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  • 1. Ahlgren, AR
    et al.
    Piitulainen, E
    Sandgren, T
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Physiology . Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Alfa1-antitrypsin deficiency and blood pressure regulation2003In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 21, p. S151-S151Conference paper (Other academic)
  • 2.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Johansson, Anders
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    A respiration monitor based on electrocardiographic and photoplethysmographic sensor fusion2004In: IEEE Engineering in Medical and Biological Society,2004, Piscataway, N.J. USA: IEEEEMBS , 2004, p. 2311-Conference paper (Refereed)
  • 3.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Johansson, Anders
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Monitorering av andning and blodtrycksförändringar baserat på EKG och hjärtljud2007In: Medicinteknik dagarna,2007, 2007Conference paper (Other academic)
  • 4.
    Ahlström, Christer
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Johansson, Anders
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Uhlin, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Ask, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Physiological Measurements.
    Noninvasive investigation of blood pressure changes using the pulse wave transit time: A novel approach in the monitoring of hemodialysis patients2005In: Journal of Artificial Organs, ISSN 1434-7229, E-ISSN 1619-0904, Vol. 8, no 3, p. 192-197Article in journal (Refereed)
    Abstract [en]

    Severe blood pressure changes are well known in hemodialysis. Detection and prediction of these are important for the well-being of the patient and for optimizing treatment. New noninvasive methods for this purpose are required. The pulse wave transit time technique is an indirect estimation of blood pressure, and our intention is to investigate whether this technique is applicable for hemodialysis treatment. A measurement setup utilizing lower body negative pressure and isometric contraction was used to simulate dialysis-related blood pressure changes in normal test subjects. Systolic blood pressure levels were compared to different pulse wave transit times, including and excluding the cardiac preejection period. Based on the results of these investigations, a pulse wave transit time technique adapted for dialysis treatment was developed and tried out on patients. To determine systolic blood pressure in the normal group, the total pulse wave transit time was found most suitable (including the cardiac preejection period). Correlation coefficients were r = 0.80 ± 0.06 (mean ± SD) overall and r = 0.81 ± 0.16 and r = 0.09 ± 0.62 for the hypotension and hypertension phases, respectively. When applying the adapted technique in dialysis patients, large blood pressure variations could easily be detected when present. Pulse wave transit time is correlated to systolic blood pressure within the acceptable range for a trend-indicating system. The method's applicability for dialysis treatment requires further studies. The results indicate that large sudden pressure drops, like those seen in sudden hypovolemia, can be detected. © The Japanese Society for Artificial Organs 2005.

  • 5.
    Ahlström, Christer
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Health Sciences.
    Johansson, Anders
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Health Sciences.
    A method for accurate localization of the first heart sound and possible applications2008In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 29, no 3, p. 417-428Article in journal (Refereed)
    Abstract [en]

    We have previously developed a method for localization of the first heart sound (S1) using wavelet denoising and ECG-gated peak-picking. In this study, an additional enhancement step based on cross-correlation and ECG-gated ensemble averaging (EA) is presented. The main objective of the improved method was to localize S1 with very high temporal accuracy in (pseudo-) real time. The performance of S1 detection and localization, with and without EA enhancement, was evaluated on simulated as well as experimental data. The simulation study showed that EA enhancement reduced the localization error considerably and that S1 could be accurately localized at much lower signal-to-noise ratios. The experimental data were taken from ten healthy subjects at rest and during invoked hyper- and hypotension. For this material, the number of correct S1 detections increased from 91% to 98% when using EA enhancement. Improved performance was also demonstrated when EA enhancement was used for continuous tracking of blood pressure changes and for respiration monitoring via the electromechanical activation time. These are two typical applications where accurate localization of S1 is essential for the results.

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  • 6.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    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.
    Matussek, Andreas
    County Hospital Ryhov, Sweden.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    PDGF-D gene polymorphism is associated with increased cardiovascular mortality in elderly men2016In: BMC Medical Genetics, E-ISSN 1471-2350, Vol. 17, no 62Article in journal (Refereed)
    Abstract [en]

    Background: Platelet-derived growth factor (PDGF) D has been reported to be active in fibroblasts, and in areas of myocardial infarction. In this longitudinal study we evaluated the association between PDGF-D polymorphism and cardiovascular mortality, and attempted to discover whether specific genotype differences regarding risk could be observed, and if gender differences could be seen. Methods: Four hundred seventy-six elderly community participants were included in this study. All participants underwent a clinical examination, echocardiography, and blood sampling including PDGF-D single nucleotide polymorphism (SNP) analyses of the rs974819 A/A, G/A and G/G SNP. The follow-up time was 6.7 years. Results: No specific genotype of rs974819 demonstrated increased cardiovascular mortality in the total population, however, the male group with genotypes A/A and G/A demonstrated an increased risk that persisted in a multivariate evaluation where adjustments were made for well-known cardiovascular risk factors (2.7 fold compared with the G/G genotype). No corresponding finding was observed in the female group. Conclusion: We report here for the first time that the genotypes G/A or A/A of the SNP rs974819 near PDGF-D exhibited a 2.7 fold increased cardiovascular mortality risk in males. Corresponding increased risk could not be observed in either the total population and thus not in the female group. However, the sample size is was small and the results should be regarded as hypothesis-generating, and thus more research in the field is recommended.

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  • 7.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Vorkapic, Emina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Ljungberg, Liza
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. 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.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Gender difference in adiponectin associated with cardiovascular mortality2015In: BMC Medical Genetics, E-ISSN 1471-2350, Vol. 16, no 9Article in journal (Refereed)
    Abstract [en]

    Background: It is important to identify cardiovascular diseases in patients at high risk. To include genetics into routine cardiological patients has therefore been discussed recently. We wanted to evaluate the association between high-molecular weight adiponectin and cardiovascular risk, and secondly in the same population evaluate if specific genotype differences regarding risk could be observed, and thirdly if gender differences could be seen. Method: Four hundred seventy-six elderly participants recruited from a rural community were included. All participants underwent a clinical examination, echocardiography, and blood sampling and the single nucleotide polymorphism (SNP) (rs266729) of adiponectin was analysed. Follow-up time was 6.7 years. Results: Those with high serum concentration of adiponectin had a more 2 fold increased cardiovascular risk, and it might be that females exhibits even higher risk where a more than 5 fold increased risk could be seen. The result could be demonstrated even in a multivariate model adjusting for well-known clinical risk factors. However, as the sample size was small the gender differences should be interpreted with caution. In the genotype evaluation the C/C carriers of the female group had a more than 9-fold increased risk of cardiovascular mortality, however the confidence interval was wide. Such genotype difference could not be found in the male group. Conclusion: High level of adiponectin was associated with increased cardiovascular risk. Also a gender difference in the genotype evaluation could be seen where the C/C carriers obtained higher risk in the female group but not in the male group. Thus, in order to identify patients at risk early, genetic analyses may add to the armamentarium used in the clinical routine. However, information should be regarded as hypothesis generating as the sample size was small and should stimulate further research in individualized cardiovascular prevention and treatment.

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  • 8.
    Bellinetto Ford, L
    et al.
    Lund University.
    Melander, O
    Lund University.
    Länne, Toste
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Nilsson, P M
    Lund University.
    INCREASED PULSE PRESSURE IS A MARKER FOR AORTIC STIFFNESS INDEPENDENT OF MEAN ARTERIAL PRESSURE, AGE, SEX, AND OTHER WELL-KNOWN CARDIOVASCULAR RISK FACTORS2009In: in JOURNAL OF HYPERTENSION, vol 27, 2009, Vol. 27, p. S23-S23Conference paper (Refereed)
    Abstract [en]

    n/a

  • 9.
    Bergstrand, Sara
    et al.
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences.
    Lindén, Maria
    n/a.
    Ek, Anna-Christina
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Lindgren, Margareta
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Tissue blood flow responses to external pressure in the sacral region using PPG and laser Doppler technique.2009In: European Pressure Ulcer Advisory Panels, Amsterdam., 2009Conference paper (Refereed)
  • 10.
    Bergstrand, Sara
    et al.
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Linden, Maria
    Mälardalen University.
    Lindgren, Margareta
    Linköping University, Department of Medicine and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Existence of Tissue Blood Flow in Response to External Pressure in the Sacral Region of Elderly Individuals - Using an Optical Probe Prototype2010In: MICROCIRCULATION, ISSN 1073-9688, Vol. 17, no 4, p. 311-319Article in journal (Refereed)
    Abstract [en]

    Pandgt;Objective: The aim was to investigate the existence of sacral tissue blood flow at different depths in response to external pressure and compression in elderly individuals using a newly developed optical probe prototype. Methods: The tissue blood flow and tissue thickness in the sacral area were measured during load in 17 individuals using laser Doppler flowmetry and photoplethysmography in a combined probe, and digital ultrasound. Results: The mean age was 68.6 +/- 7.0 years. While loading, the mean compression was 60.3 +/- 11.9%. The number of participants with existing blood flow while loading increased with increased measurement depth. None had enclosed blood flow deep in the tissue and at the same time an existing more superficial blood flow. Correlation between tissue thickness and BMI in unloaded and loaded sacral tissue was shown: r = 0.68 (P = 0.003) and r = 0.68 (P = 0.003). Conclusions: Sacral tissue is highly compressed by external load. There seems to be a difference in responses to load in the different tissue layers, as occluded blood flow in deeper tissue layers do not occur unless the blood flow in the superficial tissue layers is occluded.

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  • 11.
    Bjarnegård, Niclas
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences.
    Ahlgren, AR
    Sandgren, T
    Sonesson, B
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Physiology . Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Effects of age and sympathetic stimulation on the mechanical properties of the proximal brachial artery2003In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 21, p. S248-S249Conference paper (Other academic)
  • 12.
    Bjarnegård, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans J.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Jönsson, A.
    Department of Internal Medicin, Jönköping Hospital, Jönköping, Sweden.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    Impaired endothelial independent vasodilatation in women with type 1 diabetes2008Manuscript (preprint) (Other academic)
  • 13.
    Bjarnegård, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Jonsson, Anders
    Jönköping Hospital.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Long-term hyperglycaemia impairs vascular smooth muscle cell function in women with type 1 diabetes mellitus2009In: DIABETES and VASCULAR DISEASE RESEARCH, ISSN 1479-1641, Vol. 6, no 1, p. 25-31Article in journal (Refereed)
    Abstract [en]

    Observations of increased stiffness in the elastic aorta in women with diabetes, but not men, emphasise the need for further analysis regarding early abnormalities in arterial wall properties of women with type 1 diabetes mellitus (DM).

    Ultrasound was used to study the wall properties of the distal brachial artery (BA) in 37 type 1 diabetic women (aged 22-45 years) without evident complications and in 53 controls (C). Blood samples were drawn for later analysis.

    Flow-mediated dilatation (FMD) was slightly lower in DM than C, 8.1 +/- 4.3% vs. 10.3 +/- 4.9% (p<0.05), and nitrate-mediated dilatation (NMD) was markedly lower, 21.7 +/- 6.6% vs. 31.4 +/- 5.7% (p<0.001). Lumen diameter, intima-media thickness and distensibility were similar in DM and C. Insulin-like growth factor (IGF-1) was lower in DM than C, 231 +/- 65 vs. 349 +/- 68 ng/ml (p<0.001). Glycosylated haemoglobin (HbA(1C)) and matrix metalloproteinase (MMP-9) were independent predictors of the reduced NMD in the DM.

    Brachial artery responsiveness to an exogenous donor of nitric oxide (NO) was markedly reduced in type 1 diabetic women despite only limited reduction in endothelium-dependent dilatation. The negative association between NMD and HbA(1C) suggests that long-term hyperglycaemia impairs vascular smooth muscle cell function in DM.

  • 14.
    Bjarnegård, Niclas
    et al.
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Bengtsson, C.
    Department of Rheumatology, Lund University Hospital, Lund, Sweden .
    Brodszki, J.
    Department of Women’s Health, Lund University Hospital, Lund, Sweden.
    Sturfelt, G.
    Department of Rheumatology, Lund University Hospital, Lund, Sweden.
    Nived, O.
    Department of Rheumatology, Lund University Hospital, Lund, Sweden.
    Länne, Toste
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences.
    Increased aortic pulse wave velocity in middle-aged women with systemic lupus erythematosus2006In: Lupus, ISSN 0961-2033, Vol. 15, no 10, p. 644-650Article in journal (Refereed)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a connective tissue disease where inflammatory activity affects several organ systems. An increased risk of cardiovascular disease has been identified in these patients, even after correction for traditional risk factors. The aim of the present study was to evaluate arterial stiffness and central hemodynamics in women with SLE in comparison to controls.

    Arterial tonometry was used to measure aortic (carotid-femoral) and arm (carotid-radial) pulse wave velocity (PWV), reflected pressure waves, and aortic augmentation index (AIx) in 27 women with SLE (52 to 68 years) and 27 controls. Aortic PWV was higher in women with SLE than controls, 9.8 m/s versus 8.2 m/s (P 0.01), after correction for mean arterial pressure and body mass index, 9.5 m/s versus 8.5 m/s (P 0.05). Other parameters were similar, arm PWV, 8.4 versus 8.5 m/s, AIx 34 versus 33% and calculated central aortic pulse pressure 48 versus 43 mmHg, in SLE and controls, respectively (NS). Aortic PWV was positively associated to C-reactive protein (CRP) and complement factor 3 (C3).

    Women with SLE have increased stiffness of their elastic central arteries. This may be one factor contributing to the increased cardiovascular risk seen in this cohort.

  • 15.
    Bjarnegård, Niclas
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Bengtsson, C
    Sturfelt, G
    Nived, O
    Brodszki, J
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Increased aortic pulse wave velocity in middle ages women with systemic lupou erythematosus2004In: 14th meeting of hypertension,2004, 2004Conference paper (Other academic)
  • 16.
    Bjarnegård, Niclas
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Bengtsson, C
    Sturfelt, G
    Nived, O
    Brodszki, J
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Ökad central puls¨vågshastighet hos medelålders kvinnor med systemic lupus erythematosus2004In: Svenska Läkaresällskapets Riksstämma,2004, 2004Conference paper (Other academic)
  • 17.
    Bjarnegård, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Hedman, Kristofer
    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.
    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.
    Vascular Adaptation to Indoor Cycling Exercise in Premenopausal Women2019In: International Journal of Sports Medicine, ISSN 0172-4622, E-ISSN 1439-3964, Vol. 40, no 4, p. 245-252Article in journal (Refereed)
    Abstract [en]

    The early vascular adaptation to indoor cycling, a popular activity at many fitness centres, is incompletely evaluated. Forty two healthy women (21-45 years) underwent measurements of arterial wall properties and geometry as well as a maximal bicycle exercise test before and after a 3 months period during which 21 of the women joined indoor cycling classes at a gym 2-3 times per week, while 21 women served as time controls. Peak work load increased by in average 16% (pamp;lt;0.001) and ascending aortic diameter by 4% (pamp;lt;0.01) in the exercise group, while unchanged in control group. The exercise intervention had no significant influence on the local intima-media thickness, blood pressure or the pulse pressure wave configuration while the carotid artery distensibility (pamp;lt;0.05) was higher after the intervention. There was a positive correlation between change in () peak work load and -diameter of tubular ascending aorta (r=0.42, pamp;lt;0.01) in the exercise group. In conclusion, after only 3 months of bicycle exercise training, signs of central arterial remodelling were seen in premenopausal women, which was associated to improvement in exercise capacity.

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  • 18.
    Bjarnegård, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Arterial properties along the upper arm in humans: age-related effects and the consequence of anatomical location2010In: JOURNAL OF APPLIED PHYSIOLOGY, ISSN 8750-7587, Vol. 108, no 1, p. 34-38Article in journal (Refereed)
    Abstract [en]

    The normal aging process of the brachial artery (BA) wall is of specific interest since it is often selected as a model artery in studies of vascular function. With echo-tracking ultrasound, diameter, absolute diameter change, and intima-media thickness (IMT) were registered in 60 healthy subjects, 21-86 yr (30 men), at a proximal, upper third, and distal arterial site along the upper arm. Blood pressure was recorded noninvasively, and the distensibility coefficient (DC) was calculated. The diameter at the proximal site increased with age from 5.5 +/- 0.2 mm in the young subjects to 6.9 +/- 0.3 mm (P andlt; 0.01) in the elderly subjects, concomitantly as IMT increased from 0.40 +/- 0.01 to 0.65 +/- 0.03 mm (P andlt; 0.001). The diameter at the other sites was similar in the young and elderly subjects, whereas IMT increased slightly with age. At the proximal site, DC decreased dramatically from 40.7 +/- 2.2 to 10.1 +/- 0.8 10(-3)/kPa (P andlt; 0.001) with age, whereas hardly no change was seen in the distal upper arm. The principal transit zone between elastic to predominantly muscular artery behavior seems to be located within the proximal part of the brachial artery, emphasizing the importance of carefully defining the arterial examination site.

  • 19.
    Bjarnegård, Niclas
    et al.
    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. Reg Jonkoping Cty, Sweden.
    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.
    Cinthio, M.
    Lund Univ, Sweden.
    Ekstrand, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hedman, Kristofer
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Nylander, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Henriksson, J.
    Karolinska Inst, Sweden.
    Vascular characteristics in young women: Effect of extensive endurance training or a sedentary lifestyle2018In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 223, no 2, article id UNSP e13041Article in journal (Refereed)
    Abstract [en]

    AimTo explore whether high-level endurance training in early age has an influence on the arterial wall properties in young women. MethodsForty-seven athletes (ATH) and 52 controls (CTR), all 17-25 years of age, were further divided into runners (RUN), whole-body endurance athletes (WBA), sedentary controls (SC) and normally active controls (AC). Two-dimensional ultrasound scanning of the carotid arteries was conducted to determine local common carotid artery (CCA) geometry and wall distensibility. Pulse waves were recorded with a tonometer to determine regional pulse wave velocity (PWV) and pulse pressure waveform. ResultsCarotid-radial PWV was lower in WBA than in RUN (P amp;lt; .05), indicating higher arterial distensibility along the arm. Mean arterial pressure was lower in ATH than in CTR and in RUN than in WBA (P amp;lt; .05). Synthesized aortic augmentation index (AI@75) was lower among ATH than among CTR (-12.8 1.6 vs -2.6 +/- 1.2%, P amp;lt; .001) and in WBA than in RUN (-16.4 +/- 2.5 vs -10.7 +/- 2.0%, P amp;lt; .05), suggesting a diminished return of reflection waves to the aorta during systole. Carotid-femoral PWV and intima-media thickness (IMT), lumen diameter and radial distensibility of the CCA were similar in ATH and CTR. ConclusionElastic artery distensibility and carotid artery IMT are not different in young women with extensive endurance training over several years and in those with sedentary lifestyle. On the other hand, our data suggest that long-term endurance training is associated with potentially favourable peripheral artery adaptation, especially in sports where upper body work is added. This adaptation, if persisting later in life, could contribute to lower cardiovascular risk.

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  • 20.
    Bjarnegård, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Morsing, E
    Lund University, Sweden .
    Cinthio, M
    Lund University, Sweden .
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Brodszki, J
    Lund University, Sweden .
    Cardiovascular function in adulthood following intrauterine growth restriction with abnormal fetal blood flow2013In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 41, no 2, p. 177-184Article in journal (Refereed)
    Abstract [en]

    Objectives To examine whether intrauterine growth restriction (IUGR) is associated with increased cardiovascular risk later in life. Methods We examined 19 young adults (aged 2225 years) who were born at term after IUGR, along with 18 controls. All had been examined previously with fetal Doppler, and in the present follow-up with echocardiography, carotid echo-tracking ultrasound, applanation tonometry, blood pressure and laser Doppler, in order to characterize their cardiac and vascular geometry and/or function. Results The diameter of the ascending aorta and the left ventricular diameter were smaller in the IUGR group, but only ascending aortic diameter remained significantly smaller after adjustment for body surface area (Pandlt;0.05). The aortic pressure augmentation index was higher in the IUGR group (Pandlt;0.05). The common carotid artery diameter, intimamedia thickness and distensibility as well as left ventricular mass and function were similar in the two groups. IUGR status was found to be an independent predictor of ascending aortic diameter. Conclusions IUGR due to placental dysfunction seems to contribute to the higher systolic blood pressure augmentation and the smaller aortic dimensions that are observed in adults more than 20 years later, with possible negative consequences for future left ventricular performance due to increased aortic impedance.

  • 21.
    Bjarnegård, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Rydén Ahlgren, Å.
    Department of Clinical Physiology, Malmö University Hospital, Malmö, Sweden .
    Sonesson, B.
    Department of Vascular Surgery, Malmö University Hospital, Malmö, Sweden.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    The effect of sympathetic stimulation on proximal brachial artery mechanics in humans: differential behaviour within the length of the brachial artery2004In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 182, no 1, p. 21-27Article in journal (Refereed)
    Abstract [en]

    Aims: The mechanical properties of arteries play a major role in the regulation of blood pressure and cardiac performance. The effect of sympathetic stimulation on the mechanical properties of the proximal brachial artery was analysed in 18 healthy volunteers, nine young (25 ± 2 years) and nine elderly (69 ± 2 years).

    Methods: A non-invasive ultrasonic echo-tracking system for measurement of systolic/diastolic variation of the proximal brachial artery diameter in combination with intra-arterial pressure measurements was used to determine wall mechanics. The pressure–diameter (P–D) relationship, distensibility coefficient (DC), compliance coefficient (CC) and stiffness(β) were obtained at rest and during sympathetic stimulation induced by lower body negative pressure (LBNP).

    Results: The peripheral vascular resistance increased by 100 and 72%, respectively in the young and elderly during LBNP (P < 0.001). Simultaneously, the mechanical properties of the proximal brachial artery remained unaltered, as estimated from both P–D relationship and stiffness in young (β-index rest: 5.2 ± 0.9, LBNP: 5.5 ± 1.3, NS) as well as elderly (β-index rest: 13.6 ± 4.6, LBNP: 16.1 ± 4.7, NS).

    Conclusions: LBNP-induced sympathetic activation does not change proximal brachial artery mechanics, in contrast to earlier reports on the muscular distal brachial artery. This may imply that the transition between elastic and muscular artery behaviour is within the length of the brachial artery, where the site of transition from elastic to muscular wall structure needs to be specified in future studies.

  • 22.
    Bjarnegård, Niclas
    et al.
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Rydén Åhlgren, Åsa
    Department of Clinical Physiology, Malmö University Hospital, Malmö, Sweden.
    Sandgren, Thomas
    Department of Surgery, Malmö University Hospital, Malmö, Sweden.
    Sonesson, Björn
    Department of Vascular Surgery, Malmö University Hospital, Malmö, Sweden.
    Länne, Toste
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences.
    Age affects proximal brachial artery stiffness: differential behaviour within the length of the brachial artery?2003In: Ultrasound in Medicine and Biology, ISSN 0301-5629, Vol. 29, no 8, p. 1115-1121Article in journal (Refereed)
    Abstract [en]

    With increasing age, the diameter of central elastic arteries increases, whereas their distensibility decreases. The purpose of this study was to investigate the mechanical properties of the proximal brachial artery in relation to age and gender. Distensibility coefficient (DC), stiffness and compliance coefficient (CC) were calculated in 136 healthy males and females (range 9-82 y) using echo-tracking sonography. CC decreased with age in both genders, but CC was higher in males. Stiffness increased and DC decreased with age in an exponential manner, without any differences between genders. In conclusion, as in central elastic arteries, the distensibility of the proximal brachial artery decreases with age, in contrast to earlier reports on the muscular distal brachial artery. This may imply that the transition between elastic and muscular artery behavior is within the length of the brachial artery. In future studies using the brachial artery, the examination site needs to be defined.

  • 23.
    Björck, Hanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    Eriksson, Per
    Karolinska Institute, Stockholm.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Debasso, Rachel
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    Ljungberg, Liza
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Persson, Karin
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Gender-Specific Association of the Plasminogen Activator Inhibitor-1 4G/5G Polymorphism With Central Arterial Blood Pressure2011In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 24, no 7, p. 802-808Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The functional plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism has previously been associated with hypertension. In recent years, central blood pressure, rather than brachial has been argued a better measure of cardiovascular damage and clinical outcome. The aim of this study was to investigate the possible influence of the 4G/5G polymorphism on central arterial blood pressure in a cohort of elderly individuals. METHODS We studied 410 individuals, 216 men and 194 women, aged 70-88. Central pressures and pulse waveforms were calculated from the radial artery pressure waveform by the use of the SphygmoCor system and a generalized transfer function. Brachial pressure was recorded using oscillometric technique (Dinamap, Critikon, Tampa, FL). PAI-1 antigen was determined in plasma. RESULTS The results showed that central pressures were higher in women carrying the PAI-1 4G/4G genotype compared to female carriers of the 5G/5G genotype, (P = 0.025, P = 0.002, and P = 0.002 for central systolic-, diastolic-, and mean arterial pressure, respectively). The association remained after adjustment for potentially confounding factors related to hypertension. No association of the PAI-1 genotype with blood pressure was found in men. Multiple regression analysis revealed an association between PAI-1 genotype and plasma PAI-1 levels (P = 0.048). CONCLUSIONS Our findings show a gender-specific association of the PAI-1 4G/5G polymorphism with central arterial blood pressure. The genotype effect was independent of other risk factors related to hypertension, suggesting that impaired fibrinolytic potential may play an important role in the development of central hypertension in women.

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  • 24.
    Björck, Hanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Persson, Karin
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Rundkvist, Louise
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Hamsten, A
    Karolinska Institute.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Eriksson, P
    Karolinska Institute, Stockholm.
    Association of genetic variation on chromosome 9p21.3 and arterial stiffness2009In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 265, no 3, p. 373-381Article in journal (Refereed)
    Abstract [en]

    Genome wide association studies have consistently reported associations between a region on chromosome 9p21.3 and a broad range of vascular diseases, such as coronary artery disease (CAD), aortic and intracranial aneurysms and type-2 diabetes (T2D). However, clear associations with intermediate phenotypes have not been described so far. To shed light on a possible influence of this chromosomal region on arterial wall integrity, we analysed associations between single nucleotide polymorphisms (SNPs) and degree of stiffness of the abdominal aorta in elderly individuals.

    A total of 400 subjects, 212 men and 188 women, aged 70-88 years were included. Arterial stiffness was examined at the midpoint between the renal arteries and the aortic bifurcation. Two CAD- and aneurysm-associated SNPs (rs10757274 and rs2891168) and one T2D-associated SNP (rs1081161) within the 9p21.3 region were genotyped. Aortic compliance and distensibility coefficients were higher in carriers of the rs10757274G and rs2891168G alleles in men reflecting a decrease in aortic stiffness. Adjustment for age and mean arterial pressure had no effect on these associations. The two SNPs were not associated with intima-media thickness or lumen diameter of the abdominal aorta. There were no associations between the rs10811661 SNP and any measure of aortic stiffness.

    Impaired mechanical properties of the arterial wall may explain the association between chromosome 9p21.3 polymorphisms and vascular disease.

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  • 25.
    Björck, Hanna M.
    et al.
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    Renner, Johan
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Maleki, Shohreh
    Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institute, Sweden.
    Nilsson, Siv F.E.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Kihlberg, Johan
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Folkersen, Lasse
    Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institute, Sweden.
    Karlsson, Matts
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Ebbers, Tino
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Clinical Physiology UHL.
    Eriksson, Per
    Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institute, Sweden.
    Länne, Toste
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Characterization of Shear-Sensitive Genes in the NormalRat Aorta Identifies Hand2 as a Major Flow-ResponsiveTranscription Factor2012In: PLOS ONE, E-ISSN 1932-6203, Vol. 7, no 12Article in journal (Refereed)
    Abstract [en]

    Objective: Shear forces play a key role in the maintenance of vessel wall integrity. Current understanding regarding shear-dependent gene expression is mainly based on in vitro or in vivo observations with experimentally deranged shear, hence reflecting acute molecular events in relation to flow. Our objective was to determine wall shear stress (WSS) in the rat aorta and study flow-dependent vessel wall biology under physiological conditions.

    Methods and Results: Animal-specific aortic WSS magnitude and vector direction were estimated using computational fluid dynamic simulation based on aortic geometry and flow information acquired by MRI. Two distinct flow pattern regions were identified in the normal rat aorta; the distal part of the inner curvature being exposed to low WSS and a non-uniform vector direction, and a region along the outer curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis revealed a strong differential expression between the flow regions, particularly associated with transcriptional regulation. In particular, several genes related to Ca2+-signalling, inflammation, proliferation and oxidative stress were among the most highly differentially expressed.

    Conclusions: Microarray analysis validated the CFD-defined WSS regions in the rat aorta, and several novel flow-dependent genes were identified. The importance of these genes in relation to atherosusceptibility needs further investigation.

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  • 26.
    Blomstrand, Peter
    et al.
    County Hospital Ryhov, Jönköping, Sweden.
    Engvall, Martin
    Linköping University, Department of Medical and Health Sciences. 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 Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, 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 Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Maret, Eva
    Karolinska University Hospital, Stockholm.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Maret-Ouda, John
    Karolinska University Hospital, Stockholm.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, 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 Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Left ventricular diastolic function, assessed by echocardiography and tissue Doppler imaging, is a strong predictor of cardiovascular events, superior to global left ventricular longitudinal strain, in patients with type 2 diabetes.2015In: European heart journal cardiovascular Imaging, ISSN 2047-2412, Vol. 16, no 9, p. 1000-1007Article in journal (Refereed)
    Abstract [en]

    AIMS: The aim of the study was to determine whether left ventricular systolic function, in terms of global left ventricular longitudinal strain (GLS), and diastolic function, expressed as the ratio between early diastolic transmitral flow and mitral annular motion velocities (E/e'), can predict cardiovascular events in patients with diabetes mellitus type 2.

    METHODS AND RESULTS: We prospectively investigated 406 consecutive patients, aged 55-65 years, with diabetes mellitus, who participated in the CARDIPP study. Echocardiography, pulse pressure (pp), and glycosylated haemoglobin (HbA1c) were analysed. Twelve cases of myocardial infarction and seven cases of stroke were identified during the follow-up period of 67 ± 17 months. Univariate Cox regression analysis showed that E/e' was a strong predictor of cardiovascular events (hazards ratio 1.12; 95% confidence interval 1.06-1.18, P < 0.001). E/e' was prospectively associated with cardiovascular events independent of age, sex, GLS, left ventricular ejection fraction (LVEF), pp, and HbA1c in multivariate analysis. Receiver operating characteristic curves showed that E/e' and HbA1c were the strongest predictors for cardiovascular events, both having an area under the curve (AUC) of 0.71 followed by LVEF with an AUC of 0.65 and GLS of 0.61. In a Kaplan-Meyer analysis, the cumulative probability of an event during the follow-up period was 8.6% for patients with an E/e' ratio >15 compared with 2.6% for patients with E/e' ≤15, P = 0.011.

    CONCLUSION: In middle-aged patients with type 2 diabetes, E/e' is a strong predictor of myocardial infarction and stroke, comparable with HbA1c and superior to GLS and LVEF.

  • 27.
    Blomstrand, Peter
    et al.
    Cty Hosp Ryhov, Sweden; Jonkoping Univ, Sweden.
    Sjöblom, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Mats
    Acad Hlth and Care, Sweden.
    Wijkman, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Engvall, Martin
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain2018In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 17, article id 113Article in journal (Refereed)
    Abstract [en]

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

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  • 28. Brodszki, J
    et al.
    Bengtsson, C
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Nived, O
    Sturfelt, G
    Marsal, K
    Abnormal mechanical properties of larger arteries in postmenopausal women with systemic lupus erythematosus2004In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 13, no 12, p. 917-923Article in journal (Refereed)
    Abstract [en]

    There is limited knowledge of potential defects in arterial wall properties in female systemic lupus erythematosus (SLE) patients without manifest cardiovascular disease (CVD) and significant atherosclerotic lesions. The aim of the present study was to investigate the mechanical properties of larger vessels in these patients and to compare them with healthy controls. B-mode ultrasound was used to assess vessel wall structure and to exclude presence of plaque. The ankle/brachial pressure index was measured to exclude occlusive arterial disease. An ultrasound echo-tracking system was used to determine stiffness of the abdominal aorta, common carotid artery (CCA) and popliteal artery (PA) in 39 female patients with SLE and 55 female, healthy controls. SLE had an independent effect on stiffening of the CCA (P = 0.01) and PA (P = 0.005). In addition, larger vessel diameters were observed in the CCA (P = 0.002) after adjustments for the effects of mean arterial pressure and age. Thus, this investigation demonstrated an increased arterial stiffness and signs of premature vascular ageing in the SLE patients without manifest cardiovascular disease and without significant atherosclerotic lesions. The results of this study indicate that other mechanisms besides atherosclerosis might be involved in the pathogenesis of arterial stiffening in SLE patients.

  • 29.
    Brodszki, J
    et al.
    Univeristy of Lund.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Physiology . Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Laurini, R
    University of Lund.
    Wide-Swensson, D
    University of Lund.
    Marsál, K
    University of Lund.
    Vascular mechanical properties and endothelial function in pre-eclampsia with special reference to bilateral uterine artery notch2008In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 87, no 2, p. 154-162Article in journal (Refereed)
    Abstract [en]

    Objectives. To assess whether women with pre-eclampsia (PE) have different properties of the blood vessel wall compared to healthy pregnant controls. Further, to evaluate endothelial function and vascular mechanical properties in women with PE with special regard to its association with bilateral uterine artery notch and placental histopathology. Participants. Some 57 Caucasian pregnant women: 23 with uncomplicated pregnancies and normal uterine artery Doppler, and 34 with PE, the PE group comprising 2 subgroups according to the presence (n=20) or absence (n=14) of bilateral uterine artery notches. Methods. Ultrasonic echo-tracking assessed the elastic properties of the common carotid artery, abdominal aorta and popliteal artery. Flow-mediated dilatation (FMD) of the brachial artery was measured by ultrasonography. Histopathological examination of the placenta was carried out in 46 pregnancies: 18 uncomplicated pregnancies, 15 with PE with bilateral notch, and 13 with PE without bilateral notch. Results. There were no significant differences in carotid, aortic or popliteal vessel wall stiffness either between women with PE and controls or within the PE group. FMD was significantly lower in women with PE than in controls (p=0.03). The lowest FMD was observed in pre-eclamptic women with bilateral uterine artery notches 9.5% (SD: 5.3) compared to 11.6% (SD: 5.4) in pre-eclamptic women without bilateral uterine artery notch, and 13.4% (SD: 4.0) in controls (p=0.01). Bilateral uterine artery notching was significantly associated with a lower FMD (OR: 0.87, 95% CI: 0.77-0.98). There were significantly more placentas with high ischaemic score in the bilateral notch group than in the group with PE and normal circulation. Conclusions. There were no differences in vessel wall stiffness between women with PE and healthy controls. Women with PE showed signs of endothelial dysfunction, significantly more pronounced in women with bilateral uterine artery notch. Bilateral uterine artery notch was associated with ischaemic pathology of the placenta. Notwithstanding, a significant number of placentas in the PE group failed to show noteworthy ischaemic or other morphological changes that could explain the role of the placenta in the development of PE.

  • 30. Brodszki, J
    et al.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Marsal, K
    Ley, D
    Impaired vascular growth in late adolescence after intrauterine growth restriction2005In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 111, no 20, p. 2623-2628Article in journal (Refereed)
    Abstract [en]

    Background - Abnormal blood flow in a fetus small for gestational age indicates true fetal intrauterine growth restriction (IUGR). We tested the hypothesis that IUGR with abnormal fetal blood flow is associated with long-term abnormal vascular morphology and function in adolescence. Methods and Results - In a prospective study, vascular mechanical properties of the common carotid artery (CCA), abdominal aorta , and popliteal artery (PA) were assessed by echo-tracking sonography in 21 adolescents with IUGR and abnormal fetal aortic blood flow and in 23 adolescents with normal fetal growth and normal fetal aortic blood flow. Endothelium-dependent and -independent vasodilatation of the brachial artery was measured by high-resolution ultrasound. After adjustment for body surface area and sex, the IUGR group had significantly smaller end-diastolic vessel diameters than the referents in the abdominal aorta and PA (mean difference, 1.7 mm [95% CI, 0.62 to 2.74] and 0.6 mm [95% CI, 0.25 to 1.02], respectively) (P=0.003 and P=0.002, respectively), with a similar trend in the CCA (P=0.09). A higher resting heart rate was observed in the IUGR group (P=0.01). No differences were found in stiffness or in endothelium-dependent and -independent vasodilatation between the 2 groups. Conclusions - IUGR caused by placental insufficiency appears to be associated with impaired vascular growth persisting into young adulthood in both men and women. The smaller aortic dimensions and the higher resting heart rate seen in adolescents with previous IUGR may be of importance for future cardiovascular health. © 2005 American Heart Association, Inc.

  • 31.
    Brodszki, J
    et al.
    Lund.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Vascular surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Stale, H
    Lund.
    Batra, S
    Lund.
    Marsal, K
    Lund.
    Altered vascular function in healthy normotensive pregnant women with bilateral uterine artery notches2002In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 109, no 5, p. 546-552Article in journal (Refereed)
    Abstract [en]

    Objectives: To assess endothelial function and vascular mechanical properties in normotensive pregnant women with high resistance in the uteroplacental circulation. Design: Cross-sectional prospective study. Setting: Doppler ultrasound laboratory at university department of obstetrics and gynaecology referral centre for high risk pregnancies. Participants: Forty-two caucasian normotensive pregnant women: 23 with uncomplicated pregnancies and 19 with bilateral uterine artery notches. Methods: Flow-mediated dilatation of the brachial artery was measured by ultrasonography at 25 gestational weeks. Concentrations of nitrite and nitrate in the plasma were established at 25 and 32 gestational weeks. The elastic properties of the common carotid artery, abdominal aorta and popliteal artery were measured with an ultrasonic echo-tracking system. Results: Flow-mediated dilatation at two minutes after cuff deflation was significantly lower in the bilateral notch group compared with the control group, 8.3% and 13.7%, respectively (P = 0.0007). The ability to sustain vasodilatation was reduced in the bilateral notch group (P = 0.02). Lower values of nitrite and nitrate in the plasma were found at 32 gestational weeks in the bilateral notch group than in the control group (mean 24.76 ╡M/ L (SD 5.6) and 30.93 ╡M/L (8.2), respectively, P = 0.008). Nitrite and nitrate levels tended to be lower in the bilateral notch group even at 25 gestational weeks (29.45 ╡M/L (8.3) and 35.73 ╡M/L (11.0) in the bilateral notch and control group, respectively, P = 0.09). There was no difference in aortic, carotid or popliteal elasticity between the two groups. Conclusions: Healthy normotensive pregnant women with bilateral uterine artery notches show impaired endothelial function, but no differences in vascular mechanical properties.

  • 32.
    Cao, Ziquan
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Jensen, Lasse
    Karolinska Institute, Sweden.
    Rouhi, Pegah
    Karolinska Institute.
    Hosaka, Kayoko
    Karolinska Institute.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Steffensen, John F
    University of Copenhagen.
    Wahlberg, Eric
    Linköping University, Department of Medical and Health Sciences, Vascular surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Cao, Yihai
    Karolinska Institute.
    Hypoxia-induced retinopathy model in adult zebrafish2010In: Nature Protocols, ISSN 1754-2189, E-ISSN 1750-2799, Vol. 5, no 12, p. 1903-1910Article in journal (Refereed)
    Abstract [en]

    Hypoxia-induced vascular responses, including angiogenesis, vascular remodeling and vascular leakage, significantly contribute to the onset, development and progression of retinopathy. However, until recently there were no appropriate animal disease models recapitulating adult retinopathy available. In this article, we describe protocols that create hypoxia-induced retinopathy in adult zebrafish. Adult fli1: EGFP zebrafish are placed in hypoxic water for 3-10 d and retinal neovascularization is analyzed using confocal microscopy. It usually takes 11 d to obtain conclusive results using the hypoxia-induced retinopathy model in adult zebrafish. This model provides a unique opportunity to study kinetically the development of retinopathy in adult animals using noninvasive protocols and to assess therapeutic efficacy of orally active antiangiogenic drugs.

  • 33.
    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.
    Jennersjö, Pär
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    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 &lt; 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 &lt; 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 &lt; 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.

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  • 34.
    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.

  • 35.
    Cinthio, Magnus
    et al.
    Lund Univ, Sweden.
    Albinsson, John
    Lund Univ, Sweden.
    Erlov, Tobias
    Lund Univ, Sweden.
    Bjarnegård, Niclas
    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.
    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.
    Ryden Ahlgren, Asa
    Lund Univ, Sweden.
    LONGITUDINAL MOVEMENT OF THE COMMON CAROTID ARTERY WALL: NEW INFORMATION ON CARDIOVASCULAR AGING2018In: Ultrasound in Medicine and Biology, ISSN 0301-5629, E-ISSN 1879-291X, Vol. 44, no 11, p. 2283-2295Article in journal (Refereed)
    Abstract [en]

    Putative changes in the multiphasic pattern of longitudinal movement of the common carotid artery wall in the normal aging process are unknown. The aim of this study was to explore the phases, and resulting patterns, of the longitudinal movement of the intima-media complex of the human common carotid artery with respect to age and gender. One hundred thirty-five healthy non-smoking patients of different ages were investigated using in-house-developed ultrasound methods. The patterns of longitudinal movement seen in middle-aged and older patients were markedly different from those commonly seen in young patients, including the appearance of two additional phases of motion and, thus, new complex patterns. The displacement and maximum velocity of one of the phases, occurring at the time of aortic valve closure, increased quadratically with age in both men and women. (C) 2018 World Federation for Ultrasound in Medicine amp; Biology. All rights reserved.

  • 36.
    Dahl Jensen, Lasse
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Cao, Ziquan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Nakamura, Masaki
    Karolinska Institute, Sweden .
    Yang, Yunlong
    Karolinska Institute, Sweden .
    Brautigam, Lars
    Karolinska Institute, Sweden .
    Andersson, Patrik
    Karolinska Institute, Sweden .
    Zhang, Yin
    Karolinska Institute, Sweden .
    Wahlberg, Eric
    Linköping University, Department of Medical and Health Sciences, Vascular surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Hosaka, Kayoko
    Karolinska Institute, Sweden .
    Cao, Yihai
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
    Opposing Effects of Circadian Clock Genes Bmal1 and Period2 in Regulation of VEGF-Dependent Angiogenesis in Developing Zebrafish2012In: Cell Reports, E-ISSN 2211-1247, Vol. 2, no 2, p. 231-241Article in journal (Refereed)
    Abstract [en]

    Molecular mechanisms underlying circadian-regulated physiological processes remain largely unknown. Here, we show that disruption of the circadian clock by both constant exposure to light and genetic manipulation of key genes in zebrafish led to impaired developmental angiogenesis. A bmal1-specific morpholino inhibited developmental angiogenesis in zebrafish embryos without causing obvious nonvascular phenotypes. Conversely, a period2 morpholino accelerated angiogenic vessel growth, suggesting that Bmal1 and Period2 display opposing angiogenic effects. Using a promoter-reporter system consisting of various deleted vegf-promoter mutants, we show that Bmal1 directly binds to and activates the vegf promoter via E-boxes. Additionally, we provide evidence that knockdown of Bmal1 leads to impaired Notch-inhibition-induced vascular sprouting. These results shed mechanistic insight on the role of the circadian clock in regulation of developmental angiogenesis, and our findings may be reasonably extended to other types of physiological or pathological angiogenesis.

  • 37.
    Dahl Jensen, Lasse
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Rouhi, Pegah
    Karolinska Institute.
    Cao, Ziquan
    Karolinska Institute.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Wahlberg, Eric
    Linköping University, Department of Medical and Health Sciences, Vascular surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Cao, Yihai
    Karolinska Institute.
    Zebrafish Models to Study Hypoxia-Induced Pathological Angiogenesis in Malignant and Nonmalignant Diseases2011In: Birth Defects Research. Part C: Embryo Today Reviews, ISSN 1542-975X, Vol. 93, no 2, p. 182-193Article, review/survey (Refereed)
    Abstract [en]

    Most in vivo preclinical disease models are based on mouse and other mammalian systems. However, these rodent-based model systems have considerable limitations to recapitulate clinical situations in human patients. Zebrafish have been widely used to study embryonic development, behavior, tissue regeneration, and genetic defects. Additionally, zebrafish also provides an opportunity to screen chemical compounds that target a specific cell population for drug development. Owing to the availability of various genetically manipulated strains of zebrafish, immune privilege during early embryonic development, transparency of the embryos, and easy and precise setup of hypoxia equipment, we have developed several disease models in both embryonic and adult zebrafish, focusing on studying the role of angiogenesis in pathological settings. These zebrafish disease models are complementary to the existing mouse models, allowing us to study clinically relevant processes in cancer and nonmalignant diseases, which otherwise would be difficult to study in mice. For example, dissemination and invasion of single human or mouse tumor cells from the primary site in association with tumor angiogenesis can be studied under normoxia or hypoxia in zebrafish embryos. Hypoxia-induced retinopathy in the adult zebrafish recapitulates the clinical situation of retinopathy development in diabetic patients or age-related macular degeneration. These zebrafish disease models offer exciting opportunities to understand the mechanisms of disease development, progression, and development of more effective drugs for therapeutic intervention.

  • 38.
    Dahlén, Elsa M
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Andreasson, Thomas
    Sahlgrenska University Hospital, Göteborg.
    Cinthio, Magnus
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Primary Health Care Centres.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Is there an underestimation of intima-media thickness based on M-mode ultrasound technique in the abdominal aorta?2012In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 32, no 1, p. 1-4Article in journal (Refereed)
    Abstract [en]

    Measuring intima-media thickness (IMT) in the common carotid artery (CCA) is a valuable resource for the evaluation of subclinical atherosclerosis. The main objective of this study was to explore whether a B-mode ultrasound technique, Philips ATL, and an M-mode ultrasound technique, Wall Track System (WTS), show interchangeable results when measured in CCA and the abdominal aorta (AA). A total of 24 healthy, young subjects were examined. IMT and lumen diameter (LD) of the AA and the CCA were measured twice by two skilled ultrasonographers with two different ultrasound equipment B-mode: (Philips, ATL and M-mode: WTS).The intra-observer variability of IMT in CCA and AA using B-mode showed a coefficient of variation 8% and 9%, and with M-mode 11% and 15%, respectively. Interobserver variability of IMT in CCA and AA using B-mode was 6% and 12%, and with M-mode 11% and 18%, respectively. CCA IMT was 0·53 ± 0·07 and 0·53 ± 0·09 mm using B-mode and M-mode, respectively. However, in AA, IMT was 0·61 ± 0·5 and 0·54 ± 0·10 mm using B-mode and M-mode, respectively. Thus, AA IMT was 11·5% thicker using B-mode (P<0·01). We received adequate IMT readings from the carotid artery as well as the AA using two commonly used B-mode and M-mode techniques. B-mode technique seems to show less variability, especially in the AA. More importantly, the two techniques measured different IMT thickness in the aorta, emphasizing the importance of using similar technique when comparing the impact of absolute values of IMT on cardiovascular disease.

  • 39.
    Dahlén, Elsa M
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Bjarnegård, Niclas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, 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 Health Sciences. Östergötlands Läns Landsting, 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 Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Sagittal abdominal diameter is a more independent measure compared with waist circumference to predict arterial stiffness in subjects with type 2 diabetes - a prospective observational cohort study2013In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 12Article in journal (Refereed)
    Abstract [en]

    Background

    Anthropometric measurements are useful in clinical practice since they are non-invasive and cheap. Previous studies suggest that sagittal abdominal diameter (SAD) may be a better measure of visceral fat depots. The aim of this study was to prospectively explore and compare how laboratory and anthropometric risk markers predicted subclinical organ damage in 255 patients, with type 2 diabetes, after four years.

    Methods

    Baseline investigations were performed in 2006 and were repeated at follow-up in 2010. Carotid intima-media thickness (IMT) was evaluated by ultrasonography and aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries at baseline and at follow-up in a cohort of subjects with type 2 diabetes aged 55–65 years old.

    Results

    There were significant correlations between apolipoprotein B (apoB) (r = 0.144, p = 0.03), C - reactive protein (CRP) (r = 0.172, p = 0.009) at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r = 0.130, p = 0.049), waist circumference (WC) (r = 0.147, p = 0.027) and sagittal Abdominal Diameter (SAD) (r = 0.184, p = 0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p = 0.036). In a stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.

    Conclusions

    We conclude that apoB and CRP, but not LDL-cholesterol predicted subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes.

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  • 40.
    Dahlén, Elsa M
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Bjarnegård, Niklas
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Department of Medical and Health Sciences, Vascular surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL. Linköping University, Faculty of Health Sciences.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, West County Primary Health Care.
    Sagittal Abdominal Diameter is a more Independent Measure compared with Waist Circumference to predict Arterial Stiffness in subjects with Type 2 DiabetesManuscript (preprint) (Other academic)
    Abstract [en]

    Aim: The aim of this study was to prospectively explore how laboratory and anthropometric risk factors predicted subclinical organ damage in 255 patients, with type 2 diabetes, after four years.

    Methods: Baseline investigations were performed in 2006 and were repeated at follow-up in 2010. Carotid intima-media thickness (IMT) was evaluated by ultrasonography and aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries at baseline and at follow-up in a cohort of subjects with type 2 diabetes aged 55-65 years old.

    Results: There were significant correlations between apolipoprotein B (apoB) (r= 0.144, p=0.03), C - reactive protein (CRP) (r=0.172, p=0.009) at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r=0.130, p=0.049), waist circumference (WC) (r=0.147, p=0.027) and sagittal Abdominal Diameter (SAD) (r=0.184, p=0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p=0.036). In a stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.

    Conclusion: We conclude that apoB and CRP, but not LDL-cholesterol predicted subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes.

  • 41.
    Dahlén, Elsa M
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Clinchy, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, 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 Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, West County Primary Health Care.
    Abdominal Obesity and low grade Systemic Inflammation as Markers for Subclinical Organ Damage in type 2 diabetes2014In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 40, no 1, p. 76-81Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to explore associations between abdominal obesity, inflammatory markers, and subclinical organ damage in 740 patients with type 2 diabetes. Waist circumference (WC) and sagittal abdominal diameter (SAD) was measured. Blood samples were analyzed for; C-reactive protein (CRP), interleukin (IL) -1β and IL-6. Carotid intimamedia thickness (IMT) was evaluated by ultrasonography. Aortic pulse wave velocity (PWV) was measured with applanation tonometry.

    Abdominal obesity were significantly correlated with; IL-6, CRP (both p= <0.001, WC and SAD, respectively), IMT (WC p=0.012, SAD p=0.003) and PWV (p<0.001, for WC and SAD, respectively). In multiple linear regressions with IMT as dependent variable and age, sex, statins, systolic blood pressure (SBP), Body Mass Index (BMI), CRP and HbA1c, as independent variables, SAD (p=0.047) but not WC, remained associated with IMT. In stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.

    We conclude that SAD and WC are feasible measures of obesity that provides information on inflammation, atherosclerosis and arterial stiffness in type 2 diabetes. However, SAD was slightly more robustly associated to subclinical organ damage, compared with WC.

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  • 42.
    Dahlén, Elsa M
    et al.
    Linköping University, Department of Medicine and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Department of Medicine and Health Sciences, Vascular surgery . Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery. Linköping University, Faculty of Health Sciences.
    Engvall, Jan
    Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology. Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Linköping University, Faculty of Health Sciences.
    Lindström, T
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL. Linköping University, Faculty of Health Sciences.
    Grodzinsky, Ewa
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland. Linköping University, Department of Medicine and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL. Linköping University, Faculty of Health Sciences.
    Östgren, Carl Johan
    Linköping University, Department of Medicine and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, West County Primary Health Care.
    Complications Carotid intima-media thickness and apolipoprotein B/apolipoprotein A-I ratio in middle-aged patients with Type 2 diabetes2009In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 26, no 4, p. 384-390Article in journal (Refereed)
    Abstract [en]

    AIMS: To explore the association between carotid intima-media thickness (IMT) and the apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio compared with conventional lipids in middle-aged patients with Type 2 diabetes. METHODS: We analysed data from 247 patients with Type 2 diabetes, aged 55-66 years, in the Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care (CARDIPP-1) study. Primary care nurses measured blood pressure and anthropometric characteristics. Blood samples were taken for laboratory analyses. The carotid IMT was determined by ultrasonography at the University Hospital in Linköping and at the County Hospital Ryhov, Jönköping, Sweden. RESULTS: The ApoB/apoA-I ratio (r = 0.207, P = 0.001), apoB (r = 0.166, P = 0.009) and non-high-density lipoprotein cholesterol (non-HDL-c) (r = 0.129, P = 0.046) correlated with IMT. Conventional lipids, high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA(1c)) and systolic blood pressure were not significantly correlated to IMT. A stepwise logistic regression analysis was conducted with IMT as the dependent variable and the apoB/apoA-I ratio, HbA(1c), hsCRP, low-density lipoprotein cholesterol (LDL-c), total cholesterol, non-HDL-c and treatment with statins as independent variables. Following adjustment for age and gender, only the apoB/apoA-I ratio remained significantly associated with IMT (odds ratio 4.3, 95% confidence intervals 1.7-10.8, P = 0.002). CONCLUSIONS: We conclude that there was a significant association between the apoB/apoA-I ratio and IMT in middle-aged patients with Type 2 diabetes. The association was independent of conventional lipids, hsCRP, glycaemic control and use of statins.

  • 43.
    Dahlén, Elsa M
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Grodzinsky, Ewa
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Nyström, Fredrik
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Carotid intima-media thickness and apolipoprotein B/apolipoprotein A-I ratio in middle-aged patients with Type 2 diabetes2009In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 26, no 4, p. 384-390Article in journal (Refereed)
    Abstract [en]

    Aims To explore the association between carotid intima-media thickness (IMT) and the apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio compared with conventional lipids in middle-aged patients with Type 2 diabetes.

    Methods We analysed data from 247 patients with Type 2 diabetes, aged 55–66 years, in the Cardiovascular Risk factors in Patients with Diabetes—a Prospective study in Primary care (CARDIPP-1) study. Primary care nurses measured blood pressure and anthropometric characteristics. Blood samples were taken for laboratory analyses. The carotid IMT was determined by ultrasonography at the University Hospital in Linköping and at the County Hospital Ryhov, Jönköping, Sweden.

    Results The ApoB/apoA-I ratio (r = 0.207, P = 0.001), apoB (r = 0.166, P = 0.009) and non-high-density lipoprotein cholesterol (non-HDL-c) (r = 0.129, P = 0.046) correlated with IMT. Conventional lipids, high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA1c) and systolic blood pressure were not significantly correlated to IMT. A stepwise logistic regression analysis was conducted with IMT as the dependent variable and the apoB/apoA-I ratio, HbA1c, hsCRP, low-density lipoprotein cholesterol (LDL-c), total cholesterol, non-HDL-c and treatment with statins as independent variables. Following adjustment for age and gender, only the apoB/apoA-I ratio remained significantly associated with IMT (odds ratio 4.3, 95% confidence intervals 1.7–10.8, P = 0.002).

    Conclusions We conclude that there was a significant association between the apoB/apoA-I ratio and IMT in middle-aged patients with Type 2 diabetes. The association was independent of conventional lipids, hsCRP, glycaemic control and use of statins.

  • 44.
    De Basso, Rachel
    et al.
    Jonköping Hospital, Sweden .
    Astrand, Hakan
    Jonköping Hospital, Sweden .
    Ryden Ahlgren, Asa
    Lund University, Sweden .
    Sandgren, Thomas
    Capio Lundby Hospital, Sweden .
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Low wall stress in the popliteal artery: Other mechanisms responsible for the predilection of aneurysmal dilatation?2014In: Vascular Medicine, ISSN 1358-863X, E-ISSN 1477-0377, Vol. 19, no 2, p. 131-136Article in journal (Refereed)
    Abstract [en]

    The popliteal artery (PA) is, after aorta, the most common site for aneurysm formation. Why the PA is more susceptible than other peripheral muscular arteries is unknown. We hypothesized that the wall composition, which in turn affects wall properties, as well as the circumferential wall stress (WS) imposed on the arterial wall, might differ compared to other muscular arteries. The aim was to study the WS of the PA in healthy subjects with the adjacent, muscular, common femoral artery (CFA) as a comparison. Ninety-four healthy subjects were included in this study (45 males, aged 10-78 years and 49 females, aged 10-83 years). The diameter and intima-media thickness (IMT) in the PA and CFA were investigated with ultrasound. Together with blood pressure the WS was defined according to the law of Laplace adjusted for IMT. The diameter increased with age in both PA and CFA (pless than0.001), with males having a larger diameter than females (pless than0.001). IMT increased with age in both PA and CFA (pless than0.001), with higher IMT values in males only in PA (pless than0.001). The calculated WS was unchanged with age in both arteries, but lower in PA than in CFA in both sexes (pless than0.001). In conclusion, this study shows that the PA and CFA WS is maintained during aging, probably due to a compensatory remodelling response with an increase in arterial wall thickness. However, the stress imposed on the PA wall is quite low, indicating that mechanisms other than WS contribute to the process of pathological arterial dilatation in the PA.

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  • 45.
    De Basso, Rachel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Hedblad, Bo
    Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
    Carlson, Joyce
    Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
    Persson, Margaretha
    Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
    Östling, Gerd
    Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Increased carotid plaque burden in men with the Fibrillin-1 2/3 genotype2014In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 41, no 9, p. 637-642Article in journal (Refereed)
    Abstract [en]

    Objective: Fibrillin-1 is an important constituent of the vascular wall and earlier studies have indicated an effect of the Fibrillin-1 (FBN1) 2/3 genotype on blood pressure as well as aortic stiffness in men. The aim was to determine if the FBN1 2/3 genotype was associated with presence of carotid plaque and incident cardiovascular morbidity and mortality in middle-aged subjects.

    Material and Method: The FBN1 genotype was characterized in 5765 subjects (2424 men, 3341 women; aged 45-69 years) recruited from the Malmö Diet and Cancer Study Cardiovascular Cohort, Sweden. Plaque occurrence and intima media thickness (IMT) of the carotid artery were assessed by ultrasound. Incidence of first cardiovascular events (myocardial infarction and stroke) and cause-specific mortality was monitored during a mean of 13.2 years follow-up.

    Results: The most common FBN1 genotypes were 2/2, 2/3 and 2/4 which accounted for 92.2% (n=5317) of the subjects. There were no differences between the three genotypes regarding age, blood pressure, glucose, lipids, smoking habits, CCA diameter and IMT in men and women. Presence of plaque in the carotid artery was higher in men with genotype 2/3 as compared to the 2/2 and 2/4 genotypes, (55% vs. 46% and 50%, p=0.007). No similar difference was observed in women. No significant relationship was observed between FBN1 genotypes and incidence of CVD or all-cause mortality.

    Conclusions: The increased prevalence of plaque in the carotid artery of middle-aged men with FBN1 2/3 genotype indicates a pathological arterial wall remodeling with a more pronounced atherosclerotic burden. 

  • 46.
    De Basso, Rachel
    et al.
    Jonköping University, Sweden; Jonköping University, Sweden.
    Sandgren, Thomas
    Capio Lundby Hospital, Sweden.
    Ryden Ahlgren, Asa
    Lund University, Sweden.
    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.
    Increased cardiovascular risk without generalized arterial dilating diathesis in persons who do not have abdominal aortic aneurysm but who are first-degree relatives of abdominal aortic aneurysm patients2015In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 42, no 6, p. 576-581Article in journal (Refereed)
    Abstract [en]

    There is a strong genetic predisposition towards abdominal aortic aneurysm (AAA), but it is unknown whether persons without AAA but with first-degree relatives who are AAA patients have a generalized dilating diathesis, defect arterial wall mechanics, or increased cardiovascular risk. The aim of the study was to investigate arterial diameters and wall mechanics at multiple arterial sites in these subjects and compare them with controls without a family history of AAA. This study included 118 first-degree relatives of patients with AAA and 66 controls (age: 40-80years). The abdominal aorta, common carotid artery, common femoral artery, and popliteal artery were investigated by echo-tracking ultrasound. The relatives had no arterial dilatation, but they did tend to have smaller diameters than controls. Relatives had a higher heart rate, diastolic blood pressure, and mean arterial pressure than controls. The distensibility coefficient and the compliance coefficient were decreased in all arteries in male relatives, adjusted for age and smoking; these coefficients were normalized after adjustment for mean arterial pressure and heart rate. Female relatives had a lower compliance coefficient in the abdominal aorta, adjusted for age and smoking. After adjustment for mean arterial pressure and heart rate, the difference disappeared. No general arterial dilatation in relatives without AAA was found, supporting the hypothesis that the dilating diathesis is linked to the aneurysmal manifestation in the abdominal aorta. Although the threat of aneurysmal dilatation and rupture seems to be lacking in these subjects, heart rate, blood pressure, and arterial wall stiffness were all increased, which may indicate a higher risk of developing cardiovascular morbidity and mortality.

  • 47.
    De Basso, Rachel
    et al.
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    Åstrand, Håkan
    Department of Vascular Surgery, Jönköping Hospital, Jönköping, Sweden.
    Rydén Ahlgren, Åsa
    Clinical Physiology and Nuclearmedicine Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Sandgren, Thomas
    Department of Surgery, Capio Lundby Hospital, Gothenburg, Sweden.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Low wall stress in popliteal artery – other mechanisms responsible for the predilection of aneurysmal dilatation?Manuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: The popliteal artery (PA) is, after aorta, the most common site for aneurysm formation. Why the PA is more susceptible than other peripheral muscular arteries is unknown. We hypothesised that the wall composition, which in turn affects wall properties, as well as the circumferential wall stress imposed on the arterial wall, might differ compared to other muscular arteries. The aim was to study the circumferential wall stress of the PA in healthy subjects with the adjacent muscular common femoral artery (CFA) as a comparison.

    Material and Methods: Ninety-four healthy subjects were included in this study (45 males, range 10-78 years and 49 females, range 10-83 years). The lumen diameter (LD) and intima-media thickness (IMT) in the PA and CFA were investigated with a Philips P700 ultrasound device. Together with blood pressure the circumferential wall stress was defined according to the law of Laplace adjusted for IMT.

    Results: The diameter increased with age in both PA and CFA (P<.001), with males having larger diameter than females (P<.001). IMT increased with age in both PA and CFA (P<.001), with higher IMT values in males only in PA (P<0.001). The calculated wall stress was unchanged with age in both arteries, but lower in PA than in CFA in both male and female subjects (P<0.001).

    Conclusion: This study shows that the popliteal and common femoral artery wall stress is maintained during ageing, probably due to compensatory remodeling response with an increase in arterial wall thickness. However, the stress imposed on the popliteal artery wall is quite low, indicating that other mechanisms than wall stress contribute to the process of pathological arterial dilatation in the popliteal artery.

  • 48.
    Debasso, Rachel
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Physiology.
    Fagerlind, A
    Sandgren, T
    Rydén Ahlgren, Å
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Increased Cardiovascular Risk in First-degree Relatives (without abdominal aortic aneurysm, AAA) to AAA Patients?2007In: Artery 7,2007, 2007Conference paper (Other academic)
  • 49.
    Debasso, Rachel
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Åstrand, Håkan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Bjarnegård, Niclas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Ryden Ahlgren, A
    Sandgren, T
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    The popliteal artery, an unusual muscular artery with wall properties similar to the aorta: Implications for susceptibility to aneurysm formation?2004In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 39, no 4, p. 836-842Article in journal (Refereed)
    Abstract [en]

    Objective: The popliteal artery is, after the aorta, the most common site for aneurysm formation. Why the popliteal artery is more susceptible than other peripheral muscular arteries is unknown. An important factor may be differences in arterial wall composition as compared with other peripheral muscular arteries, which in turn affect wall properties. These are however unknown. We studied the mechanical wall properties of the popliteal artery in healthy subjects. Material and Methods: An ultrasound echo-tracking system was used to measure pulsatile changes in popliteal diameter in 108 healthy subjects (56 female, 52 male, age range, 9-82 years). In combination with blood pressure, stiffness (β), strain, cross-sectional artery wall compliance coefficient (CC), and distensibility coefficient (DC) were calculated. Intima-media thickness (IMT) was registered with a Philips P700 ultrasound scanner. Results: The popliteal diameter increased with age, and was larger in male subjects than in female subjects (P < .001). Fractional diameter change (strain) decreased with age (P < .001), and strain values were lower in male subjects than in female subjects (P < .01). Accordingly, stiffness increased with age (P < .001), with higher stiffness values in male subjects (P < .01). DC decreased with age (P < .001), with lower DC values in male subjects (P < .01). CC decreased with age, with no difference between genders (P < .001). IMT increased with age (P < .001), with higher IMT values in male subjects (P < .001). The increase in IMT did not affect distensibility. Conclusion: The wall properties of the popliteal artery are affected by age and gender, not only with an increase in diameter, but also with an age-related decrease in distensibility, with male subjects having lower distensibility than in female subjects. This seems not to be the behavior of a true muscular artery, but of a central elastic artery, such as the aorta, and might have implications for susceptibility to arterial dilatation, as well as the association of aneurysm formation between the aorta and the popliteal artery.

  • 50.
    Dong, Mei
    et al.
    Shandong University, Peoples R China .
    Yang, Xiaoyan
    Shandong University, Peoples R China .
    Lim, Sharon
    Karolinska Institute, Sweden .
    Cao, Ziquan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Honek, Jennifer
    Karolinska Institute, Sweden .
    Lu, Huixia
    Shandong University, Peoples R China .
    Zhang, Cheng
    Shandong University, Peoples R China .
    Seki, Takahiro
    Karolinska Institute, Sweden .
    Hosaka, Kayoko
    Karolinska Institute, Sweden .
    Wahlberg, Eric
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Yang, Jianmin
    Shandong University, Peoples R China .
    Zhang, Lei
    Shandong University, Peoples R China .
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Sun, Baocun
    Tianjin Medical University, Peoples R China .
    Li, Xuri
    Sun Yat Sen University, Peoples R China .
    Liu, Yizhi
    Sun Yat Sen University, Peoples R China .
    Zhang, Yun
    Shandong University, Peoples R China .
    Cao, Yihai
    Karolinska Institute, Sweden .
    Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis2013In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 18, no 1, p. 118-129Article in journal (Refereed)
    Abstract [en]

    Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown. Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice. In two genetic mouse knockout models (apolipoprotein E-/- [ApoE(-/-)] and LDL receptor(-/-) [Ldlr(-/-)] mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition. Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability. Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions. Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development. These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.

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