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  • 251.
    Nerpin, Elisabet
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Screening av förstagradsanhöriga till yngre kranskärlssjuka patienter2007Independent thesis Advanced level (degree of Master (Two Years))Oppgave
  • 252.
    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 disease2009Inngår i: XI Kardiovasculära Vårmötet 2009, Uppsala, 2009Konferansepaper (Annet vitenskapelig)
    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.

  • 253.
    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 continuum2013Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

  • 254.
    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 study2012Inngår i: BMC research notes, ISSN 1756-0500, Vol. 5, nr 1, s. 537-Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 255.
    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 elderly2014Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, nr 11, s. 2069-2074Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 256.
    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 equations2010Inngår i: Svenska Kardiovasculära vårmötet, Göteborg, 2010Konferansepaper (Annet vitenskapelig)
    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.

  • 257.
    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 men2011Inngår i: EuroPrevent, Geneve, 2011Konferansepaper (Annet vitenskapelig)
    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.

  • 258.
    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 cohort2012Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, nr 1, s. 242-246Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 259.
    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 men2011Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, nr 9, s. 2820-2827Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 260.
    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. 2007–20102018Inngår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 142, s. 94-100Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 261.
    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 smoking2018Konferansepaper (Annet vitenskapelig)
    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)

  • 262.
    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 2007-20102018Konferansepaper (Annet vitenskapelig)
    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.

  • 263.
    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 III2019Inngår i: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, nr 7, s. 969-979Artikkel i tidsskrift (Fagfellevurdert)
    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. 

  • 264.
    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 men2008Inngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, nr 8, s. 1550-5Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 265.
    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 cohort2008Konferansepaper (Fagfellevurdert)
    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.

  • 266. Ngasala, Billy E.
    et al.
    Malmberg, Maja
    Carlsson, Anja M.
    Ferreira, Pedro E.
    Petzold, Max G.
    Blessborn, Daniel
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Bergqvist, Yngve
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Gil, Jose P.
    Premji, Zul
    Bjoerkman, Anders
    Martensson, Andreas
    Efficacy and effectiveness of artemether-lumefantrine after initial and repeated treatment in children < 5 years of age with acute uncomplicated plasmodium falciparum malaria in rural Tanzania: a randomized trial2011Inngår i: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 52, nr 7, s. 873-882Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. We assessed the efficacy, effectiveness and safety of artemether-lumefantrine, which is the most widely used artemisinin-based combination therapy in Africa, against Plasmodium falciparum malaria during an extended follow-up period after initial and repeated treatment.

    Methods. We performed an open-label randomized trial of artemether-lumefantrine with supervised (n 5 180) and unsupervised intake (n = 179) in children <5 years of age with uncomplicated falciparum malaria in rural Tanzania. Recurrent infections between day 14 and day 56 were retreated within the same study arm. Main end points were polymerase chain reaction (PCR)-corrected cure rates by day 56 and day 42 after initial and repeated treatment, respectively, as estimated by survival analysis.

    Results. The PCR-corrected cure rate after initial treatment was 98.1% (95% confidence interval [CI], 94.2%-99.4%) after supervised and 95.1% (95% CI, 90.7%-98.1%) after unsupervised intake (P = .29). After retreatment of recurrent infections, the cure rates were 92.9% (95% CI, 81.8%-97.3%) and 97.6% (95% CI, 89.3%-98.8%), respectively (P = .58). Reinfections occurred in 46.9% (82 of 175) versus 50.9 % of the patients (relative risk [RR], 0.92 [95% CI, 0.74-1.14]; P 5.46) after initial therapy and 32.4% (24 of 74) versus 39.0% (32 of 82) (RR, 0.83 [95% CI, 0.54-1.27]; P 5.39) after retreatment. Median blood lumefantrine concentrations in supervised and unsupervised patients on day 7 were 304 versus 194 ng/ mL (P <.001) after initial treatment and 253 versus 164 ng/ mL (P 5.001) after retreatment. Vomiting was the most commonly reported drug-related adverse event (in 1% of patients) after both initial and repeated treatment.

    Conclusions. Artemether-lumefantrine was highly efficacious even after unsupervised administration, despite significantly lower lumefantrine concentrations, compared with concentration achieved with supervised intake, and was well-tolerated and safe after initial and repeated treatment.

  • 267. Ngasala, Billy E.
    et al.
    Malmberg, Maja
    Carlsson, Anja M.
    Ferreira, Pedro E.
    Petzold, Max G.
    Blessborn, Daniel
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Bergqvist, Yngve
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Gil, Jose P.
    Premji, Zul
    Martensson, Andreas
    Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania: an open label prospective study2011Inngår i: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 10, artikkel-id 64Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Home-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home.

    Methods: An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT) were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961.

    Results: A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5%) patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%). The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10) compared with reinfections (205 ng/mL [114-390]; n = 92), or no parasite reappearance (217 [121-374] ng/mL; n = 70; p <= 0.046).

    Conclusions: Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective, which provides evidence base for scaling-up implementation of HMM with AL in Tanzania.

  • 268. Nilsson, Erik
    et al.
    Rudholm Feldreich, Tobias
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Stenvinkel, Peter
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Pregnancy-associated plasma protein A and mortality in hemodialysis2018Inngår i: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 48, nr 8, artikkel-id e12959Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Elevated pregnancy-associated plasma protein A (PAPP-A) levels are associated with increased risk of death in ischemic heart disease as well as in hemodialysis patients. Previous research indicates that the prognostic value of PAPP-A may be stronger in patients with concomitant diabetes mellitus or signs of inflammation. We studied the association between PAPP-A and outcomes in prevalent hemodialysis patients and hypothesized that diabetes mellitus and inflammation status act as effect modifiers.

    MATERIALS AND METHODS: Circulating PAPP-A levels were quantified using ELISA. Cox proportional hazards- and quantile regression models were used for associations between PAPP-A and mortality. PAPP-A levels were log-transformed for Normality.

    RESULTS: During 60 months follow-up, 37 (40%) of the 92 participants died. Higher PAPP-A was associated with increased risk of mortality in unadjusted analysis (HR per SD = 1.4, 95% CI = 1 - 1.9, p = 0.03) and when adjusted for confounders and cardiovascular risk factors (HR = 1.8, 95% CI = 1.18-2.73, p = 0.006). An interaction between PAPP-A levels and diabetes mellitus on mortality was found (HR for the multiplicative interaction term = 2.74 95% CI = 1.02-7.37, p = 0.05). In a quantile regression adjusted for age and sex, one SD increase of PAPP-A was associated with 22 months shorter estimated time until 25% of the patients died (95% CI -35 to -9.1 months).

    CONCLUSIONS: Increased PAPP-A levels are associated with higher all-cause mortality in prevalent hemodialysis patients with concomitant diabetes mellitus. 

  • 269. Nishiyama, Chika
    et al.
    Brown, Siobhan P.
    May, Susanne
    Iwami, Taku
    Koster, Rudolph W.
    Beesems, Stefanie G.
    Kuisma, Markku
    Salo, Ari
    Jacobs, Ian
    Strömsöe, Anneli
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Apples to apples or apples to oranges?: International variation in reporting of process and outcome of care for out-of-hospital cardiac arrest2014Inngår i: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 85, nr 11, s. 1599-1609Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: Survival after out-of-hospital cardiac arrest (OHCA) varies between communities, due in part to variation in the methods of measurement. The Utstein template was disseminated to standardize comparisons of risk factors, quality of care, and outcomes in patients with OHCA. We sought to assess whether OHCA registries are able to collate common data using the Utstein template. A subsequent study will assess whether the Utstein factors explain differences in survival between emergency medical services (EMS) systems. Study design: Retrospective study.

    Setting: This retrospective analysis of prospective cohorts included adults treated for OHCA, regardless of the etiology of arrest. Data describing the baseline characteristics of patients, and the process and outcome of their care were grouped by EMS system, de-identified, and then collated. Included were core Utstein variables and timed event data from each participating registry. This study was classified as exempt from human subjects' research by a research ethics committee.

    Measurements and main results: Thirteen registries with 265 first-responding EMS agencies in 13 countries contributed data describing 125,840 cases of OHCA. Variation in inclusion criteria, definition, coding, and process of care variables were observed. Contributing registries collected 61.9% of recommended core variables and 42.9% of timed event variables. Among core variables, the proportion of missingness was mean 1.9 +/- 2.2%. The proportion of unknown was mean 4.8 +/- 6.4%. Among time variables, missingness was mean 9.0 +/- 6.3%.

    Conclusions: International differences in measurement of care after OHCA persist. Greater consistency would facilitate improved resuscitation care and comparison within and between communities.

  • 270. Nowak, Christoph
    et al.
    Hetty, Susanne
    Salihovic, Samira
    Castillejo-Lopez, Casimiro
    Ganna, Andrea
    Cook, Naomi L
    Broeckling, Corey D
    Prenni, Jessica E
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Ingelsson, Erik
    Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, nr 1, artikkel-id 8691Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Insulin resistance (IR) predisposes to type 2 diabetes and cardiovascular disease but its causes are incompletely understood. Metabolic challenges like the oral glucose tolerance test (OGTT) can reveal pathogenic mechanisms. We aimed to discover associations of IR with metabolite trajectories during OGTT. In 470 non-diabetic men (age 70.6 ± 0.6 years), plasma samples obtained at 0, 30 and 120 minutes during an OGTT were analyzed by untargeted liquid chromatography-mass spectrometry metabolomics. IR was assessed with the hyperinsulinemic-euglycemic clamp method. We applied age-adjusted linear regression to identify metabolites whose concentration change was related to IR. Nine trajectories, including monounsaturated fatty acids, lysophosphatidylethanolamines and a bile acid, were significantly associated with IR, with the strongest associations observed for medium-chain acylcarnitines C10 and C12, and no associations with L-carnitine or C2-, C8-, C14- or C16-carnitine. Concentrations of C10- and C12-carnitine decreased during OGTT with a blunted decline in participants with worse insulin resistance. Associations persisted after adjustment for obesity, fasting insulin and fasting glucose. In mouse 3T3-L1 adipocytes exposed to different acylcarnitines, we observed blunted insulin-stimulated glucose uptake after treatment with C10- or C12-carnitine. In conclusion, our results identify medium-chain acylcarnitines as possible contributors to IR.

  • 271. Nowak, Christoph
    et al.
    Salihovic, Samira
    Ganna, Andrea
    Brandmaier, Stefan
    Tukiainen, Taru
    Broeckling, Corey D
    Magnusson, Patrik K
    Prenni, Jessica E
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala university.
    Fall, Tove
    Effect of insulin resistance on monounsaturated fatty acid levels: a multi-cohort non-targeted metabolomics and mendelian randomization study2016Inngår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 12, nr 10, artikkel-id e1006379Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or β-cell responsiveness (disposition index) during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613) followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330), we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining "gold standard" measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development.

  • 272. Nowak, Christoph
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    A Mendelian randomization study of the effects of blood lipids on breast cancer risk2018Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, nr 1, artikkel-id 3957Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Observational studies have reported inconsistent associations between circulating lipids and breast cancer risk. Using results from >400,000 participants in two-sample Mendelian randomization, we show that genetically raised LDL-cholesterol is associated with higher risk of breast cancer (odds ratio, OR, per standard deviation, 1.09, 95% confidence interval, 1.02-1.18, P = 0.020) and estrogen receptor (ER)-positive breast cancer (OR 1.14 [1.05-1.24] P = 0.004). Genetically raised HDL-cholesterol is associated with higher risk of ER-positive breast cancer (OR 1.13 [1.01-1.26] P = 0.037). HDL-cholesterol-raising variants in the gene encoding the target of CETP inhibitors are associated with higher risk of breast cancer (OR 1.07 [1.03-1.11] P = 0.001) and ER-positive breast cancer (OR 1.08 [1.03-1.13] P = 0.001). LDL-cholesterol-lowering variants mimicking PCSK9 inhibitors are associated (P = 0.014) with lower breast cancer risk. We find no effects related to the statin and ezetimibe target genes. The possible risk-promoting effects of raised LDL-cholesterol and CETP-mediated raised HDL-cholesterol have implications for breast cancer prevention and clinical trials.

  • 273.
    Nyberg, André
    et al.
    Umeå universitet, Institutionen för samhällsmedicin och rehabilitering.
    Tistad, Malin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Umeå universitet, Institutionen för samhällsmedicin och rehabilitering.
    Wadell, Karin
    Umeå universitet, Institutionen för samhällsmedicin och rehabilitering.
    Can the COPD Web be used to promote self-management in patients with COPD in Swedish primary care: a controlled pragmatic pilot trial with 3 month and 12 month follow-up2019Inngår i: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 37, nr 1, s. 69-82Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    Evaluate the feasibility of the COPD Web and its study design and study procedures and to increase the understanding of the potential effect of the tool in order to provide guidance for a future large scale trial.

    DESIGN:

    Parallel-group controlled pragmatic pilot trial.

    SUBJECTS:

    There was a total of 83 patients with COPD (mean age 70 ± 8 years with a forced expiratory volume in first second percent predicted of 60 ± 17%). The intervention group (n = 43) was introduced to and had access to the COPD Web in addition to usual care, while the control group (n = 40) received usual care alone.

    MAIN OUTCOME MEASURES:

    The feasibility of the COPD Web (i.e., if and how the COPD Web was used) was automatically collected through the website, while outcomes on health, conceptual knowledge, and physical activity (PA) were collected through questionnaires at baseline, 3 months and 12 months.

    RESULTS:

    At 3 months, 77% of the intervention group was considered users, and the majority of time spent on the site was related to PA and exercises and was spent during the first month (>80%). In addition, the intervention group reported increased PA (odds ratio [OR] = 4.4, P < .001), increased conceptual knowledge in five domains (OR = 2.6-4.2, all P < .05), and altered disease management strategies (e.g., increased PA) (OR ≥ 2.7 P < .05) in comparison to the control group. The latter was also different between groups at 12 months (OR = 3.7, P = .044). Knowledge of PA was correlated with level of PA (ρ = .425-.512, P < .05) as well as to the use of PA as a strategy to manage their disease (χ2 = 11.2-32.9, P < .05).

    CONCLUSION:

    Giving patients with COPD access to the COPD Web in addition to their ordinary primary care might be an effective shorter term (3 month) strategy to promote self-management. However, these results needs to be confirmed in a definitive large-scale trial. Key points Even though self-management strategies are an important part of chronic obstructive pulmonary disease (COPD) management, access to support for such strategies are limited for a large part of the COPD-population. Promoting self-management through the COPD Web might increase short-term levels of physical activity, promote conceptual knowledge and alter disease management strategies. The primary care COPD population in this study experienced limited impact of the disease in daily life, limited exertional dyspnea, and high generic quality-of-life, but vastly reduced levels of physical activity. A future large scale study should include strategies to encourage greater exposures to the COPD Web, including an extended analysis of factors associated with using or not using the tool over time and its impact on outcome measures, objective measures of conceptual knowledge, and physical activity, and it should include a large enough sample size to enable sub-group analyses and strategies to enhance recruitment.

  • 274. Nyberg, André
    et al.
    Wadell, Karin
    Lindgren, Helena
    Tistad, Malin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Umeå universitet, Institutionen för samhällsmedicin och rehabilitering, Fysioterapin.
    Internet-based support for self-management strategies for people with COPD-protocol for a controlled pragmatic pilot trial of effectiveness and a process evaluation in primary healthcare2017Inngår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, nr 7, artikkel-id e016851Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: The use of adequate self-management strategies for people with chronic obstructive pulmonary disease (COPD) reduces healthcare use, improves health-related quality of life (HRQoL) and recovery after acute exacerbations. However, not many people with COPD receive support that promotes the use of such strategies and therefore new methods to facilitate and promote the use of self-management strategies are highly warranted. This pilot trial aims to evaluate the feasibility of the study design and study procedures considering effectiveness of the novel intervention, the COPD-web. METHODS AND ANALYSIS: The overall design is a pragmatic controlled pilot trial with preassessments and postassessments and a parallel process evaluation. Patients with the diagnosis of COPD will be eligible for the study. The intervention group will be recruited when visiting one of the six participating primary care units in Sweden. The control group will be identified from the unit's computerised registers. The intervention, the COPD-web, is an interactive web page with two sections; one directed at people with COPD and one at healthcare professionals. The sections aim to support patients' self-management skills-and to facilitate the provision of support for self-management strategies, respectively. Effectiveness with regard to patients' symptoms, HRQoL, knowledge of and readiness for COPD-related self-management, health literacy, self-efficacy for physical activity and time spent in physical activity and time being sedentary, and further, healthcare professionals' knowledge of and readiness to support COPD-related self-management strategies will be assessed using questionnaires at 3 and 12 months. The process evaluation will include observations and interviews.

    ETHICS AND DISSEMINATION: Ethical approval has been obtained. Findings will be presented at conferences, submitted for publication in peer-reviewed publications and presented to the involved healthcare professionals, patients and to patient organisations.

    TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT02696187.

  • 275. Nylander, Ruta
    et al.
    Lind, Lars
    Wikström, Johan
    Lindahl, Bertil
    Venge, Per
    Larsson, Anders
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Berglund, Lars
    Ahlström, Håkan
    Larsson, Elna-Marie
    Relation between cardiovascular disease risk markers and brain infarcts detected by magnetic resonance imaging in an elderly population2015Inngår i: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 24, nr 2, s. 312-318Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Established cardiovascular risk markers, such as hypertension, are associated with increased risk of brain infarcts. The newer markers N-terminal pro-brain natriuretic peptide, troponin I, C-reactive protein, and cystatin C may affect the risk of cardiovascular events and potentially, thereby, also stroke. We investigated the association between established and new risk markers for cardiovascular disease and brain infarcts detected by magnetic resonance imaging (MRI) at age 75.

    METHODS: Four hundred six randomly selected subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors study were examined with MRI of the brain at age 75. Blood samples, measurements, and dedicated questionnaires at age 70 were used for analysis of risk markers. A history of diseases had been obtained at age 70 and 75. MRI was evaluated regarding lacunar and cortical infarcts. Univariate associations between outcomes and risk markers were assessed with logistic regression models.

    RESULTS: One or more infarcts were seen in 23% of the subjects (20% had only lacunar infarcts, 1% had only cortical infarcts, and 2% had both). Hypertension (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.4, 4.7) and obesity (OR 1.3; CI 1.0, 1.8) were significantly associated with increased risk of brain infarction. The newer risk markers were not significantly associated with the brain infarcts.

    CONCLUSIONS: The new markers were not associated with the predominantly lacunar infarcts in our 75-year-old population, why troponin I and NT-proBNP may be associated mainly with cardioembolic infarcts as shown recently.

  • 276. Ohrmalm, Christina
    et al.
    Eriksson, Ronnie
    Jobs, Magnus
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Simonson, Magnus
    Stromme, Maria
    Bondeson, Kare
    Herrmann, Bjorn
    Melhus, Asa
    Blomberg, Jonas
    Variation-tolerant capture and multiplex detection of nucleic acids: application to detection of microbes2012Inngår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 50, nr 10, s. 3208-3215Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In contrast to ordinary PCRs, which have a limited multiplex capacity and often return false-negative results due to target variation or inhibition, our new detection strategy, VOCMA (variation-tolerant capture multiplex assay), allows variation-tolerant, target-specific capture and detection of many nucleic acids in one test. Here we demonstrate the use of a single-tube, dual-step amplification strategy that overcomes the usual limitations of PCR multiplexing, allowing at least a 22-plex format with retained sensitivity. Variation tolerance was achieved using long primers and probes designed to withstand variation at known sites and a judicious mix of degeneration and universal bases. We tested VOCMA in situations where enrichment from a large sample volume with high sensitivity and multiplexity is important (sepsis; streptococci, enterococci, and staphylococci, several enterobacteria, candida, and the most important antibiotic resistance genes) and where variation tolerance and high multiplexity is important (gastroenteritis; astrovirus, adenovirus, rotavirus, norovirus genogroups I and II, and sapovirus, as well as enteroviruses, which are not associated with gastroenteritis). Detection sensitivities of 10 to 1,000 copies per reaction were achieved for many targets. VOCMA is a highly multiplex, variation-tolerant, general purpose nucleic acid detection concept. It is a specific and sensitive method for simultaneous detection of nucleic acids from viruses, bacteria, fungi, and protozoa, as well as host nucleic acid, in the same test. It can be run on an ordinary PCR and a Luminex machine and is suitable for both clinical diagnoses and microbial surveillance.

  • 277.
    Omer, Mohammed
    et al.
    Stockholm University.
    Klomsri, Tina
    Stockholm University.
    Tedre, Matti
    Stockholm University.
    Popova, Iskra
    Stockholm University.
    Klingberg-Allvin, Marie
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    Osman, Fatumo
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    E-learning opens the door to the global community. Novice users experiences of e-learning in a Somali University2015Inngår i: Journal of Online Learning and Teaching, ISSN 1558-9528, E-ISSN 1558-9528, Vol. 11, nr 2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    E-learning has become one of the primary ways of delivering education around the globe. In Somalia, which is a country torn within and from the global community by a prolonged civil war, University of Hargeisa has in collaboration with Dalarna University in Sweden adopted, for the first time, e-learning. This study explores barriers and facilitators to e-learning usage, experienced by students in Somalia’s higher education, using the University of Hargeisa as case study. Interviews were conducted with students to explore how University of Hargeisa’s novice users perceived elearning, and what factors positively and negatively affected their e-learning experiences. The Unified Theory of Acceptance and Use of Technology (UTAUT) model was used as a framework for interpreting the results. The findings show that, in general, the students have a very positive attitude towards e-learning, and they perceived that e-learning enhanced their educational experience. The communication aspect was found to be especially important for Somali students, as it facilitated a feeling of belonging to the global community of students and scholars and alleviated the war-torn country’s isolation. However, some socio-cultural aspects of students’ communities negatively affected their e-learning experience. This study ends with recommendations based on the empirical findings to promote the use and enhance the experience of e-learning in post conflict Somali educational institutions

  • 278.
    Osman, Fatumo
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Parenthood in transition – challenges and opportunities encountered in the host country2016Konferansepaper (Fagfellevurdert)
  • 279.
    Osman, Fatumo
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Parenthood in transition – Somali-born parents’ experiences of and needs for parenting support programmes2015Konferansepaper (Fagfellevurdert)
  • 280.
    Osman, Fatumo
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Flacking, Renée
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    Schön, Ulla-Karin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Socialt arbete.
    Klingberg-Allvin, Marie
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    A support program for Somali-born parents on children's behavioral problems2017Inngår i: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 139, nr 3Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: The objectives of this study were to evaluate a culturally tailored parenting support program (Ladnaan) for Somali-born parents and to determine its effectiveness on children’s emotional and behavioral problems.

    METHODS: This randomized controlled trial included 120 Somali-born parents with children aged 11 to 16 years. The parents reported self-perceived stress in relation to parenting practices. The intervention consisted of culturally tailored societal information combined with the parenting program Connect. Parents received 12 weeks of intervention, 1 to 2 hours each week, in groups of 12 to 17 parents. Nine group leaders with a Somali background who received a standardized training program delivered the intervention. The primary outcome was a decrease in emotional and behavioral problems based on a Child Behavior Checklist. Parents were randomly allocated either to an intervention group or a wait-list control group. Covariance analyses were conducted according to intention-to-treat principles.

    RESULTS: The results showed significant improvement in the children in the intervention group for behavioral problems after a 2-month follow-up. The largest effect sizes according to Cohen’s d were in aggressive behavior (95% confidence interval [CI], 1.06 to 3.07), social problems (95% CI, 0.64 to 1.70), and externalizing problems (95% CI, 0.96 to 3.53).

    CONCLUSIONS: The large effect sizes in this study show that this 12-week culturally tailored parenting support program was associated with short-term improvements in children’s behavior. The study adds to the field of parenting interventions by demonstrating how to culturally tailor, engage, and retain parenting programs for immigrant parents.

  • 281.
    Osman, Fatumo
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Flacking, Renée
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    Schön, Ulla-Karin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Socialt arbete.
    Klingberg-Allvin, Marie
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    The impact of a culturally tailored parenting support for Somali-born parents’ and children’s mental health: A randomized controlled trial2017Konferansepaper (Fagfellevurdert)
  • 282.
    Palmcrantz, Susanne
    et al.
    Karolinska institutet.
    Tistad, Malin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Eldh, Ann Catrine
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Karolinska institutet.
    Holmqvist, Lotta Widén
    Karolinska institutet.
    Ehrenberg, Anna
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad.
    Tomson, Göran
    Karolinska institutet.
    Olsson, Christina B
    Karolinska institutet; Stockholm läns landsting.
    Wallin, Lars
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Omvårdnad. Karolinska institutet.
    Assessing feasibility and acceptability of study procedures: getting ready for implementation of national stroke guidelines in out-patient health care2015Inngår i: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 15, artikkel-id 517Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Even though Swedish national guidelines for stroke care (SNGSC) have been accessible for nearly a decade access to stroke rehabilitation in out-patient health care vary considerably. In order to aid future interventions studies for implementation of SNGSC, this study assessed the feasibility and acceptability of study procedures including analysis of the context in out-patient health care settings.

    METHODS: The feasibility and acceptability of recruitment, observations and interviews with managers, staff and patients were assessed, as well as the feasibility of surveying health care records.

    RESULTS: To identify patients from the the hospitals was feasible but not from out-patient care where a need to relieve clinical staff of the recruitment process was identified. Assessing adherence to guidelines and standardized evaluations of patient outcomes through health care records was found to be feasible and suitable assessment tools to evaluate patient outcome were identified. Interviews were found to be a feasible and acceptable tool to survey the context of the health care setting.

    CONCLUSION: In this feasibility study a variety of qualitative and quantitative data collection procedures and measures were tested. The results indicate what can be used as a set of feasible and acceptable data collection procedures and suitable measures for studying implementation of stroke guidelines in an out-patient health care context.

  • 283. Palmcrantz, Susanne
    et al.
    Widen Holmqvist, Lotta
    Sommerfeld K., Disa
    Tistad, Malin
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Ytterberg, Charlotte
    von Koch, Lena
    Differences between younger and older individuals in their use of care and rehabilitation but not in self-perceived global recovery 1 year after stroke2012Inngår i: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 321, nr 1-2, s. 29-34Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Although priorities in Swedish stroke care should be based on the ethical principles of equal care and greatest support to those in greatest need, being of working age (younger) or retired (older) might influence expectations on recovery and the provision of care and rehabilitation.

    Method: Information regarding the use of care and rehabilitation during the 1st year after stroke was retrieved from the Stockholm County Council database and the medical data was taken from the medical records. The Barthel Index was used for self-ratings of dependence pre-stroke, and the Stroke Impact Scale was used to assess self-perceived disability and a global rating of recovery at 12 months. One hundred and ninety-two individuals were included.

    Results: Results showed that the younger group received more care and rehabilitation than the older group. In the older group, comorbid conditions and pre-stroke dependence, estimated in accordance with the Barthel Index, were more common. The older group reported larger impact on self-perceived disability regarding strength, mobility, self-care and domestic life, while self-perceived global recovery did not differ between the groups.

    Conclusion: Younger individuals received more care and rehabilitation, which indicates structural inequality in the provision of health care resources. However, as no difference in self-perceived global recovery was found between the groups; the disparity in the provision of health care may also be a consequence of greatest support being given to those in greatest need. By demonstrating the necessity of involving self-rated assessments of stroke impact at different points in time and in different age groups, the results of this study add to previous knowledge of age-related differences in the provision of health care and stroke outcome. Furthermore. this suggests a way to approach evaluation of equality in the provision of health care.

  • 284.
    Pers, Liselott
    et al.
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Överbring, Annika
    Högskolan Dalarna, Akademin Hälsa och samhälle, Medicinsk vetenskap.
    Omvårdnadsåtgärder för äldre med dysfagi2007Independent thesis Basic level (degree of Bachelor)Oppgave
    Abstract [sv]

    Syftet med föreliggande systematiska litteraturstudie var att undersöka vilka omvårdnadsåtgärder som var användbara för sjuksköterskan i arbetet med äldre som led av dysfagi. Artiklar i fulltext söktes från högskolan Dalarnas biblioteks databaser och artiklarnas vetenskapliga kvalitet granskades utifrån modifierade mallar efter Forsbergs och Wengströms (2003) samt Willmans, Stoltzs och Bahtsevanis (2006) granskningsmallar. I resultatet framkom vikten av att identifiera och kartlägga äldre som led av dysfagi. Födans konsistens visade sig vara av avgörande betydelse för god sväljning. Individuellt anpassad konsistens samt mentol, kapsaicin och svartpepparolja utgjorde stimuli för sväljningsreflexen, vilka ledde till säkrare sväljning. Munvård var en lämplig omvårdnadsåtgärd då den stimulerade sväljningsreflexen samt minskade risken för aspirationspneumoni. Sjuksköterskans insikter och åtgärder var avgörande för informationen så att den äldre fick ökad kunskap om sin egenvård. Vårdpersonalen behöver mer kunskap om användbara individuella omvårdnadsåtgärder för den äldre med dysfagi.

  • 285. Petersson, H
    et al.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala University.
    Zethelius, B
    Risérus, U
    Serum fatty acid composition and insulin resistance are independently associated with liver fat markers in elderly men2010Inngår i: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 87, nr 3, s. 379-384Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To investigate the relationships of serum fatty acid (FA) composition and estimated desaturase activities with the liver fat marker alanine aminotransferase (ALT). 

    Methods: 546 Swedish elderly men of a population-based cohort participated in this cross-sectional study. FA composition was assessed in serum cholesterol esters to determine dietary fat quality (e.g. linoleic) and desaturation products (e.g. dihomo-gamma-linolenic acid). Desaturase indices, including stearoyl coenzymeA desaturase-1 (SCD-1), were calculated by FA product-to-precursor ratios. 

    Results: In linear regression analyses adjusting for lifestyle, abdominal obesity and insulin sensitivity, the dietary biomarker linoleic acid (n-6), but not n-3 FAs, was inversely related to ALT. Desaturation products including palmitoleic, oleic, gamma-linolenic and dihomo-gamma-linolenic acids, and Delta 6-desaturase and SCD-1 indices were directly related to ALT (all p < 0.05). After further adjustment for factors previously linked to fatty liver (i.e. serum lipids, adiponectin concentrations), SCD-1 index (p = 0.004) and insulin resistance (p <0.0001) were independent determinants of ALT activity, whereas waist circumference, triglycerides, non-esterified FA and adiponectin were not. 

    Conclusion: A low dietary intake of linoleic acid and elevated SCD-1 index may contribute to higher ALT activity in elderly men, even independently of obesity and insulin resistance.

  • 286. Posch, Markus
    et al.
    Schranz, Alois
    Lener, Manfred
    Senn, Werner
    Äng, Björn
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Burtscher, Martin
    Ruedl, Gerhard
    Prevalence and potential risk factors of flight-related neck, shoulder and low back pain among helicopter pilots and crewmembers: a questionnaire-based study2019Inngår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 20, nr 1, artikkel-id 44Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Flight-related neck, shoulder and low back pain are the most common musculoskeletal disorders among helicopter pilots and their crewmembers, thus becoming a growing concern. Information on the combined prevalence of these types of pain and related risks are scarce. The aim of this study was therefore to estimate pain prevalence and to evaluate potential risk factors for neck pain among helicopter pilots and crewmembers within the armed forces, the airborne police and airborne rescue organizations in Austria.

    METHODS: Among a cohort of 104 helicopter pilots and 117 crewmembers (69.8% compliance), demographics, flying experience, use of Night Vision Goggles (NVG), helicopter type flown, prevalence and intensity of musculoskeletal symptoms (pain was defined as any reported pain experience, ache or discomfort) were collected by an online-based questionnaire.

    RESULTS: For helicopter pilots the 12-month prevalence of neck pain was 67.3%, followed by low back (48.1%) and shoulder pain (43.3%). Among crewmembers, the 12-month pain prevalence were 45.3, 36.8 and 30.8% among the neck, lower back and shoulder, respectively. During this period, 41.8% of these helicopter pilots had experienced 8-30 pain days in the areas of neck (45.7%), shoulder (37.8%) and lower back (42.0%) whereas 47.8% of crewmembers self-reported 1-7 days of neck (54.7%), low back (44.2%) and shoulder (44.4%) pain in the previous year. The 3-month prevalence of neck pain was 64.4% followed by low back (42.3%) and shoulder pain (38.5%) for helicopter pilots. Among crewmembers, 41.9% suffered from neck, 29.9% from low back and 29.1% from shoulder pain the previous 3 months. Multivariate regression analysis revealed NVG use (OR 1.9, 95% CI, 1.06-3.50, p = 0.032), shoulder pain (OR 4.9, 95% CI, 2.48-9.55, p < 0.001) and low back pain (OR 2.3, 95% CI, 1.21-4.31, p = 0.011) to be significantly associated with neck pain.

    CONCLUSIONS: The 12- and 3-month prevalence of neck, shoulder and low back is considerably high among both, helicopter pilots and crewmembers confirming the existence of this growing concern. The use of NVG devices, shoulder and low back pain in the previous 12 months represent independent risk factors for neck pain. These findings highlight the need for longitudinal studies.

  • 287. Roos, Vendela
    et al.
    Elmståhl, Sölve
    Ingelsson, Erik
    Sundström, Johan
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Lind, Lars
    Alterations in multiple lifestyle factors in subjects with the metabolic syndrome independently of obesity2017Inngår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, nr 3, s. 118-123Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Many lifestyle factors have been associated with the metabolic syndrome (MetS). However, most of these studies have not considered the potential impact of obesity and have often only investigated one lifestyle factor at the time. We aimed to investigate the interplay between body mass index (BMI) and MetS with respect to multiple lifestyle factors.

    METHODS: BMI and MetS [National Cholesterol Education Program (NCEP)/Adult Treatment Panel III criteria] were assessed in a sample of 18,880 subjects aged 45-75 years from the population-based EpiHealth study. Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m(2), overweight/BMI 25-30 kg/m(2), and obesity/BMI >30 kg/m(2)) and MetS status (+/-, NCEP criteria). A wide range of lifestyle factors related to physical activity, smoking, alcohol, sleep quality, working conditions, quality of life and stress, and eating patterns were assessed using a questionnaire.

    RESULTS: Prevalent MetS (23% in the sample) was associated with less physical activity (P < 0.0001), more TV watching (P < 0.0001), more years of smoking (P < 0.0001), lower education level (P = 0.007), and experiencing a poor general quality of life (P < 0.0001). These lifestyle factors were all associated with MetS, independently of each other and independently of BMI. Similar results were generated when number of MetS components and presence/absence of individual MetS components were used as outcomes.

    CONCLUSIONS: This cross-sectional study identified alterations in a number of lifestyle factors associated with MetS independently of each other and independently of BMI. Future longitudinal studies are needed to assess causal and temporal relationships between lifestyle factors and MetS development.

  • 288. Roos, Vendela
    et al.
    Elmståhl, Sölve
    Ingelsson, Erik
    Sundström, Johan
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Lind, Lars
    Metabolic syndrome development during aging with special reference to obesity without the metabolic syndrome2017Inngår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, nr 1, s. 36-43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Obesity and its associated metabolic complications continue to increase worldwide. We investigated the development of metabolic syndrome (MetS) during aging in relation to body mass index (BMI) and exercise habits. We assigned special emphasis to the metabolic stability in individuals with obesity, but without MetS, a condition often referred to as metabolically healthy obesity.

    MATERIALS AND METHODS: Cross-sectional analysis was carried out in a sample of 19,129 men and women aged 45-75 years from the EpiHealth study. In addition, longitudinal analyses were carried out in the ULSAM study (2322 men at baseline followed from age 50 to age 77) and in the PIVUS study (1016 men and women at baseline followed from age 70 to age 80). Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m(2), overweight/BMI 25-30 kg/m(2), and obesity/BMI >30 kg/m(2)) and MetS status (+/-, National Cholesterol Education Program criteria).

    RESULTS: MetS prevalence and number of MetS components increased with age in all three samples. The PIVUS study showed that high baseline BMI, low baseline physical activity, and increasing BMI during follow-up were related to increasing MetS prevalence and increasing numbers of MetS components during follow-up. One-third to half of individuals initially belonging to the obesity without MetS category acquired MetS during aging.

    CONCLUSIONS: MetS prevalence increased during aging, especially in individuals with high BMI, low level of physical activity, and weight gain. Obesity without MetS was not a stable condition over time as many of those individuals gained metabolic disturbances during aging.

  • 289. Roth, Gregory
    et al.
    Abate, Degu
    Abate, Kalkidan Hassenn
    Abay, Solomon
    Abbasi, Nooshin
    Abbastabar, Heyadat
    Abd-Allah, Load
    Abdela, Jemal
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Murray, Christopher J. L
    Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 20172018Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 392, nr 10159, s. 1736-1788Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. 

    Methods The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODErn), to generate cause fractions and cause specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. 

    Findings At the broadest grouping of causes of death (Level 1), non-communicable diseases (NC Ds) comprised the greatest fraction of deaths, contributing to 73.4% (95% uncertainty interval [UI] 72.5-74.1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 186% (17.9-19.6), and injuries 8.0% (7.7-8.2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22.7% (21.5-23.9), representing an additional 7.61 million (7. 20-8.01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7.9% (7.08.8). The number of deaths for CMNN causes decreased by 222% (20.0-24.0) and the death rate by 31.8% (30.1-33.3). Total deaths from injuries increased by 2.3% (0-5-4-0) between 2007 and 2017, and the death rate from injuries decreased by 13.7% (12.2-15.1) to 57.9 deaths (55.9-59.2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000-289 000) globally in 2007 to 352 000 (334 000-363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118.0% (88.8-148.6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36.4% (32.2-40.6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33.6% (31.2-36.1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respirator}, infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990 neonatal disorders, lower respiratory infections, and diarrhoeal diseases were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. 

    Interpretation Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade.

  • 290.
    Rudholm Feldreich, Tobias
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Urinary osteopontin predicts incident chronic kidney disease, while plasma osteopontin predicts cardiovascular death in elderly men2016Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Background and objectives The matricellular protein osteopontin is involved in the pathogenesis of both kidney and cardiovascular disease. However, whether circulating and urinary osteopontin levels are associated with the risk of these diseases is less studied.

    Design, setting, participants and measurements A community-based cohort of elderly (Uppsala Longitudinal Study of Adult Men [ULSAM; n=741; mean age: 77 years]) was used to study the associations between plasma and urinary osteopontin, incident chronic kidney disease, and the risk of cardiovascular death during a median of 8 years of follow-up.

    Results There was no significant cross-sectional correlation between plasma and urinary osteopontin (Spearman rho=0.07, p=0.13). Higher urinary, but not plasma osteopontin, was associated with incident chronic kidney disease in multivariable models adjusted for age, cardiovascular risk factors, baseline glomerular filtration rate (GFR), urinary albumin/creatinine ratio, and inflammatory markers interleukin 6 and high sensitivity C-reactive protein (Odds ratio for 1-standard deviation (SD) of urinary osteopontin, 1.42, 95% CI (1.00-2.02), p=0.048). Conversely, plasma osteopontin, but not urinary osteopontin, was independently associated with cardiovascular death (multivariable hazard ratio per SD increase, 1.35, 95% CI (1.14-1.58), p<0.001, and 1.00, 95% CI (0.79-1.26), p=0.99, respectively). The addition of plasma osteopontin to a model with established cardiovascular risk factors significantly increased the C-statistics for the prediction of cardiovascular death (p<0.002).

    Conclusions Higher urinary osteopontin specifically predicts incident chronic kidney disease while plasma osteopontin specifically predicts cardiovascular death. Our data put forward osteopontin as an important factor in the detrimental interplay between the kidney and the cardiovascular system. The clinical implications, and why plasma and urinary osteopontin mirror different pathologies, remains to be established.

  • 291.
    Rudholm Feldreich, Tobias
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    Carlsson, Axel C
    Risérus, Ulf
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Uppsala universitet.
    The association between serum cathepsin L and mortality in older adults2016Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 254, s. 109-116Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND AIMS: Research suggests that the protease cathepsin L is causally involved in atherosclerosis. However, data on cathepsin L as a risk marker are lacking. Therefore, we investigated associations between circulating cathepsin L and cardiovascular mortality.

    METHODS: Two independent community-based cohorts were used: Uppsala Longitudinal Study of Adult Men (ULSAM); n = 776; mean age 77 years; baseline 1997-2001; 185 cardiovascular deaths during 9.7 years follow-up, and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS); n = 993; 50% women; mean age 70 years; baseline 2001-2004; 42 cardiovascular deaths during 10.0 years follow-up.

    RESULTS: Higher serum cathepsin L was associated with an increased risk for cardiovascular mortality in age- and sex-adjusted models in both cohorts (ULSAM: hazard ratio (HR) for 1-standard deviation (SD) increase, 1.17 [95% CI, 1.01-1.34], p = 0.032 PIVUS: HR 1.35 [95% CI, 1.07-1.72], p = 0.013). When merging the cohorts, these associations were independent of inflammatory markers and cardiovascular risk factors, but non-significant adjusting for kidney function. Individuals with a combination of elevated cathepsin L and increased inflammation, kidney dysfunction, or prevalent cardiovascular disease had a markedly increased risk, while no increased risk was associated with elevated cathepsin L, in the absence of these disease states.

    CONCLUSIONS: An association between higher serum cathepsin L and increased risk of cardiovascular mortality was found in two independent cohorts. Impaired kidney function appears to be an important moderator or mediator of these associations. Further studies are needed to delineate the underlying mechanisms and to evaluate whether the measurement of cathepsin L might have clinical utility.

  • 292.
    Rudholm Feldreich, Tobias
    et al.
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institutet; Uppsala universitet.
    Nowak, Christoph
    Fall, Tove
    Carlsson, Axel C
    Carrero, Juan-Jesus
    Ripsweden, Jonas
    Qureshi, Abdul Rashid
    Heimbürger, Olof
    Barany, Peter
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska Institutet.
    Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease2018Inngår i: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 32, nr 1, s. 111-119Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n = 183, 55% women, mean age 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n = 186, 73% women, mean age 62 years, 45 cardiovascular deaths during follow-up (mean 12 months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n = 89, 37% women, mean age 46 years).

    RESULTS: In age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26-2.69, p = 0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C = 0.777 to C = 0.799 and C = 0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03-2.05, p = 0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort.

    CONCLUSIONS: Our proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.

  • 293.
    Ruge, T
    et al.
    Department of Surgery, Umeå University, Umeå, Sweden.
    Södergren, A
    Department of Public Health and Clinical Medicine/Rheumatology, Umeå University Hospital, Umeå, Sweden.
    Wållberg-Jonsson, S
    e/Rheumatology, Umeå University Hospital, Umeå, Sweden.
    Larsson, A
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Department of Public Health and Caring Sciences/Section of Geriatrics, Uppsala University, Uppsala, Sweden.
    Circulating plasma levels of cathepsin S and L are not associated with disease severity in patients with rheumatoid arthritis2014Inngår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr 2, s. 371-373Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Rheumatoid arthritis (RA) is characterized by chronic synovitis and articular cartilage destruction. Increased activities of cathepsin S and cathepsin L, two potent cysteine proteases, are thought to play a role in the pathogenesis of the irreversible articular cartilage destruction. Nevertheless, data regarding the potential importance of the cathepsins as circulating biomarkers in RA patients are limited.

    Method: Subjects enrolled in this study are part of a larger study where patients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospective study. In total, 71 patients were included, along with 44 age- and sex-matched control subjects. Plasma levels of cathepsin S and L were analysed. Disease severity was assessed using the 28-joint count Disease Activity Score (DAS28).

    Results: Plasma levels of cathepsin S and L were significantly increased in patients with RA compared to healthy controls (p < 0.05 for both). However, in the patients with RA, no association between the cathepsins and the severity of the disease, as characterized by DAS28, was observed (p > 0.51).

    Conclusions: Although circulating levels of cathepsin S and L were significantly increased in patients with recently diagnosed RA, our data do not support the notion that circulating levels of cathepsins are relevant biomarkers for disease severity.

  • 294. Ruge, Toralph
    et al.
    Carlsson, Axel C.
    Ingelsson, Erik
    Risérus, Ulf
    Sundström, Johan
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Circulating endostatin and the incidence of heart failure2018Inngår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, nr 5, s. 244-249Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    Circulating levels of endostatin are elevated in many underlying conditions leading to heart failure such as hypertension, diabetes, chronic kidney disease and ischemic heart disease. Yet, the association between endostatin and the incidence of heart failure has not been reported previously in the community.

    DESIGN:

    We investigated the longitudinal association between serum endostatin levels and incident heart failure in two community-based cohorts of elderly: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 966; mean age 70 years, 51% women, 81 events, mean follow-up 10 years) and Uppsala Longitudinal Study of Adult Men (ULSAM, n = 747 men; mean age 78 years, 98 heart failure events, mean follow-up 8 years). We also investigated the cross-sectional association between endostatin and echocardiographic left ventricular systolic function and diastolic function (ejection fraction and E/A-ratio, respectively).

    RESULTS:

    Higher serum endostatin was associated with an increased risk for heart failure in both cohorts after adjustment for established heart failure risk factors, glomerular filtration rate and N-terminal pro-brain natriuretic peptide (NT-proBNP) (PIVUS: multivariable hazard ratio (HR) per 1-standard deviation (SD) increase, HR 1.46 (95%CI, 1.17-1.82, p < .001); ULSAM: HR 1.29 (95%CI, 1.00-1.68, p < .05). In cross-sectional analyses at baseline, higher endostatin was significantly associated with both worsened left ventricular systolic and diastolic function in both cohorts. Conclusion Higher serum endostatin was associated with left ventricular dysfunction and an increased heart failure risk in two community-based cohorts of elderly. Our findings encourage further experimental studies that investigate the role of endostatin in the development of heart failure.

  • 295. Ruge, Toralph
    et al.
    Carlsson, Axel C
    Jansson, Jan-Håkan
    Söderberg, Stefan
    Larsson, Anders
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    The association between circulating endostatin levels and incident myocardial infarction2018Inngår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, nr 6, s. 315-319Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Increased levels of circulating endostatin have been observed in patients with prevalent ischemic heart disease. However, the association between circulating endostatin, and incident myocardial infarction (MI) is less studied. Our main aim was to study the association between circulating endostatin and incident MI in the community adjusted for established cardiovascular risk factors in men and women.

    DESIGN: Circulating endostatin was measured in a nested case control study based on three large community-based Swedish cohorts, including 533 MI cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with adjustments for established cardiovascular risk factors.

    RESULTS: Higher endostatin was associated with a higher incidence of MI independently of established cardiovascular risk factors (OR 1.19, 95 % CI 1.03-1.37, p = 0.02), but this association was abolished after additional adjustment for C-reactive protein. Sex-stratified analyses suggest that the association was substantially stronger in women as compared to men Conclusions: In our community based sample, higher endostatin predicted incident myocardial infarction predominantly in women but not independently of CRP. Thus, our findings do not support a broad utility of endostatin measurements for the prediction of incident myocardial infarction in clinical practice.

  • 296. Ruge, Toralph
    et al.
    Carlsson, Axel C
    Kjøller, Erik
    Hilden, Jørgen
    Kolmos, Hans Jørn
    Sajadieh, Ahmad
    Kastrup, Jens
    Jensen, Gorm Boje
    Larsson, Anders
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Circulating endostatin as a risk factor for cardiovascular events in patients with stable coronary heart disease: A CLARICOR trial sub-study2019Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 284, s. 202-208Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND AIMS: Raised levels of serum endostatin, a biologically active fragment of collagen XVIII, have been observed in patients with ischemic heart disease but association with incident cardiovascular events in patients with stable coronary heart disease is uncertain.

    METHODS: The CLARICOR-trial is a randomized, placebo-controlled trial of stable coronary heart disease patients evaluating 14-day treatment with clarithromycin. The primary outcome was a composite of acute myocardial infarction, unstable angina pectoris, cerebrovascular disease or all-cause mortality. In the present sub-study using 10-year follow-up data, we investigated associations between serum endostatin at entry (randomization) and the composite outcome and its components during follow-up. The placebo group was used as discovery sample (1204 events, n = 1998) and the clarithromycin-treated group as replication sample (1220 events, n = 1979).

    RESULTS: In Cox regression models adjusting for cardiovascular risk factors, glomerular filtration rate, and current pharmacological treatment, higher serum endostatin was associated with an increased risk of the composite outcome in the discovery sample (hazard ratio per standard deviation increase 1.11, 95% CI 1.03-1.19, p = 0.004), but slightly weaker and not statistically significant in the replication sample (hazard ratio 1.06, 95% CI 1.00-1.14, p = 0.06). In contrast, strong and consistent associations were found between endostatin and cardiovascular and all-cause mortality in all multivariable models and sub-samples. Addition of endostatin to a model with established cardiovascular risk factors provided no substantial improvement of risk prediction (<1%).

    CONCLUSIONS: Raised levels of serum endostatin might be associated with cardiovascular events in patients with stable coronary heart disease. The clinical utility of endostatin measurements remains to be established.

  • 297. Ruge, Toralph
    et al.
    Carlsson, Axel C
    Larsson, Anders
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Endostatin: a promising biomarker in the cardiovascular continuum?2017Inngår i: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 11, nr 10, s. 905-916Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The current review article aims to provide an up-to-date summary of previous studies in humans that have reported the association between circulating endostatin levels and different cardiovascular phenotypes. We also aim to provide suggestions for future directions of future research evaluating endostatin as a clinically relevant cardiovascular biomarker. With a few exceptions, higher circulating levels of endostatin seem to reflect vascular and myocardial damage, and a worsened prognosis for cardiovascular events or mortality in individuals with hypertension, diabetes, kidney disease, cardiovascular disease, as well as in the general population. Circulating endostatin seems to be a promising biomarker for cardiovascular pathology, but there is not enough evidence to date to support the use of endostatin measurements in clinical practice.

  • 298. Ruge, Toralph
    et al.
    Carlsson, Axel C
    Larsson, Tobias E
    Carrero, Juan-Jesús
    Larsson, Anders
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Endostatin level is associated with kidney injury in the elderly: findings from two community-based cohorts2014Inngår i: American Journal of Nephrology, ISSN 0250-8095, E-ISSN 1421-9670, Vol. 40, nr 5, s. 417-424Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: We aimed to investigate the associations between circulating endostatin and the different aspects of renal dysfunction, namely, estimated (cystatin C) glomerular filtration rate (GFR) and urine albumin-creatinine ratio (ACR).

    METHODS: Two independent longitudinal community-based cohorts of elderly. ULSAM, n = 786 men; age 78 years; median GFR 74 ml/min/1.73 m(2); median ACR 0.80 mg/mmol); and PIVUS, n = 815; age 75 years; 51% women; median GFR; 67 ml/min/1.73 m(2); median ACR 1.39 mg/mmol. Cross-sectional associations between the endostatin levels and GFR as well as ACR, and longitudinal association between endostatin at baseline and incident CKD (defined as GFR <60 ml/min/1.73 m(2)) were assessed.

    RESULTS: In cross-sectional regression analyses adjusting for age, gender, inflammation, and cardiovascular risk factors, serum endostatin was negatively associated with GFR (ULSAM: B-coefficient per SD increase -0.51, 95% CI (-0.57, -0.45), p < 0.001; PIVUS -0.47, 95% CI (-0.54, -0.41), p < 0.001) and positively associated with ACR (ULSAM: B-coefficient per SD increase 0.24, 95% CI (0.15, 0.32), p < 0.001; PIVUS 0.13, 95% CI (0.06-0.20), p < 0.001) in both cohorts. Moreover, in longitudinal multivariable analyses, higher endostatin levels were associated with increased risk for incident CKD defined as GFR <60 ml/min/1.73 m(2) at re-investigations in both ULSAM (odds ratio per SD increase of endostatin 1.39 (95% CI 1.01-1.90) and PIVUS 1.68 (95% CI 1.36-2.07)).

    CONCLUSIONS: Higher circulating endostatin is associated with lower GFR and higher albuminuria and independently predicts incident CKD in elderly subjects. Further studies are warranted to investigate the underlying mechanisms linking endostatin to kidney pathology, and to evaluate the clinical relevance of our findings. © 2014 S. Karger AG, Basel.

  • 299. Rydell, Andreas
    et al.
    Janson, Christer
    Lisspers, Karin
    Ställberg, Björn
    Nowak, Christoph
    Carlsson, Axel C.
    Feldreich, Tobias
    Iggman, David
    Lind, Lars
    Ärnlöv, Johan
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap. Karolinska institutet.
    Endothelial dysfunction is associated with impaired lung function in two independent community cohorts2018Inngår i: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 143, s. 123-128Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Prior studies investigating the association between endothelial dysfunction and impaired lung function have been small and inconsistent. The primary aim was to investigate the association between endothelial function and lung function in two community-based cohorts.

    Methods

    We used a discovery/replication approach to study the association between endothelial function and lung function in the Prospective investigation of Obesity, Energy and Metabolism (POEM, discovery cohort, n = 490, mean age 50.3 ± 0.2 years) and the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, replication cohort, n = 892, mean age 70.2 ± 0.15 years). Spirometry and three different measures of endothelial function were performed including both the invasive forearm technique (endothelium-dependent and endothelium-independent vasodilation [EDV and EIDV, respectively] and noninvasive flow mediated dilation [FMD]).

    Results

    An age and sex adjusted association between lower EDV and lower FEV1 was found in POEM and replicated in PIVUS. After merging the two cohorts, 1 standard deviation decrease in EDV was associated with 1.57% lower FEV1 after additional adjustment for smoking status, body mass index, exercise level, and C-reactive protein (95% confidence intervals 0.63–2.51, p = 0.001). The association was slightly lower albeit still statistically significant after excluding participants without cardiovascular disease and chronic respiratory disease and appeared stronger among previous/current smokers vs. non-smokers and in men vs. women (p for interaction = 0.2 and 0.02 respectively).

    Conclusions

    Our findings suggest that even individuals with sub-clinical impairments of lung function in the community have concomitant endothelial dysfunction.

  • 300. Röijezon, Ulrik
    et al.
    Løvoll, Grunde
    Henriksson, Anders
    Tonkonogi, Michail
    Högskolan Dalarna, Akademin Utbildning, hälsa och samhälle, Medicinsk vetenskap.
    Lehto, Niklas
    An initial study on the coordination of rod and line hauling movements in distance fly casting2017Inngår i: Annals of Applied Sport Science, ISSN 2322-4479, Vol. 5, nr 2, s. 61-72Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. The double haul is a unique feature of single-handed fly casting and is used in both fly fishing and fly casting competition. The movement behaviour during the double haul has not been investigated in previous research.

    Objectives. Describe the coordination of the rod and line hauling movements during distance fly casting.

    Methods. Elite fly casters performed distance casting with four different fly rod and fly line set-ups used in fly fishing and fly casting competition. Rod and hauling movements were measured with a 3D motion analysis system.

    Results. The rod and line hauling movements were coordinated in an order whereby peak translational speed of the rod occurs prior to the peak speed of the angular rotation of the rod, and the peak speed of the angular rotation of the rod occurs prior to the peak speed of the line haul. This was consistent for all cast sequences, i.e., the back and forward false casts and the delivery cast, and for all four equipment set-ups, i.e., a shooting-head line cast with a relatively stiff fly rod and a long-belly line cast with three different fly rods with different stiffness and action curves. Results also showed differences in movement coordination between cast sequences and rod and line set-ups.

    Conclusion. Among elite casters, single-handed fly casting with double haul is coordinated in an order of events whereby the peak speed occurs first for the translation of the rod, then for the rotation of the rod and finally for the line haul.

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