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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
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    Ny era inom terapin för typ 2-diabetes – men vad är nytt?: Metformin fortfarande förstahandsval, men därefter rekommenderas att behandlingen individualiseras2018Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115Artikel i tidskrift (Refereegranskat)
    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
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    Sundrom, Johan
    Uppsala Univ, Sweden.
    Prognostic impact of systolic blood pressure variability in people with diabetes2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 4, artikel-id e0194084Artikel i tidskrift (Refereegranskat)
    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.

  • 3.
    Blomstrand, Peter
    et al.
    Cty Hosp Ryhov, Sweden; Jonkoping Univ, Sweden.
    Sjöblom, Peter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Nilsson, Mats
    Acad Hlth and Care, Sweden.
    Wijkman, Magnus
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i östra Östergötland, Medicinkliniken ViN.
    Engvall, Martin
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Länne, Toste
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Nyström, Fredrik H
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    Engvall, Jan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain2018Ingår i: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 17, artikel-id 113Artikel i tidskrift (Refereegranskat)
    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.

  • 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
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    Midlov, Patrik
    Lund University, Sweden.
    Risk factors and consequences of decreased kidney function in nursing home residents: A longitudinal study2017Ingår i: Geriatrics & Gerontology International, ISSN 1444-1586, E-ISSN 1447-0594, Vol. 17, nr 5, s. 791-797Artikel i tidskrift (Refereegranskat)
    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
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    Nyström, Fredrik H
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Cityhälsan Centrum, Norrköping.
    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 approach2019Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967Artikel i tidskrift (Refereegranskat)
    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
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen 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 protocol2018Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 8, nr 1, artikel-id e019463Artikel i tidskrift (Refereegranskat)
    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.

  • 7.
    Figtree, Gemma A.
    et al.
    Royal North Shore Hosp, Australia; Univ Sydney, Australia; Univ New South Wales, Australia.
    Rådholm, Karin
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen 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 Fraction2019Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, nr 22, s. 2591-2593Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 8.
    Figtree, Gemma A.
    et al.
    Royal North Shore Hosp, Australia; Univ Sydney, Australia; Univ New South Wales, Australia.
    Rådholm, Karin
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen 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)"2019Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, nr 3, s. 418-419Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 9.
    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
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen 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 trial2019Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, nr 2, artikel-id e022637Artikel i tidskrift (Refereegranskat)
    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.

  • 10.
    Jonasson, Hanna
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Bergstrand, Sara
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten.
    Nyström, Fredrik H
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Länne, Toste
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    Bjarnegård, Niclas
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Fredriksson, Ingemar
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Perimed AB, Sweden.
    Larsson, Marcus
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Strömberg, Tomas
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Skin microvascular endothelial dysfunction is associated with type 2 diabetes independently of microalbuminuria and arterial stiffness2017Ingår i: Diabetes & Vascular Disease Research, ISSN 1479-1641, E-ISSN 1752-8984, Vol. 14, nr 4, s. 363-371, artikel-id UNSP 1479164117707706Artikel i tidskrift (Refereegranskat)
    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.

  • 11.
    Jonasson, Hanna
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Fredriksson, Ingemar
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Perimed AB, Järfälla, Stockholm, Sweden.
    Bergstrand, Sara
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    Larsson, Marcus
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Strömberg, Tomas
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    In vivo characterization of light scattering properties of human skin in the 475- to 850-nm wavelength range in a Swedish cohort2018Ingår i: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 23, nr 12, artikel-id 121608Artikel i tidskrift (Refereegranskat)
    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.

  • 12.
    Jones, Alexandra
    et al.
    George Inst Global Hlth, Australia; Univ Sydney, Australia.
    Rådholm, Karin
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen 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 System2018Ingår i: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, nr 4, artikel-id 501Artikel i tidskrift (Refereegranskat)
    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.

  • 13.
    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
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen 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 practice2017Ingår i: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 11, nr 2, s. 184-192Artikel i tidskrift (Refereegranskat)
    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.

  • 14.
    Karlsson, Lars
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Erixon, Hanna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Ebbers, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Bolger, Ann
    Univ Calif San Francisco, CA USA.
    Carlhäll, Carljohan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Post-cardioversion Improvement in LV Function Defined by 4D Flow Patterns and Energetics in Patients With Atrial Fibrillation2019Ingår i: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, artikel-id 659Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Atrial fibrillation (AF) is a prevalent cause of cardiovascular morbidity, including thromboembolism and heart failure. Left ventricular dysfunction (LVD) detected in AF patients may be either precursor or consequence of the arrythmia. Successful cardioversion of chronic AF is often followed by a transient period of left atrial (LA) stunning, where depressed mechanical atrial contraction persists despite reinstitution of sinus rhythm. To determine if AF-associated LVD would improve with resolution of LA dysfunction, AF patients were examined immediately and 4 weeks after cardioversion to sinus rhythm. 4D flow cardiovascular magnetic resonance (CMR) assesses ventricular function according to the volumes and energetics of functional components of the LV volume. Previously, described 4D CMR markers of LVD include decreased volume and end-diastolic kinetic energy (KE) of the Direct flow, which is the portion of LV volume that passes directly from inflow to outflow in a single cycle. We hypothesize that impaired LV flow patterns and energetics will be found immediately after cardioversion during atrial stunning, and that those parameters will improve as atrial function returns. Methods: Ten patients with a history of AF underwent CMR 2-3 h (Time-1) and 4 weeks (time-2), following electrical cardioversion to sinus rhythm. 4D phase-contrast velocity data and morphological images were acquired at a 3T CMR system. Using a previously evaluated method, pathlines were emitted from the LV end diastolic volume (LVEDV) and traced forward and backward in time until end-systole. The LVEDV was automatically separated into four functional flow components whose volume and KE were calculated. Results: Left atrial fractional area change increased over the follow-up period (P = 0.001), indicating recovery of LA mechanical function. LVEF increased between Time-1 and Time-2 (P = 0.003); LVEDVI did not change (P = 0.319). Over that interval, the ratios of Direct flow/LVEDV volume and KE increased (P = 0.001 and P = 0.003, respectively), while the ratios of Residual volume/LVEDV volume and KE decreased (P = 0.001 and P = 0.005, respectively). Conclusion: Post-cardioversion recovery of LA function was associated with improvements in conventional and 4D CMR markers of LV function. Flow-specific measures demonstrate the negative but potentially reversible impact of LA dysfunction on volume and energetic aspects of LV function.

  • 15.
    Nowak, Christoph
    et al.
    Karolinska Inst, Sweden.
    Carlsson, Axel C.
    Karolinska Inst, Sweden; Uppsala Univ, Sweden.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    Nyström, Fredrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    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 diabetes2018Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, nr 8, s. 1748-1757Artikel i tidskrift (Refereegranskat)
    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.

  • 16.
    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
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen 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 register2019Ingår i: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 150, s. 174-183Artikel i tidskrift (Refereegranskat)
    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.

  • 17.
    Rådholm, Karin
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen 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 study2018Ingår i: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 20, nr 8, s. 1903-1910Artikel i tidskrift (Refereegranskat)
    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.

  • 18.
    Rådholm, Karin
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen 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 Program2018Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 138, nr 5, s. 458-468Artikel i tidskrift (Refereegranskat)
    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.

  • 19.
    Rådholm, Karin
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i västra Östergötland, Primärvården i västra länsdelen.
    Tengblad, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i västra Östergötland, Primärvården i västra länsdelen.
    Dahlén, Elsa
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i västra Östergötland, Primärvården i västra länsdelen.
    Länne, Toste
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Engvall, Jan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Nyström, Fredrik H
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    The impact of using sagittal abdominal diameter to predict major cardiovascular events in European patients with type 2 diabetes2017Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases, ISSN 0939-4753, E-ISSN 1590-3729, Vol. 27, nr 5, s. 418-422Artikel i tidskrift (Refereegranskat)
    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.

  • 20.
    Rådholm, Karin
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen 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 review2018Ingår i: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 140, s. 118-128Artikel, forskningsöversikt (Refereegranskat)
    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.

  • 21.
    Rådholm, Karin
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög. Univ New South Wales, Australia.
    Zhou, Zien
    Univ New South Wales, Australia; Shanghai Jiao Tong Univ, Peoples R China.
    Clemens, Kristin
    Western Univ, Canada; Western Univ, Canada; Lawson Hlth Res Inst, Canada.
    Neal, Bruce
    Univ New South Wales, Australia; Univ New South Wales, Australia; Imperial Coll London, England.
    Woodward, Mark
    Univ New South Wales, Australia; Univ Oxford, England; Johns Hopkins Univ, MD USA.
    Effects of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes in women versus men2019Ingår i: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sodium-glucose co-transporter-2 (SGLT2) inhibitors prevent cardiovascular complications in type 2 diabetes. We aimed to study whether they have similar effects in women and men by summarizing the effects of SGLT2 inhibitors compared to placebo on vascular and safety outcomes stratified by sex. We included patients with type 2 diabetes enrolled in the EMPA-REG OUTCOME, CANVAS Program, DECLARE TIMI-58 and CREDENCE trials. There were no differences in the risk ratios between men and women, SGLT2 versus control (placebo), for vascular efficacy outcomes or death (all P for interaction amp;gt;=.12), with clear protection shown against major adverse cardiovascular events, heart failure, vascular death and total mortality. SGLT2 inhibitor treatment was also associated with similar relative risks in women and men for the safety outcomes of amputation, fracture, genital infection and urinary tract infection (all P for interaction amp;gt;=.17). SGLT2 inhibition provided similar protection against vascular risks and death, and similar risks of serious adverse events, for women and men.

  • 22.
    Sabale, Ugne
    et al.
    AstraZeneca Nordic Balt, Sweden.
    Bodegard, Johan
    AstraZeneca Nordic Balt, Sweden.
    Svennblad, Bodil
    Uppsala University, Sweden.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    Johansson, Gunnar
    Uppsala University, Sweden.
    Ekman, Mattias
    AstraZeneca Nordic Balt, Sweden.
    Henriksson, Martin
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Nilsson, Peter
    Lund University, Sweden.
    Weight change patterns and healthcare costs in patients with newly-diagnosed type-2 diabetes in Sweden2017Ingår i: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 11, nr 3, s. 217-225Artikel i tidskrift (Refereegranskat)
    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.

  • 23.
    Samefors, Maria
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Scragg, R.
    University of Auckland, New Zealand.
    Länne, Toste
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Nyström, Fredrik H
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    Association between serum 25(OH)D-3 and cardiovascular morbidity and mortality in people with Type 2 diabetes: a community-based cohort study2017Ingår i: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 34, nr 3, s. 372-379Artikel i tidskrift (Refereegranskat)
    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.

  • 24.
    Stoll, Victoria M.
    et al.
    Univ Oxford, England.
    Hess, Aaron T.
    Univ Oxford, England.
    Rodgers, Christopher T.
    Univ Oxford, England; Univ Cambridge, England.
    Bissell, Malenka M.
    Univ Oxford, England.
    Dyverfeldt, Petter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Ebbers, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Myerson, Saul G.
    Univ Oxford, England.
    Carlhäll, Carljohan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Neubauer, Stefan
    Univ Oxford, England.
    Left Ventricular Flow Analysis Novel Imaging Biomarkers and Predictors of Exercise Capacity in Heart Failure2019Ingår i: Circulation Cardiovascular Imaging, ISSN 1941-9651, E-ISSN 1942-0080, Vol. 12, nr 5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Cardiac remodeling, after a myocardial insult, often causes progression to heart failure. The relationship between alterations in left ventricular blood flow, including kinetic energy (KE), and remodeling is uncertain. We hypothesized that increasing derangements in left ventricular blood flow would relate to (1) conventional cardiac remodeling markers, (2) increased levels of biochemical remodeling markers, (3) altered cardiac energetics, and (4) worsening patient symptoms and functional capacity. Methods: Thirty-four dilated cardiomyopathy patients, 30 ischemic cardiomyopathy patients, and 36 controls underwent magnetic resonance including 4-dimensional flow, BNP (brain-type natriuretic peptide) measurement, functional capacity assessment (6-minute walk test), and symptom quantification. A subgroup of dilated cardiomyopathy and control subjects underwent cardiac energetic assessment. Left ventricular flow was separated into 4 components: direct flow, retained inflow, delayed ejection flow, and residual volume. Average KE throughout the cardiac cycle was calculated. Results: Patients had reduced direct flow proportion and direct-flow average KE compared with controls (Pamp;lt;0.0001). The residual volume proportion and residual volume average KE were increased in patients (Pamp;lt;0.0001). Importantly, in a multiple linear regression model to predict the patients 6-minute walk test, the independent predictors were age (beta=-0.3015; P=0.019) and direct-flow average KE (beta=0.280, P=0.035; R-2 model, 0.466, P=0.002). In contrast, neither ejection fraction nor left ventricular volumes were independently predictive. Conclusions: This study demonstrates an independent predictive relationship between the direct-flow average KE and a prognostic measure of functional capacity. Intracardiac 4-dimensional flow parameters are novel biomarkers in heart failure and may provide additive value in monitoring new therapies and predicting prognosis.

  • 25.
    Viola, Frederica
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Dyverfeldt, Petter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Carlhäll, Carljohan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Ebbers, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Data Quality and Optimal Background Correction Order of Respiratory-Gated k-Space Segmented Spoiled Gradient Echo (SGRE) and Echo Planar Imaging (EPI)-Based 4D Flow MRI2019Ingår i: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background A reduction in scan time of 4D Flow MRI would facilitate clinical application. A recent study indicates that echo-planar imaging (EPI) 4D Flow MRI allows for a reduction in scan time and better data quality than the recommended k-space segmented spoiled gradient echo (SGRE) sequence. It was argued that the poor data quality of SGRE was related to the nonrecommended absence of respiratory motion compensation. However, data quality can also be affected by the background offset compensation. Purpose To compare the data quality of respiratory motion-compensated SGRE and EPI 4D Flow MRI and their dependence on background correction (BC) order. Study Type Retrospective. Subjects Eighteen healthy subjects (eight female, mean age 32 +/- 5 years). Field Strength and Sequence 5T. SGRE and EPI-based 4D Flow MRI. Assessment Data quality was investigated visually and by comparing flows through the cardiac valves and aorta. Measurements were obtained from transvalvular flow and pathline analysis. Statistical Tests Linear regression and Bland-Altman analysis were used. Wilcoxon test was used for comparison of visual scoring. Students t-test was used for comparison of flow volumes. Results No significant difference was found by visual inspection (P = 0.08). Left ventricular (LV) flows were strongly and very strongly associated with SGRE and EPI, respectively (R-2 = 0.86-0.94 SGRE; 0.71-0.79 EPI, BC0-4). LV and right ventricular (RV) outflows and LV pathline flows were very strongly associated (R-2 = 0.93-0.95 SGRE; 0.88-0.91 EPI, R-2 = 0.91-0.95 SGRE; 0.91-0.93 EPI, BC1-4). EPI LV outflow was lower than the short-axis-based stroke volume. EPI RV outflow and proximal descending aortic flow were lower than SGREs. Data Conclusion Both sequences yielded good internal data consistency when an adequate background correction was applied. Second and first BC order were considered sufficient for transvalvular flow analysis in SGRE and EPI, respectively. Higher BC orders were preferred for particle tracing. Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2019.

  • 26.
    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
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, SE-58185 Linkoping, Sweden.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen 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 intoxications2019Ingår i: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 303, artikel-id 109935Artikel i tidskrift (Refereegranskat)
    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.

  • 27.
    Westerlind, Björn
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Department of Geriatrics, County Hospital Ryhov, Region Jönköping County, Jönköping, Sweden.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    Midlöv, P.
    Department of Clinical Sciences in Malmö, Center for Primary Health Care Research, Lund University, Malmö, Sweden.
    Marcusson, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Medicinska och geriatriska akutkliniken.
    Diagnostic Failure of Cognitive Impairment in Nursing Home Residents May Lead to Impaired Medical Care2019Ingår i: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 47, nr 4-6, s. 209-218Artikel i tidskrift (Refereegranskat)
    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.

  • 28.
    Westerlind, Björn
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Department of Geriatrics, County Hospital Ryhov, Jönköping, Sweden.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen 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
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi. Futurum, Jönköping, Sweden.
    Use of non-benzodiazepine hypnotics is associated with falls in nursing home residents: a longitudinal cohort study2019Ingår i: Aging Clinical and Experimental Research, ISSN 1594-0667, E-ISSN 1720-8319, Vol. 31, nr 8, s. 1078-1095Artikel i tidskrift (Refereegranskat)
    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.

  • 29.
    Wuopio, Jonas
    et al.
    Mora Cty Hosp, Sweden.
    Östgren, Carl Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög.
    Länne, Toste
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, 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
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    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 diabetes2018Ingår i: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 27, nr 4, s. 215-221Artikel i tidskrift (Refereegranskat)
    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.

  • 30.
    Zhong, Liang
    et al.
    Natl Heart Ctr Singapore, Singapore; Natl Univ Singapore, Singapore.
    Schrauben, Eric M.
    Hosp Sick Children, Canada.
    Garcia, Julio
    Univ Calgary, Canada.
    Uribe, Sergio
    Pontificia Univ Catolica Chile, Chile.
    Grieve, Stuart M.
    Univ Sydney, Australia; Royal Prince Alfred Hosp, Australia.
    Elbaz, Mohammed S. M.
    Northwestern Univ, IL 60611 USA.
    Barker, Alex J.
    Univ Colorado, CO 80202 USA.
    Geiger, Julia
    Univ Childrens Hosp Zurich, Switzerland.
    Nordmeyer, Sarah
    German Heart Ctr, Germany; Charite, Germany.
    Marsden, Alison
    Stanford Univ, CA 94305 USA.
    Carlsson, Marcus
    Lund Univ, Sweden.
    Tan, Ru-San
    Natl Heart Ctr Singapore, Singapore; Natl Univ Singapore, Singapore.
    Garg, Pankaj
    Univ Sheffield, England.
    Westenberg, Jos J. M.
    Leiden Univ, Netherlands.
    Markl, Michael
    Northwestern Univ, IL 60611 USA.
    Ebbers, Tino
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Ödeshög. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Intracardiac 4D Flow MRI in Congenital Heart Disease: Recommendations on Behalf of the ISMRM Flow & Motion Study Group2019Ingår i: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019.

  • 31.
    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
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen 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 Trials2019Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 50, nr 2, s. 396-404Artikel i tidskrift (Refereegranskat)
    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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