity. We aimed to investigate cross-sectional associations of serum fatty acids and desaturases with abdominal obesity prevalence in a population-based cohort study. Serum cholesteryl ester fatty acids composition was measured by gas chromatography in 60-year old men (n = 1883) and women (n = 2015). Cross-sectional associations of fatty acids with abdominal obesity prevalence and anthropometric measures (e.g., sagittal abdominal diameter) were evaluated in multivariable-adjusted logistic and linear regression models, respectively. Similar models were employed to investigate relations between desaturase activities (estimated by fatty acid ratios) and abdominal obesity. In logistic regression analyses, palmitic acid, stearoyl-CoA- desaturase and Delta 6-desaturase indices were associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals) for highest versus lowest quartiles were 1.45 (1.19-1.76), 4.06 (3.27-5.05), and 3.07 (2.51-3.75), respectively. Linoleic acid, alpha-linolenic acid, docohexaenoic acid, and Delta 5-desaturase were inversely associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals): 0.39 (0.32-0.48), 0.74 (0.61-0.89), 0.76 (0.62-0.93), and 0.40 (0.33-0.49), respectively. Eicosapentaenoic acid was not associated with abdominal obesity. Similar results were obtained from linear regression models evaluating associations with different anthropometric measures. Sex-specific and linear associations were mainly observed for n3-polyunsaturated fatty acids, while associations of the other exposures were generally non-linear and similar across sexes. In accordance with findings from short-term trials, abdominal obesity was more common among individuals with relatively high proportions of palmitic acid, whilst the contrary was true for linoleic acid. Further trials should examine the potential role of linoleic acid and its main dietary source, vegetable oils, in abdominal obesity prevention.
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4.
  • Andersson, Tobias, 1976, et al. (författare)
  • Country of birth and mortality risk in hypertension with and without diabetes: the Swedish primary care cardiovascular database.
  • 2021
  • Ingår i: Journal of hypertension. - 1473-5598. ; 39:6, s. 1155-1162
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypertension and diabetes are common and are both associated with high cardiovascular morbidity and mortality. We aimed to investigate associations between mortality risk and country of birth among hypertensive individuals in primary care with and without concomitant diabetes, which has not been studied previously. In addition, we aimed to study the corresponding risks of myocardial infarction and ischemic stroke.This observational cohort study of 62557 individuals with hypertension diagnosed 2001-2008 in the Swedish Primary Care Cardiovascular Database assessed mortality by the Swedish Cause of Death Register, and myocardial infarction and ischemic stroke by the National Patient Register. Cox regression models were used to estimate study outcome hazard ratios by country of birth and time updated diabetes status, with adjustments for multiple confounders.During follow-up time without diabetes using Swedish-born as reference, adjusted mortality hazard ratios per country of birth category were Finland: 1.26 (95% confidence interval 1.15-1.38), high-income European countries: 0.84 (0.74-0.95), low-income European countries: 0.84 (0.71-1.00) and non-European countries: 0.65 (0.56-0.76). The corresponding adjusted mortality hazard ratios during follow-up time with diabetes were high-income European countries: 0.78 (0.63-0.98), low-income European countries: 0.74 (0.57-0.96) and non-European countries: 0.56 (0.44-0.71). During follow-up without diabetes, the corresponding adjusted hazard ratio of myocardial infarction was increased for Finland: 1.16 (1.01-1.34), whereas the results for ischemic stroke were inconclusive.In Sweden, hypertensive immigrants (with the exception for Finnish-born) with and without diabetes have a mortality advantage, as compared to Swedish-born.
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5.
  • Andersson, Tobias, 1976, et al. (författare)
  • Mortality trends and cause of death in patients with new-onset type 2 diabetes and controls: A 24-year follow-up prospective cohort study.
  • 2018
  • Ingår i: Diabetes research and clinical practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 138, s. 81-89
  • Tidskriftsartikel (refereegranskat)abstract
    • Our aim was to assess causes of death and temporal changes in excess mortality among patients with new-onset type 2 diabetes in Skaraborg, Sweden.Patients from the Skaraborg Diabetes Register with prospectively registered new-onset type 2 diabetes 1991-2004 were included. Five individual controls matched for sex, age, geographical area and calendar year of study entry were selected using population records. Causes of deaths until 31 December 2014 were retrieved from the Cause of Death Register. Adjusted excess mortality among patients and temporal changes of excess mortality were calculated using Poisson models. Cumulative incidences of cause-specific mortality were calculated by competing risk regression.During 24years of follow-up 4364 deaths occurred among 7461 patients in 90,529 person-years (48.2/1000 person-years, 95% CI 46.8-49.7), and 18,541 deaths in 479,428 person-years among 37,271 controls (38.7/1000 person-years, 38.1-39.2). The overall adjusted mortality hazard ratio was 1.47 (p<.0001) among patients diagnosed at study start 1991 and decreased by 2% (p<.0001) per increase in calendar year of diagnosis until 2004. Excess mortality was mainly attributed to endocrine and cardiovascular cause of death with crude subdistributional hazard ratios of 5.06 (p<.001) and 1.22 (p<.001).Excess mortality for patients with new-onset type 2 diabetes was mainly attributed to deaths related to diabetes and the cardiovascular system, and decreased with increasing year of diagnosis 1991-2004. Possible explanations could be temporal trends of earlier diagnosis due to lowered diagnostic thresholds and intensified diagnostic activities, as well as improved treatment.
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6.
  • Andersson, Tobias, 1976, et al. (författare)
  • The impact of diabetes, education and income on mortality and cardiovascular events in hypertensive patients: A cohort study from the Swedish Primary Care Cardiovascular Database (SPCCD).
  • 2020
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:8
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study we aimed to estimate the effect of diabetes, educational level and income on the risk of mortality and cardiovascular events in primary care patients with hypertension.We followed 62,557 individuals with hypertension diagnosed 2001-2008, in the Swedish Primary Care Cardiovascular Database. Study outcomes were death, myocardial infarction, and ischemic stroke, assessed using national registers until 2012. Cox regression models were used to estimate adjusted hazard ratios of outcomes according to diabetes status, educational level, and income.During follow-up, 13,231 individuals died, 9981 were diagnosed with diabetes, 4431 with myocardial infarction, and 4433 with ischemic stroke. Hazard ratios (95% confidence intervals) for diabetes versus no diabetes: mortality 1.57 (1.50-1.65), myocardial infarction 1.24 (1.14-1.34), and ischemic stroke 1.17 (1.07-1.27). Hazard ratios for diabetes and ≤9 years of school versus no diabetes and >12 years of school: mortality 1.56 (1.41-1.73), myocardial infarction 1.36 (1.17-1.59), and ischemic stroke 1.27 (1.08-1.50). Hazard ratios for diabetes and income in the lowest fifth group versus no diabetes and income in the highest fifth group: mortality 3.82 (3.36-4.34), myocardial infarction 2.00 (1.66-2.42), and ischemic stroke 1.91 (1.58-2.31).Diabetes combined with low income was associated with substantial excess risk of mortality, myocardial infarction and ischemic stroke among primary care patients with hypertension.
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7.
  • Andreasson, Anna, et al. (författare)
  • The prediction of colorectal cancer using anthropometric measures : A Swedish population-based cohort study with 22 years of follow-up
  • 2019
  • Ingår i: United European Gastroenterology journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 7:9, s. 1250-1260
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Obesity is a risk factor for colorectal cancer (CRC).Objective: The objective of this article is to investigate whether anthropometric measures reflecting visceral obesity are better predictors of CRC than body mass index (BMI).Methods: Data were analysed from the Malmo Diet and Cancer study in Sweden, comprising 16,669 women and 10,805 men (median age 56.6 and 59.1 years) followed for a median 21.5 years. Diagnoses of CRC were identified using Swedish national registers. Cox regression was used to test the associations of BMI, waist circumference (WC), waist-hip ratio, waist-to-height ratio, waist-to-hip-to-height ratio, A Body Shape Index (ABSI) and percentage body fat with the development of CRC adjusted for age, alcohol consumption, smoking, education and physical activity in men and women.Results: None of the measures were significantly associated with an increased risk for CRC in women. WC was the strongest predictor of colon cancer (CC) in men and the only measure that was independent of BMI. ABSI was the only measure significantly associated with the risk of rectal cancer in men.Conclusions: Visceral obesity, best expressed as WC, is a risk factor for CC in men but a poor predictive marker for CRC in women.
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8.
  • Andreasson, Anna, et al. (författare)
  • Waist/Hip Ratio Better Predicts Development of Severe Liver Disease Within 20 Years Than Body Mass Index : A Population-based Cohort Study
  • 2017
  • Ingår i: Clinical Gastroenterology and Hepatology. - : ELSEVIER SCIENCE INC. - 1542-3565 .- 1542-7714. ; 15:8, s. 1294-1301
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Obesity, commonly assessed based on body mass index (BMI), is associated with an increased risk for severe liver disease. It is not known if other measures of body composition are better determinants of risk for severe liver disease, and/or if these differ between women and men. We investigated the body composition measures that best predict the development of severe liver disease.METHODS: We collected data from the Malmo Diet and Cancer study in Sweden, comprising 16,784 women and 10,833 (mean age, 58.1 years at baseline), and followed patients for a median 19.8 years. We analyzed data on measures of body composition including BMI, waist/hip ratio, and others. We determined whether subjects were diagnosed with severe liver disease, or died from severe liver disease, until the end of 2014 using Swedish national registers. Associations between body composition measures and severe liver disease were assessed using Cox regression models, stratified by sex and adjusted for age, alcohol consumption, smoking, education, and physical activity.RESULTS: All studied measures of body composition were significantly associated with severe liver disease. Waist/hip ratio was the best predictor of severe liver disease in women (hazard ratio [HR] per standard deviation increment, 1.30; 95% confidence interval [CI], 1.16-1.46) and men (HR, 1.46; 95% CI, 1.31-1.63). BMI had the lowest HR in women (HR, 1.12; 95% CI, 1.00-1.27) and men (HR, 1.26; 95% CI, 1.12-1.42). The association between waist/hip ratio and development of liver disease was independent of BMI.CONCLUSIONS: In a Swedish population-based cohort study, we associated all measures of body composition with risk of severe liver disease. However, measures of abdominal obesity were best at predicting development of severe liver disease.
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9.
  • Artzi-Medvedik, Rada, et al. (författare)
  • Impaired kidney function is associated with lower quality of life among community-dwelling older adults The screening for CKD among older people across Europe (SCOPE) study
  • 2020
  • Ingår i: BMC Geriatrics. - : BMC. - 1471-2318. ; 20
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Quality of life (QoL) refers to the physical, psychological, social and medical aspects of life that are influenced by health status and function. The purpose of this study was to measure the self-perceived health status among the elderly population across Europe in different stages of Chronic Kidney Disease (CKD). Methods Our series consisted of 2255 community-dwelling older adults enrolled in the Screening for Chronic Kidney Disease (CKD) among Older People across Europe (SCOPE) study. All patients underwent a comprehensive geriatric assessment (CGA), including included demographics, clinical and physical assessment, number of medications taken, family arrangement, Geriatric Depression Scale (GDS), Cumulative Illness Rating Scale, History of falls, Lower urinary tract symptoms, and Short Physical Performance Battery (SPPB). Estimated glomerular filtration rate (eGFR) was calculated by Berlin Initiative Study (BIS) equation. Quality of life was assessed by Euro Qol questionnaire (Euro-Qol 5D) and EQ-Visual Analogue Scale (EQ-VAS). The association between CKD (eGFR < 60, < 45 ml or < 30 ml/min/1.73m(2)) and low EQoL-VAS was investigated by multivariable logistic regression models. Results CKD was found to be significantly associated with low EQoL-VAS in crude analysis (OR = 1.47, 95%CI = 1.16-1.85 for eGFR< 60; OR = 1.38, 95%CI = 1.08-1.77 for eGFR< 45; OR = 1.57, 95%CI = 1.01-2.44). Such association was no longer significant only when adjusting for SPPB (OR = 1.20, 95%CI = 0.93-1.56 for eGFR< 60; OR = 0.87, 95%CI = 0.64-1.18 for eGFR< 45; OR = 0.84, 95%CI = 0.50-1.42), CIRS and polypharmacy (OR = 1.16, 95%CI = 0.90-1.50 for eGFR< 60; OR = 0.86, 95%CI = 0.64-1.16 for eGFR< 45; OR = 1.11, 95%CI = 0.69-1.80) or diabetes, hypertension and chronic obstructive pulmonary disease (OR = 1.28, 95%CI = 0.99-1.64 for eGFR< 60; OR = 1.16, 95%CI = 0.88-1.52 for eGFR< 45; OR = 1.47, 95%CI = 0.92-2.34). The association between CKD and low EQoL-VAS was confirmed in all remaining multivariable models. Conclusions CKD may significantly affect QoL in community-dwelling older adults. Physical performance, polypharmacy, diabetes, hypertension and COPD may affect such association, which suggests that the impact of CKD on QoL is likely multifactorial and partly mediated by co-occurrent conditions/risk factors.
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10.
  • Artzi-Medvedik, Rada, et al. (författare)
  • Quality of Life and Kidney Function in Older Adults : Prospective Data of the SCOPE Study
  • 2023
  • Ingår i: Journal of Clinical Medicine. - 2077-0383. ; 12:12
  • Tidskriftsartikel (refereegranskat)abstract
    • A longitudinal alteration in health-related quality of life (HRQoL) over a two-year period and its association with early-stage chronic kidney disease (CKD) progression was investigated among 1748 older adults (>75 years). HRQoL was measured by the Euro-Quality of Life Visual Analog Scale (EQ-VAS) at baseline and at one and two years after recruitment. A full comprehensive geriatric assessment was performed, including sociodemographic and clinical characteristics, the Geriatric Depression Scale-Short Form (GDS-SF), Short Physical Performance Battery (SPPB), and estimated glomerular filtration rate (eGFR). The association between EQ-VAS decline and covariates was investigated by multivariable analyses. A total of 41% of the participants showed EQ-VAS decline, and 16.3% showed kidney function decline over the two-year follow-up period. Participants with EQ-VAS decline showed an increase in GDS-SF scores and a greater decline in SPPB scores. The logistic regression analyses showed no contribution of a decrease in kidney function on EQ-VAS decline in the early stages of CKD. However, older adults with a greater GDS-SF score were more likely to present EQ-VAS decline over time, whereas an increase in the SPPB scores was associated with less EQ-VAS decline. This finding should be considered in clinical practice and when HRQoL is used to evaluate health interventions among older adults.
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11.
  • Ballante, Flavio, et al. (författare)
  • Docking Finds GPCR Ligands in Dark Chemical Matter
  • 2020
  • Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 63:2, s. 613-620
  • Tidskriftsartikel (refereegranskat)abstract
    • High-throughput screening has revealed dark chemical matter, a set of drug-like compounds that has never shown bioactivity despite being extensively assayed. If dark molecules are found active at a therapeutic target, their extraordinary selectivity profiles make excellent starting points for drug development. We explored if ligands of therapeutically relevant G-protein-coupled receptors could be discovered by structure-based virtual screening of the dark chemical matter. Molecular docking screens against crystal structures of the A(2A) adenosine and the D-4 dopamine receptors were carried out, and 53 top-ranked molecules were evaluated experimentally. Two ligands of each receptor were discovered, and the most potent had sub-micromolar affinities. Analysis of bioactivity data showed that the ligands lacked activity at hundreds of off-targets, including several that are associated with adverse effects. Our results demonstrate that virtual screening provides an efficient means to mine the dark chemical space, which could contribute to development of drugs with improved safety profiles.
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13.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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14.
  • Bentham, James, et al. (författare)
  • A century of trends in adult human height
  • 2016
  • Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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15.
  • Bingsjö360 – Experience Sweden's Bingsjö Folk Music Festival in 360 degrees
  • 2019
  • Konstnärligt arbete (film/video)abstract
    • Every first Wednesday in July since 1969, Bingsjöstämman (Bingsjö Folk Music Festival) beckons leading folk musicians and folk music enthusiasts from all over Scandinavia to the picturesque village of Bingsjö in Sweden. Over the course of 24 hours, thousands of people gather in fields, barns, campgrounds and historic houses to enjoy scheduled concerts, impromptu musical performances and to participate in traditional dances.Captured at Bingsjöstämman in 2018, Bingsjö360 presents 18 separate video clips which combine 8K resolution VR360 video and ambisonic music recordings to represent the broad range of musical performances on display at the festival. Through this immersive music documentary experience, viewers around the world can experience the sounds, rhythms and unique visual beauty of the festival for themselves.Bingsjö360 presents new creative pathways for representing and sharing folk music tradition through cutting-edge artistic research, immersive audiovisual technology and new modes of audience interaction. By making Bingsjö360 easily accessible through an online video sharing platform, this project also aims to elevate knowledge and perception about immersive audiovisual experiences in wider society.This international artistic research project was instigated at Dalarna Audiovisual Academy at Dalarna University (Falun, Sweden) and produced in collaboration with Folkmusikens Hus, Faraway Productions (Australia), Honeypot Film Productions, Cutting Edge (Australia), Dalarnas Museum, Film i Dalarna and Benny Andersson’s record label Mono Music.
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17.
  • Braegelmann, Johannes, et al. (författare)
  • Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer
  • 2017
  • Ingår i: Clinical Cancer Research. - : American Association for Cancer Research Inc.. - 1078-0432 .- 1557-3265. ; 23:7, s. 1829-1840
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches.Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities (n = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer (n = 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq.Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancerwasmarked by high expression of CDK19. In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8were present inmetastases. In vitro, inhibition ofCDK19 and CDK8 by knockdown or treatment with a selective CDK8/ CDK19 inhibitor significantly decreased migration and invasion.Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer.
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18.
  • Britting, Sabine, et al. (författare)
  • Kidney function and other factors and their association with falls updates The screening for CKD among older people across Europe (SCOPE) study
  • 2020
  • Ingår i: BMC Geriatrics. - : BMC. - 1471-2318. ; 20
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Reduced kidney function has become a major public health concern, especially among older people, as Chronic Kidney Disease (CKD) is associated with increased risk of end stage renal disease and mortality. Falls are a serious negative health outcome in older persons with one third of people aged 65 years experiencing a fall per year and increasing fall rates with increasing age. The impact of CKD on falls in older community-dwelling persons is not well investigated. Additionally, lower urinary tract symptoms (LUTS) may also increase the risk of falls. Therefore, our aim was to investigate the impact of CKD and LUTS on falls as well as on injurious falls. Methods: The SCOPE study is an observational, multinational, multicenter, prospective cohort study involving communitydwelling older persons aged 75 years and more recruited from August 2016 to March 2018 in seven European countries. The main outcomes of the present study were any falls and any injurious falls during the 12 months before enrolment The cross-sectional association of estimated glomerular filtration rate (eGFR) and LUIS with study outcomes was investigated by logistic regression analysis adjusted for baseline characteristics of enrolled subjects. Results: Our series consisted of 2256 SCOPE participants (median age = 795 years, 55.7% female). Of them, 746 participants experienced a fall and 484 reported an injurious fall in the 12 months prior to baseline assessment CKD was not significantly associated with falls (OR = 0.95, 95%CI = 0.79-1.14 for eGFR< 60; OR = 1.02, 95%CI = 0.81-128 for eGFR< 45; OR = 1.08, 95%CI = 0.74-1.57 for eGFR< 30) or injurious falls (OR = 0.91, 95%CI = 0.67-124 for eGFR< 60; OR = 0.93, 95%CI = 0.63-137 for eGFR< 45; OR = 1.19, 95%CI = 0.62-2.29 for eGFR< 30). LUTS were found significantly associated with both falls (OR = 156, 95960 =129-1.89) and injurious falls (OR = 158, 95%0 =1.14-2.19), and such associations were confirmed in all multivariable models. Conclusions: Cross-sectional data suggest that CKD may not be associated with history of falls or injurious falls, whereas LUTS is significantly associated with the outcomes.
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19.
  • Brännström, Åke, 1975-, et al. (författare)
  • Rigorous conditions for food-web intervality in high-dimensional trophic niche spaces
  • 2011
  • Ingår i: Journal of Mathematical Biology. - : Springerlink. - 0303-6812 .- 1432-1416. ; 63:3, s. 575-592
  • Tidskriftsartikel (refereegranskat)abstract
    • Food webs represent trophic (feeding) interactions in ecosystems. Since the late 1970s, it has been recognized that food-webs have a surprisingly close relationship to interval graphs. One interpretation of food-web intervality is that trophic niche space is low-dimensional, meaning that the trophic character of a species can be expressed by a single or at most a few quantitative traits. In a companion paper we demonstrated, by simulating a minimal food-web model, that food webs are also expected to be interval when niche-space is high-dimensional. Here we characterize the fundamental mechanisms underlying this phenomenon by proving a set of rigorous conditions for food-web intervality in high-dimensional niche spaces. Our results apply to a large class of food-web models, including the special case previously studied numerically.
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20.
  • Carlsson, Axel C, et al. (författare)
  • 10-Year Associations between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients with Stable Coronary Heart Disease : A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy.
  • 2018
  • Ingår i: Journal of the American Heart Association. - 2047-9980. ; 7:9
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.
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21.
  • Carlsson, Axel C, et al. (författare)
  • Association Between Circulating Endostatin, Hypertension Duration, and Hypertensive Target-Organ Damage
  • 2013
  • Ingår i: Hypertension. - : Lippincott Williams & Wilkins. - 0194-911X .- 1524-4563. ; 62:6, s. 1146-1151
  • Tidskriftsartikel (refereegranskat)abstract
    • Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive target-organ damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 51%; n=812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with 5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher; 95% confidence interval, 0.35-0.80; P<0.001). In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage. Further studies are warranted to assess the prognostic role of endostatin in individuals with hypertension.
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22.
  • Carlsson, Axel C., et al. (författare)
  • Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes
  • 2016
  • Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS/HYPOTHESIS: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease.METHODS: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used.RESULTS: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p < 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p < 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality.CONCLUSIONS/INTERPRETATIONS: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.
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23.
  • Carlsson, Axel C., et al. (författare)
  • Blood pressure measures and their predictive ability of cardiovascular mortality : a 26-year follow-up
  • 2013
  • Ingår i: Blood Pressure Monitoring. - 1359-5237 .- 1473-5725. ; 18:2, s. 72-77
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective(s) Our aim was to calculate the predictability of different blood pressure measures for cardiovascular mortality in a cohort of both men and women. We also aimed to determine whether clinically applicable cut-off levels for cardiovascular mortality risk of these measures work well. Materials and methods A healthcare need investigation from the 1970s was used. Participants aged 46-65 were included, n=788 (390 men and 398 women). The following blood pressure measures were studied: systolic, diastolic, mean, mid, and pulse pressure. The participants were followed for 26 years with respect to cardiovascular mortality through the Swedish Cause-of-Death Register. Isolated diastolic hypertension failed to show significant associations with cardiovascular mortality. Results Combined systolic and diastolic hypertension showed twice as high cardiovascular mortality in men and women compared with those with normal blood pressure. Mid arterial blood pressure showed increased significant hazard ratios for all three grades of hypertension in men and for grades 2 and 3 in women with good predictability (area under the curve=0.72 and 0.80, respectively). Conclusions Mid arterial blood pressure is strongly associated with cardiovascular mortality. Additional studies in larger populations and with a wider age range comparing mid arterial blood pressure with clinically useful cut-offs of other blood pressure measures are required to corroborate our findings.
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24.
  • Carlsson, Axel C., et al. (författare)
  • Country of birth-specific and gender differences in prevalence of diabetes in Sweden
  • 2013
  • Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 100:3, s. 404-408
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim was to investigate country or region of birth-specific prevalence and gender differences of diabetes in residents in Sweden, using Swedish-born men and women as referent. Methods: The Apolipoprotein MOrtality RISk (AMORIS) cohort was used (184,000 men and 151,453 women) aged between 20 and 80 years, with data from the CALAB laboratory, Stockholm, 1985-1996. Diabetes was defined as fasting glucose >= 7.0 mmol/L or a hospital diagnosis of diabetes. Country of birth was obtained by linkage to Swedish Censuses 1970-1990. Standardized prevalence rate ratios (SPRR) with 95% confidence intervals (95% CI) were estimated. Results: Five groups of women and one group of men had a significantly higher prevalence than Swedish-born (based on SPRR): women born in Iraq (6.0 (95% CI 1.3-28.9)), North Africa (6.9 (95% CI 3.1-15.3)), South Asia (3.1 (95% CI 1.0-10.0)), Syria (5.3 (95% CI 1.8-16.0)), Turkey (3.7 (95% CI 1.2-10.9)) and men born in other Middle Eastern countries (2.3 (95% CI 1.0-5.5)). Swedish-born men had a higher age-standardized prevalence of diabetes (3.9%) than Swedish born women ( 2.5%). A higher prevalence among men was also seen in other Western countries. In contrast, a higher age-standardized prevalence among women was observed in immigrants from Turkey (8.9% vs. 3.1%, p < 0.001), Syria (13.1% vs. 4.0%, p = 0.002), and North Africa (16.8% vs. 6.6%, p < 0.001). Conclusion: Female immigrants to Sweden from Iraq, North Africa, South Asia, Syria, and Turkey have an increased prevalence of diabetes of substantial public health concern.
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25.
  • Carlsson, Axel C., et al. (författare)
  • Differences and time trends in drug treatment of atrial fibrillation in men and women and doctors' adherence to warfarin therapy recommendations
  • 2013
  • Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 69:2, s. 245-253
  • Tidskriftsartikel (refereegranskat)abstract
    • Little is known about prescription trends in atrial fibrillation (AF) in primary health care in Sweden. The aim was to study time trends in pharmacotherapy, in men and women with AF. We also aimed at studying doctors' adherence to CHADS2 for prescribing warfarin. CHADS2 assesses stroke risk by presence of known risk factors, i.e., congestive heart failure, hypertension, age > 75 years, diabetes, previous stroke and transient ischemic attack. Data were obtained from primary health care records that contained individual clinical data. In total, 371,036 patients were included in the sample from 2002, and 424,329 patients were included in the sample from 2007. The study population consisted of individuals aged 45+ years who were diagnosed with AF in 2002 (1,330 men and 1,096 women) and 2007 (2,748 men and 2,234 women). The pharmacotherapies prescribed in 2002 and 2007 were analyzed separately in men and women. Logistic regression was used to calculate the association between the CHADS2 score and prescribed warfarin treatment. Selective beta-blockers, anti-coagulant therapy and lipid-lowering drugs were prescribed more frequently in 2007 than in 2002. In 2007, antithrombotic and RAS-blocking agents were prescribed more frequently to men, whereas beta-1 selective beta-blockers were prescribed more frequently to women. There was no consistent association between the CHADS2 score and prescribed warfarin treatment. Pharmacotherapy of AF has improved over time, though CHADS2 guidelines need to be implemented systematically in primary health care in Sweden to decrease the risk of stroke and improve quality of life in patients with AF.
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26.
  • Carlsson, Axel C., et al. (författare)
  • Effects of prescribed antihypertensives and other cardiovascular drugs on mortality in patients with atrial fibrillation and hypertension : a cohort study from Sweden
  • 2014
  • Ingår i: Hypertension Research. - : Springer Science and Business Media LLC. - 0916-9636 .- 1348-4214. ; 37:6, s. 553-559
  • Tidskriftsartikel (refereegranskat)abstract
    • Although antihypertensive drugs are known to reduce mortality in individuals with hypertension, the effects of different cardiovascular pharmacotherapies on mortality among patients with hypertension and atrial fibrillation (AF) have been less thoroughly explored. To study mortality rates in men and women separately with hypertension and AF prescribed different cardiovascular pharmacotherapies. A cohort of men (n = 2809) and women (n = 2793) aged > 45 years diagnosed with hypertension and AF were selected using patient records. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox regression, with all-cause mortality as the outcome. Analysis was performed on the whole population and after stratification by age and sex. Independent factors were prescribed pharmacotherapies. Adjustments were made for a propensity score comprising age, comorbidities, education and marital status. The higher the number of antihypertensive drugs prescribed, the lower the mortality rate (P-value for trend 0.005). Individuals prescribed 4-5 antihypertensive drugs had a lower risk of mortality than those prescribed 0-1 drugs (HR: 0.62; 95% CI: 0.45-0.86). The HRs for the following drug classes were: loop diuretics 1.39 (95% CI: 1.08-1.78), non-selective beta-blockers 0.68 (95% CI: 0.53-0.88), angiotensin receptor blockers 0.75 (95% CI: 0.56-0.99) and statins 0.68 (95% CI: 0.53-0.88). AF patients with hypertension prescribed statins, non-selective b-blockers and angiotensin receptor blockers had low relative mortality risks, suggesting that these prescribed pharmacotherapies were beneficial. This needs to be further explored in other clinical settings.
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27.
  • Carlsson, Axel C, et al. (författare)
  • Endostatin, cathepsin S, and cathepsin L, and their association with inflammatory markers and mortality in patients undergoing hemodialysis
  • 2015
  • Ingår i: Blood Purification. - : S. Karger AG. - 0253-5068 .- 1421-9735. ; 39:4, s. 259-265
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aims: Although both endostatin and cathepsins S have been associated with higher mortality, data in patients with end-stage renal disease (ESRD) are scarce.Methods: A longitudinal cohort study of 207 prevalent patients undergoing hemodialysis.Results: Cathepsins S and L were associated with soluble receptors for tumor necrosis factor (sTNFR1 and sTNFR2, rho between 0.28 and 0.43, p < 0.001 for all). Weaker or absent associations between endostatin, cathepsins S and L were seen with other inflammatory biomarkers, that is, CRP, interleukin 6, pentraxin 3, and TNF. In Cox and Laplace regression models adjusted for age, sex, dialysis vintage, and diabetes: standard deviation increments of endostatin was associated with a lower mortality (hazard ratio 0.75, 95% confidence interval (CI) 0.57-0.98), and with 6.8 months longer median survival.Conclusions: The high levels of endostatin, cathepsins S and L, and their associations with sTNFR1 and sTNFR2 warrant further studies exploring mortality, and the angiogenic and inflammatory pathways in ESRD. (C) 2015 S. Karger AG, Basel
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28.
  • Carlsson, Axel C, et al. (författare)
  • Endostatin predicts mortality in patients with acute dyspnea - a cohort study of patients seeking care in emergency departments.
  • 2019
  • Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 75
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Increased levels of circulating endostatin predicts cardiovascular morbidity and impaired kidney function in the general population. The utility of endostatin as a risk marker for mortality in the emergency department (ED) has not been reported.AIM: Our main aim was to study the association between plasma endostatin and 90-day mortality in an unselected cohort of patients admitted to the ED for acute dyspnea. Design Circulating endostatin was analyzed in plasma from 1710 adults and related to 90-day mortality in Cox proportional hazard models adjusted for age, sex, body mass index, oxygen saturation, respiratory rate, body temperature, C-reactive protein, lactate, creatinine and medical priority according to the Medical Emergency Triage and Treatment System-Adult score (METTS-A). The predictive value of endostatin for mortality was evaluated with receiver operating characteristic (ROC) analysis and compared with the clinical triage scoring system and age.RESULTS: Each one standard deviation increment of endostatin was associated with a HR of 2.12 (95 % CI 1.31-3.44 p< 0.01) for 90-day mortality after full adjustment. Levels of endostatin were significantly increased in the group of patients with highest METTS-A (p<0.001). When tested for the outcome 90-day mortality, the area under the ROC curve (AUC) was 0.616 for METTS-A, 0.701 for endostatin, 0.708 for METTS -A and age and 0.738 for METTS-A, age and levels of endostatin.CONCLUSIONS: In an unselected cohort of patients admitted to the ED with acute dyspnea, endostatin had a string association to 90-day mortality and improved prediction of 90-day mortality in the ED beyond the clinical triage scoring system and age with 3 %.
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29.
  • Carlsson, Axel C., et al. (författare)
  • Financial stress in late adulthood and diverse risks of incident cardiovascular disease and all-cause mortality in women and men
  • 2014
  • Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Financial stress may have adverse health effects. The main aim of this study was to investigate whether having a cash margin and living alone or cohabiting is associated with incident cardiovascular disease (CVD) and all-cause mortality. Methods: Representative population-based prospective cohort study of 60-year-old women (n = 2065) and men (n = 1939) in Stockholm County, Sweden. National registers were used to identify cases of incident CVD (n = 375) and all-cause mortality (n = 385). The presence of a cash margin was determined in the questionnaire with the following question: Would you, if an unexpected situation occurred, be able to raise 10 000 SEK within a week? (This was equivalent to US$ 1250 in 1998). Results: Compared with cohabiting women with a cash margin, the risk of all-cause mortality was higher among cohabiting women without a cash margin, with hazard ratios (HRs) of 1.97 (95% confidence interval (CI) 1.06-3.66). Using cohabiting men with cash margin as referent, single men without a cash margin were at an increased risk of both incident CVD and all-cause mortality: HR 2.84 (95% CI 1.61-4.99) and 2.78 (95% CI 1.69-4.56), respectively. Single men with cash margins still had an increased risk of all-cause mortality when compared with cohabiting men with a cash margin: HR 1.67 (95% CI 1.22-2.28). Conclusions: Financial stress may increase the risks of incident CVD and all-cause mortality, especially among men. Furthermore these risks are likely to be greater in men living in single households and in women without cash margins. Living with a partner seems to protect men, but not women, from ill-health associated with financial stress due to the lack of a cash margin.
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30.
  • Carlsson, Axel C, et al. (författare)
  • Growth differentiation factor 15 (GDF-15) is a potential biomarker of both diabetic kidney disease and future cardiovascular events in cohorts of individuals with type 2 diabetes : a proteomics approach
  • 2020
  • Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 25:1, s. 37-43
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Diabetic kidney disease (DKD) is a leading risk factor for end-stage renal disease and is one of the most important risk factors for cardiovascular disease in patients with diabetes. It is possible that novel markers portraying the pathophysiological underpinning processes may be useful.Aim: To investigate the associations between 80 circulating proteins, measured by a proximity extension assay, and prevalent DKD and major adverse cardiovascular events (MACE) in type 2 diabetes.Methods: We randomly divided individuals with type 2 diabetes from three cohorts into a two-thirds discovery and one-third replication set (total n = 813, of whom 231 had DKD defined by estimated glomerular filtration rate <60 mg/mL/1.73 m2 and/or urinary albumin-creatinine ratio ≥3 g/mol). Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline.Results: Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27-2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16-1.69); myoglobin (OR 1.57, 95% CI 1.30-1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17-1.74). In patients with DKD, GDF-15 was significantly associated with increased risk of MACE after adjustments for baseline age, sex, microalbuminuria, and kidney function and (59 MACE events during 7 years follow-up, hazard ratio per standard deviation increase 1.43 [95% CI 1.03-1.98]) but not after further adjustments for cardiovascular risk factors.Conclusion: Our proteomics approach confirms and extends previous associations of higher circulating levels of GDF-15 with both micro- and macrovascular disease in patients with type 2 diabetes. Our data encourage additional studies evaluating the clinical utility of our findings.
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31.
  • Carlsson, Axel C, et al. (författare)
  • High levels of soluble tumor necrosis factor receptors 1 and 2 and their association with mortality in patients undergoing hemodialysis
  • 2015
  • Ingår i: CardioRenal Medicine. - : S. Karger AG. - 1664-3828 .- 1664-5502. ; 5:2, s. 89-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Circulating soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and 5TNFR2) are associated with chronic kidney disease (CKD) progression in patients with CKD or diabetes, and with higher mortality. However, data in patients with end-stage renal disease are scarce. Therefore, we analyzed serum levels of sTNFR1 and sTNFR2 and investigated their association with inflammatory markers and mortality in dialysis patients. Research Design and Methods: This was a longitudinal cohort study of 207 prevalent patients (median age 66 years, 56% men) undergoing hemodialysis in Stockholm, Sweden. Demographics, clinical characteristics, including comorbidities and laboratory data, were obtained at baseline, together with prospective follow-up for mortality.Results: The median sTNFR1 and sTNFR2 levels were 17,680 ng/l [95% confidence interval (CI) 17,023-18,337] and 24,450 ng/l (95% CI 23,721-25,179), respectively. During a follow-up of 31 months (interquartile range, 21-38), 77 patients died. There was no association between the levels of sTNFRs and mortality in Cox regression models, and no consistent trend towards higher or lower mortality was seen in Laplace regression models. sTNFR1 and sTNFR2 levels were highly associated with other inflammatory markers including interleukin-6, pentraxin 3 and TNF-alpha. Conclusions:Prevalent hemodialysis patients have several-fold higher levels of sTNFRs compared to previous studies in CKD stage 4 patients. As no consistent association between TNFR and mortality was observed, clinical implications of measuring these receptors to predict outcome end-stage renal disease patients provide limited results.
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32.
  • Carlsson, Axel C., et al. (författare)
  • High prevalence of diagnosis of diabetes, depression, anxiety, hypertension, asthma and COPD in the total population of Stockholm, Sweden : a challenge for public health
  • 2013
  • Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 13, s. 670-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is limited knowledge on the prevalence of disease in total populations. Such studies have historically been difficult to conduct but the development of health data registers has facilitated large-scale studies on recorded diagnoses in entire regions. The aim of this study was to analyze the prevalence of diagnosis of six common diseases in the Swedish capital region. Methods: The study population included all living persons who resided in Stockholm County, Sweden, on December 31st 2011 (N = 2 093 717). Information on all consultations between 2007 and 2011 was obtained from primary health care, specialist outpatient care and inpatient care. Prevalence was defined as the proportion of individuals with a recorded diagnosis of diabetes, depression, anxiety disorders, hypertension, asthma and chronic obstructive pulmonary disease during the five year period, respectively. Analyses were done by age and gender. Results: Hypertension had the highest five-year prevalence (12.2%), followed by depression (6.6%), diabetes mellitus (6.2%), asthma (5.9%), anxiety disorders/phobia (4.8%), and COPD (1.8%). Diabetes was more common in men (5.3% of women and 7.1% of men) while depression (8.7% in women and 4.4% in men) and anxiety (6.3% in women and 3.4% in men) were considerably more common in women. Smaller gender differences were also found for hypertension (13.0% in women and 11.4% in men), asthma (6.4% in women and 5.4% in men) and COPD (2.1% in women and 1.6% in men). Diabetes, hypertension and COPD increased markedly with age, whereas anxiety, depression and asthma were fairly constant in individuals above 18 years. During one year of observation, more than half of all patients had only been diagnosed in primary health care, with hypertension being the diagnosis with the largest proportion of patients only identified in primary health care (70.6%). Conclusion: The prevalence of common diseases in the population can be estimated by combining data gathered during consecutive years from primary care, specialist outpatient care and inpatient care. However, accuracy of disease prevalence is highly dependent on the quality of the data. The high prevalence of the six diagnoses analysed in this study calls for preventive action to minimize suffering and costs to society.
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33.
  • Carlsson, Axel C., et al. (författare)
  • High-sensitivity cardiac troponin T levels in the emergency department in patients with chest pain but no myocardial infarction
  • 2017
  • Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 228, s. 253-259
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: High-sensitivity cardiac troponin T (hs-cTnT) was recently introduced into clinical practice. The increased sensitivity has decreased the specificity. We aimed to determine the predictors for and prevalence of hs-cTnT levels above the 99th percentile in a stable population of patients without myocardial infarction (MI) who sought medical attention for chest pain in the emergency department. Methods: We included 11,847 patients with chest pain and at least one hs-cTnT measurement during 2011 and 2012. Patients with any acute reasons for an elevated hs-cTnT level were excluded. We used logistic regression to calculate adjusted odds ratios with 95% confidence intervals for the association between patient characteristics and hs-cTnT levels of >14 ng/L. We also determined 50th, 75th, 97.5th, and 99th percentile values of hs-cTnT levels in relation to age, sex, estimated glomerular filtration rate (eGFR), and presence or absence of comorbidities. Results: In total, 1360 (11%) patients had hs-cTnT levels of >14 ng/L. Men had higher troponin levels than women, and older patients had higher levels than younger patients. The strongest predictor of an elevated troponin level was a reduced eGFR. The 99th percentile for hs-cTnT among all men and among women <50 years of age with normal renal function was 20 and 12 ng/L, respectively; this level increased to 44 and 36 ng/L, respectively, at the age of 70-79 years. Conclusions: A hs-cTnT level above the 99th percentile in patients with chest pain but no MI is common and is related to sex, age, and eGFR.
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34.
  • Carlsson, Axel C (författare)
  • Hypertension : epidemiological studies of prevalence, prevention, treatment and prognoses in men and women
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background and aim: Hypertension is ranked as the leading risk factor for mortality and the third most common factor leading to disability in the world. Hence, detection, treatment, prevention and control are of high priority. The aim of this thesis was to study the prevalence of both diagnosed hypertension and newly diagnosed high blood pressure (unknown hypertension) and how well diagnosed hypertension is treated in Stockholm County, an urbanized region of Sweden. In addition, we aimed to find factors that might be helpful in the prevention and control of hypertension by studying factors associated with newly diagnosed high blood pressure, and factors associated with hypertension control. Finally, we aimed to study age-adjusted mortality in men and women with different baseline blood pressures during a 26-year follow-up. Material and methods: Two population based samples were used in the studies included in this thesis. One comprised 4232 men and women aged 60years that was used for cross-sectional studies, and one comprised 2578 men and women with a 26-year follow-up in the National Cause of Death Register. The participation rate was high (≈80%) in both studies and study participants were thoroughly investigated, making adjustments for many variables possible. Blood pressure was measured on one occasion in both studies. Results: The total prevalence of hypertension (in 60-year-olds) was 62% among men and45% among women. In Swedish-born individuals (n=3327) the prevalence was 61% in men and 44% in women, among Finnish-born individuals (n=327) it was 77% in men and 62% in women, and among non-European immigrants (n=123) the rates were 51% and 36%, respectively. Only 22 % of the men and 33 % of the women with diagnosed hypertension had a blood pressure below 140/90 mmHg. All individuals with diagnosed hypertension and a goal blood pressure had antihypertensive therapy. Both men and women had multiple cardiovascular risk factors in addition to their hypertension. Waist circumference ≥95cm (quintiles 3-5) in men and ≥88.5cm (quintiles 4-5) in women was associated with newly diagnosed high blood pressure. Secondary school was negatively associated in men, OR 0.73 (0.54-0.99), and university education was negatively associated in both men, OR 0.66 (0.52-0.85), and women, OR 0.45 (0.34-0.59). Regular physical activity was negatively associated in women OR 0.77 (61-0.99), and high alcohol consumption (> 30 g/day) was positively associated in men, OR 1.60 (1.22-2.09). Female gender was negatively associated with newly diagnosed high blood pressure, OR 0.50 (0.41-0.61). The 26-year follow-up revealed that the hazard ratio for all-cause mortality in those with very high blood pressure (mmHg, systolic/diastolic), ≥ 160 and/or 95, was 1.93 (1.38-2.70) in men and 2.29 (1.42-3.69) in women. High blood pressure, ≥ 140 and/or 90 but < 160 and 95, and prehypertension ≥ 130 and/or 85 but < 140 and 90 were significant in women but not in men. Hypertension as a risk factor appears to be independent of healthcare needs, a proxy for co-morbidities. Conclusion: High prevalence and poor control of hypertension were found in this Swedish cohort, despite better opportunities for combating hypertension than are available in most parts of the world. Based on the findings in this thesis, prevention of hypertension needs to be gender specific, and should focus on physical exercise to reduce waist circumference in both men and women. Elevated blood pressure should be given just as high priority in patients with co-morbidities as in otherwise healthy individuals. Hypertension should receive more attention in Sweden; the high prevalence and poor control may otherwise lead to premature death, and unnecessary suffering and healthcare costs. Societal changes are needed as well as intensive screening, prevention and antihypertensive therapy.
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35.
  • Carlsson, Axel C., et al. (författare)
  • Hypertriglyceridemic waist phenotype is associated with decreased insulin sensitivity and incident diabetes in elderly men
  • 2014
  • Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 22:2, s. 526-529
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the association between hypertriglyceridemic waist (HTGW) and insulin sensitivity (assessed by euglycemic clamp method), and the development of diabetes in a longitudinal community-based cohort of elderly men without diabetes at baseline.Design and Methods: The present cross-sectional study comprised 1,026, 70-year-old men without diabetes. The gold standard euglycaemic-hyperinsulinaemic clamp technique was used. Six-year follow-up on diabetes status were available in n = 667. The HTGW phenotype was defined as having waist circumference >= 90 cm, and triglycerides >= 2 mmol L-1. The men were stratified into those having normal WC and TG (n = 299), one HTGW component (n = 606), and HTGW (n = 121).Results: The association between insulin sensitivity and one HTGW component as well as HTGW was highly significant (P < 0.001) in the whole sample, as well as in individuals with high/low BMI (stratified at >= 25). In longitudinal analyses, participants with HTGW was associated with a more than fourfold increased risk for diabetes (Odds ratio 4.64, 95% CI 1.61-13.4, P = 0.004) compared to those with normal WC and TG.Conclusion: The present study both confirm and extend previous research suggesting that the HTGW-phenotype portrays an increased glucometabolic risk, also in lean individuals.
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36.
  • Carlsson, Axel C, et al. (författare)
  • Kidney injury molecule (KIM)-1 is associated with insulin resistance : results from two community-based studies of elderly individuals
  • 2014
  • Ingår i: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 103:3, s. 516-21
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND OBJECTIVES: Insulin resistance has been shown to be closely associated with glomerular filtration rate and urinary albumin/creatinine ratio, even prior to the development of diabetes. Urinary kidney injury molecule 1 (KIM-1) is a novel, highly specific marker of kidney tubular damage. The role of insulin resistance in the development of kidney tubular damage is not previously reported. Thus, we aimed to investigate the associations between insulin sensitivity (assessed by HOMA) and urinary KIM-1.DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Two community-based cohorts of elderly individuals were investigated: Prospective Investigation of the vasculature in Uppsala seniors (PIVUS, n=701; mean age 75 years, 52% women); and Uppsala Longitudinal Study of adult men (ULSAM, n=533; mean age 78 years).RESULTS: Lower insulin sensitivity was associated with higher urinary KIM-1 in both cohorts after adjustments for age, BMI, blood pressure, antihypertensive treatment, glomerular filtration rate, and urinary albumin-creatinine ratio (PIVUS: regression coefficient for 1-SD higher HOMA-IR 0.11, 95% CI 0.03-0.20, p=0.009, and ULSAM: 0.13, 95% CI 0.04-0.22, p=0.007). Results were similar in individuals without diabetes, with normal kidney function and normo-albuminuria.CONCLUSIONS: Our findings in elderly individuals support the notion that the interplay between an impaired glucose metabolism and renal tubular damage is evident even prior to the development of diabetes and overt kidney disease.
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37.
  • Carlsson, Axel C, et al. (författare)
  • Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden
  • 2018
  • Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 272, s. 41-46
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Soluble receptors for tumor necrosis factor alpha (sTNFR1 and sTNFR2) have been associated with cardiovascular diseases, and some evidence points towards a difference in associated risk between men and women. We aimed to study the association between sTNFR1 and sTNFR2 and incident myocardial infarctions (MI) and to explore the influence of established cardiovascular risk factors in men and women.METHODS: We conducted a nested case control study in three large Swedish cohorts, including 533 myocardial infarction cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.RESULTS: An association between circulating sTNFR1 and sTNFR2 and an increased risk for MI was found when comparing cases and controls. The odds ratios were significant after adjustment for established cardiovascular risk factors and C-reactive protein in women (OR 1.44, 95% CI 1.08-1.93 for TNFR1, and 1.61, 95% CI 1.11-2.34 for TNFR2), but was abolished in men. Women with a combination of elevated CRP and values in the upper quartile of TNFR1 or TNFR2 had a 5-fold higher risk of myocardial infarction versus those with normal CRP and values in the lower three quartiles of TNFR1 or TNFR2.CONCLUSIONS: As the risk estimates for TNFR1 and TNFR2 were higher and remained significant after adjustments for established cardiovascular risk factors in women but not in men, a potential role for TNFR1 and TNFR2 in identifying women with a higher MI risk is possible. The future clinical role of TNFR1 and TNFR2 in combination with CRP to identify high risk patients for coronary heart disease has yet to be determined.
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38.
  • Carlsson, Axel C., et al. (författare)
  • Neighborhood deprivation and warfarin, aspirin and statin prescription - A cohort study of men and women treated for atrial fibrillation in Swedish primary care
  • 2015
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 187, s. 547-552
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Weaimed to study differences in the prescribing of warfarin, aspirin and statins to patients with atrial fibrillation (AF) in socio-economically diverse neighborhoods. We also aimed to explore the effects of neighborhood deprivation on the relationship between CHADS2 risk score and warfarin prescription. Methods: Data were obtained from primary health care records that contained individual clinical data that were linked to national data on neighborhood of residence and a deprivation index for different neighborhoods. Logistic regression was used to estimate the potential neighborhood differences in prescribed warfarin, aspirin and statins, and the association between the CHADS2 score and prescribed warfarin treatment, in neighborhoods with high, middle (referent) and low socio-economic (SES). Results: After adjustment for age, socio-economic factors, co-morbidities and moves to neighborhoods with different SES during follow-up, adults with AF living in high SES neighborhoods were more often prescribed warfarin (men odds ratio (OR) (95% confidence interval (CI): 1.44 (1.27-1.62); and women OR (95% CI): 1.19 (1.05-1.36)) and statins (men OR (95% CI): 1.23 (1.07-1.41); women OR (95% CI): 1.23 (1.05-1.44)) compared to their counterparts residing in middle SES. Prescription of aspirin was lower in men from high SES neighborhoods (OR (95% CI): 0.75 (0.65-0.86)) than in those from middle SES neighborhoods. Higher CHADS2 risk scores were associated with higher warfarin prescription which remained after adjustment for neighborhood SES. Conclusions: The apparent inequalities in pharmacotherapy seen in the present study call for resource allocation to primary care in neighborhoods with low and middle socio-economic status.
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39.
  • Carlsson, Axel C, et al. (författare)
  • Neighborhood socioeconomic status at the age of 40 years and ischemic stroke before the age of 50 years : A nationwide cohort study from Sweden
  • 2017
  • Ingår i: International Journal of Stroke. - : SAGE PUBLICATIONS LTD. - 1747-4930 .- 1747-4949. ; 12:8, s. 815-826
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: We aimed to study the association between neighborhood socioeconomic status at the age of 40 years and risk of ischemic stroke before the age of 50 years.Methods: All individuals in Sweden were included if their 40th birthday occurred between 1998 and 2010. National registers were used to categorize neighborhood socioeconomic status into high, middle, and low and to retrieve information on incident ischemic strokes. Hazard ratios and their 95% confidence intervals were estimated.Results: A total of 1,153,451 adults (women 48.9%) were followed for a mean of 5.5 years (SD 3.5 years), during which 1777 (0.30%) strokes among men and 1374 (0.24%) strokes among women were recorded. After adjustment for sex, marital status, education level, immigrant status, region of residence, and neighborhood services, there was a lower risk of stroke in residents from high-socioeconomic status neighborhoods (hazard ratio 0.87, 95% confidence interval 0.78-0.96), and an increased risk of stroke in adults from low-socioeconomic status neighborhoods (hazard ratio 1.16, 95% confidence interval 1.06-1.27), compared to their counterparts living in middle-socioeconomic status neighborhoods. After further adjustment for hospital diagnoses of hypertension, diabetes, heart failure, and atrial fibrillation prior to the age of 40, the higher risk in neighborhoods with low socioeconomic status was attenuated, but remained significant (hazard ratio 1.12, 95% confidence interval 1.02-1.23).Conclusions: In a nationwide study of individuals between 40 and 50 years, we found that the risk of ischemic stroke differed depending on neighborhood socioeconomic status, which calls for increased efforts to prevent cardiovascular diseases in low socioeconomic status neighborhoods.
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40.
  • Carlsson, Axel C., et al. (författare)
  • Neighbourhood socioeconomic status and coronary heart disease in individuals between 40 and 50 years.
  • 2016
  • Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 102:10
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The incidence of myocardial infarction (MI) has decreased in general but not among younger middle-aged adults. We performed a cohort study of the association between neighbourhood socioeconomic status (SES) at the age of 40 and risk of MI before the age of 50 years. METHODS: All individuals in Sweden were included in the year of their 40th birthday, if it occurred between 1998 and 2010. National registers were used to categorise neighbourhood SES into high, middle and low, and to retrieve information on incident MI and coronary heart disease (CHD). Cox regression models, adjusted for marital status, education level, immigrant status and region of residence, provided an estimate of the HRs and 95% CIs for MI or CHD. RESULTS: Out of 587 933 men and 563 719 women, incident MI occurred in 2877 (0.48%) men and 932 (0.17%) women; and CHD occurred in 4400 (0.74%) men and 1756 (0.31%) women during a mean follow-up of 5.5 years. Using individuals living in middle-SES neighbourhoods as referents, living in high-SES neighbourhoods was associated with lower risk of MI in both sexes (HR (95% CI): men: 0.72 (0.64 to 0.82), women: 0.66 (0.53 to 0.81)); living in low-SES neighbourhoods was associated with a higher risk of MI (HR (95% CI): men: 1.31 (1.20 to 1.44), women: 1.28 (1.08 to 1.50)). Similar risk estimates for CHD were found. CONCLUSIONS: The results of our study suggest an increased risk of MI and CHD among residents from low-SES neighbourhoods and a lower risk in those from high-SES neighbourhoods compared with residents in middle-SES neighbourhoods.
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41.
  • Carlsson, Axel C, et al. (författare)
  • Physical activity, obesity and risk of cardiovascular disease in middle-aged men during a median of 30 years of follow-up
  • 2016
  • Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 23:4, s. 359-365
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to investigate associations between combinations of body mass index (BMI)-categories, levels of physical activity and long-term risk of cardiovascular disease.Method and results: At age 50 years, cardiovascular risk factors were assessed in 2196 participating men of the ULSAM-study. This investigation was repeated at age 60, 70, 77 and 82 years. Being physically active (PA) was defined as three hours of recreational or hard physical training per week. The men were categorized according to BMI/PA-status, as PA/normal weight (n = 593 at baseline), non-PA/normal weight (BMI < 25 kg/m2, n = 580), PA/overweight (n = 418), non-PA/overweight (BMI 25-30 kg/m2, n = 462), PA/obese (n = 62), non-PA/obese (BMI >30 kg/m2, n = 81). We used updated data on BMI and physical activity obtained at all examinations. During follow-up (median 30 years) 850 individuals suffered a cardiovascular disease (myocardial infarction, stroke or heart failure). Using updated data on BMI/PA categories, an increased risk for cardiovascular disease was seen with increasing BMI, but a high physical activity was associated with a lower risk of cardiovascular disease within each BMI category: non-PA/normal weight (hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.04-1.66), PA/overweight (HR 1.52, 95% CI 1.20-1.94), non-PA/overweight (HR 1.65, 95% CI 1.31-2.07) PA/obese (HR 2.05, 95% CI 1.44-2.92) and non-PA/obese (HR 2.39, 95% CI 1.74-3.29), using PA/normal weight men as referent.Conclusions: Although physical activity was beneficial at all levels of BMI regarding the risk of future cardiovascular disease, there was still a substantial increased risk associated with being overweight or obese during 30 years of follow-up. 
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42.
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43.
  • Carlsson, Axel C, et al. (författare)
  • Soluble TNF receptors and kidney dysfunction in the elderly
  • 2014
  • Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 25:6, s. 1313-1320
  • Tidskriftsartikel (refereegranskat)abstract
    • The importance of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in the development of kidney disease is being unraveled. Yet, community-based data regarding the role of sTNFRs are lacking. We assessed serum sTNFRs and aspects of kidney damage cross-sectionally in two independent community-based cohorts of elderly participants: Prospective Investigation of the Vasculature in Uppsala Seniors (n=815; mean age, 75 years; 51% women) and Uppsala Longitudinal Study of Adult Men (n=778; mean age, 78 years). Serum sTNFR1 correlated substantially with different aspects of kidney pathology in the Uppsala Longitudinal Study of Adult Men cohort (R=-0.52 for estimated GFR, R=0.22 for urinary albumin-to-creatinine ratio, and R=0.17 for urinary kidney injury molecule-1; P<0.001 for all), with similar correlations in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. These associations remained significant after adjustment for age, sex, inflammatory markers, and cardiovascular risk factors and were also evident in participants without diabetes. Serum sTNFR2 was associated with all three markers in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort (P<0.001 for all). Our findings from two independent community-based cohorts confirm and extend results of previous studies supporting circulating sTNFRs as relevant biomarkers for kidney damage and dysfunction in elderly individuals, even in the absence of diabetes.
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44.
  • Carlsson, Axel C, et al. (författare)
  • Soluble tumor necrosis factor receptor 1 is associated with glomerular filtration rate progression and incidence of chronic kidney disease in two community-based cohorts of elderly individuals
  • 2015
  • Ingår i: CardioRenal Medicine. - : S. Karger AG. - 1664-3828 .- 1664-5502. ; 5:4, s. 278-288
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: We aimed to explore and validate the longitudinal associations between soluble tumor necrosis factor receptor 1 (sTNFR1), glomerular filtration rate (GFR) progression, and chronic kidney disease (CKD) incidence in two independent community-based cohorts of elderly individuals with prespecified subgroup analyses in individuals without prevalent diabetes.Research design and methods: Two community-based cohorts of elderly individuals were used with 5-year follow-up data on estimated GFR: the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 437 men; mean age: 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 703; mean age: 70 years; 51% women). GFR categories were defined as >= 60, 30-60, and <30 ml/min/1.73 m(2).Results: In longitudinal multivariable logistic regression models adjusted for inflammatory markers and established cardiovascular risk factors, higher serum sTNFR1 was significantly associated with an increased risk to progress to a lower GFR category in both ULSAM and PIVUS [odds ratio (OR) per standard deviation (SD) increase 1.28 (95% CI 1.03-1.60) and OR 1.56 (95% CI 1.30-1.87), respectively]. Also, in subgroup analyses in individuals with a GFR >= 60 ml/min/1.73 m(2) at baseline, higher sTNFRs were associated with incident CKD after 5 years in both cohorts [ULSAM: OR per SD increase 1.49 (95% CI 1.16-1.9) and PIVUS: OR 1.84 (95% CI 1.50-2.26)]. Associations were similar in individuals without diabetes.Conclusions: Higher circulating sTNFR1 independently predicts the progression to a worse GFR category and CKD incidence in elderly individuals even in the absence of diabetes. Further studies are warranted to investigate the underlying mechanisms, and to evaluate the clinical relevance of our findings. 
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45.
  • Carlsson, Axel C, et al. (författare)
  • Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes : findings from two community based cohorts of elderly
  • 2014
  • Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 237:1, s. 236-242
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.
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46.
  • Carlsson, Axel C., et al. (författare)
  • The association between endostatin and kidney disease and mortality in patients with type 2 diabetes
  • 2016
  • Ingår i: Diabetes & Metabolism. - : Elsevier BV. - 1262-3636 .- 1878-1780. ; 42:5, s. 351-357
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim. - Circulating endostatin, a biologically active derivate of collagen XVIII, is considered to be a marker of kidney disease and a risk factor for its related mortality. However, less is known of the role of endostatin in diabetes and the development of diabetic nephropathy. For this reason, our study investigated the associations between circulating endostatin and the prevalence and progression of kidney disease, and its mortality risk in patients with type 2 diabetes (T2D). Methods. - This was a cohort study of 607 patients with T2D (mean age: 61 years, 44% women). Estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was used to assess the patients' kidney function decline and mortality. Results. - Of the total study cohort, 20 patients declined by >= 20% in eGFR over 4 years, and 44 died during the follow-up (mean duration: 6.7 years). At baseline, participants with diabetic nephropathy (defined as eGFR < 60 mL/min/1.73 m(2)) and/or microalbuminuria [defined as a urinary albumin-to-creatinine ratio (ACR) > 3 g/mol] had higher median levels of endostatin than those without nephropathy (62.7 mu g/L vs 57.4 mu g/L, respectively; P = 0.031). In longitudinal analyses adjusted for age, gender, baseline eGFR and ACR, higher endostatin levels were associated with a higher risk of decline (>= 20% in eGFR, OR per 1 SD increase: 1.73, 95% CI: 1.13-2.65) and a higher risk of mortality (HR per 1 SD increase: 1.57, 95% CI: 1.19-2.07). Conclusion. - In patients with T2D, circulating endostatin levels can predict the progression of kidney disease and mortality independently of established kidney disease markers. The clinical usefulness of endostatin as a risk marker in such patients merits further studies.
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47.
  • Carlsson, Axel C, et al. (författare)
  • Urinary kidney injury molecule 1 and incidence of heart failure in elderly men
  • 2013
  • Ingår i: European Journal of Heart Failure. - : Oxford University Press. - 1388-9842 .- 1879-0844. ; 15:4, s. 447-446
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: There is growing recognition of the clinical importance of cardiorenal syndrome-the bidirectional interplay between kidney and cardiac dysfunction. Yet, the role of kidney tubular damage in the development of heart failure is less studied. The objective of this study was to investigate whether urinary kidney injury molecule (KIM)-1, a specific marker of tubular damage, predisposes to an increased heart failure risk.METHODS AND RESULTS: This was a community-based cohort study [Uppsala Longitudinal study of Adult Men (ULSAM)] of 565, 77-year-old men free from heart failure at baseline. Heart failure hospitalizations were used as outcome. During follow-up (median 8.0 years), 73 participants were hospitalized for heart failure. In models adjusted for cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, LDL/HDL ratio, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, LV hypertrophy, and prevalent cardiovascular disease) and markers of kidney dysfunction and damage [cystatin C-based glomerular filtration rate (GFR) and urinary albumin/creatinine ratio], a higher urinary KIM-1/creatinine ratio was associated with higher risk for heart failure (hazard ratio upper vs. lower tertile, 1.81; 95% confidence interval 1.01-3.29; P < 0.05). Participants with a combination of low GFR (<60 mL/min/1.72 m(2)) and high KIM-1/creatinine (>128 ng/mmol) had a 3-fold increase in heart failure risk compared with participants with normal GFR and KIM-1 (P < 0.001).CONCLUSION: Our findings suggest that kidney tubular damage predisposes to an increased risk for heart failure in the community. Further studies are needed to clarify the causal role of KIM-1 in the development of heart failure, and to evaluate the clinical utility of urinary KIM-1 measurements.
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48.
  • Carlsson, Axel C, et al. (författare)
  • Urinary kidney injury molecule-1 and the risk of cardiovascular mortality in elderly men
  • 2014
  • Ingår i: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 9:8, s. 1393-1401
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND OBJECTIVES: Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997-2001; median follow-up 8.1 years; end of follow-up, 2008).RESULTS: During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C-based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m(2)), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m(2)), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).CONCLUSIONS: These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.
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49.
  • Carlsson, Axel C., et al. (författare)
  • Use of a proximity extension assay proteomics chip to discover new biomarkers associated with albuminuria
  • 2017
  • Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; :4, s. 340-348
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The underlying mechanisms for the development of albuminuria and the increased cardiovascular risk in patients with elevated albuminuria levels are incompletely understood. We therefore investigated the associations between 80 cardiovascular proteins and the urinary albumin to creatinine ratio (ACR).METHODS: We used a discovery/replication approach in two independent community-based cohorts of elderly patients: the Uppsala Longitudinal Study of Adult Men (n = 662; mean age 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (n = 757; mean age 75 years; 51% women). A proteomic chip with a panel of 80 plasma proteins associated with different aspects of cardiovascular disease was analysed. In the discovery cohort, we used a false discovery rate of 5% to take into account the multiple statistical testing. Nominal p values were used in the replication.RESULTS: Higher levels of T-cell immunoglobulin mucin-1, placenta growth factor, growth/differentiation factor-15, urokinase plasminogen activator surface receptor and kallikrein-11 were robustly associated with a higher ACR in both cohorts in multivariable linear regression models adjusted for sex, established cardiovascular risk factors, antihypertensive treatment, prevalent cardiovascular disease and glomerular filtration rate (p < 0.02 for all). All associations were also significant in separate analyses of patients without diabetes.CONCLUSIONS: We discovered and replicated associations between ACR and five cardiovascular proteins involved in tubular injury, atherosclerosis, endothelial function, heart failure, inflammation, glomerulosclerosis and podocyte injury. Our findings put forward multiplex proteomics as a promising approach to explore novel aspects of the complex detrimental interplay between kidney function and the cardiovascular system.
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50.
  • Carlsson, Axel C, et al. (författare)
  • Use of proteomics to investigate kidney function decline over 5 years
  • 2017
  • Ingår i: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 12:8, s. 1226-1235
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR. There were 231 and 206 incident cases of CKD during follow-up in the PIVUS and ULSAM studies, respectively. Proteomic profiling of 80 proteins was assessed by a multiplex assay (proximity extension assay). The assay uses two antibodies for each protein and a PCR step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations.RESULTS: In the discovery cohort from the PIVUS Study, 28 plasma proteins were significantly associated with eGFR decline per year, taking into account the multiple testing. Twenty of these proteins were significantly associated with eGFR decline per year in the replication cohort from the ULSAM Study after adjustment for age, sex, cardiovascular risk factors, medications, and urinary albumin-to-creatinine ratio (in order of significance: TNF-related apoptosis-inducing ligand receptor 2*, CD40L receptor, TNF receptor 1*, placenta growth factor*, thrombomodulin*, urokinase plasminogen activator surface receptor*, growth/differentiation factor 15*, macrophage colony-stimulating factor 1, fatty acid-binding protein*, cathepsin D, resistin, kallikrein 11*, C-C motif chemokine 3, proteinase-activated receptor 1*, cathepsin L, chitinase 3-like protein 1, TNF receptor 2*, fibroblast growth factor 23*, monocyte chemotactic protein 1, and kallikrein 6). Moreover, 11 of the proteins predicted CKD incidence (marked with * above). No protein consistently predicted eGFR decline per year independently of baseline eGFR in both cohorts.CONCLUSIONS: Several circulating proteins involved in phosphate homeostasis, inflammation, apoptosis, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction were associated with worsening kidney function. Multiplex proteomics appears to be a promising way of discovering novel aspects of kidney disease pathology.
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