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  • 1. Brück, Katharina
    et al.
    Jager, Kitty J
    Dounousi, Evangelia
    Kainz, Alexander
    Nitsch, Dorothea
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Rothenbacher, Dietrich
    Browne, Gemma
    Capuano, Vincenzo
    Ferraro, Pietro Manuel
    Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review2015Ingår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30, nr Supp. 4, s. iv6-iv16Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods.

    METHODS: For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers.

    RESULTS: We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m(2) in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval.

    CONCLUSIONS: The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study results.

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  • 2.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitetet.
    Adamsson, Viola
    Larsson, Anders
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Risérus, Ulf
    Influence of a prudent diet on circulating cathepsin S in humans2014Ingår i: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 13, nr 84Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Increased circulating cathepsin S levels have been linked to increased risk of cardiometabolic diseases and cancer. However, whether cathepsin S is a modifiable risk factor is unclear. We aimed to investigate the effects of a prudent diet on plasma cathepsin S levels in healthy individuals.

    FINDINGS: Explorative analyses of a randomized study were performed in 88 normal to slightly overweight and hyperlipidemic men and women (aged 25 to 65) that were randomly assigned to ad libitum prudent diet, i.e. healthy Nordic diet (ND) or a control group (habitual Western diet) for 6 weeks. Whereas all foods in the ND were provided, the control group was advised to consume their habitual diet throughout the study. The ND was in line with dietary recommendations, e.g. low in saturated fats, sugars and salt, but high in plant-based foods rich in fibre and unsaturated fats.The ND significantly decreased cathepsin S levels (from 20.1 (+/-4.0 SD) to 19.7 μg/L (+/-4.3 SD)) compared with control group (from 18.2 (+/-2.9 SD) to 19.1 μg/L (+/-3.8 SD)). This difference remained after adjusting for sex and change in insulin sensitivity (P = 0.03), and near significant after adjusting for baseline cathepsin S levels (P = 0.06), but not for change in weight or LDL-C. Changes in cathepsin S levels were directly correlated with change in LDL-C.

    CONCLUSIONS: Compared with a habitual control diet, a provided ad libitum healthy Nordic diet decreased cathepsin S levels in healthy individuals, possibly mediated by weight loss or lowered LDL-C. These differences between groups in cathepsin S were however not robust and therefore need further investigation.

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  • 3.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Risérus, Ulf
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, Johan
    Basu, Samar
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Association between serum cathepsin S and mortality in older adults2011Ingår i: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 306, nr 10, s. 1113-1121Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Experimental data suggest that cathepsin S, a cysteine protease, is involved in the complex pathways leading to cardiovascular disease and cancer. However, prospective data concerning a potential association between circulating cathepsin S levels and mortality are lacking. Objective To investigate associations between circulating cathepsin S levels and mortality in 2 independent cohorts of elderly men and women.

    Design, Setting, and Participants: Prospective study using 2 community-based cohorts, the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1009; mean age: 71 years; baseline period: 1991-1995; median follow-up: 12.6 years; end of follow-up: 2006) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 987; 50% women; mean age: 70 years; baseline period: 2001-2004; median follow-up: 7.9 years; end of follow-up: 2010). Serum samples were used to measure cathepsin S.

    Main Outcome Measure Total mortality.

    Results: During follow-up, 413 participants died in the ULSAM cohort (incidence rate: 3.59/100 person-years at risk) and 100 participants died in the PIVUS cohort (incidence rate: 1.32/100 person-years at risk). In multivariable Cox regression models adjusted for age, systolic blood pressure, diabetes, smoking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease, higher serum cathepsin S was associated with an increased risk for mortality (ULSAM cohort: hazard ratio [HR] for 1-unit increase of cathepsin S, 1.04 [95% CI, 1.01-1.06], P = .009; PIVUS cohort: HR for 1-unit increase of cathepsin S, 1.03 [95% CI, 1.00-1.07], P = .04). In the ULSAM cohort, serum cathepsin S also was associated with cardiovascular mortality (131 deaths; HR for quintile 5 vs quintiles 1-4, 1.62 [95% CI, 1.11-2.37]; P = .01) and cancer mortality (148 deaths; HR for 1-unit increase of cathepsin S, 1.05 [95% CI, 1.01-1.10]; P = .01).

    Conclusions Among elderly individuals in 2 independent cohorts, higher serum cathepsin S levels were associated with increased mortality risk. Additional research is needed to delineate the role of cathepsin S and whether its measurement might have clinical utility.

  • 4.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Risérus, Ulf
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, Johan
    Lind, Lars
    Larsson, Anders
    Basu, Samar
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Serum cathepsin S levels independently predicts total- and cardiovascular mortality in elderly men2011Ingår i: European Society of Cardiology Congress 2011, Stockholm, 2011Konferensbidrag (Övrigt vetenskapligt)
  • 5.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Risérus, Ulf
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, Johan
    Lind, Lars
    Larsson, Anders
    Basu, Samar
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Serum cathepsin S levels independently predicts total- and cardiovascular mortality in elderly men2010Ingår i: Kardiovaskulära vårmötet, Göteborg, 2010Konferensbidrag (Övrigt vetenskapligt)
  • 6.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Risérus, Ulf
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, Johan
    Lind, Lars
    Larsson, Anders
    Basu, Samar
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Serum cathepsin S predicts the risk for mortality in elderly men and women2011Ingår i: Kardiovaskulära vårmötet, Örebro, 2011Konferensbidrag (Övrigt vetenskapligt)
  • 7.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Risérus, Ulf
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, Johan
    Lind, Lars
    Larsson, Anders
    Basu, Samar
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Serum cathepsin S predicts the risk for mortality in elderly men and women2011Konferensbidrag (Övrigt vetenskapligt)
  • 8.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Risérus, U
    Ingelsson, E
    Helmersson, J
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Sundström, J
    Lind, L
    Larsson, A
    Basu, S
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Serum cathepsin S is associated with serum C-reactive protein and interleukin-6 independently of obesity in elderly men2010Ingår i: Journal of Clinical Epidemiology, ISSN 0895-4356, E-ISSN 1878-5921, Vol. 95, nr 9, s. 4460-4464Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Cathepsin S has been suggested provide a mechanistic link between obesity and atherosclerosis, possibly mediated via adipose tissue-derived inflammation. Previous data have shown an association between circulating cathepsin S and inflammatory markers in the obese, but to date, community-based reports are lacking. Accordingly, we aimed to investigate the association between serum levels of cathepsin S and markers of cytokine-mediated inflammation in a community-based sample, with prespecified subgroup analyses in nonobese participants.

    Methods: Serum cathepsin S, C-reactive protein (CRP), and IL-6 were measured in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men; mean age 71 years, n = 991). CRP and IL-6 were also measured at a reexamination after 7 yr.

    Results: After adjustment for age, body mass index, fasting plasma glucose, diabetes treatment, systolic blood pressure, diastolic blood pressure, hypertension treatment, serum cholesterol, serum high-density lipoprotein cholesterol, prior cardiovascular disease, smoking, and leisure time physical activity, higher cathepsin S was associated with higher CRP (regression coefficient for 1 SD increase, 0.13; 95% confidence interval 0.07–0.19; P < 0.001) and higher serum IL-6 (regression coefficient for 1 SD increase, 0.08; 95% confidence interval 0.01–0.14; P = 0.02). These associations remained similar in normal-weight participants (body mass index <25 kg/m2, n = 375). In longitudinal analyses, higher cathepsin S at baseline was associated with higher serum CRP and IL-6 after 7 yr.

    Conclusions: These results provide additional evidence for the interplay between cathepsin S and inflammatory activity and suggest that this association is present also in normal-weight individuals in the community.

  • 9.
    Jobs, Elisabeth
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Risérus, Ulf
    Ingelsson, Erik
    Sundström, Johan
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Iggman, David
    Basu, Samar
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Serum cathepsin S is associated with decreased insulin sensitivity and the development of diabetes type 2 in a community-based cohort of elderly men2012Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, nr 1, s. 163-165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE. To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes.

    RESEARCH DESIGN AND METHODS. Serum cathepsin S, insulin sensitivity (euglycaemic-hyperinsulinaemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up.

    RESULTS. After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase -0.09 [95% CI -0.14 to -0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08-2.01], P = 0.01).

    CONCLUSIONS. Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.

  • 10. Krantz, Christina
    et al.
    Accordini, Simone
    Alving, Kjell
    Corsico, Angelo G.
    Demoly, Pascal
    Ferreira, Diogenes S.
    Forsberg, Bertil
    Garcia-Aymerich, Judith
    Nerpin, Elisabet
    Högskolan Dalarna, Institutionen för hälsa och välfärd, Medicinsk vetenskap. Uppsala University.
    Survey III, The European Community Respiratory Health
    Cross-sectional study on exhaled nitric oxide in relation to upper airway inflammatory disorders with regard to asthma and perennial sensitisation2022Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 52, nr 2, s. 297-311Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitisation as a major determinant.

    Objective

    We aimed to see if there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitisation, in a multi-centre population-based study.

    Methods

    A total of 741 subjects with current asthma and 4,155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitisation status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO was assessed in adjusted multivariate regression models and test for interaction with perennial sensitisation and asthma on the relation between UAID and FeNO were made.

    Results

    UAID were associated with higher FeNO after adjusting for perennial sensitisation, asthma and other confounders: with 4.4 (0.9?7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7?9.2)% higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitisation was found in the relationship between current rhinitis and FeNO (p=0.03) and between rhinoconjunctivitis and FeNO (p=0.03). After stratification by asthma and perennial sensitisation, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitisation, with 12.1 (0.2?25.5) % higher FeNO in subjects with current rhinitis than in those without.

    Conclusions & Clinical Relevance

    Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitisation. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in the upper and lower airways and that sensitisation needs to be accounted for in the relation between FeNO and rhinitis.

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  • 11.
    Leksell, Janeth
    et al.
    Uppsala University, Akademiska sjukhuset, Uppsala.
    Toft, Eva
    Karolinska Institutet, Huddinge, Stockholm; Diabetes Unit, Ersta Hospital, Stockholm.
    Rosman, Jessica
    Uppsala University, Akademiska sjukhuset, Uppsala.
    Eriksson, Jan W
    Uppsala University, Akademiska sjukhuset, Uppsala.
    Fischier, Johan
    Karolinska University hospital, Stockholm.
    Lindholm-Olinder, Anna
    Uppsala University, Akademiska sjukhuset, Uppsala; Karolinska Institutet, Södersjukhuset, Stockholm.
    Rosenblad, Andreas
    Uppsala University, Akademiska sjukhuset, Uppsala; Karolinska Institutet, Stockholm; Uppsala University, Uppsala.
    Nerpin, Elisabet
    Högskolan Dalarna, Institutionen för hälsa och välfärd, Medicinsk vetenskap. Uppsala University, Uppsala .
    Virtual clinic for young people with type 1 diabetes: a randomised wait-list controlled study2023Ingår i: BMC Endocrine Disorders, E-ISSN 1472-6823, Vol. 23, nr 1, artikel-id 255Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The transition from paediatric to adult care for young adults with type 1 diabetes poses unique challenges. Virtual diabetes clinics using smartphone applications offer a promising approach to support self-management and enhance communication with healthcare providers. The primary objective of this study was to evaluate the effects of a virtual diabetes clinic on glycaemic control, treatment satisfaction, and quality of life among young adults diagnosed with type 1.

    METHODS: 79 participants with type 1 diabetes aged 18-25 years were included in a prospective, single-centre, randomised, wait-list controlled trial. Participants were randomly assigned to either the intervention group or the wait-list control group. The intervention group received instant access to a virtual care platform called Vista Dialog, which facilitated real-time communication between patients and healthcare providers. Glycosylated haemoglobin (HbA1c) levels, time in range (TIR), time below range (TBR), diabetes treatment satisfaction, and quality of life were assessed at baseline and after 6 months.

    RESULTS: Baseline characteristics were similar between the intervention and control groups, except for education level, where there was a skewed distribution between the groups (the intervention group had a lower education level). At the 6-month follow-up, there were no significant differences in HbA1c levels, TIR, TBR, or diabetes treatment satisfaction between the two groups. However, the intervention group demonstrated a significant decrease in the burden on physical health compared with the control group, indicating an improved quality of life.

    CONCLUSIONS: The implementation of a virtual diabetes clinic using the Vista Dialog platform did not result in significant improvements in glycaemic control or treatment satisfaction compared with usual care. However, it did show potential benefits in terms of reducing the burden on physical health and improving quality of life in young adults with type 1 diabetes. Further research is needed to explore the long-term effects and optimal use of virtual clinics in diabetes management.

    TRIAL REGISTRATION: ISRCTN number: 73,435,627 (registration date: 23/10/2019): https://doi.org/10.1186/ISRCTN73435627 . The performance and results of this trial adhere to the guidelines outlined in the CONSORT 2010 (Consolidated Standards of Reporting Trials) recommendations.

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  • 12.
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    The combined effect of low-grade albuminuria and a reduced glomerular filtration rate for the prediction of cardiovascular disease2009Ingår i: XI Kardiovasculära Vårmötet 2009, Uppsala, 2009Konferensbidrag (Övrigt vetenskapligt)
    Abstract [sv]

    Abstract Background: The combined impact of reduced glomerular filtration rate (GFR) and microalbuminuria on the risk for cardiovascular disease is scarcely studied. Thus, we aimed to identify optimal cut-offs for albuminuria and GFR for the prediction of cardiovascular mortality in a community-based cohort of elderly men and to investigate whether the combined addition of these kidney markers adds independent prognostic information. Material and methods: In a sub-sample, without cardiovascular disease at baseline, of the community-based Uppsala Longitudinal Study of Adult Men (ULSAM, n=649, mean age 71 years, median follow-up 12.9 years; 86 cardiovascular deaths during follow-up), GFR (cystatin C-based) and urinary albumin excretion rate (UAER, overnight urine collection) were calculated. Results: The following cut-off points were identified in order to achieve optimal model discrimination based on the integrated discriminative improvement: UAER 6.25 µg/min and GFR 45 ml/min/1.73m2. In Cox-proportional hazard models adjusted for established risk factors (age, systolic blood pressure, antihypertensive treatment, total cholesterol, HDL cholesterol, lipid lowering treatment, diabetes, smoking, body-mass-index and previous cardiovascular disease), participants with low-grade albuminuria only (>6.25 µg/min, HR 1.75, 95 % CI 1.05-2.89), participants with reduced GFR only (<45 ml/min/1.73m2, HR 2.56, 95 % CI 1.05-6.28) and participants with both low-grade albuminuria and reduced GFR (HR 5.91, 95% CI 2.87-12.18) were at higher risk for cardiovascular mortality compared to participants with normoalbuminuria and normal GFR.

  • 13.
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    The kidney in different stages of the cardiovascular continuum2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. The complex, interaction between the kidney and the cardiovascular system is incompletely understood, particularly at the early stages of the cardiovascular continuum.

    The overall aim of this thesis was to clarify novel aspects of the interplay between the kidney and the cardiovascular system at different stages of the cardiovascular continuum; from risk factors such as insulin resistance, inflammation and oxidative stress, via sub-clinical cardiovascular damage such as endothelial dysfunction and left ventricular dysfunction, to overt cardiovascular death.

    This thesis is based on two community-based cohorts of elderly, Uppsala Longitudinal Study of Adult Men (ULSAM) and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS).

    The first study, show that higher insulin sensitivity, measured with euglycemic-hyperinsulinemic clamp technique was associated to improve estimated glomerular filtration rate (eGFR) in participants with normal fasting plasma glucose, normal glucose tolerance and normal eGFR. In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function during follow-up. In the second study, eGFR was inversely associated with different inflammatory markers (C-reactive protein, interleukin-6, serum amyloid A) and positively associated with a marker of oxidative stress (urinary F2-isoprostanes). In line with this, the urinary albumin/creatinine ratio was positively associated with these inflammatory markers, and negatively associated with oxidative stress.

    In study three, higher eGFR was associated with better endothelial function as assessed by the invasive forearm model. Further, in study four, higher eGFR was significantly associated with higher left ventricular systolic function (ejection fraction). The 5th study of the thesis shows that higher urinary albumin excretion rate (UAER) and lower eGFR was independently associated with an increased risk for cardiovascular mortality. Analyses of global model fit, discrimination, calibration, and reclassification suggest that UAER and eGFR add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent cardiovascular disease.

    Conclusion: this thesis show that the interaction between the kidney and the cardiovascular system plays an important role in the development of cardiovascular disease and that this interplay begins at an early asymptomatic stage of the disease process.

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  • 14.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Institutionen för hälsa och välfärd, Medicinsk vetenskap. Uppsala University.
    Ferreira, D. S.
    Weyler, J.
    Schlunnsen, V.
    Jogi, R.
    Raherison Semjen, C.
    Gislasson, T.
    Demoly, P.
    Heinrich, J.
    Malinovschi, A.
    Bronchodilator response and lung function decline: Associations with exhaled nitric oxide with regard to sex and smoking status2021Ingår i: World Allergy Organization Journal, E-ISSN 1939-4551, Vol. 14, nr 5, artikel-id 100544Artikel i tidskrift (Refereegranskat)
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    fulltext
  • 15.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Helmersson-Karlqvist, Johanna
    Riserus, Ulf
    Sundström, Johan
    Larsson, Anders
    Jobs, Elisabeth
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Basu, Samar
    Ingelsson, Erik
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men: a cross-sectional study2012Ingår i: BMC research notes, ISSN 1756-0500, Vol. 5, nr 1, s. 537-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Accordingly, we aimed at investigating the associations between estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and markers of different inflammatory pathways and oxidative stress in a community based cohort of elderly men. FINDINGS: Cystatin C-based GFR, ACR, and biomarkers of cytokine-mediated inflammation (interleukin-6, high-sensitivity C-reactive protein[CRP], serum amyloid A[SAA]), cyclooxygenase-mediated inflammation (urinary prostaglandin F2alpha [PGF2alpha]), and oxidative stress (urinary F2 isoprostanes) were assessed in the Uppsala Longitudinal Study of Adult Men(n = 647, mean age 77 years). RESULTS: In linear regression models adjusting for age, BMI, smoking, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and treatment with statins, ACE-inhibitors, ASA, and anti-inflammatory agents, eGFR was inversely associated with CRP, interleukin-6, and SAA (beta-coefficient -0.13 to -0.19, p < 0.001 for all), and positively associated with urinary F2-isoprostanes (beta-coefficient 0.09, p = 0.02). In line with this, ACR was positively associated with CRP, interleukin-6, and SAA (beta- coefficient 0.09-0.12, p < 0.02 for all), and negatively associated with urinary F2-isoprostanes (beta-coefficient -0.12, p = 0.002). The associations were similar but with lower regression coefficients in a sub-sample with normal eGFR (>60 ml/min/1.73 m2, n = 514), with the exception that F2-isoprostane and SAA were no longer associated with eGFR. CONCLUSION: Our data indicate that cytokine-mediated inflammation is involved in the early stages of impaired kidney function in the elderly, but that cyclooxygenase-mediated inflammation does not play a role at this stage. The unexpected association between higher eGFR/lower albuminuria and increased F2-isoprostanes in urine merits further studies.

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  • 16.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Riserus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Andren, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Jobs, Elisabeth
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    The association between glomerular filtration rate and left ventricular function in two independent community-based cohorts of elderly2014Ingår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, nr 11, s. 2069-2074Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The cardiorenal syndrome, the detrimental bi-directional interplay between symptomatic heart failure and chronic kidney disease, is a major clinical challenge. Nonetheless, it is unknown if this interplay begins already at an asymptomatic stage. Therefore we investigated whether the glomerular filtration rate (GFR) is associated with left ventricular function in participants free from clinical heart failure and with a left ventricular ejection fraction (LVEF) > 40% and with pre-specified sub-group analyses in individuals with a GFR > 60 mL/min/m(2). Two independent community-based cohorts were used; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 911; 50% women; mean age: 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 538; mean age: 71 years). We investigated cross-sectional association between cystatin C-based GFR (estimated glomerular function [eGFR]) and systolic (LVEF), diastolic- (isovolumic relaxation time [IVRT]) and global left ventricular function (myocardial performance index [MPI]) determined by echocardiography. In both PIVUS and ULSAM, higher eGFR was significantly associated with higher LVEF (P = 0.004 [PIVUS] and P = 0.005 [ULSAM]). In PIVUS, higher eGFR was significantly associated with lower IVRT (P = 0.001) and MPI (P = 0.006), in age- and sex-adjusted models. After further adjustment for cardiovascular risk factors, the association between higher eGFR and higher LVEF was still statistically significant (P = 0.008 [PIVUS] and P = 0.02 [ULSAM]). In PIVUS, the age- and sex-adjusted association between eGFR and left ventricular function was similar in participants with eGFR > 60 mL/min/m(2). Our data suggest that the interplay between kidney and heart function begins prior to the development of symptomatic heart failure and kidney disease.

  • 17.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Riserus, Ulf
    Sundström, Johan
    Larsson, Anders
    Hallan, Stein
    Zethelius, Björn
    Berglund, Lars
    Basu, Samar
    Ärnlöv, Johan
    A Cystatin C-based glomerular filtration rate equation is a stronger predictor of cardiovascular mortality compared to creatinine-based equations2010Ingår i: Svenska Kardiovasculära vårmötet, Göteborg, 2010Konferensbidrag (Övrigt vetenskapligt)
    Abstract [sv]

    Background: Several prior studies report that decreased estimated glomerular filtration rate (eGFR) predicts cardiovascular disease in the general population, but this is less studied in a primary preventive setting. Currently, various methods are available to assess eGFR. In the present study, we aimed to evaluate different eGFR-equations (creatinine-based or cystatin C-based), for the prediction of cardiovascular death. Material and methods: In men without cardiovascular disease, participating in the community-based Uppsala Longitudinal Study of Adult Men (ULSAM, n=649, mean age 71 years, median follow-up 12.9 years; 86 cardiovascular deaths during follow-up), eGFR was calculated from circulating creatinine by using the Modification of Diet in Renal Disease formula (eGFRMDRD) and the Chronic Kidney Disease Epidemiology Collaboration formula (eGFRCKD-EPI) and from circulating cystatin C using the following formula: 77.24x-1.2623 (eGFRcyst). Results: In Cox-proportional hazard models, 1-SD increase in eGFRcyst was associated with lower risk of cardiovascular mortality after adjustment for established cardiovascular risk factors and urinary albumin excretion rate (hazard ratio 0.74, 95% CI 0.59-0.92 (p=0.007). However, the creatinine-based GFR equations were not significantly associated with cardiovascular death (for eGFRMDRD: hazard ratio 0.84, 95% CI 0.67-1.06, (p=0.14), for eGFRCKD-EP : hazard ratio 0.86, 95% CI 0.69-1.07 (p=0.17)) in multivariable models. Moreover, when eGFRcyst was incorporated to a model with established risk factors, the integrated discrimination improvement was significantly increased 0.015, (p=0.02). Also eGFRcyst, provided improved discrimination beyond established risk factors and urinary albumine excretion rate (0.012, p=0.03). No improvement in integrated discrimination were seen with eGFRMDRD (p=0.25) or eGFRCKD-EPI (p=0.36). Conclusion: In our community-based cohort of elderly men free from cardiovascular disease at baseline, eGFRcyst significantly predicted cardiovascular death while the creatinine-based eGFR-equations did not. The fact that eGFRcyst improved model discrimination beyond established cardiovascular risk factors suggest that it may be a relevant risk marker for cardiovascular death in the elderly.

  • 18.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Riserus, Ulf
    Sundström, Johan
    Larsson, Anders
    Jobs, Elisabeth
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Hallan, Stein
    Ärnlöv, Johan
    The combined contribution of albuminuria and glomerular filtration rate to the prediction of cardiovascular mortality in elderly men2011Ingår i: EuroPrevent, Geneve, 2011Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Purpose: Patients with severe chronic kidney disease are at substantially higher risk to develop cardiovascular disease, but an increased risk is also evident in individuals with only mild signs of kidney damage in the community. Cardiovascular risk prediction is particularly important in the primary prevention of cardiovascular disease. Nevertheless, data on whether the combined addition of albuminuria and estimated glomerular filtration rate (eGFR) improves cardiovascular risk prediction in individuals without cardiovascular disease in the community is scarce. Methods and results: We investigated associations between urinary albumin excretion rate (UAER), cystatin C-based eGFR and cardiovascular mortality in a community-based cohort of elderly men (ULSAM-study; n=1113, mean age 71 years, 208 cardiovascular deaths, median follow-up 12.9 years) with pre-specified analyses in participants without cardiovascular disease (n=649, 86 cardiovascular deaths). Using multivariable Cox regression, higher UAER and lower eGFR were associated with increased risk for cardiovascular mortality independently of established cardiovascular risk factors in the whole sample and in men without cardiovascular disease at baseline (sub-sample without cardiovascular disease: UAER; hazard ratio per 1-SD 1.26, 95% CI 1.05-1.51, p=0.01; eGFR: hazard ratio per 1-SD 0.74, 95% CI 0.59-0.92, p=0.007). Analyses of model discrimination, calibration, reclassification and global fit suggested that UAER and eGFR add relevant prognostic information beyond established cardiovascular risk factors also in participants without prevalent cardiovascular disease. Interestingly, established cut-offs used to diagnose microalbuminuria (UAER>20µg/min) and chronic kidney disease stage 3 (eGFR<60ml/min/1.73m2), appeared less suitable for cardiovascular risk prediction (integrated discrimination improvement (IDI) 0.006, p=0.11, while cut-offs UAER>6µg/min and eGFR<45ml/min/1.73m2 significantly improved IDI (0.047, p<0.001) Conclusion: UAER and eGFR improved cardiovascular risk prediction beyond established cardiovascular risk factors, suggesting that these kidney biomarkers may be useful in predicting cardiovascular death in the elderly.

  • 19.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Risérus, Ulf
    Helmersson-Karlqvist, Johanna
    Sundström, Johan
    Jobs, Elisabeth
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Association between glomerular filtration rate and endothelial function in an elderly community cohort2012Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, nr 1, s. 242-246Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Endothelial dysfunction is prevalent among individuals with chronic kidney disease. However, the association between glomerular filtration rate and endothelial function in the community is unclear and needs to be investigated in the general population.

    METHODS: In the community-based Prospective Investigation of the Vasculature of Uppsala Seniors study (PIVUS, n = 952, mean age 70, women 49.3%), we investigated cross-sectional associations between estimated cystatin C-based glomerular filtration rate (eGFR), and 3 measures representing different aspects of endothelial function (endothelial-dependent vasodilation [EDV], endothelial independent vasodilatation [EIDV], and flow-mediated dilatation [FMD]). We also performed pre-specified sub-group analyses in participants with normal eGFR (>60 ml/min/1.73 m(2)).

    RESULTS: In the whole cohort, 10 ml/min/1.73 m(2) higher eGFR was associated with 3% higher EDV (p = 0.001) and 2% higher EIDV (p = 0.007), adjusted for age and sex. The associations were attenuated and no longer statistically significant after adjusting for established cardiovascular risk factors. In participants with eGFR >60 ml/min/1.73 m(2), 10 ml higher eGFR was associated with 2% higher EDV (p = 0.04) after adjusting for sex and age. eGFR was not associated to FMD in any model or sub-sample.

    CONCLUSION: This community-based study suggests that eGFR is associated with endothelial function also in persons with normal kidney function, but that this association is largely explained by confounding by established cardiovascular risk factors. Thus, our data do not support the notion of a direct causal interplay between renal and vascular function prior to the development of CKD.

  • 20.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ingelsson, Erik
    Risérus, Ulf
    Sundström, Johan
    Larsson, Anders
    Jobs, Elisabeth
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Hallan, Stein
    Zethelius, Björn
    Berglund, Lars
    Basu, Samar
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    The combined contribution of albuminuria and glomerular filtration rate to the prediction of cardiovascular mortality in elderly men2011Ingår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, nr 9, s. 2820-2827Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Cardiovascular risk prediction is particularly important in the primary prevention of cardiovascular disease (CVD). Yet, data on whether the combined addition of albuminuria and estimated glomerular filtration rate (eGFR) improves cardiovascular risk prediction in individuals without CVD in the community is scarce.

    METHODS: We investigated associations between urinary albumin excretion rate (UAER), cystatin C-based eGFR and cardiovascular mortality in a community-based cohort of elderly men (ULSAM study; n = 1113, mean age 71 years, 208 cardiovascular deaths, median follow-up 12.9 years) with prespecified analyses in participants without CVD (n = 649, 86 cardiovascular deaths).

    RESULTS: Using multivariable Cox regression, higher UAER and lower eGFR were associated with increased risk for cardiovascular mortality independently of established cardiovascular risk factors in the whole sample and in men without CVD at baseline [subsample without CVD: UAER; hazard ratio (HR) per 1 SD 1.26, 95% confidence interval (CI) 1.05-1.51, P = 0.01; eGFR: HR per 1 SD 0.74, 95% CI 0.59-0.92, P = 0.007]. Analyses of model discrimination, calibration, reclassification and global fit suggested that UAER and eGFR also add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent CVD. Interestingly, established cutoffs used to diagnose microalbuminuria (UAER > 20 μg/min) and chronic kidney disease Stage 3 (eGFR < 60 mL/min/1.73 m(2)), appeared less suitable for cardiovascular risk prediction [integrated discrimination improvement (IDI) 0.006, P = 0.11], while cutoffs UAER > 6 μg/min and eGFR < 45 mL/min/1.73 m(2) significantly improved IDI (0.047, P < 0.001).

    CONCLUSIONS: UAER and eGFR improved cardiovascular risk prediction beyond established cardiovascular risk factors, suggesting that these kidney biomarkers may be useful in predicting cardiovascular death in elderly men.

  • 21.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala University.
    Jacinto, Tiago
    Fonseca, João A.
    Alving, Kjell
    Janson, Christer
    Malinovschi, Andrei
    Systemic inflammatory markers in relation to lung function in NHANES. 2007–20102018Ingår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 142, s. 94-100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Low-grade systemic inflammation, mainly assessed by C-reactive protein (CRP), has been associated with impaired lung function. Few studies have studied if CRP, blood eosinophils, and blood neutrophils offer additive information in relation to lung function. Objectives To analyse associations between lung function and CRP, blood eosinophils, and blood neutrophils, with special regard to additive information of combining the inflammatory markers. Methods Cross-sectional study on 7753 participants, 20–80 years of age, in the National Health and Nutrition Examination Survey. Gender-based tertiles for CRP, blood eosinophils, and blood neutrophils were analysed in relation to the following lung function parameters: forced expiratory volume in 1 s (FEV1% predicted), forced vital capacity (FVC % predicted), and FEV1/FVC ratio. Results CRP, blood eosinophils, and blood neutrophils levels were inversely related to FEV1 and FVC. Only blood eosinophils and blood neutrophils were inversely related to FEV1/FVC ratio. Further, lower lung function was found with increased number of elevated inflammatory markers in the highest tertile (one, two or three vs. non elevated) for FEV1 (β-coeff., −2.20, −4.43, and −6.43, p < 0.001) and FVC (β-coeff., −1.70, −3.15 and −5.33, p < 0.001), respectively. Conclusions & clinical relevance CRP, blood eosinophils, and blood neutrophils offer independent and additive information in relation to lower FEV1 and FVC in the general population. This indicates that a combination of biomarkers yields more information than the biomarkers assessed individually.

  • 22.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Jarvis, Debbie
    Olivieri, M
    Gislason, T
    Olin, AC
    Jansson, Christer
    Malinovschi, Andrei
    Different relation between exhaled nitric oxide and lung function with regard to current smoking2018Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Background: Exhaled nitric oxide (FeNO) is a non-invasive marker of airway inflammation. Smokingreduces FeNO by 30-60%. Weak positive relation between lung function and FeNO has been inconsistently described. This has not been separately for smokers. Therefore we investigated the relation between lung function and FeNO with regard to smoking.

    Methods: FeNO and lung function post-bronchodilation (BD) were measured in 4813 subjects from the European Community Respiratory Health Survey III. GLI reference values were used. Smoking habits were self-reported.

    Results: Current smokers with FEV1 <lower limit of normal (LLN) had lower FeNO levels (ppb, geometric mean (95%CI)) than subjects with FEV1 ≥LLN: 10.1 (9.1, 11.1) vs 11.7 (11.3, 12.2), p=0.005, while the opposite was found in non-smokers: 20.0 (18.4, 21.6) vs 18.5 (18.2, 18.8), p=0.03. This interaction with current smoking was significant both before and after adjustments for study centres, age, BMI and gender (p=0.001 and p=0.004). Current smokers with FEV1/FVC <LLN had lower FeNO than current smokers with FEV1/FVC ≥LLN: 10.5 (9.4, 11.6) vs 11.6 (11.2, 12.1), p=0.04, and the opposite was found in non-smokers: 20.8 (19.1, 22.7) vs 18.4 (18.1, 18.8), p<0.001. There was a significant interaction with current smoking both in unadjusted and adjusted models (both p<0.001).

    Conclusion: Higher FeNO relates with lower FEV1 and FEV1/FVC-ratio among non-smoking individuals, suggesting that the obstruction is related with airways inflammation. In current smokers, higher FeNO relates with better preserved lung function and this finding warrants further studies to understand the underlying mechanisms. Presented on behalf of ECRHS III (www.ecrhs.org)

  • 23.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Joao, F. A
    Alving, Kjell
    Jansson, Christer
    Malinovschi, Andrei
    Blood cell counts and C-reactive protein inrelation to lung function in NHANES 2007-20102018Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Background:

    Low-grade systemic inflammation is associated with impaired lung function. Few studies have examined if C-reactive protein (CRP), blood eosinophil (B-Eos), and blood neutrophil (B-Neu) counts offer additive information in relation to lung function. The aim of this study was to analyse associations between CRP, BEos, and B-Neu and effects on lung function, with special regards to additive information.

    Methods:

    Cross-sectional study on 7,753 participants, 20-80 years of age, in the National Health and Nutrition Examination Survey. Gender-based tertiles for CRP, B-Eos, and B-Neu were analyzed in relation to forced expiratory volume in 1 second (FEV1 % predicted), forced vital capacity (FVC % predicted), and FEV1/FVC ratio.

    Results:

    CRP, B-Eos, and B-Neu were inversely related to FEV1 and FVC. Only B-Eos and B-Neu were inversely related to FEV1/FVC ratio. Further, lower lung function was found with increased number of elevated

    inflammatory markers in the highest tertile (one, two or three vs. non elevated) for FEV1 (% predicted): β-coefficients (95% CI) -2.20(-2.98, -1.41), -4.43 (-5.39, -3.45), and -6.43(-8.07, -4.79), all P=0.001; FVC (% predicted): -1.70 (-2.42, -0.98), -3.17 (-4.06, -2.29), and -5.34 (-6.85, -3.84), all P=0.001.

    Conclusion:

    CRP, B-Eos, and B-Neu offer independent and additive information in relation to lower FEV1 and FVC in the general population. This indicates that a combination of biomarkers yields more information than the biomarkers assessed individually. The mechanisms appear to be different, as B-Neu and B-Eos seem to relate more closely to obstructive impairment, e.g., lower FEV1/FVC ratio, which was not found for CRP.

  • 24.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Olivieri, M
    Gislason, T
    Olin, A C
    Nielsen, R
    Johannessen, A
    Ferreira, D S
    Marcon, A
    Heinric, J
    Malinovschi, A
    Determinants of fractional exhaled nitric oxide in healthy men and women from the European Community Respiratory Health Survey III2019Ingår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, nr 7, s. 969-979Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: The fractional exhaled nitric oxide (FE NO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FE NO as a reliable biomarker, it is important to investigate factors that influence FE NO in healthy individuals. Men have higher levels of FE NO than women, but it is unclear whether determinants of FE NO differ by sex.

    OBJECTIVE: To identify determinants of FE NO in men and women without lung diseases.

    METHOD: FE NO was validly measured in 3,881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease RESULTS: Exhaled NO levels were 21.3% higher in men compared with women p<0.001. Being in the upper age quartile (60.3-67.6 years) men had 19.2 ppb (95% CI: 18.3, 20.2) higher FE NO than subjects in the lowest age quartile (39.7-48.3 years) p=0.02. Women in the two highest age quartiles (54.6-60.2 and 60.3-67.6 years) had 15.4 ppb (14.7, 16.2), p=0.03 and 16.4 ppb (15.6, 17.1), p=<0.001 higher FE NO, compared with the lowest age quartile. Height was related to 8% higher FE NO level in men (p<0.001) and 5% higher FE NO levels in women (p=0.008). Men who smoked had 37% lower FE NO levels and women had 30% lower levels compared with never-smokers (p<0.001 for both). Men and women sensitized to both grass and perennial allergens had higher FE NO levels compared with non-sensitized subjects 26% and 29%, p<0.001 for both.

    CONCLUSION & CLINICAL RELEVANCE: FE NO levels were higher in men than women. Similar effects of current smoking, height, and IgE sensitization were found in both sexes. FE NO started increasing at lower age in women than in men, suggesting that interpretation of FE NO levels in adults aged over 50 years should take into account age and sex. 

  • 25.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Risérus, U
    Ingelsson, E
    Sundström, J
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Larsson, A
    Basu, S
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Insulin sensitivity, measured with euglycaemic-hyperinsulinaemic clamp is independently associated with glomerular filtration rate in elderly men2008Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, nr 8, s. 1550-5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE—To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR. RESEARCH DESIGN AND METHODS—We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C–based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years. RESULTS—Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69–1.68]; P < 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n = 443; P < 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR <50 ml/min per 1.73 m2) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40–0.84]; P < 0.004). CONCLUSIONS—Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality.

  • 26.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Risérus, Ulf
    Ingelsson, Erik
    Sundström, Johan
    Jobs, Magnus
    Larsson, Anders
    Basu, Samar
    Ärnlöv, Johan
    Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort2008Konferensbidrag (Refereegranskat)
    Abstract [en]

    Objective: To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with pre-specified subgroup analyses in normoglycemic individuals with normal GFR. Research Design and Methods: We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C-based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men, ULSAM; n=1070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years. Results: Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19, 95% CI 0.69-1.68, p<0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, 2-hour glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, smoking), and lifestyle factors (BMI, physical activity, consumption of tea, coffee and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR remained statistically significant also in participants with normal fasting plasma glucose, normal glucose tolerance and normal GFR (n=443, p<0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR<50ml/min/1.73 m2) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58, 95 % CI 0.40-0.84, p<0.004). Conclusion: Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, prior to the onset of diabetes or pre-diabetic glucose elevations. Further studies are needed in order to establish causality.

  • 27.
    Nerpin, Elisabet
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala University.
    Toft, E.
    Fischier, J.
    Lindholm-Olinder, A.
    Leksell, Janeth
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Uppsala University.
    A virtual clinic for the management of diabetes-type 1: study protocol for a randomised wait-list controlled clinical trial2020Ingår i: BMC Endocrine Disorders, E-ISSN 1472-6823, Vol. 20, nr 1Artikel i tidskrift (Refereegranskat)
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  • 28.
    Rydell, Andreas
    et al.
    Karolinska Institutet, Huddinge; Region Dalarna, Falun.
    Nerpin, Elisabet
    Högskolan Dalarna, Institutionen för hälsa och välfärd, Medicinsk vetenskap. Uppsala University, Uppsala .
    Zhou, XingWu
    Uppsala University, Uppsala.
    Lind, Lars
    Uppsala University, Uppsala.
    Lindberg, Eva
    Uppsala University, Uppsala.
    Theorell Haglöw, Jenny
    Uppsala University, Uppsala.
    Fall, Tove
    Uppsala University, Uppsala.
    Janson, Christer
    Uppsala University, Uppsala.
    Lisspers, Karin
    Uppsala University, Uppsala.
    Elmståhl, Sölve
    Lund University, Malmö.
    Zaigham, Suneela
    Uppsala University, Uppsala; Lund University, Malmö.
    Melander, Olle
    Lund University, Malmö; Skåne University Hospital, Malmö.
    Nilsson, Peter M
    Lund University, Malmö.
    Ärnlöv, Johan
    Högskolan Dalarna, Institutionen för hälsa och välfärd, Medicinsk vetenskap. Karolinska Institutet, Huddinge; Region Dalarna, Falun.
    Malinovschi, Andrei
    Uppsala University, Uppsala.
    Cardiovascular disease-linked plasma proteins are mainly associated with lung volume2023Ingår i: ERJ Open Research, E-ISSN 2312-0541, Vol. 9, nr 2, artikel-id 00321-2022Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio.

    METHODS: We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort.

    RESULTS: Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity.

    CONCLUSIONS: Five proteins were associated with both FEV1 and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.

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