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  • 1.
    Andreasson, Anna
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Stockholm Univ, Stress Res Inst, Stockholm, Sweden.;Macquarie Univ, Dept Psychol, N Ryde, NSW, Australia..
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Huddinge, Sweden.
    Önnerhag, Kristina
    Skane Univ Hosp, Dept Gastroenterol & Hepatol, Malmo, Sweden..
    Hagström, Hannes
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Digest Dis, Div Hepatol, Stockholm, Sweden..
    Waist/Hip Ratio Better Predicts Development of Severe Liver Disease Within 20 Years Than Body Mass Index: A Population-based Cohort Study2017In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 15, no 8, p. 1294-1301Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Obesity, commonly assessed based on body mass index (BMI), is associated with an increased risk for severe liver disease. It is not known if other measures of body composition are better determinants of risk for severe liver disease, and/or if these differ between women and men. We investigated the body composition measures that best predict the development of severe liver disease.

    METHODS: We collected data from the Malmo Diet and Cancer study in Sweden, comprising 16,784 women and 10,833 (mean age, 58.1 years at baseline), and followed patients for a median 19.8 years. We analyzed data on measures of body composition including BMI, waist/hip ratio, and others. We determined whether subjects were diagnosed with severe liver disease, or died from severe liver disease, until the end of 2014 using Swedish national registers. Associations between body composition measures and severe liver disease were assessed using Cox regression models, stratified by sex and adjusted for age, alcohol consumption, smoking, education, and physical activity.

    RESULTS: All studied measures of body composition were significantly associated with severe liver disease. Waist/hip ratio was the best predictor of severe liver disease in women (hazard ratio [HR] per standard deviation increment, 1.30; 95% confidence interval [CI], 1.16-1.46) and men (HR, 1.46; 95% CI, 1.31-1.63). BMI had the lowest HR in women (HR, 1.12; 95% CI, 1.00-1.27) and men (HR, 1.26; 95% CI, 1.12-1.42). The association between waist/hip ratio and development of liver disease was independent of BMI.

    CONCLUSIONS: In a Swedish population-based cohort study, we associated all measures of body composition with risk of severe liver disease. However, measures of abdominal obesity were best at predicting development of severe liver disease.

  • 2.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Bandstein, Nadia
    Karolinska Univ Hosp, Dept Emergency Med, C1-63, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    Roos, Andreas
    Karolinska Univ Hosp, Dept Emergency Med, C1-63, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    Hammarsten, Ola
    Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Clin Chem & Transfus Med, Gothenburg, Sweden..
    Holzmann, Martin J.
    Karolinska Univ Hosp, Dept Emergency Med, C1-63, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    High-sensitivity cardiac troponin T levels in the emergency department in patients with chest pain but no myocardial infarction2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 228, p. 253-259Article in journal (Refereed)
    Abstract [en]

    Background: High-sensitivity cardiac troponin T (hs-cTnT) was recently introduced into clinical practice. The increased sensitivity has decreased the specificity. We aimed to determine the predictors for and prevalence of hs-cTnT levels above the 99th percentile in a stable population of patients without myocardial infarction (MI) who sought medical attention for chest pain in the emergency department. Methods: We included 11,847 patients with chest pain and at least one hs-cTnT measurement during 2011 and 2012. Patients with any acute reasons for an elevated hs-cTnT level were excluded. We used logistic regression to calculate adjusted odds ratios with 95% confidence intervals for the association between patient characteristics and hs-cTnT levels of >14 ng/L. We also determined 50th, 75th, 97.5th, and 99th percentile values of hs-cTnT levels in relation to age, sex, estimated glomerular filtration rate (eGFR), and presence or absence of comorbidities. Results: In total, 1360 (11%) patients had hs-cTnT levels of >14 ng/L. Men had higher troponin levels than women, and older patients had higher levels than younger patients. The strongest predictor of an elevated troponin level was a reduced eGFR. The 99th percentile for hs-cTnT among all men and among women <50 years of age with normal renal function was 20 and 12 ng/L, respectively; this level increased to 44 and 36 ng/L, respectively, at the age of 70-79 years. Conclusions: A hs-cTnT level above the 99th percentile in patients with chest pain but no MI is common and is related to sex, age, and eGFR.

  • 3.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Calamia, Michael
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Kidney injury molecule (KIM)-1 is associated with insulin resistance: Results from two community-based studies of elderly individuals2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 103, no 3, p. 516-521Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Insulin resistance has been shown to be closely associated with glomerular filtration rate and urinary albumin/creatinine ratio, even prior to the development of diabetes. Urinary kidney injury molecule 1 (KIM-1) is a novel, highly specific marker of kidney tubular damage. The role of insulin resistance in the development of kidney tubular damage is not previously reported. Thus, we aimed to investigate the associations between insulin sensitivity (assessed by HOMA) and urinary KIM-1.

    DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Two community-based cohorts of elderly individuals were investigated: Prospective Investigation of the vasculature in Uppsala seniors (PIVUS, n=701; mean age 75 years, 52% women); and Uppsala Longitudinal Study of adult men (ULSAM, n=533; mean age 78 years).

    RESULTS: Lower insulin sensitivity was associated with higher urinary KIM-1 in both cohorts after adjustments for age, BMI, blood pressure, antihypertensive treatment, glomerular filtration rate, and urinary albumin-creatinine ratio (PIVUS: regression coefficient for 1-SD higher HOMA-IR 0.11, 95% CI 0.03-0.20, p=0.009, and ULSAM: 0.13, 95% CI 0.04-0.22, p=0.007). Results were similar in individuals without diabetes, with normal kidney function and normo-albuminuria.

    CONCLUSIONS: Our findings in elderly individuals support the notion that the interplay between an impaired glucose metabolism and renal tubular damage is evident even prior to the development of diabetes and overt kidney disease.

  • 4.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carrero, Juan-Jesús
    Stenvinkel, Peter
    Bottai, Matteo
    Barany, Peter
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Endostatin, Cathepsin S, and Cathepsin L, and Their Association with Inflammatory Markers and Mortality in Patients Undergoing Hemodialysis2015In: Blood Purification, ISSN 0253-5068, E-ISSN 1421-9735, Vol. 39, no 4, p. 259-265Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIMS: Although both endostatin and cathepsins S have been associated with higher mortality, data in patients with end-stage renal disease (ESRD) are scarce.

    METHODS: A longitudinal cohort study of 207 prevalent patients undergoing hemodialysis.

    RESULTS: Cathepsins S and L were associated with soluble receptors for tumor necrosis factor (sTNFR1 and sTNFR2, rho between 0.28 and 0.43, p < 0.001 for all). Weaker or absent associations between endostatin, cathepsins S and L were seen with other inflammatory biomarkers, that is, CRP, interleukin 6, pentraxin 3, and TNF. In Cox and Laplace regression models adjusted for age, sex, dialysis vintage, and diabetes: standard deviation increments of endostatin was associated with a lower mortality (hazard ratio 0.75, 95% confidence interval (CI) 0.57-0.98), and with 6.8 months longer median survival.

    CONCLUSIONS: The high levels of endostatin, cathepsins S and L, and their associations with sTNFR1 and sTNFR2 warrant further studies exploring mortality, and the angiogenic and inflammatory pathways in ESRD.

  • 5.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carrero, Juan-Jesús
    Stenvinkel, Peter
    Bottai, Matteo
    Barany, Peter
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    High levels of soluble tumor necrosis factor receptors 1 and 2 and their association with mortality in patients undergoing hemodialysis2015In: Cardiorenal medicine, ISSN 1664-3828, Vol. 5, no 2, p. 89-95Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Circulating soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) are associated with chronic kidney disease (CKD) progression in patients with CKD or diabetes, and with higher mortality. However, data in patients with end-stage renal disease are scarce. Therefore, we analyzed serum levels of sTNFR1 and sTNFR2 and investigated their association with inflammatory markers and mortality in dialysis patients.

    RESEARCH DESIGN AND METHODS: This was a longitudinal cohort study of 207 prevalent patients (median age 66 years, 56% men) undergoing hemodialysis in Stockholm, Sweden. Demographics, clinical characteristics, including comorbidities and laboratory data, were obtained at baseline, together with prospective follow-up for mortality.

    RESULTS: The median sTNFR1 and sTNFR2 levels were 17,680 ng/l [95% confidence interval (CI) 17,023-18,337] and 24,450 ng/l (95% CI 23,721-25,179), respectively. During a follow-up of 31 months (interquartile range, 21-38), 77 patients died. There was no association between the levels of sTNFRs and mortality in Cox regression models, and no consistent trend towards higher or lower mortality was seen in Laplace regression models. sTNFR1 and sTNFR2 levels were highly associated with other inflammatory markers including interleukin-6, pentraxin 3 and TNF-α.

    CONCLUSIONS: Prevalent hemodialysis patients have several-fold higher levels of sTNFRs compared to previous studies in CKD stage 4 patients. As no consistent association between TNFR and mortality was observed, clinical implications of measuring these receptors to predict outcome end-stage renal disease patients provide limited results.

  • 6.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Carrero, Juan Jesus
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Feldreich, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Stenemo, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Use of Proteomics To Investigate Kidney Function Decline over 5 Years2017In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 12, no 8, p. 1226-1235Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence.

    DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR. There were 231 and 206 incident cases of CKD during follow-up in the PIVUS and ULSAM studies, respectively. Proteomic profiling of 80 proteins was assessed by a multiplex assay (proximity extension assay). The assay uses two antibodies for each protein and a PCR step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations.

    RESULTS: In the discovery cohort from the PIVUS Study, 28 plasma proteins were significantly associated with eGFR decline per year, taking into account the multiple testing. Twenty of these proteins were significantly associated with eGFR decline per year in the replication cohort from the ULSAM Study after adjustment for age, sex, cardiovascular risk factors, medications, and urinary albumin-to-creatinine ratio (in order of significance: TNF-related apoptosis-inducing ligand receptor 2*, CD40L receptor, TNF receptor 1*, placenta growth factor*, thrombomodulin*, urokinase plasminogen activator surface receptor*, growth/differentiation factor 15*, macrophage colony-stimulating factor 1, fatty acid-binding protein*, cathepsin D, resistin, kallikrein 11*, C-C motif chemokine 3, proteinase-activated receptor 1*, cathepsin L, chitinase 3-like protein 1, TNF receptor 2*, fibroblast growth factor 23*, monocyte chemotactic protein 1, and kallikrein 6). Moreover, 11 of the proteins predicted CKD incidence (marked with * above). No protein consistently predicted eGFR decline per year independently of baseline eGFR in both cohorts.

    CONCLUSIONS: Several circulating proteins involved in phosphate homeostasis, inflammation, apoptosis, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction were associated with worsening kidney function. Multiplex proteomics appears to be a promising way of discovering novel aspects of kidney disease pathology.

  • 7.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Jansson, Jan-Håkan
    Department of Public Health and Clinical Medicine, Research Unit Skellefteå, Umeå University, Umeå, Sweden.
    Söderberg, Stefan
    Department of Public Health and Clinical Medicine, Heart Centre, Umeå University, Umeå, Sweden.
    Ruge, Toralph
    Dept of Medicine Solna, Karolinska Institutet and Function of Emergency Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ärnlöv, Johan
    Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; School of Health and Social Sciences, Dalarna University, Falun, Sweden.
    Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden2018In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 272, p. 41-46Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS:

    Soluble receptors for tumor necrosis factor alpha (sTNFR1 and sTNFR2) have been associated with cardiovascular diseases, and some evidence points towards a difference in associated risk between men and women. We aimed to study the association between sTNFR1 and sTNFR2 and incident myocardial infarctions (MI) and to explore the influence of established cardiovascular risk factors in men and women.

    METHODS:

    We conducted a nested case control study in three large Swedish cohorts, including 533 myocardial infarction cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.

    RESULTS:

    An association between circulating sTNFR1 and sTNFR2 and an increased risk for MI was found when comparing cases and controls. The odds ratios were significant after adjustment for established cardiovascular risk factors and C-reactive protein in women (OR 1.44, 95% CI 1.08-1.93 for TNFR1, and 1.61, 95% CI 1.11-2.34 for TNFR2), but was abolished in men. Women with a combination of elevated CRP and values in the upper quartile of TNFR1 or TNFR2 had a 5-fold higher risk of myocardial infarction versus those with normal CRP and values in the lower three quartiles of TNFR1 or TNFR2.

    CONCLUSIONS:

    As the risk estimates for TNFR1 and TNFR2 were higher and remained significant after adjustments for established cardiovascular risk factors in women but not in men, a potential role for TNFR1 and TNFR2 in identifying women with a higher MI risk is possible. The future clinical role of TNFR1 and TNFR2 in combination with CRP to identify high risk patients for coronary heart disease has yet to be determined.

  • 8.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Juhlin, C Christofer
    Larsson, Tobias E
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes: Findings from two community based cohorts of elderly2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 237, no 1, p. 236-242Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.

    METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).

    RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.

    CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.

  • 9.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Tobias E
    Bottai, Matteo
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Urinary Kidney Injury Molecule-1 and the Risk of Cardiovascular Mortality in Elderly Men2014In: Clinical journal of the American Society of Nephrology : CJASN, ISSN 1555-905X, Vol. 9, no 8, p. 1393-1401Article in journal (Refereed)
    Abstract [en]

    Background and objectives

    Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.

    Design, setting, participants, & measurements

    This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997–2001; median follow-up 8.1 years; end of follow-up, 2008).

    Results

    During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C–based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m2), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m2), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).

    Conclusions

    These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.

  • 10.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Larsson, Tobias E
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Urinary kidney injury molecule 1 and incidence of heart failure in elderly men2013In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 15, no 4, p. 441-446Article in journal (Refereed)
    Abstract [en]

    AIMS:

    There is growing recognition of the clinical importance of cardiorenal syndrome-the bidirectional interplay between kidney and cardiac dysfunction. Yet, the role of kidney tubular damage in the development of heart failure is less studied. The objective of this study was to investigate whether urinary kidney injury molecule (KIM)-1, a specific marker of tubular damage, predisposes to an increased heart failure risk.

    METHODS AND RESULTS:

    This was a community-based cohort study [Uppsala Longitudinal study of Adult Men (ULSAM)] of 565, 77-year-old men free from heart failure at baseline. Heart failure hospitalizations were used as outcome. During follow-up (median 8.0 years), 73 participants were hospitalized for heart failure. In models adjusted for cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, LDL/HDL ratio, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, LV hypertrophy, and prevalent cardiovascular disease) and markers of kidney dysfunction and damage [cystatin C-based glomerular filtration rate (GFR) and urinary albumin/creatinine ratio], a higher urinary KIM-1/creatinine ratio was associated with higher risk for heart failure (hazard ratio upper vs. lower tertile, 1.81; 95% confidence interval 1.01-3.29; P < 0.05). Participants with a combination of low GFR (<60 mL/min/1.72 m(2)) and high KIM-1/creatinine (>128 ng/mmol) had a 3-fold increase in heart failure risk compared with participants with normal GFR and KIM-1 (P < 0.001).

    CONCLUSION:

    Our findings suggest that kidney tubular damage predisposes to an increased risk for heart failure in the community. Further studies are needed to clarify the causal role of KIM-1 in the development of heart failure, and to evaluate the clinical utility of urinary KIM-1 measurements.

  • 11.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Larsson, Tobias E
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Soluble TNF Receptors and Kidney Dysfunction in the Elderly2014In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 25, no 6, p. 1313-1320Article in journal (Refereed)
    Abstract [en]

    The importance of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in the development of kidney disease is being unraveled. Yet, community-based data regarding the role of sTNFRs are lacking. We assessed serum sTNFRs and aspects of kidney damage cross-sectionally in two independent community-based cohorts of elderly participants: Prospective Investigation of the Vasculature in Uppsala Seniors (n=815; mean age, 75 years; 51% women) and Uppsala Longitudinal Study of Adult Men (n=778; mean age, 78 years). Serum sTNFR1 correlated substantially with different aspects of kidney pathology in the Uppsala Longitudinal Study of Adult Men cohort (R=-0.52 for estimated GFR, R=0.22 for urinary albumin-to-creatinine ratio, and R=0.17 for urinary kidney injury molecule-1; P<0.001 for all), with similar correlations in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. These associations remained significant after adjustment for age, sex, inflammatory markers, and cardiovascular risk factors and were also evident in participants without diabetes. Serum sTNFR2 was associated with all three markers in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort (P<0.001 for all). Our findings from two independent community-based cohorts confirm and extend results of previous studies supporting circulating sTNFRs as relevant biomarkers for kidney damage and dysfunction in elderly individuals, even in the absence of diabetes.

  • 12.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Li, Xinjun
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Holzmann, Martin J.
    Karolinska Univ Hosp, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Internal Med, S-10401 Stockholm, Sweden..
    Wändell, Per
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Gasevic, Danijela
    Univ Edinburgh, Coll Med & Vet Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland..
    Sundquist, Jan
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Sundquist, Kristina
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Neighbourhood socioeconomic status and coronary heart disease in individuals between 40 and 50 years2016In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 10, p. 775-782Article in journal (Refereed)
    Abstract [en]

    Objective The incidence of myocardial infarction (MI) has decreased in general but not among younger middle-aged adults. We performed a cohort study of the association between neighbourhood socioeconomic status (SES) at the age of 40 and risk of MI before the age of 50 years.

    Methods All individuals in Sweden were included in the year of their 40th birthday, if it occurred between 1998 and 2010. National registers were used to categorise neighbourhood SES into high, middle and low, and to retrieve information on incident MI and coronary heart disease (CHD). Cox regression models, adjusted for marital status, education level, immigrant status and region of residence, provided an estimate of the HRs and 95% CIs for MI or CHD.

    Results Out of 587 933 men and 563 719 women, incident MI occurred in 2877 (0.48%) men and 932 (0.17%) women; and CHD occurred in 4400 (0.74%) men and 1756 (0.31%) women during a mean follow-up of 5.5 years. Using individuals living in middle-SES neighbourhoods as referents, living in high-SES neighbourhoods was associated with lower risk of MI in both sexes (HR (95% CI): men: 0.72 (0.64 to 0.82), women: 0.66 (0.53 to 0.81)); living in low-SES neighbourhoods was associated with a higher risk of MI (HR (95% CI): men: 1.31 (1.20 to 1.44), women: 1.28 (1.08 to 1.50)). Similar risk estimates for CHD were found.

    Conclusions The results of our study suggest an increased risk of MI and CHD among residents from low-SES neighbourhoods and a lower risk in those from high-SES neighbourhoods compared with residents in middle-SES neighbourhoods.

  • 13.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.
    Li, Xinjun
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Holzmann, Martin J.
    Karolinska Univ Hosp, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    Ärnlov, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Wändell, Per
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden..
    Gasevic, Danijela
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Coll Med & Vet Med, Edinburgh, Midlothian, Scotland..
    Sundquist, Jan
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Sundquist, Kristina
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden..
    Neighborhood socioeconomic status at the age of 40 years and ischemic stroke before the age of 50 years: A nationwide cohort study from Sweden2017In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 12, no 8, p. 815-826Article in journal (Refereed)
    Abstract [en]

    Objective: We aimed to study the association between neighborhood socioeconomic status at the age of 40 years and risk of ischemic stroke before the age of 50 years.

    Methods: All individuals in Sweden were included if their 40th birthday occurred between 1998 and 2010. National registers were used to categorize neighborhood socioeconomic status into high, middle, and low and to retrieve information on incident ischemic strokes. Hazard ratios and their 95% confidence intervals were estimated.

    Results: A total of 1,153,451 adults (women 48.9%) were followed for a mean of 5.5 years (SD 3.5 years), during which 1777 (0.30%) strokes among men and 1374 (0.24%) strokes among women were recorded. After adjustment for sex, marital status, education level, immigrant status, region of residence, and neighborhood services, there was a lower risk of stroke in residents from high-socioeconomic status neighborhoods (hazard ratio 0.87, 95% confidence interval 0.78-0.96), and an increased risk of stroke in adults from low-socioeconomic status neighborhoods (hazard ratio 1.16, 95% confidence interval 1.06-1.27), compared to their counterparts living in middle-socioeconomic status neighborhoods. After further adjustment for hospital diagnoses of hypertension, diabetes, heart failure, and atrial fibrillation prior to the age of 40, the higher risk in neighborhoods with low socioeconomic status was attenuated, but remained significant (hazard ratio 1.12, 95% confidence interval 1.02-1.23).

    Conclusions: In a nationwide study of individuals between 40 and 50 years, we found that the risk of ischemic stroke differed depending on neighborhood socioeconomic status, which calls for increased efforts to prevent cardiovascular diseases in low socioeconomic status neighborhoods.

  • 14.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Division of Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Nordquist, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Larsson, Tobias E.
    Carrero, Juan-Jesús
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. gSchool of Health and Social Studies, Dalarna University, Falun , Sweden.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Soluble Tumor Necrosis Factor Receptor 1 Is Associated with Glomerular Filtration Rate Progression and Incidence of Chronic Kidney Disease in Two Community-Based Cohorts of Elderly Individuals2015In: Cardiorenal Medicine, ISSN 1664-3828, Vol. 5, no 4, p. 278-288Article in journal (Refereed)
    Abstract [en]

    Objective: We aimed to explore and validate the longitudinal associations between soluble tumor necrosis factor receptor 1 (sTNFR1), glomerular filtration rate (GFR) progression, and chronic kidney disease (CKD) incidence in two independent community-based cohorts of elderly individuals with prespecified subgroup analyses in individuals without prevalent diabetes. Research Design and Methods: Two community-based cohorts of elderly individuals were used with 5-year follow-up data on estimated GFR: the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 437 men; mean age: 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 703; mean age: 70 years; 51% women). GFR categories were defined as >= 60, 30-60, and = 60 ml/min/1.73 m(2) at baseline, higher sTNFRs were associated with incident CKD after 5 years in both cohorts [ULSAM: OR per SD increase 1.49 (95% CI 1.16-1.9) and PIVUS: OR 1.84 (95% CI 1.50-2.26)]. Associations were similar in individuals without diabetes. Conclusions: Higher circulating sTNFR1 independently predicts the progression to a worse GFR category and CKD incidence in elderly individuals even in the absence of diabetes. Further studies are warranted to investigate the underlying mechanisms, and to evaluate the clinical relevance of our findings.

  • 15.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Hypertriglyceridemic Waist Phenotype Is Associated with Decreased Insulin Sensitivity and Incident Diabetes in Elderly Men2014In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 22, no 2, p. 526-529Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the association between hypertriglyceridemic waist (HTGW) and insulin sensitivity (assessed by euglycemic clamp method), and the development of diabetes in a longitudinal community-based cohort of elderly men without diabetes at baseline. Design and Methods: The present cross-sectional study comprised 1,026, 70-year-old men without diabetes. The gold standard euglycaemic-hyperinsulinaemic clamp technique was used. Six-year follow-up on diabetes status were available in n = 667. The HTGW phenotype was defined as having waist circumference >= 90 cm, and triglycerides >= 2 mmol L-1. The men were stratified into those having normal WC and TG (n = 299), one HTGW component (n = 606), and HTGW (n = 121). Results: The association between insulin sensitivity and one HTGW component as well as HTGW was highly significant (P < 0.001) in the whole sample, as well as in individuals with high/low BMI (stratified at >= 25). In longitudinal analyses, participants with HTGW was associated with a more than fourfold increased risk for diabetes (Odds ratio 4.64, 95% CI 1.61-13.4, P = 0.004) compared to those with normal WC and TG. Conclusion: The present study both confirm and extend previous research suggesting that the HTGW-phenotype portrays an increased glucometabolic risk, also in lean individuals.

  • 16.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ruge, Toralph
    Kjøller, Erik
    Hilden, Jørgen
    Kolmos, Hans Jørn
    Sajadieh, Ahmad
    Kastrup, Jens
    Jensen, Gorm Boje
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Nowak, Christoph
    Jakobsen, Janus Christian
    Winkel, Per
    Gluud, Christian
    Ärnlöv, Johan
    10-Year Associations between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients with Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy.2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 9, article id e008299Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.

    METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).

    CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.

    CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.

  • 17.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ruge, Toralph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Association between circulating endostatin, hypertension duration, and hypertensive target-organ damage2013In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 62, no 6, p. 1146-1151Article in journal (Refereed)
    Abstract [en]

    Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive target-organ damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 51%; n=812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with ≥5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher; 95% confidence interval, 0.35-0.80; P<0.001). In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage. Further studies are warranted to assess the prognostic role of endostatin in individuals with hypertension.

  • 18.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Starrin, Bengt
    Gigante, Bruna
    Leander, Karin
    Hellenius, Mai-Lis
    de Faire, Ulf
    Financial stress in late adulthood and diverse risks of incident cardiovascular disease and all-cause mortality in women and men2014In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 14, p. 17-Article in journal (Refereed)
    Abstract [en]

    Background: Financial stress may have adverse health effects. The main aim of this study was to investigate whether having a cash margin and living alone or cohabiting is associated with incident cardiovascular disease (CVD) and all-cause mortality. Methods: Representative population-based prospective cohort study of 60-year-old women (n = 2065) and men (n = 1939) in Stockholm County, Sweden. National registers were used to identify cases of incident CVD (n = 375) and all-cause mortality (n = 385). The presence of a cash margin was determined in the questionnaire with the following question: Would you, if an unexpected situation occurred, be able to raise 10 000 SEK within a week? (This was equivalent to US$ 1250 in 1998). Results: Compared with cohabiting women with a cash margin, the risk of all-cause mortality was higher among cohabiting women without a cash margin, with hazard ratios (HRs) of 1.97 (95% confidence interval (CI) 1.06-3.66). Using cohabiting men with cash margin as referent, single men without a cash margin were at an increased risk of both incident CVD and all-cause mortality: HR 2.84 (95% CI 1.61-4.99) and 2.78 (95% CI 1.69-4.56), respectively. Single men with cash margins still had an increased risk of all-cause mortality when compared with cohabiting men with a cash margin: HR 1.67 (95% CI 1.22-2.28). Conclusions: Financial stress may increase the risks of incident CVD and all-cause mortality, especially among men. Furthermore these risks are likely to be greater in men living in single households and in women without cash margins. Living with a partner seems to protect men, but not women, from ill-health associated with financial stress due to the lack of a cash margin.

  • 19.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med, Dept Neurobiol, Care Sci & Soc, Karlskrona, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Carrero, Juan Jesus
    Karolinska Inst, Div Renal Med, Dept Clin Sci, Intervent & Technol, Karlskrona, Sweden..
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stenemo, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalarna Univ, Sch Hlth & Social Sci, Dalarna, Sweden..
    Use of a proximity extension assay proteomics chip to discover new biomarkers associated with albuminuria2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, no 4, p. 340-348Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The underlying mechanisms for the development of albuminuria and the increased cardiovascular risk in patients with elevated albuminuria levels are incompletely understood. We therefore investigated the associations between 80 cardiovascular proteins and the urinary albumin to creatinine ratio (ACR).

    METHODS: We used a discovery/replication approach in two independent community-based cohorts of elderly patients: the Uppsala Longitudinal Study of Adult Men (n = 662; mean age 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (n = 757; mean age 75 years; 51% women). A proteomic chip with a panel of 80 plasma proteins associated with different aspects of cardiovascular disease was analysed. In the discovery cohort, we used a false discovery rate of 5% to take into account the multiple statistical testing. Nominal p values were used in the replication.

    RESULTS: Higher levels of T-cell immunoglobulin mucin-1, placenta growth factor, growth/differentiation factor-15, urokinase plasminogen activator surface receptor and kallikrein-11 were robustly associated with a higher ACR in both cohorts in multivariable linear regression models adjusted for sex, established cardiovascular risk factors, antihypertensive treatment, prevalent cardiovascular disease and glomerular filtration rate (p < 0.02 for all). All associations were also significant in separate analyses of patients without diabetes.

    CONCLUSIONS: We discovered and replicated associations between ACR and five cardiovascular proteins involved in tubular injury, atherosclerosis, endothelial function, heart failure, inflammation, glomerulosclerosis and podocyte injury. Our findings put forward multiplex proteomics as a promising approach to explore novel aspects of the complex detrimental interplay between kidney function and the cardiovascular system.

  • 20.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wandell, Per E.
    Gigante, Bruna
    Leander, Karin
    Hellenius, Mai-Lis
    de Faire, Ulf
    Response to: Modifiable lifestyle risks, cardiovascular disease, and all-cause mortality2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 173, no 3, p. 560-560Article in journal (Refereed)
  • 21.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wandell, Per
    Gasevic, Danijela
    Sundquist, Jan
    Sundquist, Kristina
    Neighborhood deprivation and warfarin, aspirin and statin prescription - A cohort study of men and women treated for atrial fibrillation in Swedish primary care2015In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 187, p. 547-552Article in journal (Refereed)
    Abstract [en]

    Background: Weaimed to study differences in the prescribing of warfarin, aspirin and statins to patients with atrial fibrillation (AF) in socio-economically diverse neighborhoods. We also aimed to explore the effects of neighborhood deprivation on the relationship between CHADS2 risk score and warfarin prescription. Methods: Data were obtained from primary health care records that contained individual clinical data that were linked to national data on neighborhood of residence and a deprivation index for different neighborhoods. Logistic regression was used to estimate the potential neighborhood differences in prescribed warfarin, aspirin and statins, and the association between the CHADS2 score and prescribed warfarin treatment, in neighborhoods with high, middle (referent) and low socio-economic (SES). Results: After adjustment for age, socio-economic factors, co-morbidities and moves to neighborhoods with different SES during follow-up, adults with AF living in high SES neighborhoods were more often prescribed warfarin (men odds ratio (OR) (95% confidence interval (CI): 1.44 (1.27-1.62); and women OR (95% CI): 1.19 (1.05-1.36)) and statins (men OR (95% CI): 1.23 (1.07-1.41); women OR (95% CI): 1.23 (1.05-1.44)) compared to their counterparts residing in middle SES. Prescription of aspirin was lower in men from high SES neighborhoods (OR (95% CI): 0.75 (0.65-0.86)) than in those from middle SES neighborhoods. Higher CHADS2 risk scores were associated with higher warfarin prescription which remained after adjustment for neighborhood SES. Conclusions: The apparent inequalities in pharmacotherapy seen in the present study call for resource allocation to primary care in neighborhoods with low and middle socio-economic status.

  • 22.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wandell, Per
    Sundquist, Kristina
    Johansson, Sven-Erik
    Sundquist, Jan
    Effects of prescribed antihypertensives and other cardiovascular drugs on mortality in patients with atrial fibrillation and hypertension: a cohort study from Sweden2014In: Hypertension Research, ISSN 0916-9636, E-ISSN 1348-4214, Vol. 37, no 6, p. 553-559Article in journal (Refereed)
    Abstract [en]

    Although antihypertensive drugs are known to reduce mortality in individuals with hypertension, the effects of different cardiovascular pharmacotherapies on mortality among patients with hypertension and atrial fibrillation (AF) have been less thoroughly explored. To study mortality rates in men and women separately with hypertension and AF prescribed different cardiovascular pharmacotherapies. A cohort of men (n = 2809) and women (n = 2793) aged > 45 years diagnosed with hypertension and AF were selected using patient records. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox regression, with all-cause mortality as the outcome. Analysis was performed on the whole population and after stratification by age and sex. Independent factors were prescribed pharmacotherapies. Adjustments were made for a propensity score comprising age, comorbidities, education and marital status. The higher the number of antihypertensive drugs prescribed, the lower the mortality rate (P-value for trend 0.005). Individuals prescribed 4-5 antihypertensive drugs had a lower risk of mortality than those prescribed 0-1 drugs (HR: 0.62; 95% CI: 0.45-0.86). The HRs for the following drug classes were: loop diuretics 1.39 (95% CI: 1.08-1.78), non-selective beta-blockers 0.68 (95% CI: 0.53-0.88), angiotensin receptor blockers 0.75 (95% CI: 0.56-0.99) and statins 0.68 (95% CI: 0.53-0.88). AF patients with hypertension prescribed statins, non-selective b-blockers and angiotensin receptor blockers had low relative mortality risks, suggesting that these prescribed pharmacotherapies were beneficial. This needs to be further explored in other clinical settings.

  • 23.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Physical activity, obesity and risk of cardiovascular disease in middle-aged men during a median of 30 years of follow-up2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 4, p. 359-365Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    We aimed to investigate associations between combinations of body mass index (BMI)-categories, levels of physical activity and long-term risk of cardiovascular disease.

    METHOD AND RESULTS:

    At age 50 years, cardiovascular risk factors were assessed in 2196 participating men of the ULSAM-study. This investigation was repeated at age 60, 70, 77 and 82 years. Being physically active (PA) was defined as three hours of recreational or hard physical training per week. The men were categorized according to BMI/PA-status, as PA/normal weight (n = 593 at baseline), non-PA/normal weight (BMI < 25 kg/m(2), n = 580), PA/overweight (n = 418), non-PA/overweight (BMI 25-30 kg/m(2), n = 462), PA/obese (n = 62), non-PA/obese (BMI >30 kg/m(2), n = 81). We used updated data on BMI and physical activity obtained at all examinations. During follow-up (median 30 years) 850 individuals suffered a cardiovascular disease (myocardial infarction, stroke or heart failure). Using updated data on BMI/PA categories, an increased risk for cardiovascular disease was seen with increasing BMI, but a high physical activity was associated with a lower risk of cardiovascular disease within each BMI category: non-PA/normal weight (hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.04-1.66), PA/overweight (HR 1.52, 95% CI 1.20-1.94), non-PA/overweight (HR 1.65, 95% CI 1.31-2.07) PA/obese (HR 2.05, 95% CI 1.44-2.92) and non-PA/obese (HR 2.39, 95% CI 1.74-3.29), using PA/normal weight men as referent.

    CONCLUSIONS:

    Although physical activity was beneficial at all levels of BMI regarding the risk of future cardiovascular disease, there was still a substantial increased risk associated with being overweight or obese during 30 years of follow-up.

  • 24.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Östgren, C. J.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Lanne, T.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nyström, F. H.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    The association between endostatin and kidney disease and mortality in patients with type 2 diabetes2016In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 42, no 5, p. 351-357Article in journal (Refereed)
    Abstract [en]

    Aim. - Circulating endostatin, a biologically active derivate of collagen XVIII, is considered to be a marker of kidney disease and a risk factor for its related mortality. However, less is known of the role of endostatin in diabetes and the development of diabetic nephropathy. For this reason, our study investigated the associations between circulating endostatin and the prevalence and progression of kidney disease, and its mortality risk in patients with type 2 diabetes (T2D). Methods. - This was a cohort study of 607 patients with T2D (mean age: 61 years, 44% women). Estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was used to assess the patients' kidney function decline and mortality. Results. - Of the total study cohort, 20 patients declined by >= 20% in eGFR over 4 years, and 44 died during the follow-up (mean duration: 6.7 years). At baseline, participants with diabetic nephropathy (defined as eGFR < 60 mL/min/1.73 m(2)) and/or microalbuminuria [defined as a urinary albumin-to-creatinine ratio (ACR) > 3 g/mol] had higher median levels of endostatin than those without nephropathy (62.7 mu g/L vs 57.4 mu g/L, respectively; P = 0.031). In longitudinal analyses adjusted for age, gender, baseline eGFR and ACR, higher endostatin levels were associated with a higher risk of decline (>= 20% in eGFR, OR per 1 SD increase: 1.73, 95% CI: 1.13-2.65) and a higher risk of mortality (HR per 1 SD increase: 1.57, 95% CI: 1.19-2.07). Conclusion. - In patients with T2D, circulating endostatin levels can predict the progression of kidney disease and mortality independently of established kidney disease markers. The clinical usefulness of endostatin as a risk marker in such patients merits further studies.

  • 25.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Östgren, Carl Johan
    Department of Medical and Health Sciences, Linköping University, Linköping, Sweden..
    Nystrom, Fredrik H
    Department of Medical and Health Sciences, Linköping University, Linköping, Sweden..
    Länne, Toste
    Department of Medical and Health Sciences, Linköping University, Linköping, Sweden..
    Jennersjö, Pär
    Department of Medical and Health Sciences, Linköping University, Linköping, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes2016In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 15, article id 40Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease.

    METHODS: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used.

    RESULTS: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p < 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p < 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality.

    CONCLUSIONS/INTERPRETATIONS: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.

  • 26.
    Carlsson, Axel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wändell, Per
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Borné, Yan
    Engström, Gunnar
    Leander, Karin
    Gigante, Bruna
    Hellenius, Mai-Lis
    de Faire, Ulf
    Differences inanthropometric measures in immigrants and Swedish-born individuals: Results from two community based cohort studies2014In: Preventive Medicine, ISSN 0091-7435, E-ISSN 1096-0260, Vol. 69, p. 151-156Article in journal (Refereed)
    Abstract [en]

    Aim

    To study differences in body mass index (BMI), waist–hip ratio (WHR), waist circumference (WC), sagittal abdominal diameter (SAD), waist–hip–height ratio (WHHR) and percent body fat in immigrants and Swedish-born men and women in two large population-based samples.

    Methods

    A cross-sectional analysis of 60-year-old individuals, n = 4 232. To replicate the results, we also assessed another large independent cohort cross-sectionally, the Malmö Diet and Cancer Study (MDC, n = 26 777). The data from both cohorts were collected in the 1990s in Sweden.

    Results

    Significant differences between Finnish-born, Middle Eastern and women from the rest of the world were seen for all anthropometric measures, using Swedish-born women as referent. However, WHHR was the only anthropometric measure that identified all these three groups of immigrant women as different from Swedish-born women with high statistical certainty (p < 0.001). Apart from WHHR that identified differences in anthropometry in all immigrant groups of men using Swedish-born men as referent, few significant differences were seen in anthropometry among groups of immigrant men. These finding were observed in both cohorts, and remained after adjustments for smoking, physical activity and educational level.

    Conclusion

    The present study confirms previous findings of more obesity among immigrants and is the first to report that WHHR measurements may detect anthropometric differences between different ethnic groups better than other anthropometrical measures.

  • 27.
    Corsonello, Andrea
    et al.
    INRCA Ancona, Ancona, Fermo & Cosenza, Italy.
    Roller-Wirnsberger, Regina
    Med Univ Graz, Dept Internal Med, Graz, Austria.
    Di Rosa, Mirko
    INRCA Ancona, Ancona, Fermo & Cosenza, Italy.
    Fabbietti, Paolo
    INRCA Ancona, Ancona, Fermo & Cosenza, Italy.
    Wirnsberger, Gerhard
    Med Univ Graz, Dept Internal Med, Graz, Austria.
    Kostka, Tomasz
    Med Univ Lodz, Dept Geriatr, Hlth Ageing Res Ctr, Lodz, Poland.
    Guligowska, Agnieszka
    Med Univ Lodz, Dept Geriatr, Hlth Ageing Res Ctr, Lodz, Poland.
    Tap, Lisanne
    Erasmus Univ, Med Ctr Rotterdam, Dept Internal Med, Sect Geriatr Med, Rotterdam, Netherlands.
    Mattace-Raso, Francesco
    Erasmus Univ, Med Ctr Rotterdam, Dept Internal Med, Sect Geriatr Med, Rotterdam, Netherlands.
    Gil, Pedro
    Hosp Clin San Carlos, Dept Geriatr Med, Madrid, Spain.
    Guardado-Fuentes, Lara
    Hosp Clin San Carlos, Dept Geriatr Med, Madrid, Spain.
    Meltzer, Itshak
    Ben Gurion Univ Negev, Fac Hlth Sci, Recanati Sch Community Hlth Profess, Beer Sheva, Israel.
    Yehoshua, Ilan
    Maccabi Healthcare Serv Southern Reg, Tel Aviv, Israel.
    Artzi-Medevdik, Rada
    Ben Gurion Univ Negev, Fac Hlth Sci, Recanati Sch Community Hlth Profess, Beer Sheva, Israel;Maccabi Healthcare Serv Southern Reg, Tel Aviv, Israel.
    Formiga, Francesc
    Bellvitge Univ Hosp IDIBELL, Internal Med Dept, Geriatr Unit, Barcelona, Spain;Bellvitge Univ Hosp IDIBELL, Nephrol Dept, Barcelona, Spain.
    Moreno-Gonzalez, Rafael
    Bellvitge Univ Hosp IDIBELL, Internal Med Dept, Geriatr Unit, Barcelona, Spain;Bellvitge Univ Hosp IDIBELL, Nephrol Dept, Barcelona, Spain.
    Weingart, Christian
    Friedrich Alexander Univ Erlangen Nurnberg, Krankenhaus Barmherzige Bruder Regensburg, Dept Gen Internal Med & Geriatr, Erlangen, Germany;Friedrich Alexander Univ Erlangen Nurnberg, Inst Biomed Aging, Erlangen, Germany.
    Freiberger, Ellen
    Friedrich Alexander Univ Erlangen Nurnberg, Krankenhaus Barmherzige Bruder Regensburg, Dept Gen Internal Med & Geriatr, Erlangen, Germany;Friedrich Alexander Univ Erlangen Nurnberg, Inst Biomed Aging, Erlangen, Germany.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Care Sci & Soc, Dept Neurobiol, Div Family Med, Huddinge, Sweden.
    Lattanzio, Fabrizia
    INRCA Ancona, Ancona, Fermo & Cosenza, Italy.
    Estimated glomerular filtration rate and functional status among older people: A systematic review2018In: European journal of internal medicine, ISSN 0953-6205, E-ISSN 1879-0828, Vol. 56, p. 39-48Article, review/survey (Refereed)
    Abstract [en]

    Background: The association between chronic kidney disease (CKD) and functional status may change as a function of the equation used to estimate glomerular filtration rate (eGFR). We reviewed the predictive value of different eGFR equations in regard to frailty and disability outcomes. Methods: We searched Pubmed from inception to March 2018 for studies investigating the association between eGFR and self-reported and/or objective measures of frailty or disability. Cross-sectional and longitudinal studies were separately analysed. Results: We included 16 studies, one of which reporting both cross-sectional and longitudinal data. Three out of 7 cross-sectional studies compared different eGFR equations in regard to their association with functional status: two studies showed that cystatin C-based, but not creatinine-based eGFR may be associated with hand-grip strength or frailty; another study showed that two different creatinine-based eGFR equations may be similarly associated with disability. Four out of 10 longitudinal studies provided comparative data: two studies reported similar association with disability for different creatinine-based eGFR equations; one study showed that creatinine-based eGFR was not associated with frailty, but a not significant trend for association was observed with cystatin C-based eGFR; one study showed that cystatin C-based but not creatinine-based eGFR may predict incident mobility disability, while both methods may predict gait speed decline. High heterogeneity was observed in regard to confounders included in reviewed studies. None of them included the most recently published equations. Conclusion: Available data do not support the superiority of one of the eGFR equations in terms of measuring or predicting functional decline.

  • 28.
    Corsonello, Andrea
    et al.
    INRCA Ancona, Ancona, Italy;INRCA, Fermo, Italy;INRCA, Cosenza, Italy.
    Tap, Lisanne
    Erasmus Univ, Geriatr Med Sect, Dept Internal Med, Med Ctr Rotterdam, Rotterdam, Netherlands.
    Roller-Wirnsberger, Regina
    Med Univ Graz, Dept Internal Med, Auenbruggerpl 15, A-8036 Graz, Austria.
    Wirnsberger, Gerhard
    Med Univ Graz, Dept Internal Med, Auenbruggerpl 15, A-8036 Graz, Austria.
    Zoccali, Carmine
    Osped Riuniti Reggio Calabria, CNR, IFC, Clin Epidemiol & Pathophysiol Hypertens & Renal D, Reggio Di Calabria, Italy.
    Kostka, Tomasz
    Med Univ Lodz, Dept Geriatr, Hlth Ageing Res Ctr, Lodz, Poland.
    Guligowska, Agnieszka
    Med Univ Lodz, Dept Geriatr, Hlth Ageing Res Ctr, Lodz, Poland.
    Mattace-Raso, Francesco
    Erasmus Univ, Geriatr Med Sect, Dept Internal Med, Med Ctr Rotterdam, Rotterdam, Netherlands.
    Gil, Pedro
    Hosp Clin San Carlos, Dept Geriatr Med, Madrid, Spain.
    Guardado Fuentes, Lara
    Hosp Clin San Carlos, Dept Geriatr Med, Madrid, Spain.
    Meltzer, Itshak
    Ben Gurion Univ Negev, Fac Hlth Sci, Recanati Sch Community Hlth Profess, Beer Sheva, Israel.
    Yehoshua, Ilan
    Maccabi Healthcare Serv Southern Reg, Tel Aviv, Israel.
    Formiga-Perez, Francesc
    Bellvitge Univ Hosp, Internal Med Dept, IDIBELL, Geriatr Unit, Barcelona, Spain;Bellvitge Univ Hosp, Nephrol Dept, IDIBELL, Barcelona, Spain.
    Moreno-Gonzalez, Rafael
    Bellvitge Univ Hosp, Internal Med Dept, IDIBELL, Geriatr Unit, Barcelona, Spain;Bellvitge Univ Hosp, Nephrol Dept, IDIBELL, Barcelona, Spain.
    Weingart, Christian
    Friedrich Alexander Univ Erlangen Nurnberg, Krankenhaus Barmherzige Bruder Regensburg, Dept Gen Internal Med & Geriatr, Erlangen, Germany;Friedrich Alexander Univ Erlangen Nurnberg, Inst Biomed Aging, Erlangen, Germany.
    Freiberger, Ellen
    Friedrich Alexander Univ Erlangen Nurnberg, Krankenhaus Barmherzige Bruder Regensburg, Dept Gen Internal Med & Geriatr, Erlangen, Germany;Friedrich Alexander Univ Erlangen Nurnberg, Inst Biomed Aging, Erlangen, Germany.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Stockholm, Sweden.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Stockholm, Sweden.
    Bustacchini, Silvia
    INRCA Ancona, Ancona, Italy;INRCA, Fermo, Italy;INRCA, Cosenza, Italy.
    Lattanzio, Fabrizia
    INRCA Ancona, Ancona, Italy;INRCA, Fermo, Italy;INRCA, Cosenza, Italy.
    Design and methodology of the screening for CKD among older patients across Europe (SCOPE) study: a multicenter cohort observational study2018In: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 19, article id 260Article in journal (Refereed)
    Abstract [en]

    Background: Decline of renal function is common in older persons and the prevalence of chronic kidney disease (CKD) is rising with ageing. CKD affects different outcomes relevant to older persons, additionally to morbidity and mortality which makes CKD a relevant health burden in this population. Still, accurate laboratory measurement of kidney function is under debate, since current creatinine-based equations have a certain degree of inaccuracy when used in the older population. The aims of the study are as follows: to assess kidney function in a cohort of 75+ older persons using existing methodologies for CKD screening; to investigate existing and innovative biomarkers of CKD in this cohort, and to align laboratory and biomarker results with medical and functional data obtained from this cohort. The study was registered at ClinicalTrials.gov, identifier NCT02691546, February 25th 2016. Methods/design: An observational, multinational, multicenter, prospective cohort study in community dwelling persons aged 75 years and over, visiting the outpatient clinics of participating institutions. The study will enroll 2450 participants and is carried out in Austria, Germany, Israel, Italy, the Netherlands, Poland and Spain. Participants will undergo clinical and laboratory evaluations at baseline and after 12 and 24 months-follow-up. Clinical evaluation also includes a comprehensive geriatric assessment (CGA). Local laboratory will be used for 'basic' parameters (including serum creatinine and albumin-to-creatinine ratio), whereas biomarker assessment will be conducted centrally. An intermediate telephone follow-up will be carried out at 6 and 18 months. Discussion: Combining the use of CGA and the investigation of novel and existing independent biomarkers within the SCOPE study will help to provide evidence in the development of European guidelines and recommendations in the screening and management of CKD in older people.

  • 29.
    Dahlgren, K.
    et al.
    Umea Univ, Dept Surg, Emergency Care, Umea, Sweden..
    Holzmann, M. J.
    Karolinska Univ Hosp, Dept Emergency Med, Solna, Sweden..
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wandelld, P.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Family Med, Huddinge, Sweden..
    Hasselstrom, J.
    Karolinska Inst, Ctr Family Med, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    Ruge, T.
    Umea Univ, Dept Surg, Emergency Care, SE-90185 Umea, Sweden..
    The use of a Swedish telephone medical advice service by the elderly - a population-based study2017In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 35, no 1, p. 98-104Article in journal (Refereed)
    Abstract [en]

    Objective: The present study aimed to describe contact made by the elderly to Sweden's nationwide medical helpline, Healthcare Guide 1177 by Phone (HGP). Other objectives were to study potential gender differences and the association between different HGP referral levels and acute visits to hospital-based emergency departments and acute visits to primary care centres. Design: De-identified data from recorded calls to HGP was extracted for analysis (n=7477 for the oldest age group). Information about acute visits to emergency departments and to primary care reception was extracted from the patient administration system.Setting: Vasterbotten County, Sweden.Subjects: Patients over 80 years.Main outcome measures: Calling and visiting frequencies for different age groups as well as reasons for contact and individual recommendations. Results: The utilisation rate of the telephone advice service for the oldest age group was high, with an incidence rate of 533 per 1000 person-years. Women had a 1.17 times higher incidence rate compared with men. The most common reason for contact was drug-related questions (17% of all contacts). Calls that were recommended to care by a medical specialist correlated with total emergency department visits (r=0.30, p<0.05) and calls that were given advice correlated with acute primary healthcare visits (r=0.38, p=0.005). Conclusion: The high utilisation of the telephone advice service by the elderly gives the telephone advice service a unique ability to function as a gatekeeper to further healthcare. Our data suggest that with the telephone advice service's present guidelines, a significant proportion of all calls are being directed to further medical help. The high frequency of drug-related questions raises concerns about the elderly's medication regimens.

  • 30.
    de Waard, Anne-Karien M.
    et al.
    Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr, Dept Gen Practice, Utrecht, Netherlands.
    Hollander, Monika
    Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr, Dept Gen Practice, Utrecht, Netherlands.
    Korevaar, Joke C.
    Nivel Netherlands Inst Hlth Serv Res, Utrecht, Netherlands.
    Nielen, Mark M. J.
    Nivel Netherlands Inst Hlth Serv Res, Utrecht, Netherlands.
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Stockholm, Sweden.
    Lionis, Christos
    Univ Crete, Sch Med, Clin Social & Family Med, Iraklion, Greece.
    Seifert, Bohumil
    Charles Univ Prague, Fac Med 1, Inst Gen Practice, Prague, Czech Republic.
    Thilsing, Trine
    Univ Southern Denmark, Dept Publ Hlth, Res Unit Gen Practice, Odense C, Denmark.
    de Wit, Niek J.
    Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr, Dept Gen Practice, Utrecht, Netherlands.
    Schellevis, Francois G.
    Vrije Univ Amsterdam Med Ctr, Amsterdam Publ Hlth Res Inst, Dept Gen Practice & Elderly Care Med, Amsterdam, Netherlands.
    Angelaki, Agapi
    Univ Crete, Sch Med, Clin Social & Family Med, Iraklion, Greece.
    Holzmann, Martin J.
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Kral, N.
    Charles Univ Prague, Fac Med 1, Inst Gen Practice, Prague, Czech Republic.
    Sondergaard, Jens
    Sonderlund, Anders L.
    Univ Southern Denmark, Dept Publ Hlth, Res Unit Gen Practice, Odense C, Denmark.
    Wandell, P.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Stockholm, Sweden.
    Selective prevention of cardiometabolic diseases: activities and attitudes of general practitioners across Europe2019In: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 29, no 1, p. 88-93Article in journal (Refereed)
    Abstract [en]

    Background: Cardiometabolic diseases (CMDs) are the number one cause of death. Selective prevention of CMDs by general practitioners (GPs) could help reduce the burden of CMDs. This measure would entail the identification of individuals at high risk of CMDsubut currently asymptomaticufollowed by interventions to reduce their risk. No data were available on the attitude and the extent to which European GPs have incorporated selective CMD prevention into daily practice.

    Methods: A survey among 575 GPs from the Czech Republic, Denmark, Greece, the Netherlands and Sweden was conducted between September 2016 and January 2017, within the framework of the SPIMEU-project.

    Results: On average, 71% of GPs invited their patients to attend for CMD risk assessment. Some used an active approach (47%) while others used an opportunistic approach (53%), but these values differed between countries. Most GPs considered selective CMD prevention as useful (82%) and saw it as part of their normal duties (84%). GPs who did find selective prevention useful were more likely to actively invite individuals compared with their counterparts who did not find prevention useful. Most GPs had a disease management programme for individuals with risk factor(s) for cardiovascular disease (71%) or diabetes (86%).

    Conclusions: Although most GPs considered selective CMD prevention as useful, it was not universally implemented. The biggest challenge was the process of inviting individuals for risk assessment. It is important to tailor the implementation of selective CMD prevention in primary care to the national context, involving stakeholders at different levels.

  • 31.
    de Waard, Anne-Karien M.
    et al.
    Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Huispost STR 6-131,POB 85500, NL-3508 GA Utrecht, Netherlands..
    Wändell, Per E.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Solna, Sweden..
    Holzmann, Martin J.
    Karolinska Univ Hosp, Funct Area Emergency Med, Solna, Sweden.;Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    Korevaar, Joke C.
    NIVEL Netherlands Inst Hlth Serv Res, Utrecht, Netherlands..
    Hollander, Monika
    Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Huispost STR 6-131,POB 85500, NL-3508 GA Utrecht, Netherlands..
    Gornitzki, Carl
    Karolinska Inst, Univ Lib, Solna, Sweden..
    de Wit, Niek J.
    Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Huispost STR 6-131,POB 85500, NL-3508 GA Utrecht, Netherlands..
    Schellevis, Francois G.
    NIVEL Netherlands Inst Hlth Serv Res, Utrecht, Netherlands.;Vrije Univ Amsterdam Med Ctr, Dept Gen Practice & Elderly Care Med, Amsterdam, Netherlands..
    Lionis, Christos
    Univ Crete, Clin Social & Family Med, Iraklion, Greece..
    Söndergaard, Jens
    Univ Southern Denmark, Res Unit Gen Practice, Odense, Denmark..
    Seifert, Bohumil
    Charles Univ Prague, Dept Gen Practice, Prague, Czech Republic..
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Solna, Sweden.
    Barriers and facilitators to participation in a health check for cardiometabolic diseases in primary care: A systematic review2018In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 25, no 12, p. 1326-1340Article, review/survey (Refereed)
    Abstract [en]

    Background: Health checks for cardiometabolic diseases could play a role in the identification of persons at high risk for disease. To improve the uptake of these health checks in primary care, we need to know what barriers and facilitators determine participation.

    Methods: We used an iterative search strategy consisting of three steps: (a) identification of key-articles; (b) systematic literature search in PubMed, Medline and Embase based on keywords; (c) screening of titles and abstracts and subsequently full-text screening. We summarised the results into four categories: characteristics, attitudes, practical reasons and healthcare provider-related factors.

    Results: Thirty-nine studies were included. Attitudes such as wanting to know of cardiometabolic disease risk, feeling responsible for, and concerns about one's own health were facilitators for participation. Younger age, smoking, low education and attitudes such as not wanting to be, or being, worried about the outcome, low perceived severity or susceptibility, and negative attitude towards health checks or prevention in general were barriers. Furthermore, practical issues such as information and the ease of access to appointments could influence participation.

    Conclusion: Barriers and facilitators to participation in health checks for cardiometabolic diseases were heterogeneous. Hence, it is not possible to develop a one size fits all' approach to maximise the uptake. For optimal implementation we suggest a multifactorial approach adapted to the national context with special attention to people who might be more difficult to reach. Increasing the uptake of health checks could contribute to identifying the people at risk to be able to start preventive interventions.

  • 32.
    Feldreich, T
    et al.
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.; Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Stockholm, Sweden.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Stockholm, Sweden.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.; Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Stockholm, Sweden .
    Urinary Osteopontin Predicts Incident Chronic Kidney Disease, while Plasma Osteopontin Predicts Cardiovascular Death in Elderly Men2017In: Cardiorenal Medicine, Vol. 7, no 3, p. 245-254Article in journal (Refereed)
    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 men (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. = 0.07, p = 0.13). Higher urinary osteopontin, but not plasma osteopontin, was associated with incident chronic kidney disease in multivariable models adjusted for age, cardiovascular risk factors, baseline glomerular filtration rate, urinary albumin/ creatinine ratio, and the 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 osteopon-tin 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, remain to be established.

  • 33.
    Feldreich, T. Rudholm
    et al.
    Dalarna Univ, Med Sci, Falun, Sweden..
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Helmersson-Karlqvist, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Higher circulating osteopontin specifically predicts cardiovascular death while urinary osteopontin predicts kidney disease progression2016In: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, p. 1282-1282Article in journal (Refereed)
  • 34.
    Feldreich, T. Rudholm
    et al.
    Dalarna Univ, Med Sci, Falun, Sweden..
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Riserus, U
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Larsson, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    The association between serum cathepsin l and mortality in older adults2016In: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, p. 1283-1283Article in journal (Refereed)
  • 35.
    Feldreich, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. School of Health and Social Studies, Dalarna University, Falun, .
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. School of Health and Social Studies, Dalarna University, Falun, .
    The association between serum cathepsin L and mortality in older adults2016In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 254, p. 109-116Article in journal (Refereed)
    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.

  • 36.
    Feldreich, Tobias
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Nowak, Christoph
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Carrero, Juan-Jesus
    Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Solna, Sweden.
    Ripsweden, Jonas
    Karolinska Inst, Div Med Imaging & Technol, Dept Clin Sci Intervent & Technol, Campus Flemingsberg, Stockholm, Sweden.
    Qureshi, Abdul Rashid
    Karolinska Univ Hosp, Div Renal Med, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Heimburger, Olof
    Karolinska Univ Hosp, Div Renal Med, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Barany, Peter
    Karolinska Univ Hosp, Div Renal Med, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Stenvinkel, Peter
    Karolinska Univ Hosp, Div Renal Med, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Vuilleumier, Nicolas
    Geneva Univ Hosp, Dept Genet Lab Med & Pathol, Geneva, Switzerland;Geneva Fac Med, Dept Med Specialties, Geneva, Switzerland.
    Kalra, Philip A.
    Univ Manchester, Manchester Acad Hlth Sci Ctr, Div Cardiovasc Sci, Manchester, Lancs, England;Salford Royal NHS Fdn Trust, Dept Renal, Med, Stott Lane, Salford, Lancs, England.
    Green, Darren
    Univ Manchester, Manchester Acad Hlth Sci Ctr, Div Cardiovasc Sci, Manchester, Lancs, England;Salford Royal NHS Fdn Trust, Dept Renal, Med, Stott Lane, Salford, Lancs, England.
    Arnlov, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease2019In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 32, no 1, p. 111-119Article in journal (Refereed)
    Abstract [en]

    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 63years, 46 cardiovascular deaths during follow-up (mean 43months)]. 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 62years, 45 cardiovascular deaths during follow-up (mean 12months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n=89, 37% women, mean age 46years).

    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.

  • 37. Gasevic, Danijela
    et al.
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Center for Family and Community Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institute.
    Lesser, Iris A.
    Mancini, G. B. John
    Lear, Scott A.
    The association between "hypertriglyceridemic waist" and sub-clinical atherosclerosis in a multiethnic population: a cross-sectional study2014In: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 13, p. 38-Article in journal (Refereed)
    Abstract [en]

    Background: "Hypertriglyceridemic waist" (HTGW) phenotype, an inexpensive early screening tool for detection of individuals at risk for type 2 diabetes and cardiovascular disease was found to be associated with subclinical atherosclerosis in various patient populations such as those with diabetes mellitus, chronic kidney disease, and those infected with human immunodeficiency virus. However, less is known regarding an association between HTGW and subclinical atherosclerosis in the apparently healthy, multiethnic population. Therefore, the aim of the study was to explore the association between HTGW and sub-clinical atherosclerosis in an apparently healthy, multiethnic population; and to investigate whether the effect of HTGW on sub-clinical atherosclerosis persists over and above the traditional atherosclerosis risk factors. Methods: We studied 809 individuals of Aboriginal, Chinese, European and South Asian origin who were assessed for indices of sub-clinical atherosclerosis (intima-media thickness (IMT), total area and presence of carotid plaques), socio-demographic and lifestyle characteristics, anthropometrics, lipids, glucose, blood pressure, and family history of cardiovascular disease. Results: We found that, compared to individuals without HTGW and after adjusting for age, ethnicity, smoking, and physical activity; men and women with HTGW had a significantly higher: IMT (men: B (95%CI = 0.084 (0.037, 1.133), p < 0.001; women: B (95%CI) = 0.041 (0.006, 0.077), p = 0.020); and total area (men: B (95%CI = 0.202 (0.058, 0.366), p = 0.005; women: B (95%CI) = 0.115 (0.006, 0.235), p = 0.037). The association between HTGW waist and presence of plaques was significant for men (OR (95%CI) = 1.904 (1.040, 3.486), p = 0.037 vs. men without HTGW), but not for women (p = 0.284). Once analyses were adjusted for additional, traditional risk factors for atherosclerosis, the effect of HTGW on sub-clinical atherosclerosis was no longer significant. Conclusions: In conclusion, HTGW may serve as an early marker of subclinical atherosclerosis in men and women, irrespective of ethnicity. However, once individuals are assessed for all traditional risk factors for atherosclerosis, the additional assessment for HTGW is not warranted.

  • 38.
    Hagström, Hannes
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Andreasson, Anna
    Karolinska Inst, Dept Med, Stockholm, Sweden;Stockholm Univ, Stress Res Inst, Stockholm, Sweden;Macquarie Univ, Dept Psychol, N Ryde, NSW, Australia.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Stockholm, Sweden.
    Jerkeman, Mats
    Lund Univ, Dept Oncol, Clin Sci, Lund, Sweden.
    Carlsten, Mattias
    Karolinska Inst, Ctr Hematol & Regenerat Med, Dept Med, Stockholm, Sweden.
    Body composition measurements and risk of hematological malignancies: A population-based cohort study during 20 years of follow-up2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 8, article id e0202651Article in journal (Refereed)
    Abstract [en]

    High body mass index (BMI) is associated with development of hematological malignancies (HMs). However, although BMI is a well-established measurement of excess weight, it does not fully reflect body composition and can sometimes misclassify individuals. This study aimed at investigating what body composition measurements had highest association with development of HM. Body composition measurements on 27,557 individuals recorded by healthcare professionals as part of the Malmo Diet and Cancer study conducted in Sweden between 1991-1996 were matched with data from national registers on cancer incidence and causes of death. Cox regression models adjusted for age and sex were used to test the association between one standard deviation increments in body composition measurements and risk of HM. During a median follow-up of 20 years, 564 persons developed an HM. Several body composition measurements were associated with risk of developing an HM, but the strongest association was found for multiple myeloma (MM). Waist circumference (HR 1.31, p = 0.04) and waist-hip ratio (HR 1.61, p = 0.05) had higher risk estimates than BMI (HR 1.18, p = 0.07) for MM. In conclusion, our study shows that measurements of abdominal adiposity better predict the risk of developing HM, particularly MM, compared to BMI.

  • 39.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with mortality in a community-based cohort of older Swedish men2013In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 227, no 2, p. 408-413Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    Neutrophil gelatinase-associated lipocalin (NGAL) indicates tubular kidney damage, neutrophil activation and possibly atherogenesis, however the prospective association between urinary NGAL (u-NGAL) and cardiovascular death in the community is not known.

    METHODS

    This study evaluates the association between urinary and serum NGAL and mortality in a Swedish population of 597 men aged 78 years. During the study (median follow-up 8.1 years) 261 men died, 90 of cardiovascular causes.

    RESULTS

    U-NGAL was associated with increased all-cause and cardiovascular mortality (HR 2.0 for quartile 4 vs. quartile 1, 95% CI 1.0-4.0, P < 0.05) in Cox regression models independently of cardiovascular risk factors, CRP and cystatin C estimated glomerular filtration rate (eGFRCysC) but not urinary Albumin (u-Alb). A combination of low eGFRCysC (≤60 mL/min), high u-Alb (≥3 mg/mmol Cr) and high u-NGAL (≥1.19 μg/mmol Cr) was associated with a 9-fold increased cardiovascular mortality (P < 0.001) and a 3-fold increased all-cause mortality (P < 0.001). Serum NGAL was associated with increased all-cause mortality risk independent of other cardiovascular risk factors (HR 1.4 for quartile 4 vs.1, 95% CI 1.0-1.9, P < 0.05) but not after adjustment with CRP, eGFRCysC or u-Alb.

    CONCLUSION

    This community study is the first to show that the tubular kidney biomarker u-NGAL associated with increased cardiovascular and all-cause mortality independent of cardiovascular risk factors and glomerular filtration. Additional research is needed to evaluate the utility of NGAL in clinical practice.

  • 40.
    Helmersson-Karlqvist, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Härmä, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Increased urinary cystatin C indicated higher risk of cardiovascular death in a community cohort2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 234, no 1, p. 108-113Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Urinary cystatin C (u-CysC) is a new biomarker for acute tubular kidney dysfunction and may also indicate chronic tubular dysfunction. Chronic kidney disease is an important cardiovascular risk factor, however it is not known if u-CysC is a risk marker for cardiovascular death.

    METHODS: The association between u-CysC and cardiovascular mortality was investigated in a Swedish community-based cohort of 604 men aged 78 years. During follow-up (mean 6.7 years), 203 participants died, of which 90 due to cardiovascular causes.

    RESULTS: High u-CysC (>0.029 mg/mmol Cr) was associated with a more than 2-fold risk of cardiovascular death (multivariable hazard ratio for quintile 5 vs. 1: 2.5, 95% CI 1.2-5.2, P < 0.05) in Cox regression models independent of cardiovascular risk factors, glomerular filtration rate (eGFR) and urinary Albumin. Participants with low eGFR (≤60 mL/min), albuminuria (≥3 mg/mmol Cr) and high u-CysC (>0.029 mg/mmol Cr) combined had a significantly higher cardiovascular mortality risk compared to participants with one or two of these biomarkers normal (hazard ratio 15, 95% CI: 6.7-36, P < 0.001, compared to all three biomarkers normal).

    CONCLUSIONS: This study is the first to show that increased concentrations of the tubular kidney biomarker u-CysC indicated risk of cardiovascular death independently of other cardiovascular risk factors, glomerular filtration and albuminuria. Additional research is needed to further establish the usefulness of u-CysC in clinical practice.

  • 41.
    Ivert, Torbjörn
    et al.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden.
    Malmström, Håkan
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;Swedish Orphan Biovitrum Sobi, Biostat Data Management & Med Writing Res & Dev, Stockholm, Sweden.
    Hammar, Niklas
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;AstraZeneca, Global Med Affairs, Med Evidence & Observat Res, Molndal, Sweden.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.
    Wändell, Per E.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.
    Holzmann, Martin J.
    Karolinska Univ Hosp, Dept Emergency Med, Huddinge, Sweden;Karolinska Inst, Dept Internal Med, Solna, Sweden.
    Jungner, Ingmar
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Ärnlov, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Walldius, Göran
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Cardiovascular events in patients under age fifty with early findings of elevated lipid and glucose levels - The AMORIS study2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 8, article id e0201972Article in journal (Refereed)
    Abstract [en]

    Background: The long-term trajectories of lipid and glucose levels in subjects who experience a major cardiovascular (CV) event at a young age has not been well studied. Our objective was to investigate lipid, lipoprotein, apolipoprotein (apo), and glucose levels in individuals experiencing a CV event before 50 years of age.

    Methods and findings: A first CV event [non-fatal myocardial infarction (MI), coronary revascularisation, or CV related death] before age 50 was recorded in 2,939 (cumulative incidence 1.2% in males and 0.3% in females) of 361,353 individuals included in the prospective Swedish AMORIS (Apolipoprotein-related MOrtality RISk) study with health examinations 1985-1996 and follow-up through 2011. In a nested case-control analysis, cases with a CV event were matched to randomly selected controls. Population risk factor trajectories were calculated up to 20 years prior to an event. Total cholesterol (TC), triglyceride (TG), and glucose levels were higher in cases than in controls as early as 20 years prior to the event with differences increasing over time. Low density lipoprotein, apoB, and the apoB/apoA-1 ratio were higher and increased over time, while HDL and apoA-1 were lower in cases compared to controls. The odds ratio was 2.5 (95% confidence interval 1.6-3.7) for TC >= 5 mmol/L and TG >= 1.7 mmol/L in cases versus controls. The adjusted population-attributable fractions including lipids, glucose, diabetes, smoking, hypertension, and obesity indicated that about 50% of CV events before age 50 may be associated with elevated lipid and glucose levels.

    Conclusions: Elevated TC, TG, LDL, apoB, and glucose levels and high apoB/apo A-1 ratio documented two decades before a CV event in subjects younger than 50 years may account for about half of CV events before age 50, which calls for early recognition and possibly treatment of modifiable CV risk factors in young individuals.

  • 42. Jallow, Amadou
    et al.
    Ljunggren, Gunnar
    Wandell, Per
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Prevalence, incidence, mortality and co-morbidities amongst human immunodeficiency virus ( HIV) patients in Stockholm County, Sweden - The Greater Stockholm HIV Cohort Study2015In: AIDS Care, ISSN 0954-0121, E-ISSN 1360-0451, Vol. 27, no 2, p. 142-149Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to develop a multidisciplinary guideline that supports the care and vocational rehabilitation of HIV-infected people with employment-related problems. The guideline was developed according to the "evidence-based guideline development" method developed by the Dutch Institute for Health Care Improvement. This method consists of the following steps: forming a multidisciplinary core group and an expert panel, formulating key questions, searching and appraising the available literature, formulating considerations and recommendations, peer reviewing the draft guideline, and authorizing the final guideline. All relevant professional associations were represented in the core group that was assembled to develop the guideline, i.e., HIV doctors, HIV nurses, general practitioners, occupational health physicians, psychologists, social workers, occupational health nurses, vocational experts, and insurance physicians. Five key questions for the guideline were formulated with the following themes: determinants of employment, disclosure and stigma, self-management, interventions, and the organization of care. In the literature review on these topics, 45 studies met the inclusion criteria. The methodological quality of the included articles was poor. Factors such as patient preferences and medical/ethical issues were considered. The recommendations in the guideline are a weighting of the scientific evidence and the considerations of the core group. The guideline, as well as its summary for daily practice, clarifies the most important barriers and facilitators to people with HIV either staying at work or returning to work, and it constitutes a clinical, easy-to-use guideline for health-care providers and how they can support people with HIV who want to work.

  • 43.
    Jallow, Amadou
    et al.
    Sunnfjord Apotek, Forde, Norway..
    Ljunggren, Gunnar
    Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Box 6909, SE-10239 Stockholm, Sweden.;Karolinska Inst, Dept Learning Informat Management & Eth, Med Management Ctr, Berzelius Vag 3, SE-17177 Stockholm, Sweden..
    Wandell, Per
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Huddinge, Sweden..
    Wahlstrom, Lars
    Karolinska Inst, Ctr Psychiat Res, Stockholm, Sweden..
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Huddinge, Sweden..
    HIV-infection and psychiatric illnesses: A double edged sword that threatens the vision of a contained epidemic The Greater Stockholm HIV Cohort Study2017In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 74, no 1, p. 22-28Article in journal (Refereed)
    Abstract [en]

    Context: The Greater Stockholm HIV Cohort Study is an initiative to provide longitudinal information regarding the health of people living with HIV. Objective: Our aim was to explore the prevalence of HIV and its association with psychiatric co-morbidities. Design, setting and participants: All patients with a recorded diagnosis of HIV ( any position of the ICD-10 codes B20-B24) were identified during the period 2007-2014 and related to the total population in Stockholm by January 1, 2015, N = 2.21 million. The age at diagnosis, gender, and first occurrence of an HIV diagnosis was recorded. Analyses were done by age and gender. Prevalence of psychiatric co-morbidities amongst HIV patients were recorded. Main outcome measures: Age-adjusted odds ratios with 95% confidence intervals were calculated with logistic regression for prevalent psychiatric co-morbidities in HIV infected individuals compared to the prevalence in the general population. Results: The total prevalence of HIV was 0.16%; females 0.10% (n Z 1134) and males 0.21% (n Z 2448). HIV-infected people were more frequently diagnosed with psychiatric illnesses and drug abuse. In females and males with HIV-diagnosis respectively, drug dependence disorder was 7.5 (7.76% vs 1.04%) and 5.1 (10.17% vs 1.98%) times higher, psychotic disorders were 6.3 (2.65% vs 0.42%) and 2.9 (1.43% vs 0.49%) times higher, bipolar disorder was 2.5 (1.41% vs 0.57%) and 3 (1.02% vs 0.34%) times higher, depression diagnosis was 1.5 (8.47% vs 5.82%) and 3.4 (10.17% vs 2.97%) higher, trauma-related disorder was 1.5 (6.00% vs 4.10%) respectively 2.9 (4.45% vs 1.56%) times higher, anxiety disorder was 1.2 (6.88% vs 5.72%) and 2.2 (6.54% vs 2.93%) times higher than in their non-infected peers. Conclusion: Despite effective ART, many individuals with HIV have an impaired mental health and a history of drug abuse that may threaten the vision of a contained epidemic. (C) 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  • 44. Lagerin, Annica
    et al.
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nilsson, Gunnar
    Westman, Jeanette
    Tornkvist, Lena
    District nurses' preventive home visits to 75-year-olds: An opportunity to identify factors related to unsafe medication management2014In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 42, no 8, p. 786-794Article in journal (Refereed)
    Abstract [en]

    Aims: To investigate factors related to unsafe medication management among 75-year-olds during preventive home visits, and to describe the interventions district nurses used. Methods: An explorative study. During a 9- to 12-month period, 36 DNs used the Safe Medication Assessment (SMA) tool during preventive home visits to 75-year-olds who used at least one drug (n=113). Results: One or more factors related to unsafe medication management were identified in 84% of the 75-year-olds. More than 40% used five or more drugs, and 34.5% reported symptoms potentially indicative of adverse effects of their drugs. Nearly 30% had prescribers from more than two medical units, and 7.1% of the older persons were appraised as having reduced cognitive ability. DNs intervened in more than two-thirds of the cases and used a variety of nursing care interventions to improve the safety of medication management. Conclusions: Preventive home visits seem to provide a unique opportunity to promote safe medication management. Several factors related to unsafe medication management were identified, and several different nursing care interventions were carried out to ensure safe medication management. Use of the SMA tool in preventive home visits seems to be advantageous in improving the safety of medication management among older persons.

  • 45.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Alfred Nobels Alle 23, S-14152 Huddinge, Sweden..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Dept Hlth & Social Sci, S-79188 Falun, Sweden..
    Impact of physical activity on cardiovascular status in obesity2017In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 47, no 2, p. 167-175Article in journal (Refereed)
    Abstract [en]

    Background We have recently shown that being physically active (PA) counteracts, but not eliminates the increased risk of future cardiovascular disease in overweight and obese subjects. To investigate this further, we studied the impact of being normal weight, overweight and obese on multiple markers of subclinical cardiovascular disease in relation to physical activity. Materials and methods At age 70, 1016 subjects were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Being PA was defined as performing regular heavy exercise (self-reported). According to body mass index (BMI)/PA groups, the participants were categorized as PA/normal weight (BMI < 25 kg/m(2), n = 104), non-PA/normal weight (n = 234), PA/overweight (BMI 25-29.9 kg/m(2), n = 133), non-PA/overweight (n = 295), PA/obese (BMI = 30 kg/m(2), n = 54) and non-PA/obese (n = 169). Several different measurements of endothelial reactivity and arterial compliance (plethysmography and ultrasound), cartotid artery atherosclerosis and echocardiography were performed, and seven markers of coagulation/ fibrinolysis were measured. Results Physically active subjects with obesity showed impaired vasoreactivity in the forearm resistance vessels, increased left ventricular mass and impaired left ventricular systolic and diastolic functions, together with impaired coagulation/fibrinolysis when compared to PA/normal-weight subjects (P < 0.05 to < 0.001). The majority of these disturbances were seen also in PA/overweight subjects when compared to PA/normal-weight subjects (P < 0.05 to < 0.001). Conclusions Our data provide additional support for the notion that an increased level of self-reported physical activity does not fully eliminate the deleterious cardiovascular consequences associated with overweight and obesity.

  • 46.
    Ljunggren, Gunnar
    et al.
    Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Huddinge, Sweden.;Karolinska Inst, Dept Learning, Informat, Med Management Ctr,Management & Eth, Huddinge, Sweden..
    Wandell, Per
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Sandstrom, Ylva Kristoferson
    Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Wahlström, Lars
    Karolinska Inst, Ctr Psychiat Res, Stockholm, Sweden..
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Depression in hypertensive patients: the role of comorbidities Reply2016In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 34, no 7, p. 1441-1442Article in journal (Refereed)
  • 47.
    Lundback, Magnus
    et al.
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden..
    Gasevic, Danijela
    Univ Edinburgh, Coll Med & Vet Med, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Rullman, Eric
    Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Ruge, Toralph
    Karolinska Univ Hosp, Dept Emergency Med, C1 63, S-14186 Stockholm, Sweden..
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Huddinge, Sweden.
    Holzmann, Martin J.
    Karolinska Univ Hosp, Dept Emergency Med, C1 63, S-14186 Stockholm, Sweden.;Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    Sex-specific risk of emergency department revisits and early readmission following myocardial infarction2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 243, p. 54-58Article in journal (Refereed)
    Abstract [en]

    Background: Readmissions within 30 days after hospitalization have been introduced as a measure of quality of care. There is a paucity of data regarding sex-specific risk of early readmissions after myocardial infarction (MI). Objectives: To investigate the association between sex and revisits to the emergency department (ED), and readmissions after MI. Methods: All patients with chest pain, diagnosed with MI at the Karolinska University Hospital during 2011 and 2012 were included. National Health care registers were used for information about patient characteristics, outcomes, and medication. We calculated risk ratios (RR) with 95% confidence intervals (CI) in women versus men, for revisits to the ED, readmission to hospital within 30, and 180 days, and to undergo coronary angiography, or revascularization, and to receive guideline-directed cardiovascular medication. Results: In total there were 667 patients with MI during the study period, of whom 197 (30%) were women. Womenwere older (mean age 73 vs. 65 years), and had more comorbidities thanmen. The 30-day risk of revisits to the ED was 1.56 times greater in women thanmen (adjusted RR 1.56 (1.09-2.25)). Throughout the first year; women were more likely to be readmitted than men, with the most striking difference found within 30 days (22% vs. 13%) of discharge (adjusted RR 1.54 (95% CI, 1.00-2.36)). There were no differences between men and women in new cardiovascular medication, coronary angiographies or revascularizations. Conclusions: Women have an increased risk of revisits to the ED, and readmissions to hospital during the first year after a MI.

  • 48.
    Malmström, H.
    et al.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Wandell, P.
    Karolinska Inst, Dept Neurobiol, Stockholm, Sweden..
    Holzmann, M. J.
    Karolinska Inst, Dept Internal Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Emergency Med, Huddinge, Sweden..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalama Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Jungner, I.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Walldius, G.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Hammar, N.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Dept Neurobiol, Stockholm, Sweden..
    Low fructosamine levels and mortality: a 25-year follow-up of 215,011 Swedish non-diabetic subjects2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, p. S52-S53Article in journal (Refereed)
  • 49.
    Nowak, Christoph
    et al.
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden.
    Östgren, Carl Johan
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Nyström, Fredrik H.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Alam, Moudud
    Dalarna Univ, Sch Technol & Business Studies Stat, Falun, Sweden.
    Feldreich, Tobias
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carrero, Juan-Jesus
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Henriksen, Egil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Cordeiro, Antonio C.
    Dante Pazzanese Inst Cardiol, Dept Hypertens & Nephrol, Sao Paulo, Brazil.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ärnlöv, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 8, p. 1748-1757Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. Methods We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. Results Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (+/- SD) of 6.4 +/- 2.3 years. We replicated associations (< 5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit alpha (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. Conclusions/interpretation We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event.

  • 50. Nystrom, Petter K.
    et al.
    Carlsson, Axel C.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Leander, Karin
    de Faire, Ulf
    Hellenius, Mai-Lis
    Gigante, Bruna
    Obesity, Metabolic Syndrome and Risk of Atrial Fibrillation: A Swedish, Prospective Cohort Study2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 5, article id e0127111Article in journal (Refereed)
    Abstract [en]

    Aim We aimed to investigate whether different measures of obesity could similarly predict atrial fibrillation, and whether the atrial fibrillation risk associated with obesity is dependent on presence of metabolic syndrome. Material and Methods We performed our study in a population-based longitudinal cardiovascular study, comprising 1 924 men and 2 097 women, aged 60 years, from Stockholm. Body mass index, waist circumference, sagittal abdominal diameter and components of metabolic syndrome (systolic- and diastolic blood pressure, fasting glucose, triglycerides, high-density lipoprotein-cholesterol) were recorded at baseline. Participants were classified by their body mass index (normal weight, overweight or obese), waist circumference (normal, semi-elevated or elevated), and according to presence of metabolic syndrome. Atrial fibrillation risk was estimated by Cox proportional hazards regression models, adjusted for common atrial fibrillation risk factors, expressed as HR and 95% CI. Results During a mean follow-up of 13.6 years, 285 incident atrial fibrillation cases were recorded. One standard deviation increment of each obesity measure was associated with increased atrial fibrillation risk as: bodymass index 1.25 (1.12 - 1.40), waist circumference 1.35 (1.19 - 1.54) and sagittal abdominal diameter 1.28 (1.14 - 1.44). Compared to normal weight subjects without metabolic syndrome, increased atrial fibrillation risk was noted for overweight subjects with metabolic syndrome, 1.67 (1.16 - 2.41), obese subjects without metabolic syndrome, 1.75 (1.11 - 2.74) and obese subjects withmetabolic syndrome, 1.92 (1.34 - 2.74). Compared to subjects with normal waist circumference without metabolic syndrome, subjects with elevated waist circumference and metabolic syndrome suffered increased atrial fibrillation risk, 2.03 (1.44 - 2.87). Conclusions Body mass index, waist circumference and sagittal abdominal diameter could similarly predict atrial fibrillation. Obesity was associated with an increased atrial fibrillation risk regardless of metabolic syndrome, whereas overweight and elevated waist circumference was associated with increased atrial fibrillation risk only if metabolic syndrome was present.

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