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  • 1.
    Alvarsson, Michael
    et al.
    Institutionen för molekylär medicin och kirurgi, Karolinska institutet - PO Endokrinologi och njurmedicin Stockholm, Sweden Institutionen för molekylär medicin och kirurgi, Karolinska institutet - PO Endokrinologi och njurmedicin Stockholm, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Ny era inom terapin för typ 2-diabetes – men vad är nytt?: Metformin fortfarande förstahandsval, men därefter rekommenderas att behandlingen individualiseras2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Article in journal (Refereed)
    Abstract [en]

    n/a

  • 2.
    Bell, Katy J. L.
    et al.
    Univ Sydney, Australia.
    Azizi, Lamiae
    Univ Sydney, Australia.
    Nilsson, Peter M.
    Lund Univ, Sweden.
    Hayen, Andrew
    UTS, Australia.
    Irwig, Les
    Univ Sydney, Australia.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Sundrom, Johan
    Uppsala Univ, Sweden.
    Prognostic impact of systolic blood pressure variability in people with diabetes2018In: PLOS ONE, E-ISSN 1932-6203, Vol. 13, no 4, article id e0194084Article in journal (Refereed)
    Abstract [en]

    Objective Blood pressure variability (BPV) has been associated with risk of cardiovascular events in observational studies, independently of mean BP levels. In states with higher autonomic imbalance, such as in diabetes, the importance of BP variability may theoretically be even greater. We aimed to investigate the incremental value of BPV for prediction of cardiovascular and all-cause mortality in patients with type 2 diabetes. Methods We identified 9,855 patients without pre-existing cardiovascular disease who did not change BP-lowering treatment during the observation period from a Swedish primary health care cohort of patients with type 2 diabetes. BPV was summarized as the standard deviation (SD), coefficient of variation (CV), or variation independent of mean (VIM). Patients were followed for a median of 4 years and associations with cardiovascular and all-cause mortality were investigated using Cox proportional hazards models. Results BPV was not associated with cardiovascular specific or all-cause mortality in the total sample. In patients who were not on BP-lowering drugs during the observation period (n = 2,949), variability measures were associated with all-cause mortality: hazard ratios were 1.05, 1.04 and 1.05 for 50% increases in SD, CV and VIM, respectively, adjusted for Framingham risk score risk factors, including mean BP. However, the addition of the variability measures in this subgroup only led to very minimal improvement in discrimination, indicating they may have limited clinical usefulness (change in C-statistic ranged from 0.000-0.003 in all models). Conclusions Although BPV was independently associated with all-cause mortality in diabetes patients in primary care who did not have pre-existing cardiovascular disease or BP-lowering drugs, it may be of minimal clinical usefulness above and beyond that of other routinely measured predictors, including mean BP.

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  • 3.
    Blomstrand, Peter
    et al.
    Cty Hosp Ryhov, Sweden; Jonkoping Univ, Sweden.
    Sjöblom, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Mats
    Acad Hlth and Care, Sweden.
    Wijkman, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Engvall, Martin
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain2018In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 17, article id 113Article in journal (Refereed)
    Abstract [en]

    Aims: Obesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons. Methods: We prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight amp;lt; 25 kg/m(2), overweight 25-29 kg/m(2), and obesity amp;gt;= 30 kg/m(2) ). Echocardiography was performed at the beginning of the study and after 4-years in the patient group. Results: Univariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/e (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. - 18.6% (2.3%) for normal weight patients, 53% (8%) vs. - 17.5% (2.3%) for overweight, and 49% (9%) vs. - 16.2% (3.0%) for obese (p amp;lt; 0.05 vs. p amp;lt;0.05). Corresponding results in the control group were 58% (6%) vs. -22.3% (3.0%), 55% (7%) vs. - 20.8% (3.1%) and 54% (8%) - 19.6% (4.0%) (p amp;lt;0.05 vs. p amp;lt;0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by - 1.0 (9.0) % (n =187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n =179) (p amp;lt;0.05). Conclusion: Overweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons.

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  • 4.
    Borgström Bolmsjö, Beata
    et al.
    Lund University, Sweden.
    Molstad, Sigvard
    Lund University, Sweden.
    Gallagher, Martin
    University of Sydney, Australia.
    Chalmers, John
    University of Sydney, Australia.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Midlov, Patrik
    Lund University, Sweden.
    Risk factors and consequences of decreased kidney function in nursing home residents: A longitudinal study2017In: Geriatrics & Gerontology International, ISSN 1444-1586, E-ISSN 1447-0594, Vol. 17, no 5, p. 791-797Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of the present study was to study the renal function and the relationship of deterioration in renal function with major outcomes in elderly nursing home residents. A second aim was to compare the internationally recommended formulae for estimated glomerular filtration rate (eGFR) consisting of both creatinine and cystatin C in a nursing home population. Methods: A total of 429 patients from 11 nursing homes were included during 2008-2011. GFR was estimated, from formulae based on both creatinine and cystatin C, at baseline and after 1 and 2 years. The patients were divided into groups based on chronic kidney disease level, and comparisons were made for mortality, morbidity, the use of medications and between the different formulae for eGFR. Results: Survival was lower in the groups with lower renal function. Over 60% of the residents had impaired renal function. Those with impaired renal function were older, had a higher number of medications and a higher prevalence of heart failure. Higher number of medications was associated with a greater risk of rapid decline in renal function with an odds ratio of 1.2 (95% confidence interval 1.06-1.36, P = 0.003). The compared eGFR formulae based on both cystatin C and creatinine were in excellent concordance with each other. Conclusions: Decreased renal function was associated with increased mortality. A majority of nursing home residents had declining renal function, which should be considered when prescribing medications. The more medications, the higher the risk for rapidly declining renal function.

  • 5.
    Carlsson, Axel C.
    et al.
    Karolinska Inst, Sweden.
    Nowak, Christoph
    Karolinska Inst, Sweden.
    Lind, Lars
    Uppsala Univ, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Nyström, Fredrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.
    Sundstrom, Johan
    Uppsala Univ, Sweden.
    Carrero, Juan Jesus
    Karolinska Inst, Sweden.
    Riserus, Ulf
    Uppsala Univ, Sweden.
    Ingelsson, Erik
    Stanford Univ, CA 94305 USA; Stanford Univ, CA 94305 USA; Stanford Univ, CA 94305 USA; Uppsala Univ, Sweden.
    Fall, Tove
    Uppsala Univ, Sweden.
    Arnlov, Johan
    Karolinska Inst, Sweden; Dalarna Univ, Sweden.
    Growth differentiation factor 15 (GDF-15) is a potential biomarker of both diabetic kidney disease and future cardiovascular events in cohorts of individuals with type 2 diabetes: a proteomics approach2020In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 125, no 1, p. 37-43Article in journal (Refereed)
    Abstract [en]

    Background: Diabetic kidney disease (DKD) is a leading risk factor for end-stage renal disease and is one of the most important risk factors for cardiovascular disease in patients with diabetes. It is possible that novel markers portraying the pathophysiological underpinning processes may be useful. Aim: To investigate the associations between 80 circulating proteins, measured by a proximity extension assay, and prevalent DKD and major adverse cardiovascular events (MACE) in type 2 diabetes. Methods: We randomly divided individuals with type 2 diabetes from three cohorts into a two-thirds discovery and one-third replication set (total n = 813, of whom 231 had DKD defined by estimated glomerular filtration rate amp;lt;60 mg/mL/1.73 m(2) and/or urinary albumin-creatinine ratio amp;gt;= 3 g/mol). Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline. Results: Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27-2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16-1.69); myoglobin (OR 1.57, 95% CI 1.30-1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17-1.74). In patients with DKD, GDF-15 was significantly associated with increased risk of MACE after adjustments for baseline age, sex, microalbuminuria, and kidney function and (59 MACE events during 7 years follow-up, hazard ratio per standard deviation increase 1.43 [95% CI 1.03-1.98]) but not after further adjustments for cardiovascular risk factors. Conclusion: Our proteomics approach confirms and extends previous associations of higher circulating levels of GDF-15 with both micro- and macrovascular disease in patients with type 2 diabetes. Our data encourage additional studies evaluating the clinical utility of our findings.

  • 6.
    Chow, Clara K.
    et al.
    Univ Sydney, Australia; Westmead Hosp, Australia; Univ New South Wales, Australia.
    Thiagalingam, Aravinda
    Univ Sydney, Australia; Westmead Hosp, Australia; Univ New South Wales, Australia.
    Santo, Karla
    Univ Sydney, Australia.
    Kok, Cindy
    Univ Sydney, Australia; Univ New South Wales, Australia.
    Thakkar, Jay
    Univ Sydney, Australia; Westmead Hosp, Australia; Univ New South Wales, Australia.
    Stepien, Sandrine
    Univ Sydney, Australia; Univ New South Wales, Australia.
    Billot, Laurent
    Univ Sydney, Australia; Univ New South Wales, Australia.
    Jan, Stephen
    Univ Sydney, Australia; Univ New South Wales, Australia.
    Joshi, Rohina
    Univ Sydney, Australia; Univ New South Wales, Australia.
    Hillis, Graham S.
    Univ Western Australia, Australia.
    Brieger, David
    Univ Sydney, Australia; Concord Repatriat Gen Hosp, Australia.
    Chew, Derek P.
    Flinders Univ S Australia, Australia.
    Rådholm, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Atherton, John J.
    Royal Brisbane and Womens Hosp, Australia; Univ Queensland, Australia.
    Bhindi, Ravinay
    Royal North Shore Hosp, Australia.
    Collins, Nicholas
    John Hunter Hosp, Australia.
    Coverdale, Steven
    Sunshine Coast Univ Hosp, Australia.
    Hamilton-Craig, Christian
    Prince Charles Hosp, Australia; Univ Queensland, Australia.
    Kangaharan, Nadarajah
    Royal Darwin Hosp, Australia; Alice Springs Hosp, Australia.
    Maiorana, Andrew
    Curtin Univ, Australia; Fiona Stanley Hosp, Australia.
    McGrady, Michelle
    Royal Prince Alfred Hosp, Australia.
    Shetty, Pratap
    Wollongong Hosp, Australia.
    Thompson, Peter
    Sir Charles Gairdner Hosp, Australia.
    Rogers, Anthony
    Univ Sydney, Australia; Univ New South Wales, Australia.
    Redfern, Julie
    Univ Sydney, Australia; Westmead Hosp, Australia; Univ New South Wales, Australia.
    TEXT messages to improve MEDication adherence and Secondary prevention (TEXTMEDS) after acute coronary syndrome: a randomised clinical trial protocol2018In: BMJ Open, E-ISSN 2044-6055, Vol. 8, no 1, article id e019463Article in journal (Refereed)
    Abstract [en]

    Background Identifying simple, low-cost and scalable means of supporting lifestyle change and medication adherence for patients following a cardiovascular (CV) event is important. Objective The TEXTMEDS (TEXT messages to improve MEDiGation adherence and Secondary prevention) study aims to investigate whether a cardiac education and support programme sent via mobile phone text message improves medication adherence and risk factor levels in patients following an acute coronary syndrome (ACS). Study design A single-blind, multicentre, randomised clinical trial of 1400 patients after an ACS with 12 months follow-up. The intervention group will receive multiple weekly text messages that provide information, motivation, support to adhere to medications, quit smoking (if relevant) and recommendations for healthy diet and exercise. The primary endpoint is the percentage of patients who are adherent to cardioprotective medications and the key secondary outcomes are mean systolic blood pressure (BP) and low density lipoprotein cholesterol. Secondary outcomes will also include total cholesterol, mean diastolic BP, the percentage of participants who are adherent to each cardioprotective medication class, the percentage of participants who achieve target levels of CV risk factors, major vascular events, hospital readmissions and all-cause mortality. The study will be augmented by formal economic and proGess evaluations to assess acceptability, utility and Gost-effectiveness. Summary The study will provide multicentre randomised trial evidence of the effects of a text message-based programme on cardioprotective medication adherence and levels of CV risk factors. Ethics and dissemination Primary ethics approval was received from Western Sydney Local Health District Human Research EthiGs Committee (HREC2012/12/4.1 (3648) AU RED HREC/13ANMEAD/15). Results will be disseminated via peer-reviewed publications and presentations at international conferences.

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  • 7.
    Ekstrom, Magnus Pär
    et al.
    Lund Univ, Sweden.
    Blomberg, Anders
    Umea Univ, Sweden.
    Bergström, Göran
    Univ Gothenburg, Sweden.
    Brandberg, John
    Univ Gothenburg, Sweden.
    Caidahl, Kenneth
    Univ Gothenburg, Sweden.
    Engström, Gunnar
    Lund Univ, Sweden.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Eriksson, Maria
    Karolinska Inst, Sweden.
    Gränsbo, Klas
    Lund Univ, Sweden.
    Hansen, Tomas
    Uppsala Univ, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Sweden.
    Nilsson, Lars
    Umea Univ, Sweden.
    Nilsson, Ulf
    Umea Univ, Sweden.
    Olin, Anna-Carin
    Univ Gothenburg, Sweden.
    Persson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Rosengren, Annika
    Univ Gothenburg, Sweden.
    Sandelin, Martin
    Uppsala Univ, Sweden.
    Sköld, Magnus
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Sundström, Johan
    Karolinska Inst, Sweden; Karolinska Inst, Sweden.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Söderberg, Stefan
    Umea Univ, Sweden.
    Tanash, Hanan A.
    Lund Univ, Sweden.
    Torén, Kjell
    Sahlgrens Univ Hosp, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Lindberg, Eva
    Uppsala Univ, Sweden.
    The association of body mass index, weight gain and central obesity with activity-related breathlessness: the Swedish Cardiopulmonary Bioimage Study2019In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 74, no 10, p. 958-964Article in journal (Refereed)
    Abstract [en]

    Introduction Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) amp;gt;30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear. Methods This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score amp;gt;= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex. Results We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; pamp;lt;0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness. Conclusion Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.

  • 8.
    Feldreich, Tobias
    et al.
    Dalarna Univ, Sweden.
    Nowak, Christoph
    Karolinska Inst, Sweden.
    Carlsson, Axel C.
    Karolinska Inst, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Nyström, Fredrik H
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.
    Sundstrom, Johan
    Uppsala Univ, Sweden.
    Carrero-Roig, Juan-Jesus
    Karolinska Inst, Sweden.
    Leppert, Jerzy
    Uppsala Univ, Sweden.
    Hedberg, Par
    Uppsala Univ, Sweden.
    Giedraitis, Vilmantas
    Uppsala Univ, Sweden.
    Lind, Lars
    Uppsala Univ, Sweden.
    Cordeiro, Antonio
    Dante Pazzanese Inst Cardiol, Brazil.
    arnlov, Johan
    Dalarna Univ, Sweden; Karolinska Inst, Sweden.
    The association between plasma proteomics and incident cardiovascular disease identifies MMP-12 as a promising cardiovascular risk marker in patients with chronic kidney disease2020In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 307, p. 11-15Article in journal (Refereed)
    Abstract [en]

    Background and aims: Previous proteomics efforts in patients with chronic kidney disease (CKD) have predominantly evaluated urinary protein levels. Therefore, our aim was to investigate the association between plasma levels of 80 cardiovascular disease-related proteins and the risk of major adverse cardiovascular events (MACE) in patients with CKD. Methods: Individuals with CKD stages 3-5 (eGFR below 60 ml min-1 [1.73 m]-2) from three community-based cohorts (PIVUS, ULSAM, SAVA), one diabetes cohort (CARDIPP) and one cohort with peripheral artery disease patients (PADVA) with information on 80 plasma protein biomarkers, assessed with a proximity extension assay, and follow-up data on incident MACE, were used as discovery sample. To validate findings and to asses generalizability to patients with CKD in clinical practice, an outpatient CKD-cohort (Malnutrition, Inflammation and Vascular Calcification (MIVC)) was used as replication sample. Results: In the discovery sample (total n = 1316), 249 individuals experienced MACE during 7.0 +/- 2.9 years (range 0.005-12.9) of follow-up, and in the replication sample, 71 MACE events in 283 individuals over a mean +/- SD change of 2.9 +/- 1.2 years (range 0.1-4.0) were documented. Applying Bonferroni correction, 18 proteins were significantly associated with risk of MACE in the discovery cohort, adjusting for age and sex in order of significance, GDF-15, FGF-23, REN, FABP4, IL6, TNF-R1, AGRP, MMP-12, AM, KIM-1, TRAILR2, TNFR2, CTSL1, CSF1, PlGF, CA-125, CCL20 and PAR-1 (p < 0.000625 for all). Only matrix metalloproteinase 12 (MMP-12) was significantly associated with an increased risk of MACE in the replication sample (hazard ratio (HR) per SD increase, 1.36, 95% CI (1.07-1.75), p = 0.013). Conclusions: Our proteomics analyses identified plasma MMP-12 as a promising cardiovascular risk marker in patients with CKD.

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  • 9.
    Figtree, Gemma A.
    et al.
    Royal North Shore Hosp, Australia; Univ Sydney, Australia; Univ New South Wales, Australia.
    Rådholm, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög. Univ New South Wales, Australia.
    Barrett, Terrance D.
    Janssen Res and Dev LLC, NJ USA.
    Perkovic, Vlado
    Univ New South Wales, Australia.
    Mahaffey, Kenneth W.
    Stanford Univ, CA 94305 USA.
    de Zeeuw, Dick
    Univ Groningen, Netherlands.
    Fulcher, Greg
    Royal North Shore Hosp, Australia; Univ Sydney, Australia.
    Matthews, David R.
    Univ Oxford, England.
    Shaw, Wayne
    Janssen Res and Dev LLC, NJ USA.
    Neal, Bruce
    Univ New South Wales, Australia; Imperial Coll London, England.
    Effects of Canagliflozin on Heart Failure Outcomes Associated With Preserved and Reduced Ejection Fraction2019In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 22, p. 2591-2593Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 10.
    Figtree, Gemma A.
    et al.
    Royal North Shore Hosp, Australia; Univ Sydney, Australia; Univ New South Wales, Australia.
    Rådholm, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög. Univ New South Wales, Australia; Imperial Coll London, England.
    Neal, Bruce
    Univ New South Wales, Australia.
    Response by Figtree et al to Letter Regarding Article, "Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program (Canagliflozin Cardiovascular Assessment Study)"2019In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 3, p. 418-419Article in journal (Other academic)
    Abstract [en]

    n/a

  • 11. Hagstrom, Emil
    et al.
    Bergstrom, Goran
    Rosengren, Annika
    Brolin, Elin B.
    Brandberg, John
    Cederlund, Kerstin
    Engstrom, Gunnar
    Engvall, Jan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Eriksson, Maria J.
    Goncalves, Isabel
    James, Stefan
    Jernberg, Tomas
    Lilja, Mikael
    Magnusson, Martin
    Persson, Anders
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Persson, Margaretha
    Sandstrom, Anette
    Schmidt, Caroline
    Skoglund Larsson, Linn
    Sundstrom, Johan
    Swahn, Eva
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Heart Center, Department of Cardiology in Linköping.
    Soderberg, Stefan
    Toren, Kjell
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Lind, Lars
    University of Gothenburg, Gothenburg, Sweden.
    IMPACT OF BODY WEIGHT AT AGE 20 AND WEIGHT GAIN DURING ADULTHOOD ON MIDLIFE CORONARY ARTERY CALCIUM IN 15,000 MEN AND WOMEN: AN INTERIM ANALYSIS OF THE SWEDISH CARDIOPULMONARY BIOIMAGE STUDY2019In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 73, no 9, p. 1692-1692Article in journal (Other academic)
    Abstract [en]

    Background

    Elevated body weight in adolescence is strongly associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, or to weight gain with subsequent high adult weight is not known. Using data from the Swedish CArdioPulmonary bioImage Study (SCAPIS), we investigated the association between weight at age 20, weight gain to midlife and coronary artery calcium score (CACS) at midlife.

    Methods

    In the first 15,810 participants in SCAPIS (mean age 58 years, 52% women), data on CACS at midlife, self-reported body weight at age 20 and weight at examination in SCAPIS were recorded.

    Results

    CACS in midlife was significantly higher with increasing weight at age 20 (p<0.001 for both sexes), and then increased with weight gain until midlife at all levels of body weight at age 20 after adjusting for age, height, smoking, alcohol intake, education level, exercise levels and LDL cholesterol. However, the association with weight gain was only significant in men (p = 0.047), not in women (p=0.474). No significant interaction was seen between weight at age 20 and midlife weight with CACS. The effect of weight at age 20 on CACS was significantly more marked in men than in women, as was the effect of weight gain (p<0.001 for both interactions).

    Conclusion

    Weight at age 20 and weight gain to midlife were both related to CACS, but much more markedly so in men than in women, indicating a generally larger effect of both early adult weight and further weight gain until midlife on CACS in men, compared to women.

  • 12.
    Islam, Sheikh Mohammed Shariful
    et al.
    Univ New South Wales, Australia; Univ Sydney, Australia; Deakin Univ, Australia.
    Chow, Clara K.
    Univ New South Wales, Australia; Univ Sydney, Australia; Westmead Hosp, Australia.
    Redfern, Julie
    Univ New South Wales, Australia; Univ Sydney, Australia.
    Kok, Cindy
    Univ New South Wales, Australia.
    Rådholm, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög. Univ New South Wales, Australia.
    Stepien, Sandrine
    Univ New South Wales, Australia.
    Rodgers, Anthony
    Univ New South Wales, Australia; Univ Sydney, Australia.
    Hackett, Maree L.
    Univ New South Wales, Australia; Univ Cent Lancashire, England; Univ Sydney, Australia.
    Effect of text messaging on depression in patients with coronary heart disease: a substudy analysis from the TEXT ME randomised controlled trial2019In: BMJ Open, E-ISSN 2044-6055, Vol. 9, no 2, article id e022637Article in journal (Refereed)
    Abstract [en]

    Objective We aimed to evaluate the effects on depression scores of a lifestyle-focused cardiac support programme delivered via mobile phone text messaging among patients with coronary heart disease (CHD). Design Substudy and secondary analysis of a parallel-group, single-blind randomised controlled trial of patients with CHD. Setting A tertiary hospital in Sydney, Australia. Intervention The Tobacco, Exercise and dieT MEssages programme comprised four text messages per week for 6 months that provided education, motivation and support on diet, physical activity, general cardiac education and smoking, if relevant. The programme did not have any specific mental health component. Outcomes Depression scores at 6 months measured using the Patient Health Questionnaire-9 (PHQ-9). Treatment effect across subgroups was measured using log-binomial regression model for the binary outcome (depressed/not depressed, where depressed is any score of PHQ-9 amp;gt;= 5) with treatment, subgroup and treatment by subgroup interaction as fixed effects. Results Depression scores at 6 months were lower in the intervention group compared with the control group, mean difference 1.9 (95% CI 1.5 to 2.4, pamp;lt;0.0001). The frequency of mild or greater depressive symptoms (PHQ-9 scores amp;gt;= 5) at 6 months was 21/333 (6.3%) in the intervention group and 86/350 (24.6%) in the control group (relative risk (RR) 0.26, 95% CI 0.16 to 0.40, pamp;lt;0.001). This proportional reduction in depressive symptoms was similar across groups defined by age, sex, education, body mass index, physical activity, current smoking, current drinking and history of depression, diabetes and hypertension. In particular, the rates of PHQ-9 amp;gt;= 5 among people with a history of depression were 4/44 (9.1%) vs 29/62 (46.8%) in intervention vs control (RR 0.19, 95% CI 0.07 to 0.51, pamp;lt;0.001), and were 17/289 (5.9%) vs 57/288 (19.8%) among others (RR 0.30, 95% CI 0.18 to 0.50, pamp;lt;0.001). Conclusions Among people with CHD, a cardiac support programme delivered via mobile phone text messaging was associated with fewer symptoms of mild-to-moderate depression at 6 months in the treatment group compared with controls.

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  • 13.
    Jonasson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Bergstrand, Sara
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Faculty of Medicine and Health Sciences.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Normative data and the influence of age and sex on microcirculatory function in a middle-aged cohort: results from the SCAPIS study2020In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 318, no 4, p. H908-H915Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to assess normative values for comprehensive forearm skin microcirculatory function: oxygen saturation, tissue fraction of red blood cells (RBCs), and speed-resolved perfusion. Furthermore, to examine the influence of age and sex on microcirculatory function. Measurements were performed using a noninvasive probe-based system, including diffuse reflectance spectroscopy and laser-Doppler flowmetry, yielding output data in absolute units. The study was conducted within the Swedish CArdioPulmonary BioImage Study (SCAPIS) and included 1,765 men and women aged 50-65 yr from the Linkoping general population. Normative values are given at baseline, at the end of a 5-min occlusion of the brachial artery and during hyperemia after occlusion release. We found a consistent age distribution, in which the oldest individuals had the lowest peak oxygen saturation (P &lt; 0.001) and the highest baseline low-speed perfusion (P &lt; 0.001). Women had higher peak oxygen saturation (P &lt; 0.001), lower RBC tissue fraction, in general (P &lt; 0.001), lower baseline perfusion in all speed regions (P = 0.01). and lower peak high-speed perfusion at hyperemia (P &lt; 0.001). The normative data can be used as reference values in future studies of disease-specific populations. The results show that age and sex are important aspects to consider in studies of microvascular function. Women and younger age were factors associated with higher peak oxygen saturation after ischemia. This is a novel parameter that reflects overall microcirculatory function associated with vascular dilation capacity. NEW & NOTEWORTHY This study expands experimental microcirculatory research to clinical use by providing normative values on microcirculatory function in a large population-based cohort. Women and younger age were factors associated with higher peak oxygen saturation after ischemia, which implies that age and sex are important aspects to consider in studies of micmvascular function. This study is the first step toward using microcirculatory assessment as a tool to improve diagnosis. prognosis. and treatment in disease-specific populations.

  • 14.
    Jonasson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Bergstrand, Sara
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Bjarnegård, Niclas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Skin microvascular endothelial dysfunction is associated with type 2 diabetes independently of microalbuminuria and arterial stiffness2017In: Diabetes & Vascular Disease Research, ISSN 1479-1641, E-ISSN 1752-8984, Vol. 14, no 4, p. 363-371, article id UNSP 1479164117707706Article in journal (Refereed)
    Abstract [en]

    Skin and kidney microvascular functions may be affected independently in diabetes mellitus. We investigated skin microcirculatory function in 79 subjects with diabetes type 2, where 41 had microalbuminuria and 38 not, and in 41 age-matched controls. The oxygen saturation, fraction of red blood cells and speed-resolved microcirculatory perfusion (% red blood cells x mm/s) divided into three speed regions: 0-1, 1-10 and above 10 mm/s, were assessed during baseline and after local heating of the foot with a new device integrating diffuse reflectance spectroscopy and laser Doppler flowmetry. Arterial stiffness was assessed as carotid-femoral pulse wave velocity. Subjects with diabetes and microalbuminuria had significantly higher carotid-femoral pulse wave velocity compared to subjects without microalbuminuria and to controls. The perfusion for speeds 0-1 mm/s and red blood cell tissue fraction were reduced in subjects with diabetes at baseline and after heating, independent of microalbuminuria. These parameters were correlated to HbA1c. In conclusion, the reduced nutritive perfusion and red blood cell tissue fraction in type 2 diabetes were related to long-term glucose control but independent of microvascular changes in the kidneys and large-vessel stiffness. This may be due to different pathogenic pathways in the development of nephropathy, large-vessel stiffness and cutaneous microvascular impairment.

  • 15.
    Jonasson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Järfälla, Stockholm, Sweden.
    Bergstrand, Sara
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    In vivo characterization of light scattering properties of human skin in the 475- to 850-nm wavelength range in a Swedish cohort2018In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 23, no 12, article id 121608Article in journal (Refereed)
    Abstract [en]

    We have determined in vivo optical scattering properties of normal human skin in 1734 subjects, mostly with fair skin type, within the Swedish CArdioPulmonary bioImage Study. The measurements were performed with a noninvasive system, integrating spatially resolved diffuse reflectance spectroscopy and laser Doppler flowmetry. Data were analyzed with an inverse Monte Carlo algorithm, accounting for both scattering, geometrical, and absorbing properties of the tissue. The reduced scattering coefficient was found to decrease from 3.16 ± 0.72 to 1.13 ± 0.27 mm-1 (mean ± SD) in the 475- to 850-nm wavelength range. There was a negative correlation between the reduced scattering coefficient and age, and a significant difference between men and women in the reduced scattering coefficient as well as in the fraction of small scattering particles. This large study on tissue scattering with mean values and normal variation can serve as a reference when designing diagnostic techniques or when evaluating the effect of therapeutic optical systems.

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  • 16.
    Jones, Alexandra
    et al.
    George Inst Global Hlth, Australia; Univ Sydney, Australia.
    Rådholm, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög. George Inst Global Hlth, Australia.
    Neal, Bruce
    George Inst Global Hlth, Australia; Univ Sydney, Australia; Imperial Coll London, England.
    Defining Unhealthy: A Systematic Analysis of Alignment between the Australian Dietary Guidelines and the Health Star Rating System2018In: Nutrients, E-ISSN 2072-6643, Vol. 10, no 4, article id 501Article in journal (Refereed)
    Abstract [en]

    The Australian Dietary Guidelines (ADGs) and Health Star Rating (HSR) front-of-pack labelling system are two national interventions to promote healthier diets. Our aim was to assess the degree of alignment between the two policies. Methods: Nutrition information was extracted for 65,660 packaged foods available in The George Institutes Australian FoodSwitch database. Products were classified core or discretionary based on the ADGs, and a HSR generated irrespective of whether currently displayed on pack. Apparent outliers were identified as those products classified core that received HSR amp;lt;= 2.0; and those classified discretionary that received HSR amp;gt;= 3.5. Nutrient cut-offs were applied to determine whether apparent outliers were high in salt, total sugar or saturated fat, and outlier status thereby attributed to a failure of the ADGs or HSR algorithm. Results: 47,116 products (23,460 core; 23,656 discretionary) were included. Median (Q1, Q3) HSRs were 4.0 (3.0 to 4.5) for core and 2.0 (1.0 to 3.0) for discretionary products. Overall alignment was good: 86.6% of products received a HSR aligned with their ADG classification. Among 6324 products identified as apparent outliers, 5246 (83.0%) were ultimately determined to be ADG failures, largely caused by challenges in defining foods as core or discretionary. In total, 1078 (17.0%) were determined to be true failures of the HSR algorithm. Conclusion: The scope of genuine misalignment between the ADGs and HSR algorithm is very small. We provide evidence-informed recommendations for strengthening both policies to more effectively guide Australians towards healthier choices.

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  • 17.
    Kalkan, Almina
    et al.
    AstraZeneca Nordic Balt, Sweden.
    Bodegård, Johan
    AstraZeneca Nordic Balt, Sweden.
    Sundstrom, Johan
    Uppsala University, Sweden.
    Svennblad, Bodil
    Uppsala University, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Nilsson Nilsson, Peter
    Lund University, Sweden.
    Johansson, Gunnar
    Uppsala University, Sweden.
    Ekman, Manias
    AstraZeneca Nordic Balt, Sweden.
    Increased healthcare utilization costs following initiation of insulin treatment in type 2 diabetes: A long-term follow-up in clinical practice2017In: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 11, no 2, p. 184-192Article in journal (Refereed)
    Abstract [en]

    Aims: To compare long-term changes in healthcare utilization and costs for type 2 diabetes patients before and after insulin initiation, as well as healthcare costs after insulin versus non-insulin anti-diabetic (NIAD) initiation. Methods: Patients newly initiated on insulin (n = 2823) were identified in primary health care records from 84 Swedish primary care centers, between 1999 to 2009. First, healthcare costs per patient were evaluated for primary care, hospitalizations and secondary outpatient care, before and up to seven years after insulin initiation. Second, patients prescribed insulin in second line were matched to patients prescribed NIAD in second line, and the healthcare costs of the matched groups were compared. Results: The total mean annual healthcare cost increased from 1656 per patient 2 years before insulin initiation to 3814 seven years after insulin initiation. The total cumulative mean healthcare cost per patient at year 5 after second-line treatment was 13,823 in the insulin group compared to 9989 in the NIAD group. Conclusions: Initiation of insulin in type 2 diabetes patients was followed by increased healthcare costs. The increases in costs were larger than those seen in a matched patient population initiated on NIAD treatment in second-line. (C) 2016 The Author(s). Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe. This is an open access article under the CC BY-NC-ND license.

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  • 18.
    Nord, Magnus
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Valla.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Marcusson, Jan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Johansson, Maria
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Activity and Health.
    Staff experiences of a new tool for comprehensive geriatric assessment in primary care (PASTEL): a focus group study Primary care staff experiences of geriatric assessment2020In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 38, no 2, p. 132-145Article in journal (Refereed)
    Abstract [en]

    Objective: Comprehensive geriatric assessment (CGA) is recommended for the management of frailty. Little is known about professionals experiences of CGA; therefore we wanted to investigate the experiences of staff in primary care using a new CGA tool: the Primary care Assessment Tool for Elderly (PASTEL). Design: Focus group interviews. Manifest qualitative content analysis. Setting: Nine primary health care centres in Sweden that participated in a CGA intervention. These centres represent urban as well as rural areas. Subjects: Nine nurses, five GPs and one pharmacist were divided into three focus groups. Main outcome measures: Participants experiences of conducting CGA with PASTEL. Results: The analysis resulted in four main categories. A valuable tool for selected patients: The participants considered the assessment tool to be feasible and valuable. They stated that having enough time for the assessment interview was essential but views about the ideal patient for assessment were divided. Creating conditions for dialogue: The process of adapting the assessment to the individual and create conditions for dialogue was recognised as important. Managing in-depth conversations: In-depth conversations turned out to be an important component of the assessment. Patients were eager to share their stories, but talking about the future or the end of life was demanding. The winding road of actions and teamwork: PASTEL was regarded as a good preparation tool for care planning and a means of support for identifying appropriate actions to manage frailty but there were challenges to implement these actions and to obtain good teamwork. Conclusion: The participants reported that PASTEL, a tool for CGA, gave a holistic picture of the older person and was helpful in care planning.

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  • 19.
    Nowak, Christoph
    et al.
    Karolinska Inst, Sweden.
    Carlsson, Axel C.
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Alam, Moudud
    Dalarna Univ, Sweden.
    Feldreich, Tobias
    Dalarna Univ, Sweden.
    Sundstrom, Johan
    Uppsala Univ, Sweden.
    Carrero, Juan-Jesus
    Karolinska Inst, Sweden.
    Leppert, Jerzy
    Uppsala Univ, Sweden.
    Hedberg, Par
    Uppsala Univ, Sweden.
    Henriksen, Egil
    Uppsala Univ, Sweden.
    Cordeiro, Antonio C.
    Dante Pazzanese Inst Cardiol, Brazil.
    Giedraitis, Vilmantas
    Uppsala Univ, Sweden.
    Lind, Lars
    Uppsala Univ, Sweden.
    Ingelsson, Erik
    Stanford Univ, CA 94305 USA.
    Fall, Tove
    Uppsala Univ, Sweden.
    Arnlov, Johan
    Karolinska Inst, Sweden; Dalarna Univ, 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 (amp;lt; 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.

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  • 20.
    Olofsson, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Odeshog Hlth Care Ctr, Sweden.
    Matussek, A.
    Reg Jonkoping Cty, Sweden; Karolinska Inst, Sweden; Karolinska Univ Lab, Sweden.
    Ehricht, R.
    Abbott Alere Technol GmbH, Germany; InfectoGnost Res Campus, Germany; Leibniz Inst Photon Technol, Germany.
    Lindgren, Per-Eric
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Reg Jonkoping Cty, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Differences in molecular epidemiology of Staphylococcus aureus and Escherichia coli in nursing home residents and people in unassisted living situations2019In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 101, no 1, p. 76-83Article in journal (Refereed)
    Abstract [en]

    Background: The usefulness of colonization pressure as a working model and proxy for infection transmission is limited due to the inability to grade or quantify the specific risk within environments that are subject to change. Aim: To elaborate on the colonization pressure model by comparing the molecular epidemiology of two bacteria, Staphylococcus aureus and Escherichia coli, among residents in a nursing home and people in unassisted living situations. Methods: A cross-sectional study of 73 elderly residents from a village in south-central Sweden was conducted. Of these, 35 were residents of a nursing home, and 34 lived in an own place of residence in the same geographical area. Samples of two representative bacterial species were collected from multiple body sites and analysed for molecular diversity. Findings: Combining all body sites, 47% of the participants were colonized with S. aureus and 93% with E. coli. The nursing home group, the group in unassisted living situations, and both units combined, held 16, 17, and 29 different S. aureus spa types, respectively. The corresponding numbers of different E. coli serogenotypes were 34, 28, and 48. Diabetes mellitus was associated with more frequent colonization with S. aureus. Conclusion: The molecular diversity of bacteria found within different forms of accommodation was within the same range. Hospital quality hygiene might have contributed to the absence of homogenization of the molecular diversity within the nursing home group. Diabetes mellitus might have played a role in a patient selection characterized by advanced age. (C) 2018 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  • 21.
    Pikkemaat, Miriam
    et al.
    Husensjo Hlth Care Ctr, Sweden; Lund Univ, Sweden.
    Andersson, Tobias
    Narhalsan Norrmalm Hlth Ctr, Sweden; Univ Gothenburg, Sweden.
    Melander, Olle
    Lund Univ, Sweden.
    Chalmers, John
    UNSW Sydney, Australia.
    Rådholm, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög. UNSW Sydney, Australia.
    Bostrom, Kristina Bengtsson
    Univ Gothenburg, Sweden; RandD Ctr Skaraborg Primary Care, Sweden.
    C-peptide predicts all-cause and cardiovascular death in a cohort of individuals with newly diagnosed type 2 diabetes. The Skaraborg diabetes register2019In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 150, p. 174-183Article in journal (Refereed)
    Abstract [en]

    Aims

    To study the association between baseline level of C-peptide and all-cause death, cardiovascular death and cardiovascular complications among persons with newly diagnosed type 2 diabetes.

    Methods

    The Skaraborg Diabetes Register contains data on baseline C-peptide concentrations among 398 persons <65 years with newly diagnosed type 2 diabetes 1996–1998. National registries were used to determine all-cause death, cardiovascular death and incidence of myocardial infarction and ischemic stroke until 31 December 2014. The association between baseline C-peptide and outcomes were evaluated with adjustment for multiple confounders by Cox regression analysis. Missing data were handled by multiple imputation.

    Results

    In the imputed and fully adjusted model there was a significant association between 1 nmol/l increase in C-peptide concentration and all-cause death (HR 2.20, 95% CI 1.49–3.25, p < 0.001, number of events = 104), underlying cardiovascular death (HR 2.69, 1.49–4.85, p = 0.001, n = 35) and the composite outcome of underlying cardiovascular death, myocardial infarction or ischemic stroke (HR 1.61, 1.06–2.45, p = 0.027, n = 90).

    Conclusions

    Elevated C-peptide levels at baseline in persons with newly diagnosed type 2 diabetes are associated with increased risk of all-cause and cardiovascular mortality. C-peptide might be used to identify persons at high risk of cardiovascular complications and premature death.

  • 22.
    Rådholm, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög. Univ New South Wales, Australia.
    Chalmers, John
    Univ New South Wales, Australia.
    Ohkuma, Toshiaki
    Univ New South Wales, Australia; Kyushu Univ, Japan.
    Peters, Sanne
    Univ Oxford, England.
    Poulter, Neil
    Imperial Coll, England.
    Hamet, Pavel
    Univ Montreal, Canada.
    Harrap, Stephen
    Univ Melbourne, Australia; Royal Melbourne Hosp, Australia.
    Woodward, Mark
    Univ New South Wales, Australia; Univ Oxford, England; Johns Hopkins Univ, MD USA.
    Use of the waist-to-height ratio to predict cardiovascular risk in patients with diabetes: Results from the ADVANCE-ON study2018In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 20, no 8, p. 1903-1910Article in journal (Refereed)
    Abstract [en]

    Aims Patients with type 2 diabetes have a high risk of cardiovascular disease (CVD). Central obesity has been particularly associated with this risk relationship. We aimed to evaluate waist to height ratio (WHtR) as a predictor of risk in such patients. Methods WHtR was evaluated as a predictor of the risk of CVD and mortality amongst 11125 participants with type 2 diabetes in the ADVANCE and ADVANCE-ON studies, and was compared with body mass index (BMI), waist circumference and waist hip ratio (WHR). Primary outcome was a composite of death from CVD, non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes were myocardial infarction, stroke, cardiovascular death and death from any cause. Cox models were used, with bootstrapping to compare associations between anthropometric measures for the primary outcome. Results Median follow-up time was 9.0 years. There was a positive association between WHtR and adverse outcomes. The hazard ratio (HR) (confidence interval), per SD higher WHtR, was 1.16 (1.11-1.22) for the primary endpoint, with no heterogeneity by sex or region, but a stronger effect in individuals aged 66 years or older. The other 3 anthropometric measurements showed similar associations, although there was evidence that WHtR marginally outperformed BMI and WHR. Based on commonly used BMI cut-points, the equivalent WHtR cut-points were estimated to be 0.55 and 0.6, with no evidence of a difference across subgroups. Conclusions In patients with diabetes, WHtR is a useful indicator of future adverse risk, with similar effects in different population subgroups.

  • 23.
    Rådholm, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög. Univ New South Wales, Australia.
    Figtree, Gemma
    Royal North Shore Hosp, Sydney, NSW, Australia.
    Perkovic, Vlado
    Univ New South Wales, Australia; Univ Sydney, Australia.
    Solomon, Scott D.
    Harvard Med Sch, MA USA; Brigham and Womens Hosp, MA 02115 USA.
    Mahaffey, Kenneth W.
    Stanford Univ, CA 94305 USA.
    de Zeeuw, Dick
    Univ Groningen, Netherlands.
    Fulcher, Greg
    Royal North Shore Hosp, Sydney, NSW, Australia.
    Barrett, Terrance D.
    Janssen Res and Dev LLC, NJ USA.
    Shaw, Wayne
    Janssen Res and Dev LLC, NJ USA.
    Desai, Mehul
    Janssen Res and Dev LLC, NJ USA.
    Matthews, David R.
    Univ Oxford, England; Univ Oxford, England.
    Neal, Bruce
    Univ New South Wales, Australia; Univ New South Wales, Australia; Univ Sydney, Australia; Imperial Coll London, England.
    Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 138, no 5, p. 458-468Article in journal (Refereed)
    Abstract [en]

    Background: Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events. We report the effects on heart failure (HF) and cardiovascular death overall, in those with and without a baseline history of HF, and in other participant subgroups. Methods: The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) enrolled 10142 participants with type 2 diabetes mellitus and high cardiovascular risk. Participants were randomly assigned to canagliflozin or placebo and followed for a mean of 188 weeks. The primary end point for these analyses was adjudicated cardiovascular death or hospitalized HF. Results: Participants with a history of HF at baseline (14.4%) were more frequently women, white, and hypertensive and had a history of prior cardiovascular disease (all Pamp;lt;0.001). Greater proportions of these patients were using therapies such as blockers of the renin angiotensin aldosterone system, diuretics, and -blockers at baseline (all Pamp;lt;0.001). Overall, cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo (16.3 versus 20.8 per 1000 patient-years; hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.67-0.91), as was fatal or hospitalized HF (HR, 0.70; 95% CI, 0.55-0.89) and hospitalized HF alone (HR, 0.67; 95% CI, 0.52-0.87). The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF (HR, 0.61; 95% CI, 0.46-0.80) compared with those without HF at baseline (HR, 0.87; 95% CI, 0.72-1.06; P interaction =0.021). The effects of canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without HF at baseline (all interaction P values amp;gt;0.130), except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of HF (P=0.03). Conclusions: In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease, canagliflozin reduced the risk of cardiovascular death or hospitalized HF across a broad range of different patient subgroups. Benefits may be greater in those with a history of HF at baseline. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01032629 and NCT01989754.

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  • 24.
    Rådholm, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Tengblad, Anders
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Dahlén, Elsa
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    The impact of using sagittal abdominal diameter to predict major cardiovascular events in European patients with type 2 diabetes2017In: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 27, no 5, p. 418-422Article in journal (Refereed)
    Abstract [en]

    Background and aims: Obesity is associated with diabetes type 2 and one of the most important risk factors for cardiovascular disease. We explored if sagittal abdominal diameter (SAD) is a better predictor of major cardiovascular events than waist circumference (WC) and body mass index (BMI) in type 2 diabetes. Methods and results: The CARDIPP study consists of a cohort of patients with type 2 diabetes. In this study we used data from 635 participants with no previous myocardial infarction or stroke, with a mean follow-up time of 7.1 years. SAD, WC and BMI were measured at baseline and the end-point was first cardiovascular event, measured as a composite of ICD-10 codes for acute myocardial infarction, stroke or cardiovascular mortality. SAD was significantly higher in the major cardiovascular event group compared to participants that did not suffer a major cardiovascular event during follow-up (p amp;lt; 0.001). SAD amp;gt; 25 cm was the only anthropometric measurement that remained associated with major cardiovascular events when adjusted for modifiable and non-modifiable factors (hazard ratio 2.81, 95% confidence interval 1.37-5.76, p = 0.005). Conclusion: SAD with the cut off level of amp;gt; 25 cm, if confirmed in larger studies, may be used as a more independent risk-assessment tool compared with WC in clinical practice, to identify persons with type 2 diabetes at high cardiovascular risk. (C) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  • 25.
    Rådholm, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög. UNSW Sydney, Australia.
    Wu, Jason H. Y.
    UNSW Sydney, Australia.
    Wong, Muh Geot
    UNSW Sydney, Australia; Royal North Shore Hosp, Australia.
    Foote, Celine
    UNSW Sydney, Australia; Concord Repatriat Gen Hosp, Australia.
    Fulcher, Gregory
    Royal North Shore Hosp, Australia; Univ Sydney, Australia.
    Mahaffey, Kenneth W.
    Stanford Univ, CA 94305 USA.
    Perkovic, Vlado
    UNSW Sydney, Australia.
    Neal, Bruce
    UNSW Sydney, Australia; Univ Sydney, Australia; Imperial Coll London, England.
    Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular disease, death and safety outcomes in type 2 diabetes - A systematic review2018In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 140, p. 118-128Article, review/survey (Refereed)
    Abstract [en]

    Aim: Sodium glucose co-transporter 2 (SGLT2) inhibitors appear to protect against increased risks of cardiovascular and kidney disease in patients with type 2 diabetes but also cause some harms. Whether effects are comparable across drug class or specific to individual compounds is unclear. This meta-analysis assessed the class and individual compound effects of SGLT2 inhibition versus control on cardiovascular events, death, kidney disease and safety outcomes in patients with type 2 diabetes. Methods: MEDLINE, EMBASE, the Cochrane Library and regulatory databases were systematically searched for data from randomized clinical trials that included reporting of cardiovascular events, deaths or safety outcomes. We used fixed effects models and inverse variance weighting to calculate relative risks with the 95% confidence intervals. Results: The analyses included data from 82 trials, four overviews and six regulatory reports and there were 1,968 major cardiovascular events identified for analysis. Patients randomly assigned to SGLT2 had lower risks of major cardiovascular events (RR 0.85, 95% CI 0.77-0.93), heart failure (RR 0.67, 95% CI 0.55-0.80), all-cause death (RR 0.79, 95% CI 0.70-0.88) and serious decline in kidney function (RR 0.59, 0.49-0.71). Significant adverse effects were observed for genital infections (RR 3.06, 95% CI 2.73-4.43), volume depletion events (RR 1.24, 95% CI 1.07-1.43) and amputation (RR 1.44 95% CI 1.13-1.83). There was a high likelihood of differences in the associations of the individual compounds with cardiovascular death, hypoglycaemia and amputation (all I-2 amp;gt; 80%) and a moderate likelihood of differences in the associations with non-fatal stroke, all-cause death, urinary tract infection and fracture (all I-2 amp;gt; 30%). Conclusion: There are strong overall associations of SGLT2 inhibition with protection against major cardiovascular events, heart failure, serious decline in kidney function and all-cause death. SGLT2 inhibitors were also associated with infections, volume depletion effects and amputation. Some associations appear to differ between compounds. (C) 2018 Elsevier B.V. All rights reserved.

  • 26.
    Sabale, Ugne
    et al.
    AstraZeneca Nordic Balt, Sweden.
    Bodegard, Johan
    AstraZeneca Nordic Balt, Sweden.
    Svennblad, Bodil
    Uppsala University, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Johansson, Gunnar
    Uppsala University, Sweden.
    Ekman, Mattias
    AstraZeneca Nordic Balt, Sweden.
    Henriksson, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Peter
    Lund University, Sweden.
    Weight change patterns and healthcare costs in patients with newly-diagnosed type-2 diabetes in Sweden2017In: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 11, no 3, p. 217-225Article in journal (Refereed)
    Abstract [en]

    Aims: To describe weight-change pathways in patients with type 2 diabetes (T2D) and associated healthcare costs using repeated BMI measurements and healthcare utilization data. Methods: Patients with newly-diagnosed T2D with body mass index (BMI, kg/m(2)) at diagnosis and subsequent measures at year 1-3 were identified. Based on three-year BMI change, patients were assigned to one of 27 BMI change pathways defined by annual BMI change: BMI NE arrow (amp;gt;= 1 BMI unit increase), BMI -amp;gt; (amp;lt;1 BMI unit change), and BMI SE arrow (amp;gt;= 1 BMI unit decrease). Mean annual and three-year cumulative healthcare costs were estimated for each pathway by combining Swedish unit costs with resource use from primary care and national patient registers. Results: Cohort consisted of 15,819 patients; 44% women, mean age of 61 years, HbA1c of 6.7% (50 mmol/mol), BMI of 30.6 kg/m(2). Most common BMI pathways (mean costs): BMI -amp;gt;-amp;gt;-amp;gt; ((sic)5,311), BMI SE arrow -amp;gt;-amp;gt;((sic)5,461), and BMI -amp;gt;-amp;gt;SE arrow((sic)6,281). General trends: BMI)-amp;gt;-amp;gt;-amp;gt; linked to lowest, BMI NE arrow -amp;gt;NE arrow linked to highest costs. Conclusion: In patients with newly -diagnosed T2D, weight stability was the most common BMI change pattern over 3 years and associated with lowest healthcare costs. Relationship between weight change and healthcare costs appears complex warranting further investigation. (C) 2017 The Authors. Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe.

  • 27.
    Samefors, Maria
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Scragg, R.
    University of Auckland, New Zealand.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Association between serum 25(OH)D-3 and cardiovascular morbidity and mortality in people with Type 2 diabetes: a community-based cohort study2017In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 34, no 3, p. 372-379Article in journal (Refereed)
    Abstract [en]

    Aim We aimed to explore the association between vitamin D and cardiovascular morbidity and mortality in people with Type 2 diabetes recruited from a community-based study because there is limited and inconsistent research of this group. Methods A prospective community-based cohort study among people aged 55-66 years with Type 2 diabetes as part of The Cardiovascular Risk in Type 2 Diabetes -A Prospective Study in Primary Care (CARDIPP). We analysed serum 25-hydroxyvitamin D-3 [25(OH)D-3] at baseline. Cox regression analyses were used to calculate hazard ratios (HR) for the first myocardial infarction, stroke or cardiovascular mortality according to 25(OH)D-3. Results We examined 698 people with a mean follow-up of 7.3 years. Serum 25(OH)D-3 was inversely associated with the risk of cardiovascular morbidity and mortality: HR 0.98 [95% confidence interval (CI) 0.96 to 0.99, P = 0.001]. Compared with the fourth quartile (Q4) [25(OH)D-3 amp;gt; 61.8 nmol/l], HR (with 95% CI) was 3.46 (1.60 to 7.47) in Q1 [25(OH)D-3 amp;lt; 35.5 nmol/l] (P = 0.002); 2.26 (1.01 to 5.06) in Q2 [25(OH)D-3 35.5-47.5 nmol/l] (P = 0.047); and 1.62 (0.70 to 3.76) in Q3 [25(OH)D-3 47.5-61.8 nmol/l] (P = 0.26) when adjusting for age, sex and season. The results remained significant after adjusting also for cardiovascular risk factors, physiological variables including parathyroid hormone and previous cardiovascular disease (P = 0.027). Conclusions Low 25(OH)D-3 is associated with an increased risk of cardiovascular morbidity and mortality in people with Type 2 diabetes independent of parathyroid hormone. Vitamin D could be considered as a prognostic factor. Future studies are needed to explore whether vitamin D deficiency is a modifiable risk factor in Type 2 diabetes.

  • 28.
    Samefors, Maria
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Scragg, Robert
    Univ Auckland, New Zealand.
    Nyström, Fredrik H
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Is there an association between serum 25(OH)D-3 and mental well-being in patients with type 2 diabetes? Results from a cohort study in primary care2020In: HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM, ISSN 1109-3099, Vol. 19, p. 361-367Article in journal (Refereed)
    Abstract [en]

    Purpose There are limited and inconsistent results on the correlation between vitamin D and mental health in patients with type 2 diabetes (T2D). Thus, our aim was to explore the association between vitamin D and mental well-being in a community-based sample of participants with T2D. Methods We analyzed serum 25-hydroxyvitamin D-3 (25(OH)D-3) in 698 patients with T2D at the baseline examination. The cohort was reinvestigated after 4 years. Data from SF-36 questionnaires measuring vitality and mental health at baseline and after 4 years were used for analyses. Results Serum 25(OH)D-3 was inversely associated with poor mental health at baseline (odds ratio (OR) for 10 nmol/l increase in 25(OH)D-3, 0.90 (95% confidence interval (CI) 0.83-0.96, p = 0.003)) but not at follow-up (p &gt; 0.05). Serum 25(OH)D-3 was not associated with vitality at baseline (p &gt; 0.05). At follow-up, there was an inverse association between 25(OH)D-3 and low vitality (OR for 10 nmol/l increase in 25(OH)D-3, 0.89 (95% CI 0.82-0.97, p = 0.009)) but not after adjustment. Conclusion We found an inverse association between 25(OH)D-3 and mental health in patients with T2D at baseline. We found no association between 25(OH)D-3 and vitality after adjustment. Future studies are needed to determine the association between vitamin D and mental well-being in patients with T2D.

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  • 29.
    Samefors, Maria
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Tengblad, A.
    Wetterhalsan, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Sunlight Exposure and Vitamin D Levels in Older People-An Intervention Study in Swedish Nursing Homes2020In: The Journal of Nutrition, Health & Aging, ISSN 1279-7707, E-ISSN 1760-4788, Vol. 24, p. 1047-1052Article in journal (Refereed)
    Abstract [en]

    Objectives Older people are recommended to take oral vitamin D supplements, but the main source of vitamin D is sunlight. Our aim was to explore whether active encouragement to spend time outdoors could increase the levels of serum 25-hydroxyvitamin D (25(OH)D) and increase the mental well-being of nursing home residents. Design A cluster randomized intervention trial. Setting Nursing homes in southern Sweden. Participants In total 40 people &gt;65 years. Intervention The intervention group was encouraged to go outside for 20-30 minutes between 11 a.m. and 3 p.m. every day for two months during the summer of 2018. Measurements We analyzed serum 25(OH)D before and after the summer. Data from SF-36 questionnaires measuring vitality and mental health were used for the analyses. Results In the intervention group, the baseline median (interquartile range (IQR)) of serum 25(OH)D was 42.5 (23.0) nmol/l and in the control group it was 52.0 (36.0) nmol/l. In the intervention group, the 25(OH)D levels increased significantly during the summer (p=0.011). In the control group, there was no significant change. The intervention group reported better self-perceived mental health after the summer compared to before the summer (p=0.015). In the control group, there was no difference in mental health. Conclusion Active encouragement to spend time outdoors during summertime improved the levels of serum 25(OH)D and self-perceived mental health significantly in older people in nursing homes and could complement or replace oral vitamin D supplementation in the summer.

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  • 30.
    Simona Chisalita, Ioana
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Endocrinology.
    Wijkman, Magnus
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Davidson, Lee Ti
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Spångeus, Anna
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Nyström, Fredrik H
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Toe brachial index predicts major acute cardiovascular events in patients with type 2 diabetes independently of arterial stiffness2020In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 161, article id 108040Article in journal (Refereed)
    Abstract [en]

    Objective: Our aim was to analyze the predictive value of toe brachial index (TBI) as a risk marker for future major adverse cardiovascular events (MACE) and all-cause mortality in patients with type 2 diabetes (T2D). Methods: TBI was measured in 741 patients with T2D in 2005-2008. Conventional risk factors for vascular disease as well as non-invasive measurements such as pulse-wave velocity (PWV) and intima-media thickness (IMT) of the carotid arteries were estimated. MACE was defined as cardiovascular death or hospitalization for non fatal myocardial infarction or non fatal stroke. Patients were followed for incidence of MACE using the national Swedish Cause of Death Registry and the Inpatient Register. Results: During the follow-up for a period of 9 years MACE occurred in 97 patients and 85 patients died. TBI tertile, 1 versus 3, was significantly related to MACE (HR 2.67, 95%CI 1.60-4.50; p &lt; 0.001) and to all-cause mortality (HR 1.98, 95%CI 1.16-3.83; p = 0.01). TBI tertile 1 as compared to TBI tertile 3 predicted MACE, but not all-cause mortality, independently of age, sex, diabetes duration and treatment, antihypertensive treatment, previous cardiovascular diseases, office systolic blood pressure, HbA1c, LDL cholesterol, estimated glomerular filtration rate, body mass index, current smoking PWV, IMT and carotid plaque presence (HR 3.39, 95%CI 1.53-7.51; p = 0.003 and HR 1.81, 95%CI 0.87-3.76; p = 0.1, respectively). Conclusions: Low TBI predicts an increased risk for MACE independently of arterial stiffness in patients with type 2 diabetes. Trial registration: Clinical Trials.gov number NCT 01049737. Registered January 14, 2010. (C) 2020 Elsevier B.V. All rights reserved.

  • 31.
    Sundstrom, Johan
    et al.
    Uppsala Univ, Sweden; Univ New South Wales, Australia.
    Lind, Lars
    Uppsala Univ, Sweden.
    Lampa, Erik
    Uppsala Univ, Sweden.
    Angeras, Oskar
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Bachus, Erasmus
    Lund Univ, Sweden.
    Bergstrom, Goran
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Carlberg, Bo
    Umea Univ, Sweden.
    Engstrom, Gunnar
    Lund Univ, Sweden.
    Engvall, Jan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Eriksson, Mats
    Karolinska Univ Hosp, Sweden.
    Gigante, Bruna
    Danderyd Hosp, Sweden; Danderyd Hosp, Sweden.
    Hagstrom, Emil
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Hjelmgren, Ola
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Jansson, Jan-Hakan
    Umea Univ, Sweden.
    Jernberg, Tomas
    Danderyd Hosp, Sweden.
    Mannila, Maria
    Karolinska Univ Hosp, Sweden.
    Nyström, Fredrik H
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.
    Oldgren, Jonas
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Persson, Margaretha
    Lund Univ, Sweden.
    Sandstrom, Anette
    Umea Univ, Sweden.
    Swahn, Eva
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Cardiology in Linköping.
    Soderberg, Stefan
    Umea Univ, Sweden.
    Toren, Kjell
    Univ Gothenburg, Sweden; Sahlgrenska Univ, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Rosengren, Annika
    Univ Gothenburg, Sweden; Sahlgrenska Univ, Sweden.
    Weight gain and blood pressure2020In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 38, no 3, p. 387-394Article in journal (Refereed)
    Abstract [en]

    Objective: Although the causality of the obesity--hypertension association is established, the potential for prevention is not. We hypothesized that weight gain between early adulthood and mid-life is associated with higher mid-life blood pressure. Methods: We investigated the hypothesis using a large contemporaneous population-based mid-life cohort of men and women aged 50-64 years. Recalled body weight at age 20 years was self-reported, and mid-life body weight and office blood pressures were measured in accordance with a detailed protocol. Results: On average, men had gained 14.9 (95% CI 14.6-15.2) kg of weight, and women 14.6 (95% CI 14.4-14.9) kg, between age 20 years and the mid-life examination, corresponding to 0.40 (95% CI 0.39-0.41) kg/year for men and women. Both weight at age 20 years and weight at the mid-life examination were associated with mid-life blood pressures. On average, a 10 kg weight increase between age 20 years and mid-life was associated with 2.2 (95% CI 0.9-3.5) mmHg higher systolic and 1.7 (95% CI 0.9-2.5) mmHg higher diastolic mid-life blood pressure in men, and 3.2 (2.5-4.0) mmHg higher systolic and 2.4 (1.9-2.9) mmHg higher diastolic mid-life blood pressure in women. Mid-life weight was more closely associated than weight at age 20 years with mid-life blood pressure. For a given mid-life weight, blood pressure was higher in persons with higher weight gain from age 20 years. Conclusion: In sum, weight gain between early adulthood and mid-life was associated with higher mid-life blood pressure. The magnitude of the association indicates a potentially great public health impact of strategies to prevent weight gain throughout adulthood.

  • 32.
    Toren, Kjell
    et al.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Schioler, Linus
    Univ Gothenburg, Sweden.
    Lindberg, Anne
    Umea Univ, Sweden.
    Andersson, Anders
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Behndig, Annelie F.
    Umea Univ, Sweden.
    Bergstrom, Goran
    Univ Gothenburg, Sweden.
    Blomberg, Anders
    Umea Univ, Sweden.
    Caidahl, Kenneth
    Karolinska Inst, Sweden.
    Engvall, Jan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Eriksson, Maria
    Karolinska Univ Hosp, Sweden.
    Hamrefors, Viktor
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Janson, Christer
    Uppsala Univ, Sweden.
    Kylhammar, David
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Lindberg, Eva
    Uppsala Univ, Sweden.
    Linden, Anders
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Malinovschi, Andrei
    Uppsala Univ, Sweden.
    Persson, Lennart
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Sandelin, Martin
    Uppsala Univ, Sweden.
    Strom, Jonas Eriksson
    Umea Univ, Sweden.
    Tanash, Hanan A.
    Lund Univ, Sweden.
    Vikgren, Jenny
    Sahlgrens Univ Hosp, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Wollmer, Per
    Lund Univ, Sweden.
    Skold, C. Magnus
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Chronic airflow limitation and its relation to respiratory symptoms among ever-smokers and never-smokers: a cross-sectional study2020In: BMJ OPEN RESPIRATORY RESEARCH, ISSN 2052-4439, Vol. 7, no 1, article id e000600Article in journal (Refereed)
    Abstract [en]

    Background The diagnosis of chronic obstructive pulmonary disease is based on the presence of persistent respiratory symptoms and chronic airflow limitation (CAL). CAL is based on the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1:FVC) after bronchodilation, and FEV1:FVC less than the fifth percentile is often used as a cut-off for CAL. The aim was to investigate if increasing percentiles of FEV1:FVC were associated withany respiratory symptom(cough with phlegm, dyspnoea or wheezing) in a general population sample of never-smokers and ever-smokers. Methods In a cross-sectional study comprising 15 128 adults (50-64 years), 7120 never-smokers and 8008 ever-smokers completed a respiratory questionnaire and performed FEV(1)and FVC after bronchodilation. We calculated theirz-scores for FEV1:FVC and defined the fifth percentile using the Global Lung Function Initiative (GLI) reference value, GLI(5)and increasing percentiles up to GLI(25). We analysed the associations between different strata of percentiles and prevalence ofany respiratory symptomusing multivariable logistic regression for estimation of OR. Results Among all subjects, regardless of smoking habits, the odds ofany respiratory symptomwere elevated up to the GLI(15-20)strata. Among never-smokers, the odds ofany respiratory symptomwere elevated at GLI(&lt;5)(OR 3.57, 95% CI 2.43 to 5.23) and at GLI(5-10)(OR 2.57, 95% CI 1.69 to 3.91), but not at higher percentiles. Among ever-smokers, the odds ofany respiratory symptomwere elevated from GLI(&lt;5)(OR 4.64, 95% CI 3.79 to 5.68) up to GLI(&gt;= 25)(OR 1.33, 95% CI 1.00 to 1.75). Conclusions The association between percentages of FEV1:FVC and respiratory symptoms differed depending on smoking history. Our results support a higher percentile cut-off for FEV1:FVC for never-smokers and, in particular, for ever-smokers.

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  • 33.
    Vavruch, Camilla
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nowak, C.
    Karolinska Inst, Sweden.
    Feldreich, T.
    Dalarna Univ, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Sundstrom, J.
    Uppsala Univ, Sweden.
    Soderberg, S.
    Umea Univ, Sweden.
    Lind, L.
    Uppsala Univ, Sweden.
    Nyström, Fredrik H
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum, Norrköping.
    Arnlov, J.
    Karolinska Inst, Sweden; Dalarna Univ, Sweden.
    Using proximity extension proteomics assay to discover novel biomarkers associated with circulating leptin levels in patients with type 2 diabetes2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 13097Article in journal (Refereed)
    Abstract [en]

    We aimed to discover novel associations between leptin and circulating proteins which could link leptin to the development of cardiovascular disease in patients with type 2 diabetes (T2DM). In a discovery phase, we investigated associations between 88 plasma proteins, assessed with a proximity extension assay, and plasma leptin in a cohort of middle-aged patients with T2DM. Associations passing the significance threshold of a False discovery rate of 5% (corresponding to p&lt;0.0017) were replicated in patients with T2DM in an independent cohort. We also investigated if proteins mediated the longitudinal association between plasma leptin and the incidence of major cardiovascular events (MACE). One protein, adipocyte fatty acid binding protein (A-FABP), was significantly associated with leptin in both the discovery phase [95% CI (0.06, 0.17) p=0.00002] and the replication cohort [95% CI (0.12, 0.39) p=0.0003]. Multiplicative interaction analyses in the two cohorts suggest a stronger association between A-FABP and leptin in men than in women. In longitudinal analyses, the association between leptin and MACE was slightly attenuated after adding A-FABP to the multivariate model. Our analysis identified a consistent association between leptin and A-FABP in two independent cohorts of patients with T2DM, particularly in men.Trial registration: ClinicalTrials.gov identifier NCT 01049737.

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  • 34.
    Walz, Lotta
    et al.
    Karolinska Inst, Sweden; MSD, Sweden.
    Jonsson, Anna K.
    Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, SE-58185 Linkoping, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, SE-58185 Linkoping, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Druid, Henrik
    Karolinska Inst, Sweden; Natl Board Forens Med, Dept Forens Med, SE-17177 Linkoping, Sweden.
    Metformin - Postmortem fatal and non-fatal reference concentrations in femoral blood and risk factors associated with fatal intoxications2019In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 303, article id 109935Article in journal (Refereed)
    Abstract [en]

    Background amp; objectives: To improve the interpretation of fatal intoxications by establishing fatal and non-fatal reference concentrations of metformin in postmortem femoral blood and to further evaluate risk factors associated with fatal metformin intoxication. Methods: All forensic autopsies in Sweden where metformin was detected in femoral blood 2011-2016 were identified in the National Board of Forensic Medicine databases (NFMD). The cases were classified as single substance intoxications, A (n = 22), multiple substance intoxications, B (N = 7) and postmortem controls, C (N = 13). The control group consisted of cases where metformin was detected, but the cause of death excluded the incapacitation by metformin or other substances. Strict inclusion criteria were used, and all postmortem cases were assessed by two independent reviewers. All other cases where the inclusion criteria of groups A-C where not met formed group O (N = 78). The forensic findings logged in the NFMD where linked to national registers whereby information on comorbidities, dispensed drugs and clinical data could be obtained. Results: The mean age was 66 +/- 10 years in the total study population and did not differ between the groups. The proportion of men was 64% in group A, 71% in B, 77% in C and 74% in group O. The median values of metformin in group A (48.5 mu g/g; range 13.0-210 mu g/g) and B (21.0 mu g/g; range 4.40-95.0 mu g/g) were significantly (p amp;lt; 0.001 and p = 0.015 respectively) higher than those of the control group C (2.30 mu g/g; range 0.70-21.0 mu g/g). The median concentration of metformin in group A and B was also significantly higher than in group O (4.60 mg/g; range 0.64-54.0 mu g/g) (p amp;lt; 0.001 and p = 0.040 respectively). The results suggest that intoxication with metformin as a cause of death should be considered when the postmortem femoral blood level exceeds about 10 mg/g, although higher levels may be seen in postmortem in cases without incapacitation. The metformin intoxication was confirmed to be intentional in 23% (n = 5) of the single intoxications. Underlying factors identified as important for the remaining fatal metformin intoxications included living alone, any contraindication for the use of metformin, known alcohol abuse and a history of stroke or cardiovascular disease. Conclusions: The reported post mortem femoral blood concentrations of metformin can hopefully contribute to a better interpretation of results in suspected poisonings and obscure cases. Living in a single household, history of cardiovascular disease and contraindications, predominantly alcohol abuse, were associated with fatal metformin intoxication. (C) 2019 Elsevier B.V. All rights reserved.

  • 35.
    Westerlind, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Department of Geriatrics, County Hospital Ryhov, Region Jönköping County, Jönköping, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Midlöv, P.
    Department of Clinical Sciences in Malmö, Center for Primary Health Care Research, Lund University, Malmö, Sweden.
    Marcusson, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine and Geriatrics.
    Diagnostic Failure of Cognitive Impairment in Nursing Home Residents May Lead to Impaired Medical Care2019In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 47, no 4-6, p. 209-218Article in journal (Refereed)
    Abstract [en]

    Background/Objectives: Dementia and cognitive impairment are common in nursing homes. Few studies have studied the impact of unnoted cognitive impairment on medical care. This study aimed to estimate the prevalence of diagnostic failure of cognitive impairment in a sample of Swedish nursing home residents and to analyze whether diagnostic failure was associated with impaired medical care. 

    Method: A total of 428 nursing home residents were investigated during 2008–2011. Subjects without dementia diagnosis were grouped by result of the Mini Mental State Examination (MMSE), where subjects with <24 points formed a possible dementia group and the remaining subjects a control group. A third group consisted of subjects with diagnosed dementia. These three groups were compared according to baseline data, laboratory findings, drug use, and mortality. 

    Results: Dementia was previously diagnosed in 181 subjects (42%). Among subjects without a dementia diagnosis, 72% were cognitively impaired with possible dementia (MMSE <24). These subjects were significantly older, did not get anti-dementia treatment, and had higher levels of brain natriuretic peptide compared to the diagnosed dementia group, but the risks of malnutrition and pressure ulcers were similar to the dementia group. 

    Conclusions: Unnoted cognitive impairment is common in nursing home residents and may conceal other potentially treatable conditions such as heart failure. The results highlight a need to pay increased attention to cognitive impairment among nursing home residents.

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  • 36.
    Westerlind, Björn
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Department of Geriatrics, County Hospital Ryhov, Jönköping, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Mölstad, Sigvard
    Department of Clinical Sciences in Malmö, Center for Primary Health Care Research, Lund University, Malmö, Sweden.
    Midlöv, Patrik
    Department of Clinical Sciences in Malmö, Center for Primary Health Care Research, Lund University, Malmö, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Futurum, Jönköping, Sweden.
    Use of non-benzodiazepine hypnotics is associated with falls in nursing home residents: a longitudinal cohort study2019In: Aging Clinical and Experimental Research, ISSN 1594-0667, E-ISSN 1720-8319, Vol. 31, no 8, p. 1078-1095Article in journal (Refereed)
    Abstract [en]

    Background

    Falls and related injuries are common among older people, and several drug classes are considered to increase fall risk.

    Aims

    This study aimed to investigate the association between the use of certain drug classes and falls in older nursing home residents in Sweden, and relate these to different age groups.

    Methods

    Information on falls that occurred in the previous year and regular use of possible fall risk drugs including non-benzodiazepine hypnotics (zopiclone and zolpidem) was collected from 331 nursing home residents during 2008–2011. Over the following 6 months, the occurrence of serious falls, requiring a physician visit or hospital care, was registered. Association between serious falls and drug use was compared between an older (≥ 85 years) and a younger group.

    Results

    An increased fall risk (Downton Fall Risk Index ≥ 3) was found in 93% of the study subjects (aged 65–101 years). Baseline data indicated an association between falls that occurred in the previous year and regular use of non-benzodiazepine hypnotics (p = 0.005), but not with the other studied drug classes. During the following 6 months, an association between use of non-benzodiazepine hypnotics and serious falls in the older group (p = 0.017, odds ratio 4.311) was found. No association was found between the other studied drug classes and serious falls.

    Discussion

    These results indicate an association between falls and the use of non-benzodiazepine hypnotics, compounds that previously have been considered generally well-tolerated in older people.

    Conclusions

    Caution is advocated when using non-benzodiazepine hypnotics regularly in older people living in nursing homes.

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  • 37.
    Wuopio, Jonas
    et al.
    Mora Cty Hosp, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lind, Lars
    Uppsala Univ, Sweden.
    Ruge, Toralph
    Karolinska Univ Hosp, Sweden.
    Carlsson, Axel C.
    Karolinska Inst, Sweden.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Arnlov, Johan
    Karolinska Inst, Sweden; Dalarna Univ, Sweden.
    The association between circulating endostatin and a disturbed circadian blood pressure pattern in patients with type 2 diabetes2018In: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 27, no 4, p. 215-221Article in journal (Refereed)
    Abstract [en]

    Background: Endostatin, cleaved from collagen XVIII in the extracellular matrix, is a promising circulating biomarker for cardiovascular damage. It possesses anti-angiogenic and anti-fibrotic functions and has even been suggested to be involved in blood pressure regulation. Less is known if endostatin levels relate to circadian blood pressure patterns. In the present paper we studied the association between circulating levels of endostatin and nocturnal dipping in blood pressure.Methods: We used the CARDIPP-study, a cohort of middle aged, type 2 diabetics (n=593, 32% women), with data on both 24-hour and office blood pressure, serum-endostatin, cardiovascular risk factors, and incident major cardiovascular events. Nocturnal dipping was defined as a amp;gt;10% difference between day- and night-time blood pressures.Results: Two-hundred four participants (34%) were classified as non-dippers. The mean endostatin levels were significantly higher in non-dippers compared to dippers (meanstandard deviation: 62.6 +/- 1.8 mu g/l vs. 58.7 +/- 1.6 mu g/l, respectively, p=.007). Higher serum levels of endostatin were associated with a diminished decline in nocturnal blood pressure adjusted for age, sex, HbA1c, mean systolic day blood pressure, hypertension treatment, glomerular filtration rate, and prevalent cardiovascular disease (regression coefficient per SD increase of endostatin -0.01, 95% CI, -0.02-(-0.001), p=.03). Structural equation modelling analyses suggest that endostatin mediates 7% of the association between non-dipping and major cardiovascular events.Conclusion: We found an independent association between higher circulating levels of endostatin and a reduced difference between day- and night-time systolic blood pressure in patients with type 2 diabetes. Yet endostatin mediated only a small portion of the association between non-dipping and cardiovascular events arguing against a clinical utility of our findings.

  • 38.
    Zhou, Zien
    et al.
    Univ New South Wales, Australia; Shanghai Jiao Tong Univ, Peoples R China.
    Lindley, Richard I.
    George Inst Global Hlth, Australia; Univ Sydney, Australia.
    Rådholm, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög. George Inst Global Hlth, Australia; Univ Sydney, Australia.
    Jenkins, Bronwyn
    Royal North Shore Hosp, Australia.
    Watson, John
    Univ New South Wales, Australia.
    Perkovic, Vlado
    Univ New South Wales, Australia; Univ Sydney, Australia; Royal North Shore Hosp, Australia.
    Mahaffey, Kenneth W.
    Stanford Univ, CA 94305 USA.
    de Zeeuw, Dick
    Univ Groningen, Netherlands.
    Fulcher, Greg
    Univ Sydney, Australia; Royal North Shore Hosp, Australia.
    Shaw, Wayne
    Janssen Res and Dev LLC, NJ USA.
    Oh, Richard
    Janssen Res and Dev LLC, NJ USA.
    Desai, Mehul
    Janssen Res and Dev LLC, NJ USA.
    Matthews, David R.
    Univ Oxford, England; Univ Oxford, England.
    Neal, Bruce
    Univ New South Wales, Australia; Univ New South Wales, Australia; Univ Sydney, Australia; Imperial Coll London, England.
    Canagliflozin and Stroke in Type 2 Diabetes Mellitus Results From the Randomized CANVAS Program Trials2019In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 50, no 2, p. 396-404Article in journal (Refereed)
    Abstract [en]

    Background and Purpose-This study reports the detailed effects of canagliflozin on stroke, stroke subtypes, and vascular outcomes in participants with and without cerebrovascular disease (stroke or transient ischemic attack) at baseline from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program. Methods-The CANVAS Program, comprising 2 similarly designed and conducted clinical trials, randomly assigned 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk to canagliflozin or placebo. Its primary outcome was a composite of major adverse cardiovascular events. The main outcome of interest for this report was fatal or nonfatal stroke. Additional exploratory outcomes were stroke subtypes and other vascular outcomes defined according to standard criteria. Results-There were 1 958 (19%) participants with prior stroke or transient ischemic attack at baseline. These individuals were older, more frequently women, and had higher rates of heart failure, atrial fibrillation, and microvascular disease (all Pamp;lt;0.001) compared with those without such a history. There were 309 participants with stroke events during followup (123 had prior stroke or transient ischemic attack at baseline and 186 did not), at a rate of 7.93/1000 patient-years among those assigned canagliflozin and 9.62/1000 patient-years among placebo (hazard ratio, 0.87; 95% CI, 0.691.09). Analysis of stroke subtypes found no effect on ischemic stroke (n=253, hazard ratio, 0.95; 95% CI, 0.74-1.22), a significant reduction for hemorrhagic stroke (n=30, hazard ratio, 0.43; 95% CI, 0.20-0.89) and no effect on undetermined stroke (n=29, hazard ratio, 1.04; 95% CI, 0.48-2.22). Effects on other cardiovascular outcomes were comparable among participants with and without stroke or transient ischemic attack at baseline. Conclusions-There were too few events in the CANVAS Program to separately define the effects of canagliflozin on stroke, but benefit is more likely than harm. The observed possible protective effect for hemorrhagic stroke was based on small numbers but warrants further investigation.

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