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  • 1.
    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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Sundrom, Johan
    Uppsala Univ, Sweden.
    Prognostic impact of systolic blood pressure variability in people with diabetes2018In: PLoS ONE, ISSN 1932-6203, 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.

  • 2.
    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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    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.

  • 3.
    Carlsson, Axel C.
    et al.
    Karolinska Institute, Sweden; 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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    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. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jennersjö, Pär
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine.
    Larsson, Anders
    Uppsala University, Sweden.
    Arnlov, Johan
    Uppsala University, Sweden; Dalarna University,Falun Sweden.
    Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes2016In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 15, no 1, p. 40-Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease. Methods: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used. Results: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p < 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p < 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality. Conclusions/Interpretations: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.

  • 4.
    Carlsson, Axel Carl
    et al.
    Division of Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, 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, 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.
    Larsson, Anders
    Department of Medical Sciences, Uppsala University, Uppsala, 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.
    Ärnlöv, Johan
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
    The association between endostatin and kidney disease and mortality in patients with type 2 diabetes2016In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 42, no 5, p. 351-357Article in journal (Refereed)
    Abstract [en]

    AIM: Circulating endostatin, a biologically active derivate of collagen XVIII, is considered to be a marker of kidney disease and a risk factor for its related mortality. However, less is known of the role of endostatin in diabetes and the development of diabetic nephropathy. For this reason, our study investigated the associations between circulating endostatin and the prevalence and progression of kidney disease, and its mortality risk in patients with type 2 diabetes (T2D).

    METHODS: This was a cohort study of 607 patients with T2D (mean age: 61 years, 44% women). Estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was used to assess the patients' kidney function decline and mortality.

    RESULTS: Of the total study cohort, 20 patients declined by ≥20% in eGFR over 4 years, and 44 died during the follow-up (mean duration: 6.7 years). At baseline, participants with diabetic nephropathy (defined as eGFR<60mL/min/1.73m(2)) and/or microalbuminuria [defined as a urinary albumin-to-creatinine ratio (ACR)>3g/mol] had higher median levels of endostatin than those without nephropathy (62.7μg/L vs 57.4μg/L, respectively; P=0.031). In longitudinal analyses adjusted for age, gender, baseline eGFR and ACR, higher endostatin levels were associated with a higher risk of decline (≥20% in eGFR, OR per 1 SD increase: 1.73, 95% CI: 1.13-2.65) and a higher risk of mortality (HR per 1 SD increase: 1.57, 95% CI: 1.19-2.07).

    CONCLUSION: In patients with T2D, circulating endostatin levels can predict the progression of kidney disease and mortality independently of established kidney disease markers. The clinical usefulness of endostatin as a risk marker in such patients merits further studies.

  • 5.
    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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    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, ISSN 2044-6055, 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.

  • 6.
    Ingves, Simon
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Vilhelmsson, Nathalie
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ström, Edvin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Guldbrand, Hans
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    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.
    A randomized cross-over study of the effects of macronutrient composition and meal frequency on GLP-1, ghrelin and energy expenditure in humans2017In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 93, p. 20-26Article in journal (Refereed)
    Abstract [en]

    Objective: Little is known about human postprandial increase of energy expenditure and satiety-associated hormones in relation to both meal frequency and macronutrient composition. Design: Randomized cross-over study with four conditions for each participant. Methods: Seven men and seven women (mean age 23 +/- 1.5 years) were randomly assigned to the order of intake of a 750 kcal drink with the same protein content while having either 20 energy-percent (E%) or 55 E% from carbohydrates and the remaining energy from fat. Participants were also randomized to consume the drinks as one large beverage or as five 150 kcal portions every 30 min, starting in the fasting state in the morning. Energy expenditure (EE) was determined every 30 min by indirect calorimetry. Hormonal responses and suppression of hunger (by visual-analogue scales) were also studied. A p amp;lt; 0.013 was considered statistically significant following Bonferroni-correction. Results: The area under the curve (AUC) for EE was higher during the 2.5 h after the high-carbohydrate drinks (p = 0.005 by Wilcoxon) and also after ingesting one drink compared with five (p = 0.004). AUC for serum active GLP-1 was higher after single drinks compared with five beverages (p = 0.002). Although GLP-1 levels remained particularly high at the end of the test during the low-carbohydrate meals, the AUC did not differ compared with the high-carbohydrate occasions (low-carbohydrate: 58.9 +/- 18 pg/ml/h, high-carbohydrate: 45.2 +/- 16 pg/ml/h, p = 0.028). Hunger sensations were suppressed more after single beverages compared with five small drinks (p = 0.009). Conclusions: We found higher EE during 2.5 h following one large drink compared with five smaller beverages. Since hunger was also suppressed more efficiently, and serum GLP-1 levels were higher after one compared with five smaller drinks, our findings do not support nibbling to avoid hunger or to keep up EE from morning to noon.

  • 7.
    Jansson, S. P. O.
    et al.
    University of Örebro, Sweden.
    Fall, K.
    University of Örebro, Sweden.
    Brus, O.
    University of Örebro, Sweden.
    Magnuson, A.
    University of Örebro, Sweden.
    Wandell, P.
    Karolinska Institute, 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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Rolandsson, O.
    Umeå University, Sweden.
    Letter: Response to Carlsson et al.: Prevalence and incidence of diabetes mellitus: a nationwide population-based pharmaco-epidemiological study in Sweden in DIABETIC MEDICINE, vol 33, issue 8, pp 1150-11522016In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 33, no 8, p. 1150-1152Article in journal (Other academic)
    Abstract [en]

    n/a

  • 8.
    Jansson, S. P. O.
    et al.
    University of Örebro, Sweden.
    Fall, K.
    University of Örebro, Sweden; University of Örebro, Sweden.
    Brus, O.
    University of Örebro, Sweden.
    Magnuson, A.
    University of Örebro, Sweden.
    Wandell, P.
    Karolinska Institute, 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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Rolandsson, O.
    Umeå University, Sweden.
    Prevalence and incidence of diabetes mellitus: a nationwide population-based pharmaco-epidemiological study in Sweden2015In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 32, no 10, p. 1319-1328Article in journal (Refereed)
    Abstract [en]

    Aim To investigate the changes in prevalence and incidence of pharmacologically and non-pharmacologically treated diabetes in Sweden during 2005 to 2013. Methods We obtained data on gender, date of birth and pharmacologically and non-pharmacologically treated diabetes from national registers for all Swedish residents. Results During the study period a total of 240 871 new cases of pharmacologically treated diabetes was found. The age-standardized incidence during the follow-up was 4.34 and 3.16 per 1000 individuals in men and women, respectively. A decreasing time trend in incidence for men of 0.6% per year (0.994, 95% CI 0.989-0.999) and for women of 0.7% per year (0.993, 95% CI 0.986-0.999) was observed. The age-standardized prevalence increased from 41.9 and 29.9 per 1000 in 2005/2006 to 50.8 and 34.6 in 2012/2013 in men and women, respectively. This corresponds to an annually increasing time trend for both men (1.024, 95% CI 1.022-1.027) and women (1.019, 95% CI 1.016-1.021). The total age-standardized prevalence of pharmacologically and non-pharmacologically treated diabetes (2012) was 46.9 per 1000 (55.6 for men and 38.8 for women). This corresponds to an annually increasing time trend (2010-2012) for both men (1.017, 95% CI 1.013-1.021) and women (1.012, 95% CI 1.008-1.016). Conclusions The prevalence of pharmacologically treated diabetes increased moderately during 8 years of follow-up, while the incidence decreased modestly. This is in contrast to the results reported by most other studies. The total prevalence of diabetes (both pharmacologically and non-pharmacologically treated) in Sweden is relatively low, from a global viewpoint.

  • 9.
    Jennersjö, Pär
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Guldbrand, Hans
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, West County Primary Health Care.
    Björne, Stefan
    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. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Lindström, Torbjörn
    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.
    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.
    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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    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.
    A prospective observational study of all-cause mortality in relation to serum 25-OH vitamin D-3 and parathyroid hormone levels in patients with type 2 diabetes2015In: Diabetology and Metabolic Syndrome, ISSN 1758-5996, E-ISSN 1758-5996, Vol. 7, no 53Article in journal (Refereed)
    Abstract [en]

    Background: Low levels of vitamin D have been related to increased mortality and morbidity in several non-diabetic studies. We aimed to prospectively study relationships between serum 25-OH vitamin D-3 (vitamin D) and of serum parathyroid hormone (PTH) to total mortality in type 2 diabetes. We also aimed to compare the levels of these potential risk-factors in patients with and without diabetes. Methods: The main study design was prospective and observational. We used baseline data from 472 men and 245 women who participated in the "Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care" study. Patients were 55-66 years old at recruitment, and an age-matched non-diabetic sample of 129 individuals constituted controls for the baseline data. Carotid-femoral pulse-wave velocity (PWV) was measured with applanation-tonometry and carotid intima-media thickness (IMT) with ultrasound. Patients with diabetes were followed for all-cause mortality using the national Swedish Cause of Death Registry. Results: Levels of vitamin D were lower in patients with diabetes than in controls, also after correction for age and obesity, while PTH levels did not differ. Nine women and 24 men died during 6 years of median follow up of the final cohort (n = 698). Vitamin D levels were negatively related to all-cause mortality in men independently of age, PTH, HbA1c, waist circumference, 24-h systolic ambulatory-blood pressure (ABP) and serum-apoB (p = 0.049). This finding was also statistically significant when PWV and IMT were added to the analyses (p = 0.028) and was not affected statistically when medications were also included in the regression-analysis (p = 0.01). In the women with type 2 diabetes, levels of PTH were positively related with all-cause mortality in the corresponding calculations (p = 0.016 without PWV and IMT, p = 0.006 with PWV and IMT, p = 0.045 when also adding medications to the analysis), while levels of vitamin D was without statistical significance (p greater than 0.9). Conclusions: Serum vitamin D in men and serum PTH in women give prognostic information in terms of total-mortality that are independent of regular risk factors in addition to levels of ABP, IMT and PWV.

  • 10.
    Jennersjö, Pär
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). 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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Pedometer-determined physical activity level and change in arterial stiffness in Type 2 diabetes over 4 years2016In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 33, no 7, p. 992-997Article in journal (Refereed)
    Abstract [en]

    Aim To explore prospectively the correlation between the level of pedometer-determined physical activity at the start of the study and the change in pulse wave velocity from baseline to 4 years later in people with Type 2 diabetes.

    Methods We analysed data from 135 men and 53 women with Type 2 diabetes, aged 54–66 years. Physical activity was measured with waist-mounted pedometers on 3 consecutive days and the numbers of steps/day at baseline were classified into four groups: <5000 steps/day, 5000–7499 steps/day, 7500–9999 steps/day and ≥10 000 steps/day. Pulse wave velocity was measured using applanation tonometry over the carotid and femoral arteries at baseline and after 4 years.

    Results The mean (±sd; range) number of steps/day was 8022 (±3765; 956–20 921). The participants with the lowest level of physical activity had a more pronounced increase in the change in pulse wave velocity compared with the participants with the highest. When change in pulse wave velocity was analysed as a continuous variable and adjusted for sex, age, diabetes duration, HbA1c, BMI, systolic blood pressure, pulse wave velocity at baseline, β-blocker use, statin use, unemployment, smoking and diabetes medication, the number of steps/day at baseline was significantly associated with a less steep increase in change in pulse wave velocity (P=0.005). Every 1000 extra steps at baseline corresponded to a lower increase in change in pulse wave velocity of 0.103 m/s.

    Conclusions We found that a high level of pedometer-determined physical activity was associated with a slower progression of arterial stiffness over 4 years in middle-aged people with Type 2 diabetes.

  • 11.
    Lannering, Christina
    et al.
    Futurum, Sweden.
    Ernsth Bravell, Marie
    Jonköping University, Sweden.
    Midlov, Patrik
    Lund 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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Molstad, Sigvard
    Lund University, Sweden.
    Factors related to falls, weight-loss and pressure ulcers - more insight in risk assessment among nursing home residents2016In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 25, no 7-8, p. 940-950Article in journal (Refereed)
    Abstract [en]

    Aims and objectivesTo describe how the included items in three different scales, Downton Fall Risk Index, the short form of Mini Nutritional Assessment and the Modified Norton Scale are associated to severe outcomes as falls, weight loss and pressure ulcers. BackgroundFalls, malnutrition and pressure ulcers are common adverse events among nursing home residents and risk scoring are common preventive activities, mainly focusing on single risks. In Sweden the three scales are routinely used together with the purpose to improve the quality of prevention. DesignLongitudinal quantitative study. MethodsDescriptive analyses and Cox regression analyses. ResultsOnly 4% scored no risk for any of these serious events. Longitudinal risk scoring showed significant impaired mean scores indicating increased risks. This confirms the complexity of this populations status of general condition. There were no statistical significant differences between residents categorised at risk or not regarding events. Physical activity increased falls, but decreased pressure ulcers. For weight loss, cognitive decline and the status of general health were most important. ConclusionsRisk tendencies for falls, malnutrition and pressure ulcers are high in nursing homes, and when measure them at the same time the majority will have several of these risks. Items assessing mobility or items affecting mobility were of most importance. Care processes can always be improved and this study can add to the topic. Relevance to clinical practiceA more comprehensive view is needed and prevention can not only be based on total scores. Mobility is an important factor for falls and pressure ulcers, both as a risk factor and a protective factor. This involves a challenge for care - to keep the inmates physical active and at the same time prevent falls.

  • 12.
    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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala". 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.

  • 13.
    Rådholm, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Festin, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Falk, Magnus
    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, Research & Development Unit in Local Health Care.
    Midlöv, Patrik
    Department of Clinical Sciences in Malmö, Center for Primary Health Care Research Lund University, Malmö, Sweden.
    Mölstad, Sigvard
    Department of Clinical Sciences in Malmö, Center for Primary Health Care Research Lund University, Malmö, 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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Blood pressure and all-cause mortality: a prospective study of nursing home residents2016In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 45, no 6, p. 826-832Article in journal (Refereed)
    Abstract [en]

    Aim: To explore the natural course of blood pressure development and its relation to mortality in a nursing home cohort.

    Methods: A cohort of 406 nursing home residents in south east Sweden was followed prospectively for 30 months. Participants were divided into four groups based on systolic blood pressure (SBP) at baseline. Data were analysed using a Cox regression model with all-cause mortality as the outcome measurement; paired Student t-tests were used to evaluate blood pressure development over time.

    Results: During follow-up, 174 (43%) people died. Participants with SBP <120 mmHg had a hazard ratio for mortality of 1.56 (95% confidence interval, 1.08–2.27) compared with those with SBP 120–139 mmHg, adjusted for age and sex. Risk of malnutrition or present malnutrition was most common in participants with SBP <120 mmHg; risk of malnutrition or present malnutrition estimated using the Mini Nutritional Assessment was found in 78 (71%). The levels of SBP decreased over time independent of changes in anti-hypertensive medication.

    Conclusions: In this cohort of nursing home residents, low SBP was associated with increased all-cause mortality. SBP decreased over time; this was not associated with altered anti-hypertensive treatment. The clinical implication from this study is that there is a need for systematic drug reviews in elderly persons in nursing homes, paying special attention to those with low SBP.

  • 14.
    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". 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.

  • 15.
    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.

  • 16.
    Rådholm, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Wiréhn, Ann-Britt
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis.
    Chalmers, J.
    The George Institute for Global Health, University of Sydney, NSW, 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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Use of antidiabetic and antidepressant drugs is associated with increased risk of myocardial infarction: a nationwide register study2016In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 33, no 2, p. 218-223Article in journal (Refereed)
    Abstract [en]

    Aims

    To explore the gender- and age-specific risk of developing a first myocardial infarction in people treated with antidiabetic and/or antidepressant drugs compared with people with no pharmaceutical treatment for diabetes or depression.

    Methods

    A cohort of all Swedish residents aged 45–84 years (n = 4 083 719) was followed for a period of 3 years. Data were derived from three nationwide registers. The prescription and dispensing of antidiabetic and antidepressant drugs were used as markers of disease. All study subjects were reallocated according to treatment and the treatment categories were updated every year. Data were analysed using a Cox regression model with a time-dependent variable. The outcome of interest was first fatal or non-fatal myocardial infarction.

    Results

    During follow-up, 42 840 people had a first myocardial infarction, 3511 of which were fatal. Women aged 45–64 years, receiving both antidiabetic and antidepressant drugs had a hazard ratio for myocardial infarction of 7.4 (95% CI 6.3–8.6) compared with women receiving neither. The corresponding hazard ratio for men was 3.1 (95% CI 2.8–3.6).

    Conclusions

    The combined use of antidiabetic and antidepressant drugs was associated with a higher risk of myocardial infarction compared with use of either group of drugs alone. The increase in relative risk was greater in middle-aged women than in middle-aged men.

  • 17.
    Sabale, Ugne
    et al.
    AstraZeneca Nordic-Baltic, Södertälje, Sweden..
    Bodegard, Johan
    AstraZeneca Nordic-Baltic, Södertälje, Sweden..
    Sundstrom, Johan
    Uppsala University, Uppsala, 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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Nilsson, Peter
    Lund University, Malmö, Sweden..
    Johansson, Gunnar
    Uppsala University, Uppsala, Sweden..
    Svennblad, Bodil
    Uppsala University, Uppsala, Sweden..
    Henriksson, Martin
    AstraZeneca Nordic-Baltic, Södertälje, Sweden..
    Healthcare utilization and costs following newly diagnosed type-2 diabetes in Sweden: A follow-up of 38,956 patients in a clinical practice setting2015In: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 9, no 5, p. 330-337Article in journal (Refereed)
    Abstract [en]

    Aims: To describe healthcare resource use patterns and estimate healthcare costs of newly diagnosed Type 2 diabetes mellitus (T2DM) patients in Sweden. Methods: Patients with a newly diagnosed T2DM between 1999 and 2009 were identified from 84 Swedish primary care centres. Healthcare resource use data, excluding pharmaceuticals, were extracted from electronic patient records and a national patient register, and reported as per patient mean number of primary care contacts, laboratory tests and hospitalizations. Per patient mean healthcare costs are reported as annual and cumulative costs. Results: During a median (maximum) of 4.6 (9.0) years follow-up; 38,956 patients (183,513 patient years) on average made 81 primary care contacts, was hospitalized 2.14 times, and took 31 laboratory tests. Mean per patient annual healthcare costs were (sic)4128 (95% CI, 4054-4199) the first year after diagnosis, (sic)2708 (95% CI, 2641-2776) the second year, and (sic)3030 (95% CI, 2854-3204) in year 9 (2012 values). Mean per patient cumulative healthcare costs were (sic)26,503 (95% CI, 26,025-26,970) at 9 years of follow-up. Hospitalizations accounted for the majority of healthcare costs. Conclusions: Although newly diagnosed T2DM patients require a substantial amount of healthcare services in primary care, hospitalizations account for the majority of healthcare costs. (C) 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  • 18.
    Schernthaner, G.
    et al.
    Rudolfstiftung Hospital Vienna, Austria.
    Duran-Garcia, S.
    Hospital University of Valme, Spain.
    Hanefeld, M.
    GWT TUD GmbH, Germany.
    Langslet, G.
    Oslo University Hospital, Norway.
    Niskanen, L.
    University of Helsinki, Finland.
    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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Malvolti, E.
    AstraZeneca, Turkey.
    Hardy, E.
    AstraZeneca LP, DE USA.
    Efficacy and tolerability of saxagliptin compared with glimepiride in elderly patients with type 2 diabetes: a randomized, controlled study (GENERATION)2015In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 17, no 7, p. 630-638Article in journal (Refereed)
    Abstract [en]

    Aims: To assess the efficacy and safety of adjunctive saxagliptin vs glimepiride in elderly patients with type 2 diabetes (T2D) and inadequate glycaemic control. Methods: In this multinational, randomized, double-blind, phase IIIb/IV study (GENERATION; NCT01006603), patients aged greater than= 65 years were randomized (1:1) to receive saxagliptin 5 mg/day or glimepiride less than= 6 mg/day, added to metformin, during a 52-week treatment period. The primary endpoint was achievement of glycated haemoglobin (HbA1c) less than7.0% at week 52 without confirmed/severe hypoglycaemia. The key secondary endpoint was incidence of confirmed/severe hypoglycaemia. Safety and tolerability were also assessed. Results: Of 720 patients randomized (360 in each treatment group; mean age 72.6 years; mean T2D duration 7.6 years), 574 (79.8%) completed the study (saxagliptin 80.3%; glimepiride 79.2%). Similar proportions of patients achieved the primary endpoint with saxagliptin and glimepiride (37.9 vs 38.2%; odds ratio 0.99, 95% confidence interval 0.73, 1.34; p=0.9415); however, a significant treatment-by-age interaction effect was detected (p=0.0389): saxagliptin was numerically (but not significantly) superior to glimepiride for patients aged less than75 years (39.2 vs 33.3%) and numerically inferior for patients aged greater than= 75 years (35.9 vs 45.5%). The incidence of confirmed/severe hypoglycaemia was lower with saxagliptin vs glimepiride (1.1 vs 15.3%; nominal pless than0.0001). Saxagliptin was generally well tolerated, with similar incidences of adverse events compared with glimepiride. Conclusion: As avoiding hypoglycaemia is a key clinical objective in elderly patients, saxagliptin is a suitable alternative to glimepiride in patients with T2D aged greater than= 65 years.

  • 19.
    Vavruch, Camilla
    et al.
    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. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Lindström, Torbjörn
    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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    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.
    Serum leptin levels are independently related to the incidence of ischemic heart disease in a prospective study of patients with type 2 diabetes2015In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 14, no 62Article in journal (Refereed)
    Abstract [en]

    Background: New and clinically useful markers of cardiovascular risk are of essence in type 2 diabetes since ischemic heart disease is a major cause of death in these patients. Methods: We analyzed baseline data from 476 men and 244 women who participated in "Cardiovascular Risk factors in Patients with Diabetes -a Prospective study in Primary care" study. All participants had type 2 diabetes and were 55-66 years old at recruitment during year 2005 to 2008. Except for established traditional risk markers for vascular disease, we also estimated vascular complications non-invasively by performance of carotid-femoral pulse-wave velocity (PWV, with applanation-tonometry) and intima-media thickness of carotid arteries (IMT, with B-mode ultrasound). Patients were followed for incidence of ischemic heart disease mortality and morbidity until end of the year 2012, using the national Swedish Cause of Death and Hospitalization Registries. Results: During the follow-up period of a median of 6 years 47 men and 10 women died or were hospitalized for ischemic heart disease including myocardial infarction. Leptin levels were positively related to the hazard ratio (HR) in men (HR for each log 10 unit 4.9, CI 1.99 to 11.8) and women (HR 11.5, CI 1.47 to 89.7). Leptin predicted ischemic heart disease independently of age, HbA1c, BMI, systolic blood pressure and LDL-cholesterol/HDL-cholesterol ratio (men: HR 12.9 CI 3.2-53, women: HR 19.9, CI 1.2-327) This finding of increased risk related to high leptin levels was also statistically significant when carotid-femoral PWV and IMT were both added to the equations in men (hazard ratio 9.2 CI 2.1-41). Conclusions: Our data support the use of serum leptin in type 2 diabetes to add independent prognostic information in terms of ischemic heart disease when compared with traditional cardiovascular risk factors. In the men of the cohort this prognostic information was in addition also to data on IMT and PWV, two non-invasive measurements of the extent of vascular disease. The power to detect a similar relationship in women was less strong due to lower incidence of cardiovascular disease. Trial registration: ClinicalTrials. gov:

  • 20.
    Walz, Lotta
    et al.
    Karolinska Institute, Sweden; MSD AB, Sweden.
    Jonsson, Anna K.
    National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Zilg, Brita
    Karolinska Institute, Sweden; National Board Forens Med, 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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Druid, Henrik
    Karolinska Institute, Sweden.
    Risk Factors for Fatal Hyperglycaemia Confirmed by Forensic Postmortem Examination - A Nationwide Cohort in Sweden2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 10, p. e0164950-Article in journal (Refereed)
    Abstract [en]

    Aims/Hypothesis The aim of this study was to identify risk factors associated with confirmed fatal hyperglycaemia, which could predispose potentially preventable deaths in individuals on glucose lowering drugs. Methods A retrospective register-based case-control study conducted on a nationwide cohort with individuals who died due to hyperglycaemia as determined by forensic postmortem examination, in Sweden August 2006 to December 2012. Vitreous glucose was used to diagnose hyperglycaemia postmortem. The forensic findings stored in the National Forensic Medicine Database were linked to nationwide registers. Cases that died due to confirmed hyperglycemia with dispensed glucose lowering drugs were identified and living controls with dispensed glucose lowering drugs were randomly selected in the Swedish prescribed drug register and matched on age and sex. Information on comorbidities, dispensed pharmaceuticals, clinical data and socioeconomic factors were obtained for cases and controls. Adjusted multiple logistic regression models were used to identify risk factors associated with fatal hyperglycaemia. Results During the study period 322 individuals, mostly males (79%) with the mean age of 53.9 years (SD. +/- 14) died due to confirmed hyperglycaemia. Risk factors for fatal hyperglycaemia included; insulin treatment (OR = 4.40; 95% CI, 1.96, 9.85), poor glycaemic control (OR = 2.00 95% CI, 1.23, 3.27), inadequate refill-adherence before death (OR = 3.87; 95% CI, 1.99, 7.53), microvascular disease (OR = 3.26; 95% CI, 1.84, 5.79), psychiatric illness (OR = 2.30; 95% CI, 1.32, 4.01), substance abuse (OR = 8.85; 95% CI, 2.34, 35.0) and/or living alone (OR = 2.25; 95% CI, 1.21, 4.18). Conclusions/ Interpretation Our results demonstrate the importance of clinical attention to poor glycaemic control in subjects with psychosocial problems since it may indicate serious non-adherence, which consequently could lead to fatal hyperglycaemia.

  • 21.
    Westerlind, Björn
    et al.
    County Hospital Ryhov, 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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Mölstad, Sigvard
    Lund University, Sweden.
    Midlöv, Patrik
    Lund University, Sweden.
    Prevalence and predictive importance of anemia in Swedish nursing home residents - a longitudinal study2016In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 16, article id 206Article in journal (Refereed)
    Abstract [en]

    Background: Anemia is common in elderly people and especially in nursing home residents. Few studies have been performed on the consequences of anemia in a nursing home population. This study explored the prevalence of anemia in nursing homes in Sweden, including risk factors and mortality associated with anemia or hemoglobin (Hb) decline. Methods: Three hundred ninety patients from 12 nursing homes were included during 2008-2011. Information about medication, blood samples, questionnaire responses and information about physical and social activities was recorded. The baseline characteristics of the patients were compared for subjects with and without anemia. Vital status was ascertained during the following 7 years from baseline to compare the survival. Hb levels amp;lt;120 g/L in women and amp;lt;130 g/L in men were used to define anemia. For 220 of the subjects Hb change during one year was registered and the quartiles in Hb change were compared in terms of baseline characteristics and mortality. Results: The prevalence of anemia at baseline was 52% among men and 32% among women. The men with anemia had a two-year mortality significantly higher (61%) than the men without anemia (29%, p = 0.001) but there was no statistical difference in two- year survival in women. In anemic men there was a higher mortality (Hazard Ratio = 1.58) during a total follow-up period of up to 7 years after adjustment for age, increased B-type natriuretic peptide (BNP) and decreased estimated Glomerular Filtration Rate (eGFR). Among men, but not women, we found baseline correlations between anemia and elevated BNP (amp;gt;100 ng/L) and severely reduced eGFR (amp;lt;30 ml/min). When the lowest quartile of Hb change (decline amp;gt;9 g/L) was compared with the highest (improvement amp;gt;6 g/L) the mortality was higher in the lowest quartile (p = 0.03). Conclusions: Anemia is common in nursing home residents in Sweden, especially among men for whom it is related to higher mortality. A rapid Hb drop is associated with higher mortality. Regardless of earlier Hb values, monitoring Hb regularly in a nursing home population seems important for catching rapid Hb decline correlated with higher mortality.

  • 22.
    Wijkman, Magnus
    et al.
    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.
    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).
    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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    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.
    Aortic pulse wave velocity predicts incident cardiovascular events in patients with type 2 diabetes treated in primary care2016In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 30, no 7, p. 1223-1228Article in journal (Refereed)
    Abstract [en]

    Aims: The aim was to evaluate the predictive value of aortic pulse wave velocity (aPWV) on incident cardiovascular events in patients with type 2 diabetes without previous cardiovascular disease who were treated in primary care, after adjustment for traditional risk factors. Methods: We measured aPWV in 627 patients who participated in the epidemiological study CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes-a Prospective Study in Primary Care; ClinicalTrials.gov identifier NCT01049737) and who did not have previously known myocardial infarction or stroke. The outcome variable was a composite endpoint consisting of cardiovascular mortality, hospitalization for myocardial infarction and hospitalization for stroke. Results: During a median follow-up time of almost eight years, the unadjusted HR per each increment of aPWV by 1 m/s was 1.239 (95% CI 1.114-1.379, P amp;lt; 0.001) for the primary endpoint. Following adjustments for age, sex, diabetes duration, office systolic blood pressure, resting heart rate, total cholesterol, HbA1c, estimated glomerular filtration rate and smoking status, the adjusted hazard ratio was 1.142 (95% CI 1.003-1.301, P = 0.044). Conclusions: In primary preventive patients with type 2 diabetes treated in primary care, aPWV predicted a composite outcome of incident cardiovascular events independently of diabetes-specific and traditional risk factors. (C) 2016 Elsevier Inc. All rights reserved.

  • 23.
    Wijkman, Magnus
    et al.
    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.
    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, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    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.
    Diastolic orthostatic hypertension and cardiovascular prognosis in type 2 diabetes: a prospective cohort study2016In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 15, no 83, p. 1-10Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In patients with type 2 diabetes, the prognostic impact of an orthostatic rise in blood pressure is not known. Therefore, the aim of this study was to determine the prognostic implications of the diastolic orthostatic blood pressure response in a cohort of patients with type 2 diabetes. We also evaluated associations between different orthostatic blood pressure responses and markers of subclinical cardiovascular organ damage.

    METHODS: Office blood pressures were measured in the sitting and in the standing position in 749 patients with type 2 diabetes who participated in the CARDIPP study (Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care). Diastolic orthostatic hypertension was defined as a rise of diastolic blood pressure ≥10 mmHg and diastolic orthostatic hypotension was defined as a drop of diastolic blood pressure ≥10 mmHg. Recruitment took place between the years 2005-2008, and patients were followed until any of the primary outcome events (cardiovascular death or hospitalization for either myocardial infarction or stroke) occurred or until December 31st, 2014. Measurements of aortic pulse wave velocity and of carotid intima-media thickness were performed at base-line.

    RESULTS: Diastolic orthostatic hypertension was found in 140 patients (18.7 %) and was associated with significantly lower risk of cardiovascular events (crude hazard ratio compared with patients with normal systolic and diastolic orthostatic blood pressure response: 0.450, 95 % C.I. 0.206-0.987, P = 0.046). Diastolic orthostatic hypotension was found in 31 patients (4.1 %) and was associated with higher values for aortic pulse wave velocity and carotid intima-media thickness, compared with patients with normal systolic and diastolic orthostatic blood pressure response.

    CONCLUSIONS: Diastolic orthostatic hypertension is common in patients with type 2 diabetes, and may be a novel marker for decreased cardiovascular risk in these patients.

  • 24.
    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, 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. 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.

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