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Sökning: WFRF:(Hultdin Johan)

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1.
  • Bergemalm, Daniel, 1977-, et al. (författare)
  • Systemic Inflammation in Preclinical Ulcerative Colitis
  • 2021
  • Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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2.
  • Bölenius, Karin, et al. (författare)
  • Minor improvement of venous blood specimen collection practices in primary health care after a large-scale educational intervention
  • 2013
  • Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 51:2, s. 303-310
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Venous blood specimen collection is a common health care practice that has to follow strict guidelines, non-compliance among sampling staff may compromise patient safety. We evaluated a large-scale 2 h educational intervention that emphasised guideline adherence to assess possible improvements of venous blood specimen collection practices.Methods: Blood specimen haemolysis is usually caused by inadequate venous blood specimen collection and handling, reflecting overall pre-analytical handling. We monitored haemolysis of serum samples with haemolysis index corresponding to ≥150 mg/L of free haemoglobin for specimens sent from 11 primary health care centres and analysed on a Vitros 5,1 clinical chemistry analyser before (2008, n=6652 samples) and after (2010, n=6121 samples) the intervention.Results: The total percentage of haemolysed specimens was 11.8% compared to 10.5% (p=0.022) before the intervention. As groups, rural primary health care centres demonstrated a significant reduction [Odds ratios (OR)=0.744] of haemolysed specimens after intervention, whereas urban primary health care centres demonstrated a significant increase (OR=1.451) of haemolysis.Conclusions: A large-scale 2 h educational intervention to make venous blood specimen collection staff comply with guideline practices had minor effects on collection practices. Educational interventions may be effective in wards/care centres demonstrating venous blood specimen collection practices with larger deviations from guidelines.
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3.
  • Hansén, Nike, et al. (författare)
  • Adipokines are possible risk markers for aortic stenosis requiring surgery
  • 2023
  • Ingår i: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 57:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Aortic stenosis (AS) is the most prevalent valvular heart disease among adults. The adipocyte-derived hormones, leptin and adiponectin, have profound metabolic actions. We examined whether these adipokines are independently associated with future aortic valve replacement (AVR).Design: In this longitudinal case-control study, we identified 336 cases who had undergone AVR due to AS, and who had previously participated in population-based health surveys. Two referents were matched to each case and leptin and adiponectin concentrations were analysed from stored baseline survey samples. Uni- and multivariable logistic regression analyses were used to estimate the risk of future AVR. An additional cohort was identified for validation including 106 cases with AVR and 212 matched referents.Results: Median age (interquartile range (IQR)) in years at survey was 59.9 (10.4) and at surgery 68.3 (12.7), and 48% were women. An elevated concentration of leptin was not associated with future AVR (odds ratio [95% confidence interval]) (1.10 [0.92–1.32]), although leptin was associated with a higher risk in patients with coronary artery disease (CAD) having more than 5 years between survey and AVR (1.41 [1.08–1.84]). Adiponectin was not associated with higher risk for future AVR (0.95 [0.82–1.11]), although after stratification for age, higher levels were associated with reduced risk for AVR in persons aged ≥60 years at surgery (0.79 [0.64–0.98]). In the validation study, leptin was associated with future AVR whereas adiponectin was not. None of the associations remained significant after adjustment for body mass index (BMI).Conclusions: The adipokine leptin may promote the development of AS.
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4.
  • Holmgren, Anders, et al. (författare)
  • Troponin T but not C-reactive protein is associated with future surgery for aortic stenosis : a population based nested case-referent study
  • 2020
  • Ingår i: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: High-sensitivity troponin T (hs-TnT) and high-sensitivity C reactive protein (hs-CRP) may convey prognostic information in patients with aortic stenosis (AS). This study evaluated if hs-TnT and hs-CRP associate with myocardial mass, and risk of future surgery for AS.Methods: In total, 336 patients (48% women) with surgery for AS with previous participation in large population surveys were identified. Preoperatively, myocardial mass and the presence of coronary artery disease (CAD) were assessed. Two matched referents were allocated for each case, and hs-TnT and hs-CRP were determined in stored plasma from the baseline survey. Conditional logistic regression analysis was used to estimate the risk (OR (95% CI)) related to one (natural logarithm) SD increase in hs-TnT and hs-CRP. Kaplan-Mayer and Cox regression analyses were used to evaluate time to surgery.Results: Median age (IQR) was 59.8 (10.3) years at survey, and median time between survey and surgery was 10.9 (9.3) years. Hs-TnT was independently associated with surgery for AS (1.24 (1.06–1.44)) irrespective of CAD, whereas Hs-CRP was not (1.05 (0.90–1.22)). Elevated hs-TnT levels at survey associated with shorter time to surgery (p<0.001), and with increased myocardial mass (p=0.002). Hs-CRP did not associate with time to surgery or with myocardial mass.Conclusions: Hs-TnT—but not hs-CRP—was associated with increased risk of—and shorter time to—future surgery for AS. Hs-TnT associated with myocardial mass at surgery which indicates that hs-TnT could be a potential biomarker for determining intervention.
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5.
  • Ljungberg, Johan, et al. (författare)
  • Early impairment of renal function (shrunken pore syndrome) is associated with increased risk for future surgery for aortic stenosis
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction Renal insufficiency is a known risk factor for cardiovascular disease. However, it is unknown if early impairment in renal function is associated with increased risk for aortic stenosis (AS). Recently a new approach was proposed to detect early impairment in renal function by using the ratio between glomerular filtration rate (GFR) calculated by cystatin C and GFR calculated by creatinine. Purpose To evaluate if the ratio between GFR cystatin C and GFR creatinine is associated with increased risk for AS requiring surgery and further, to evaluate if the ratio associates with survival. Methods We identified 334 patients that underwent surgery for AS after participation in population surveys (median age (interquartile range) 59.4 (10.3) years at survey and 68.3 (12.7) at surgery, 48% females). For each patient, two matched referents were allocated. Circulating levels of cystatin C and creatinine were determined at baseline (survey). Estimated glomerular filtration rates (eGFR) were calculated using the CAPA and Lund-Malmö-Revised formulas. Uni- and multivariable conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval]) related to one (ln) standard deviation increase in cystatin C, creatinine, eGFR cystatin C, eGFR creatinine, and in the ratio between eGFR cystatin C and eGFR creatinine, respectively. Results A high ratio was associated with lower risk for AS requiring surgery (OR 0.84 [0.73–0.97]). After stratification for sex, this effect was seen in women but not in men (0.74 [0.60–0.92] and 0.93 [0.76 [0.76–1.13], respectively). After further stratification for CAD, the association remained in women with CAD, but the effect was not seen in men with CAD (0.60 [0.44–0.83] and 0.96 [0.76 [0.75–1.23]). A high ratio was associated with longer survival in the entire cohort (HR 0.84 [0.75–0.95]). Conclusion A high ratio between eGFR based on cystatin C and eGFR based on creatinine was associated with lower risk for surgery for AS in those with CAD with a clear sex-difference. Early renal impairment is thus associated with future risk for AS requiring surgery. Further, a high ratio relates to longer survival. 
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6.
  • Ljungberg, Johan, et al. (författare)
  • Lipoprotein(a) and the Apolipoprotein B/A1 Ratio Independently Associate With Surgery for Aortic Stenosis Only in Patients With Concomitant Coronary Artery Disease
  • 2017
  • Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 6:12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Aortic stenosis (AS) has different clinical phenotypes, including AS with or without concomitant coronary artery disease (CAD). It is unknown whether these phenotypes share the same risk factors. In particular, lipoprotein(a) [Lp(a)] and apolipoproteins (Apo) are associated with AS, but it is unknown whether these associations differ among phenotypes. In this prospective analysis we examined the impact of Lp(a) and Apo in subgroups of patients with AS.METHODS AND RESULTS: We identified 336 patients (mean age at survey 56.7 years, 48% female) who underwent surgery for AS after a median 10.9 years (interquartile range 9.3 years), participants in 1 of 3 large population surveys. For each patient, 2 matched referents were allocated. Lp(a) and Apo were analyzed in the baseline samples. Uni- and multivariable logistic regression analyses were used to estimate risks related to a 1 (ln) standard deviation increase in Lp(a) and the ratio of Apo B to Apo A1 (Apo B/A1 ratio). High levels of Lp(a) predicted surgery for AS in 203 patients with concomitant CAD (odds ratio [95% confidence intervals]) (1.29 [1.07-1.55]), but not in 132 patients without CAD (1.04 [0.83-1.29]) in the fully adjusted model. Similarly, a high Apo B/A1 ratio predicted surgery in patients with concomitant CAD (1.43 [1.16-1.76]) but not in those without CAD (0.87 [0.69-1.10]).CONCLUSIONS: High levels of Lp(a) and a high Apo B/A1 ratio were associated with surgery for AS in patients with concomitant CAD but not in those with isolated AS. This finding may lead to a new avenue of research for targeted risk factor interventions in this population.
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7.
  • Ljungberg, Johan, et al. (författare)
  • Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk for future surgery for aortic stenosis
  • 2019
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 79:7, s. 524-530
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, a new approach was proposed to detect mild impairment in renal function: a reduced ratio between estimated glomerular filtration rate (eGFR) calculated by cystatin C and eGFR calculated by creatinine. We aimed to evaluate if this ratio is associated with aortic stenosis (AS) requiring surgery. We identified 336 patients that first participated in population surveys and later underwent surgery for AS (median age [interquartile range] 59.8 [10.3] years at survey and 68.3 [12.7] at surgery, 48% females). For each patient, two matched referents were allocated. Cystatin C and creatinine were determined in stored plasma. eGFR(cystatin C) and eGFR(creatinine) and their ratio were estimated. Conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval (CI)]) related to one (ln) standard deviation increase in the ratio between eGFR(cystatin C) and eGFR(creatinine). A high ratio was associated with lower risk for AS requiring surgery (OR [95% CI]) (OR 0.84 [0.73-0.97]), especially in women (0.74 [0.60-0.92] vs. 0.93 [0.76-1.13] in men). After further stratification for coronary artery disease (CAD), the association remained in women with CAD but not in women without CAD (0.60 [0.44-0.83] and 0.89 [0.65-1.23], respectively). In conclusion, a high ratio between eGFR(cystatin C) and eGFR(creatinine) was associated with lower risk for surgery for AS, especially in women. Mild impairment of renal function is thus associated with future risk for AS requiring surgery.
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8.
  • Ljungberg, Johan, et al. (författare)
  • Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement
  • 2018
  • Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 138:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Aortic valve stenosis (AS) is the most common indication for cardiac valve surgery; untreated AS is linked to high mortality. The etiological background of AS is unknown. Previous human studies were typically based on case-control studies. Biomarkers identified in prospective studies could lead to novel mechanistic insights. Methods: Within a large population survey with blood samples obtained at baseline, 334 patients were identified who later underwent surgery for AS (median age [interquartile range], 59.9 [10.4] years at survey and 68.3 [12.7] at surgery; 48% female). For each case, 2 matched referents were allocated. Plasma was analyzed with the multiplex proximity extension assay for screening of 92 cardiovascular candidate proteins. Conditional logistic regression models were used to assess associations between each protein and AS, with correction for multiple testing. A separate set of 106 additional cases with 212 matched referents was used in a validation study. Results: Six proteins (growth differentiation factor 15, galectin-4, von Willebrand factor, interleukin 17 receptor A, transferrin receptor protein 1, and proprotein convertase subtilisin/kexin type 9) were associated with case status in the discovery cohort; odds ratios ranged from 1.25 to 1.37 per SD increase in the protein signal. Adjusting the multivariable models for classical cardiovascular risk factors at baseline yielded similar results. Subanalyses of case-referent triplets (n=133) who showed no visible coronary artery disease at the time of surgery in the index person supported associations between AS and growth differentiation factor 15 (odds ratio, 1.40; 95% confidence interval, 1.10-1.78) and galectin-4 (odds ratio, 1.27; 95% confidence interval, 1.02-1.59), but these associations were attenuated after excluding individuals who donated blood samples within 5 years before surgery. In triplets (n=201), which included index individuals with concurrent coronary artery disease at the time of surgery, all 6 proteins were robustly associated with case status in all sensitivity analyses. In the validation study, the association of all but 1 (interleukin 17 receptor A) of these proteins were replicated in patients with AS with concurrent coronary artery disease but not in patients with AS without coronary artery disease. Conclusions: We provide evidence that 5 proteins were altered years before AS surgery and that the associations seem to be driven by concurrent atherosclerotic disease.
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9.
  • Lökk, Johan, et al. (författare)
  • Shifts in B12 opinions in primary health care of Sweden.
  • 2001
  • Ingår i: Scandinavian Journal of Public Health. - 1403-4948 .- 1651-1905. ; 29:2, s. 122-128
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: The diagnosis and management of vitamin B12 deficiency varies between countries and within countries. The aim of the study was to map current attitudes and values behind clinical decision-making in Swedish primary health care, which has a unique B12 tradition: two patients out of three are treated with oral high-dose cyanocobalamin. Most patients with B12-associated problems are managed in primary health care by general practitioners (GPs). METHODS: The study was designed to elucidate possible opinion shifts among GPs during the period 1996-1998. GPs (n=499), stratified and randomized, received a questionnaire with 24 statements on B12-associated clinical and laboratory problems, to be evaluated by a visuo-analogue scale. RESULTS: The majority of GPs in primary health care in Sweden accepted homocysteine and methylmalonic acid (MMA) as markers for functional deficiency of vitamin B12. The evaluation of classical markers of B12 deficiency was wary and balanced. There was a consensus of the need for B12 therapy to risk groups such as patients with atrophic gastritis or previous gastric surgery. The answers also appeared to reflect an improvement of professional knowledge and competence concerning B12-associated problems among Swedish GPs between 1996 and 1998. CONCLUSIONS: The overriding conclusion was that B12-associated opinions of Swedish GPs were stable within the period studied, with marginal improvements of knowledge and competence.
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10.
  • Lökk, Johan, et al. (författare)
  • Vitamin B12 in primary health care and geriatrics - attitudes, knowledge, competence.
  • 2001
  • Ingår i: International Journal of Geriatric Psychiatry. - : Wiley. - 0885-6230 .- 1099-1166. ; 16:10, s. 987-992
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The objective of the study was to test attitudes, knowledge and competence of Swedish general practitioners and geriatricians concerning B12-associated problems in 1998. METHODS: Postal questionnaires were sent to a random sample of 485 GPs and a total sample of 613 geriatricians. The response rates were 70% in the GP group and 69% in the geriatrician group. The questionnaire contained 24 statements to be evaluated by a visuo-analogue scale. RESULTS: There were small numerical differences between the two physician groups. The geriatricians were more aware of risk groups for B12 deficiency. GPs were less categorical concerning low hit rate in the laboratory testing of clinical conclusions. There were statistical differences in both directions for statements on pitfalls in laboratory diagnostics. GPs were somewhat less prone to give risk groups prophylactic B12 therapy. CONCLUSIONS: GPs and geriatricians appeared to be familiar with the current debate on B12-associated problems, suggesting that health care quality will be unaffected by patient transfer from hospital care to primary health care. Copyright 2001 John Wiley & Sons, Ltd.
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