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  • 301. Greve, Anders M.
    et al.
    Gerdts, Eva
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gohlke-Baerwolf, Christa
    Rossebo, Anne B.
    Hammer-Hansen, Sophia
    Kober, Lars
    Willenheimer, Ronnie
    Wachtell, Kristian
    Differences in Cardiovascular Risk Profile Between Electrocardiographic Hypertrophy Versus Strain in Asymptomatic Patients With Aortic Stenosis (from SEAS Data)2011In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 108, no 4, p. 541-547Article in journal (Refereed)
    Abstract [en]

    Electrocardiograms are routinely obtained in clinical follow-up of patients with asymptomatic aortic stenosis (AS). The association with aortic valve, left ventricular (LV) response to long-term pressure load, and clinical covariates is unclear and the clinical value is thus uncertain. Data from clinical examination, electrocardiogram, and echocardiogram in 1,563 patients in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study were used. Electrocardiograms were Minnesota coded for arrhythmias and atrioventricular and intraventricular blocks; LV hypertrophy was assessed by Sokolow-Lyon voltage and Cornell voltage duration criteria; and strain by T-wave inversion and ST-segment depression. Degree of AS severity was evaluated by echocardiography as peak aortic jet velocity and LV mass was indexed by body surface area. After adjustment for age, gender, LV mass index, heart rate, systolic and diastolic blood pressures, blood glucose, digoxin, antiarrhythmic drugs, drugs acting on the renin angiotensin system, diuretics, beta blockers and calcium receptor blockers; peak aortic jet velocity was significantly greater in patients with electrocardiographic strain (mean difference 0.13 m/s, p <0.001) and LV hypertrophy by Sokolow-Lyon voltage criteria (mean difference 0.12 m/s, p = 0.004). After similar adjustment, LV mass index was significantly greater in patients with electrocardiographic strain (mean difference 14.8 g/cm(2), p <0.001) and LV hypertrophy by Sokolow-Lyon voltage criteria and Cornell voltage duration criteria (mean differences 8.8 and 17.8 g/cm(2), respectively, p <0.001 for the 2 comparisons). In multiple comparisons patients with electrocardiographic strain had increased peak aortic jet velocity, blood glucose, and uric acid, whereas patients with LV hypertrophy by Sokolow-Lyon voltage criteria were younger and patients with LV hypertrophy by Cornell voltage duration criteria more often were women. In conclusion, electrocardiographic criteria for LV hypertrophy and strain are independently associated with peak aortic jet velocity and LV mass index. Moreover, clinical covariates differ significantly between patients with electrocardiographic strain and those with LV hypertrophy by Sokolow-Lyon voltage criteria and Cornell voltage duration criteria. 

  • 302. Greve, Anders M.
    et al.
    Gerdts, Eva
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Dept Med Skellefta, Skellefta, Sweden.
    Gohlke-Baerwolf, Christa
    Rossebo, Anne B.
    Nienaber, Christoph A.
    Ray, Simon
    Egstrup, Kenneth
    Pedersen, Terje R.
    Kober, Lars
    Willenheimer, Ronnie
    Wachtell, Kristian
    Prognostic importance of atrial fibrillation in asymptomatic aortic stenosis: The Simvastatin and Ezetimibe in Aortic Stenosis study2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 166, no 1, p. 72-76Article in journal (Refereed)
    Abstract [en]

    Background: The frequency and prognostic importance of atrial fibrillation (AF) in asymptomatic mild-to-moderate aortic stenosis (AS) has not been well described. Methods: Clinical examination, electrocardiography and echocardiography were obtained in asymptomatic patients with mild-to-moderate AS and preserved left ventricular (LV) systolic function, randomized to simvastatin/ezetimibe combination vs. placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. At inclusion, AF was categorized as episodic or longstanding. Rhythm change was assessed on annual in-study electrocardiograms. Impact of AF on cardiovascular morbidity and mortality was determined by adjusting for biomarkers, clinical- and echocardiographic covariates. Results: Mean follow-up was 4.3 +/- 0.8 years (6,721 patient-years of follow-up). At baseline, episodic AF was present in 87 patients (5.6%), longstanding AF in 55 (3.5%) and no AF in 1,421 (90.9%). Incidence of new-onset AF was 1.2%/year; highest in those with impaired LV function. In multivariable analysis, longstanding AF was compared to no AF at baseline, associated with a 4.1-fold higher risk of heart failure (CI 1.2 to 13.8, p = 0.02) and a 4.8-fold higher risk of non-hemorrhagic stroke (CI 1.7 to 13.6, p = 0.003). Conclusion: Rate of AF is moderate in asymptomatic AS. Longstanding but not episodic AF was, independently predictive of increased risk of heart failure and non-hemorrhagic stroke. New-onset AF was associated with cardiac decompensation. (c) 2011 Elsevier Ireland Ltd. All rights reserved.

  • 303. Greve, Anders M.
    et al.
    Olsen, Michael H.
    Bella, Jonathan N.
    Lonnebakken, Mai T.
    Gerdts, Eva
    Okin, Peter M.
    Palmieri, Vittorio
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nieminen, Markku S.
    Omvik, Per
    Dahlof, Bjorn
    Devereux, Richard B.
    Wachtell, Kristian
    Contrasting Hemodynamic Mechanisms of Losartan- vs. Atenolol-Based Antihypertensive Treatment: A LIFE Study2012In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 25, no 9, p. 1017-1023Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Pharmaceutical differences in central hemodynamics might influence cardiac response to antihypertensive treatment despite similar lowering of brachial blood pressure (BP). METHODS Data from all patients with at least two echocardiographic examinations in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) echocardiographic substudy (n = 801); high-risk patients on losartan- vs. atenolol-based antihypertensive therapy. Echocardiography was performed annually for 4 years to measure stroke index (SI), heart rate, cardiac index (CI), conduit artery stiffness assessed as pulse pressure/stroke index (PP/SI) and total peripheral resistance index (TPRI). RESULTS Atenolol- and losartan-based therapy reduced BP similarly (cumulative difference in mean brachial blood pressure 0.3 mm Hg, P = 0.65). After 4 years the cumulative means of SI and heart rate were 1.8 ml/m(2) higher and 5.7 beats/min lower on atenolol-based treatment, respectively (both P < 0.001). This kept CI below baseline in atenolol-treated patients, whereas in the losartan group CI was unchanged from baseline throughout the study. TPRI was decreased more and remained lower in the losartan group (cumulative difference in mean TPRI 287 dynes/sec(-5)/cm/m(2), P < 0.001). These findings partly explained univariate differences in systolic- and diastolic function indices between the two treatments; fully adjusted losartan was only associated with a smaller left atrial diameter (cumulative mean difference 0.07 cm; 95% confidence intervals, -0.13 to -0.01, P = 0.03). CONCLUSIONS Contrasting hemodynamics impacted cardiac response to similar reductions in brachial BP on losartan- vs. atenolol-based therapy. The similar reduction of PP/SI suggests that the antihypertensive regimens used in the LIFE study had comparable effects on arterial stiffness (LIFE study; NCT00338260)

  • 304. Grogan, Martha
    et al.
    Hawkins, Philip N.
    Kristen, Arnt V.
    Berk, John L.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lin, Hollis
    Merkel, Madeline
    McManus, Anastasia
    Powell, Christine
    Vest, John
    Karsten, Verena
    Judge, Daniel P.
    Identifying Mixed Phenotype: Evaluating the Presence of Polyneuropathy in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Cardiomyopathy2019In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 25, no 8, p. S9-S10Article in journal (Other academic)
  • 305.
    Grzymala-Lubanski, Bartosz
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Anticoagulation treatment in patients with a mechanical heart valve2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Every year about 2,500 patients in Sweden undergo surgery for heart valve disease, primarily in the aortic valve.  In contrast to the mitral valve, which can be repaired in 70% of the cases, the aortic valve is normally replaced by a mechanical or biological prosthesis. A mechanical heart valve (MHV) necessitates lifelong anticoagulation treatment with a vitamin K antagonist, most commonly warfarin, due to the high thrombogenicity of the prosthesis. The quality of the warfarin treatment is crucial in these patients. Compared to other countries, treatment quality in Sweden is very high; nonetheless, there is always room for improvement. One of the ways to achieve this improvement is to implement computerized dosing assistance. Treatment recommendations for anticoagulation intensity are based on few and old studies, making these recommendations uncertain. There is therefore a need for studies designed to establish the appropriate level of anticoagulation therapy.

    Aim

    The aim of these studies was to investigate the efficacy and safety of anticoagulation treatment among patients with mechanical heart valve prostheses in Sweden; to assess whether computerized dosing can increase the treatment quality; to investigate the influence of the treatment quality, measured by Time in Therapeutic Range (TTR) and INR variability, on the risk of complications and, finally, to establish the optimal intensity of anticoagulation treatment in this group of patients.

    Methods

    Data were obtained from AuriculA – a national quality registry established in 2006, which currently includes approximately 50% of all patients treated with oral anticoagulation in Sweden.

    Study II used only data from AuriculA. 769,933 warfarin-dosing suggestions proposed by the dosing algorithm in AuriculA were analysed. Accepted dose suggestions (590,939) were compared with 178,994 manually-changed doses in regard to the resultant INR value, measured as mean error (deviation from target INR) and hit rate (number of INR samples within the target range 2-3).

    In study III, AuriculA was used to identify patients in Sundsvall and Malmö in the period 2008 – 2011 who were receiving warfarin for a mechanical heart valve prosthesis, as well as to retrieve their INR data. Data on background characteristics and bleedings or thromboembolic complications were manually retrieved from medical records by two investigators.  A total of 534 patients with mechanical heart valve prostheses were divided into quartiles based on TTR and were compared regarding the risk of complications.

    For Studies I and IV, data from AuriculA were merged with the Swedish National Patient Register, SWEDEHEART/ Heart surgery, and the Swedish Cause of Death Register, comprising in total 77,423 patients on warfarin with 217,804 treatment years. Every treatment period registered in AuriculA was given an individual identification number. During the study period a patient could have any number of treatment periods. The number of complications in total and in different patient groups within the study population was investigated. Complications were defined by ICD-10 codes. Major bleeding was defined as an event necessitating hospital treatment and given a discharge diagnosis with one of the ICD-10 codes reflecting bleeding, as listed in the Appendix. Bleeding events were divided into intracranial, gastrointestinal and other bleedings. Thromboembolic complications consist of venous events (deep vein thrombosis, pulmonary embolism, venous stroke) or arterial events (stroke, TIA, acute myocardial infarction, peripheral arterial embolism).

    Data were analysed using both simple, descriptive statistical methods and various tests such as Mann-Whitney (or two sample Wilcoxon), T-test, Chi 2 test, ANOVA, multivariate analysis with logistic regression and survival analysis with Cox Regression with proportional hazard assumption.

    Results

    Treatment quality 

    Mean TTR among all patients in Study I was 76.5% whereas patients with mechanical heart valve prostheses had a TTR of 74.5%. The annual incidence of major bleeding or thromboembolic events among all patients was 2.24% and 2.65%, respectively. The incidence of intracranial bleeding was 0.37% per year in the general population and 0.51% among patients with mechanical heart valve prostheses, who also had a higher bleeding rate in total (3.37% per year).

    Both the mean and median errors were smaller (0.44 vs. 0.48 and 0.3 vs. 0.4, respectively) and the hit rate was higher (0.72 vs. 0.67) when the dose suggested by the algorithm was accepted, compared to when it was manually changed.

    TTR 

    In Study III there was no significant difference in the risk of thromboembolism regardless of TTR level. Risk of bleeding in quartiles I and II was more than two times higher than in the quartile with TTR >82.9.

    In Study IV, lower TTR (≤70%) was associated with a significantly higher rate of complications when compared with TTR >70%. Bleeding risk was higher in the group with lower TTR (HR=2.43, CI 2.02-2.89, p<0.001). After dividing patients into TTR quartiles, the rate of complications in total was significantly higher in quartiles I to III compared with quartile IV, which had the highest TTR. Risk of thromboembolism, major bleeding and death was higher in the first and second quartile compared to the quartile with the highest TTR.

    INR variability 

    Higher INR variability above mean (≥0.40) was related to a higher rate of complications compared with lower INR variability (<0.40) as shown in Study IV. Bleeding risk was higher in the group with INR variability ≥0.40 (HR = 2.15, CI 1.75-2.61, p<0.001).

    Comparison of quartile IV, which had the lowest INR variability, with the other three revealed that quartiles I and II, which had the highest INR variability, had significantly worse outcomes for all complications except for thromboembolic events, plus also death in quartile II.

    TTR and INR variability combined 

    High variability and low TTR combined was associated with a higher risk of bleedings (HR 2.50, CI 1.99-3.15), death (3.34, CI 2.62-4-27) and thrombosis (1.55, CI 1.21-1.99) compared to the best group.

    Level of anticoagulation

    Higher warfarin treatment intensity (mean INR 2.8-3.2 vs. 2.2-2.7) was associated with a higher rate of bleedings (HR 1.29, CI 1.06-1.58), death (1.73, CI 1.38-2.16) and complications in total (1.24, CI 1.06-1.41) after adjustment for MHV position, age and comorbidity.

    Conclusion

    Warfarin treatment quality is crucial for patients with mechanical heart valve prostheses. Computerized dosing assistance could help maintain high warfarin treatment quality.

    Well-managed treatment with TTR ≥70% and INR variability below mean <0.40 is associated with a lower risk of serious complications compared with a lower TTR and higher INR variability.

    No benefit of higher warfarin treatment intensity was found for any valve type or position.

  • 306.
    Grzymala-Lubanski, Bartosz
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Internal medicine, Sundsvall Hospital.
    Labaf, Ashkan
    Department for Coagulation Disorders, University of Lund, Malmö, Sweden.
    Englund, Erling
    Department of Research and Development, County Council of Västernorrland, Sundsvall Hospital, Sundsvall, Sweden.
    Svensson, Peter J.
    Department for Coagulation Disorders, University of Lund, Malmö, Sweden.
    Själander, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mechanical heart valve prosthesis and warfarin: treatment quality and prognosis2014In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 133, no 5, p. 795-798Article in journal (Refereed)
    Abstract [en]

    Introduction: Every year about 2500 patients in Sweden undergo surgery due to heart valve disease. A mechanical heart valve prosthesis causes risk of thromboembolic stroke or thrombus formation in the valve while anticoagulant treatment increases the risk of bleeding. Treatment quality with warfarin is crucial for patients with mechanical valve prostheses. It has previously been shown that poorly controlled warfarin treatment increases mortality in this patient group. TTR (Time in Therapeutic Range) on warfarin has been shown to affect the risk of complications in atrial fibrillation, but has not been studied in patients with mechanical heart valves. Our aim is to evaluate the impact of TTR on the risk of complications in this patient group. Materials and Methods: A non-randomized, prospective study of 534 adults with mechanical heart valve prostheses from Malmo and Sundsvall registered in the Swedish National Quality Registry Auricula between 01.01.2008 and 31.12.2011. Quartiles regarding individual TTR levels were compared regarding risk of complications. Results: The risk of complications was significantly higher at lower TTR levels for all complications (p = 0.005), bleeding (p = 0.01) and death (p = 0.018) but not for thromboembolism. In multivariate analysis the risk was significantly increased at lower TTR levels for bleeding and all complications but not for death or thromboembolism. Conclusion: Patients with a lower warfarin treatment quality measured by TTR have a higher risk of complications such as severe bleeding or death. A TTR of 83% or higher at the individual level should be obtained for best outcome.

  • 307.
    Grzymala-Lubanski, Bartosz
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Själander, Sara
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Renlund, Henrik
    Svensson, Peter J.
    Själander, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Computer aided warfarin dosing in the Swedish national quality registry AuriculA: algorithmic suggestions are performing better than manually changed doses2013In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 131, no 2, p. 130-134Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Warfarin treatment with a high time in therapeutic range (TTR) is correlated to fewer complications. The TTR in Sweden is generally high but varies partly depending on local expertise and traditions. A dosing algorithm could minimize variations and increase treatment quality. Here we evaluate the performance of a computerized dosing algorithm.

    MATERIALS AND METHODS: 53.779 warfarin treated patients from 125 centers using the Swedish national quality registry AuriculA. If certain criteria are met, the algorithm gives one of seven possible dose suggestions, which can be unchanged, decreased or increased weekly dose by 5, 10 or 15%. The outcome evaluated by the resulting INR value was compared between dose suggestions arising from the algorithm that were accepted and those that were manually changed. There were no randomization, and outcomes were retrospectively analyzed.

    RESULTS: Both the algorithm-based and the manually changed doses had worse outcome if only two instead of three previous INR values were available. The algorithm suggestions were superior to manual dosing regarding percent samples within the target range 2-3 (hit-rate) or deviation from INR 2.5 (mean error). Of the seven possible outcomes from the algorithm, six were significantly superior and one equal to the manually changed doses when three previous INR:s were present.

    CONCLUSIONS: The algorithm-based dosing suggestions show better outcome in most cases. This can make dosing of warfarin easier and more efficient. There are however cases where manual dosing fares better. Here the algorithm will be improved to further enhance its dosing performance in the future.

  • 308.
    Grönlund, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Albano, Amanda
    Gustavsson, Sandra
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wiklund, Urban
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Significant beat-to-beat variability of E/e’ irrespective of respiration2013In: International cardiovascular forum, ISSN 2409-3424, Vol. 1, no 2, p. 88-89Article in journal (Refereed)
    Abstract [en]

    The E/e’ ratio is commonly used in Doppler echocardiographic examinations to estimate the pulmonary capillary wedge pressure. The rationale of using this ratio is to combine left ventricular (LV) filling (E) and relaxation (e’) velocities to indirectly assess left atrial pressure. However, the accuracy of this index has recently been questioned, particularly in patients with controlled heart failure. Likewise, the potential beat-to-beat variability of such measurements remains undetermined. The cardiovascular system is subject to several oscillations with the potential of influencing LV function and its intra-cavitary pressures, hence measurements of its filling and relaxation velocities. The aim of this pilot study was to assess the beat-to-beat variability of the E/e’ ratio in one minute long examination in healthy subjects, and patients with various severity of amyloid heart disease. The results show that despite critical application of the standard echocardiographic recording recommendations, E/e’ beat-to-beat variability was 36 % (22 to 50%) in healthy subjects and 17 % (11-26%) in patients, and where the most severe amyloid heart disease had the least variability. Thus, clinical use of a single or few cardiac beats might not necessarily reflect an accurate ratio between the two velocities, and hence casts doubt over their diagnostic value.

  • 309. Grøntved, Anders
    et al.
    Koivula, Robert W
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Østergaard, Lars
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Skåne University Hospital Malmö, Malmö, Sweden.
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Skåne University Hospital Malmö, Malmö, Sweden.
    Bicycling to Work and Primordial Prevention of Cardiovascular Risk: A Cohort Study Among Swedish Men and Women2016In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, no 11, article id e004413Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bicycling to work may be a viable approach for achieving physical activity that provides cardiovascular health benefits. In this study we investigated the relationship of bicycling to work with incidence of obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance across a decade of follow-up in middle-aged men and women.

    METHODS AND RESULTS: We followed 23 732 Swedish men and women with a mean age of 43.5 years at baseline who attended a health examination twice during a 10-year period (1990-2011). In multivariable adjusted models we calculated the odds of incident obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance, comparing individuals who commuted to work by bicycle with those who used passive modes of transportation. We also examined the relationship of change in commuting mode with incidence of these clinical risk factors. Cycling to work at baseline was associated with lower odds of incident obesity (odds ratio [OR]=0.85, 95% CI 0.73-0.99), hypertension (OR=0.87, 95% CI 0.79-0.95), hypertriglyceridemia (OR=0.85, 95% CI 0.76-0.94), and impaired glucose tolerance (OR=0.88, 95% CI 0.80-0.96) compared with passive travel after adjusting for putative confounding factors. Participants who maintained or began bicycling to work during follow-up had lower odds of obesity (OR=0.61, 95% CI 0.50-0.73), hypertension (OR=0.89, 95% CI 0.80-0.98), hypertriglyceridemia (OR=0.80, 95% CI 0.70-0.90), and impaired glucose tolerance (OR=0.82, 95% CI 0.74-0.91) compared with participants not cycling to work at both times points or who switched from cycling to other modes of transport during follow-up.

    CONCLUSIONS: These data suggest that commuting by bicycle to work is an important strategy for primordial prevention of clinical cardiovascular risk factors among middle-aged men and women.

  • 310.
    Gu, Weigang
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Thrombectomy versus intravenous thrombolysis for treating acute anterior and posterior circulation stroke2016In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 41, p. 145-145Article in journal (Other academic)
  • 311. Gueyffier, Francois
    et al.
    Marchant, Ivanny
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Modeling the impact of cardiovascular prevention strategies: toward better information for public health decisions2012In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 30, no 1, p. 51-52Article in journal (Refereed)
  • 312.
    Gustafsson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Grönlund, Christer
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Discriminating hereditary transthyretin cardiomyopathy from hypertrophic cardiomyopathy using an echocardiographic and ECG based classification tree2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no Supplement 1, Meeting abstract P5254, p. 929-929Article in journal (Other academic)
  • 313.
    Gustafsson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Grönlund, Christer
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology. Umeå Heart Centre.
    Can echocardiography differentiate hereditary transthyretin amyloidosis from hypertrophic cardiomyopathy?2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no Supplement: 1, p. 213-213Article in journal (Other academic)
    Abstract [en]

    Purpose: Hereditary transthyretin amyloidosis (ATTR) andhypertrophic cardiomyopathy (HCM) have many phenotypic similarities when examined by echocardiography. As the two conditions have different treatment strategies it is of importance to accurately diagnose these patients early in the disease. This study aimed to identify the most accurate echocardiographic method in differentiating these two conditions by using traditional and speckle tracking echocardiographyas well as myocardial texture analysis.

    Methods: We investigated 40 healthy controls, 33 patients with biopsy proven ATTR and 20 with HCM. All patients had septal thickness >12 mm. We measured left ventricular (LV) global strain as intrinsic systolic function and LV E/e' to estimate filling pressures. We also tested septal cyclic integrated backscatter (cIBS) and septal entropy as both being measures for myocardial highly reflection pattern whereas cIBS showing motion of highly reflective echoes and entropy the distribution of highly reflective echoes.

    Results: LV global strain, cIBS and E/e' were not useful in differentiating ATTR from HCM. However, septal entropy was found to be significantly different and showed an area under the curve from ROC analysis of 0.66 separating ATTR from HCM.

    Conclusion: After using detailed analysis of different aspects of LV morphology and function we found that myocardial texture behavior from entropy analysis was the only method useful in differentiating patients with ATTR fromHCM.

  • 314.
    Gustafsson, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ventricular rotation and the rotation axis: a new concept in cardiac function2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: The twisting motion of the left ventricle (LV), with clockwise rotation at the base and counter clockwise rotation at the apex during systole, is a vital part of LV function. Even though LV rotation has been studied for decades, the rotation pattern has not been described in detail. By the introduction of speckle tracking echocardiography measuring rotation has become easy of access. However, the axis around which the LV rotates has never before been assessed. The aims of this thesis were to describe the rotation pattern of the LV in detail (study I), to assess RV apical rotation (study II), develop a method to assess the rotation axis (study III) and finally to study the effect of regional ischemia to the rotation pattern of the LV (study IV).

    Methods: Healthy humans were examined in study I-III and the final study populations were 40 (60±14 years), 14 (62±11 years) and 39 (57±16 years) subjects, respectively. In study IV six young pigs (32-40kg) were studied. Standard echocardiographic examinations were performed. In study IV the images were recorded before and 4 minutes after occlusion of left anterior descending coronary artery (LAD). Rotation was measured in short axis images by using a speckle tracking software. By development of custom software, the rotation axis of the LV was calculated at different levels in every image frame throughout the cardiac cycle.

    Results: Study I showed significant difference in rotation between basal and apical rotations, as well as significant differences between segments at basal and mid ventricular levels. The rotation pattern of the LV was associated with different phases of the cardiac cycle. Study II found significant difference in rotation between the LV and the RV. RV rotation was heterogeneous and bi-directional, creating a ´tightening belt action´ to reduce it circumference. Study III indicated that the new method could assess the rotation axis of the LV. The motion of the rotation axes in healthy humans displayed a physiological and consistent pattern. Study IV found a significant difference in the rotation pattern, between baseline and after LAD occlusion, by measuring the rotation axes, but not by conventional measurements of rotation. AV-plane displacement and wall motion score (WMS) were also significantly changed after inducing regional ischemia.

    Conclusion: There are normally large regional differences in LV rotation, which can be associated anatomy, activation pattern and cardiac phases, indicating its importance to LV function. In difference to the LV, the RV did not show any functional rotation. However, its heterogeneous circumferential motion could still be of importance to RV function and may in part be the result of ventricular interaction. The rotation axis of the LV can now be assessed by development of a new method, which gives a unique view of the rotation pattern. The quality measurements and results in healthy humans indicate that it has a potential clinical implication in identifying pathological rotation. This was supported by the experimental study showing that the rotation axis was more sensitive than traditional measurements of rotation and as sensitive as AV-plane displacement and WMS in detecting regional myocardial dysfunction.

  • 315.
    Gustafsson, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Larsson, M
    School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden.
    Bjällmark, A
    School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Aroch, Roman
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The effect of acute myocardial ischemia on the rotation axis of the left ventricleManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: We have developed a method to assess the axis around which the left ventricle (LV) rotates. The aim was to assess the effect of acute regional ischemia on the otation axis.

    Method: Mid‐LAD occlusion was induced in six anesthetised pigs and echocardiographic images were recorded at baseline and after LAD occlusion. The rotation axis was calculated at three different levels of the LV throughout the cardiac cycle. Results: The direction of the rotation axis was significantly changed (p<0.01) after LAD occlusion, being directed towards the ischemic area. AV‐plane displacement was significantly reduced (p<0.05) during ischemia. No significant difference in twist or otation amplitudes was found.

    Conclusion: This new method of assessing rotational function seems as sensitive as AV‐plane displacement and superior to traditional rotation and twist parameters in detecting dysfunction in acute ischemic myocardium. The rotation axis method has the advantage of potentially identifying areas with dysfunction.

  • 316.
    Gustafsson, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Larsson, M
    School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden.
    Bjällmark, A
    School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Brodin, LA
    School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The rotation axis of the left ventricle: a new concept derived from ultrasound data in healthy individualsManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: The axis around which the left ventricle (LV) rotates has never previously been described. The aim was to develop a method to calculate the spatial motion of the rotation axis throughout the cardiac cycle.

    Method: By constructing a model of the LV, based on dimensions and rotation values at the basal, mid ventricular and apical levels, a rotation axis could be calculated at each level in 39 healthy subjects. The transition plane, defined as the level without rotation, where basal and apical rotation meet was also calculated.

    Results: The rotation axis was not congruent to the longitudinal axis of the LV at any time point. A significant and specific mean direction for each of the rotation axes for the majority of the tested time points displayed a physiological pattern.

    Conclusion: This new method introduces a new concept in cardiac function and provides further insight into the complexity of LV mechanics.

  • 317.
    Gustafsson, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Assessment of regional rotation patterns improves the understanding of the systolic and diastolic left ventricular function: an echocardiographic speckle-tracking study in healthy individuals2009In: European Journal of Echocardiography, ISSN 1525-2167, E-ISSN 1532-2114, no 10, p. 56-61Article in journal (Refereed)
    Abstract [en]

    AIM To elucidate the complexity of left ventricular motion throughout the cardiac cycle, we studied regional rotation in detail. METHODS AND RESULTS: Regional rotation in six subdivisions of the circumference at three levels was studied by using speckle-tracking echocardiography in 40 healthy subjects. At the basal level the inferoseptal segments rotated significantly more clockwise during systole than the opposing anterolateral segments. At the papillary level the inferoseptal segments differed significantly from the anterolateral segments, where the inferoseptal segments rotated clockwise and the anterolateral segments rotated counter-clockwise. The apical level showed significant difference in regional rotation only at aortic valve opening. In early systole, untwist before the main systolic twist was seen at the basal and apical levels; however, the duration of the basal untwist was much longer than that of the apical. The diastolic phases of rotation at the basal and apical levels matched the different filling phases. CONCLUSION: Large regional differences in rotation are present at the basal and papillary levels in healthy subjects. The diastolic untwist matches the phases of both the E-wave and A-wave and seems to be related with intraventricular pressure differences, indicating that untwist plays an important role in the filling of the ventricle.

  • 318.
    Gustafsson, Ulf
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Apical circumferential motion of the right and the left ventricles in healthy subjects described with speckle tracking2008In: Journal of the American Society of Echocardiography, ISSN 0894-7317, E-ISSN 1097-6795, Vol. 21, no 12, p. 1326-1330Article in journal (Refereed)
    Abstract [en]

    Background

    The aim of this study was to determine whether right ventricular (RV) apical rotation could be of importance in RV function and compare this with left ventricular (LV) apical rotation.

    Methods

    Short-axis images at the apical level of both ventricles were simultaneously recorded in 14 healthy subjects (mean age, 62 ± 11 years).

    Results

    There was a significant difference in mean rotation between the two ventricles in the time interval between 50% of ejection and aortic valve closure (P < .05). At aortic valve closure, LV rotation was 10.9 ± 4.8° counterclockwise, and RV rotation was 1.1 ± 5.8° clockwise. The anterior and inferior parts of the right ventricle rotated in opposite directions toward the septum. The septal segments of both ventricles rotated inferiorly, thus likely reducing interventricular stress.

    Conclusion

    This study showed clear differences in apical rotation between the two ventricles. Whereas the left ventricle displayed uniform rotation, the right ventricle showed heterogeneous rotation, resulting overall in almost no rotation but in a “tightening belt” motion.

  • 319.
    Gustavsson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Grönlund, Christer
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Can echocardiography and ECG discriminate hereditary transthyretin V30M amyloidosis from hypertrophic cardiomyopathy?2015In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 22, no 3, p. 163-170Article in journal (Refereed)
    Abstract [en]

    Objective: Hereditary transthyretin (ATTR) amyloidosis with increased left ventricular wall thickness could easily be misdiagnosed by echocardiography as hypertrophic cardiomyopathy (HCM). Our aim was to create a diagnostic tool based on echocardiography and ECG that could optimise identification of ATTR amyloidosis. Methods: Data were analysed from 33 patients with biopsy proven ATTR amyloidosis and 30 patients with diagnosed HCM. Conventional features from ECG were acquired as well as two dimensional and Doppler echocardiography, speckle tracking derived strain and tissue characterisation analysis. Classification trees were used to select the most important variables for differentiation between ATTR amyloidosis and HCM. Results: The best classification was obtained using both ECG and echocardiographic features, where a QRS voltage >30 mm was diagnostic for HCM, whereas in patients with QRS voltage <30 mm, an interventricular septal/posterior wall thickness ratio (IVSt/PWt) >1.6 was consistent with HCM and a ratio <1.6 supported the diagnosis of ATTR amyloidosis. This classification presented both high sensitivity (0.939) and specificity (0.833). Conclusion: Our study proposes an easily interpretable classification method for the differentiation between HCM and increased left ventricular myocardial thickness due to ATTR amyloidosis. Our combined echocardiographic and ECG model could increase the ability to identify ATTR cardiac amyloidosis in clinical practice.

  • 320.
    Gustavsson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Pilebro, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Westermark, P.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gender related differences in cardiac function in patients with hereditary transthyretin amyloidosis2015In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 17, p. 64-65Article in journal (Other academic)
  • 321. Haas, Jan
    et al.
    Frese, Karen S
    Peil, Barbara
    Kloos, Wanda
    Keller, Andreas
    Nietsch, Rouven
    Feng, Zhu
    Müller, Sabine
    Kayvanpour, Elham
    Vogel, Britta
    Sedaghat-Hamedani, Farbod
    Lim, Wei-Keat
    Zhao, Xiaohong
    Fradkin, Dmitriy
    Köhler, Doreen
    Fischer, Simon
    Franke, Jennifer
    Marquart, Sabine
    Barb, Ioana
    Li, Daniel Tian
    Amr, Ali
    Ehlermann, Philipp
    Mereles, Derliz
    Weis, Tanja
    Hassel, Sarah
    Kremer, Andreas
    King, Vanessa
    Wirsz, Emil
    Isnard, Richard
    Komajda, Michel
    Serio, Alessandra
    Grasso, Maurizia
    Syrris, Petros
    Wicks, Eleanor
    Plagnol, Vincent
    Lopes, Luis
    Gadgaard, Tenna
    Eiskjær, Hans
    Jørgensen, Mads
    Garcia-Giustiniani, Diego
    Ortiz-Genga, Martin
    Crespo-Leiro, Maria G
    Deprez, Rondal H Lekanne Dit
    Christiaans, Imke
    van Rijsingen, Ingrid A
    Wilde, Arthur A.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bolognesi, Martino
    Bellazzi, Riccardo
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bermejo, Justo Lorenzo
    Monserrat, Lorenzo
    Villard, Eric
    Mogensen, Jens
    Pinto, Yigal M
    Charron, Philippe
    Elliott, Perry
    Arbustini, Eloisa
    Katus, Hugo A
    Meder, Benjamin
    Atlas of the clinical genetics of human dilated cardiomyopathy2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 18, p. 1123-U43Article in journal (Refereed)
    Abstract [en]

    Aim: We were able to show that targeted Next-Generation Sequencing is well suited to be applied in clinical routine diagnostics, substantiating the ongoing paradigm shift from low- to high-throughput genomics in medicine. By means of our atlas of the genetics of human DCM, we aspire to soon be able to apply our findings to the individual patient with cardiomyopathy in daily clinical practice. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.

  • 322. Haas, Michael S
    et al.
    Alicot, Elisabeth M
    Schuerpf, Franziska
    Chiu, Isaac
    Li, Jinan
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Moore, Francis D
    Carroll, Michael C
    Blockade of self-reactive IgM significantly reduces injury in a murine model of acute myocardial infarction2010In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 87, no 4, p. 618-627Article in journal (Refereed)
    Abstract [en]

    The findings in this study identify potential therapeutics [i.e. N2 peptide or 21G6 F(ab')(2)] that prevent specific IgM binding to ischaemic antigens in the heart, resulting in a significant reduction in cardiac I/R injury.

  • 323. Hadimeri, Ursula
    et al.
    Wärme, Anna
    Nasic, Salmir
    Fransson, Sven-Göran
    Wigelius, Ann
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Angiography and phlebography in a hemodialysis population: A retrospective analysis of interventional results2019In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040Article in journal (Refereed)
    Abstract [en]

    Objective: To clarify the reasons and beneficial effects and duration of arteriovenous fistula patency after radiological interventions in arteriovenous fistula. The patients investigated were referred due to arteriovenous fistula access flow problems.

    Material and methods: In 174 patients, 522 radiological investigations and endovascular treatments such as percutaneous transluminal angioplasty were analyzed, retrospectively. All investigations were performed due to clinical suspicion of impaired arteriovenous fistula function.

    Results: Arterial stenosis was significantly more frequent among patients with diabetic nephropathy (p < 0.001) and interstitial nephritis (p < 0.001). According to the venous stenosis, the diagnosis did not affect the frequency (p = 0.22) or the degree (p = 0.39) of stenosis. The degree of stenosis prior to percutaneous transluminal angioplasty correlated significantly with the degree of remaining stenosis after intervention (p < 0.001). Of the 174 patients, 123 (71%) performed a total of 318 investigations including percutaneous transluminal angioplasty. Repeated percutaneous transluminal angioplasty was performed significantly more often in patients with diabetic nephropathy. The median times to the first percutaneous transluminal angioplasty and to the subsequent percutaneous transluminal angioplasties were 9.5 and 5 months, respectively. Arteriovenous fistula in patients with diabetic nephropathy performed similar to most other diagnoses, although performing more percutaneous transluminal angioplasty/patient than most other diagnoses.

    Conclusion: Many patients could maintain long-term patency of arteriovenous fistula, including those with diabetic nephropathy, with repeated interventions; this motivates a closer follow-up for these patients. Clinically significant stenosis should be dilated as meticulously and as soon as possible. Occlusions of the arteriovenous fistula in most instances can be successfully thrombolyzed or dilated upon early diagnosis.

  • 324. Hagstad, Stig
    et al.
    Backman, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Obstructive Lung Disease In Northern Sweden (OLIN) Studies, Norrbotten County Council, Luleå, Sweden.
    Bjerg, Anders
    Ekerljung, Linda
    Ye, Xiong
    Hedman, Linnea
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Obstructive Lung Disease In Northern Sweden (OLIN) Studies, Norrbotten County Council, Luleå, Sweden.
    Lindberg, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Unit of Research , Education and Development - Luleå, Umeå University .
    Torén, Kjell
    Lötvall, Jan
    Rönmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Obstructive Lung Disease In Northern Sweden (OLIN) Studies, Norrbotten County Council, Luleå, Sweden.
    Lundbäck, Bo
    Prevalence and risk factors of COPD among never-smokers in two areas of Sweden: Occupational exposure to gas, dust or fumes is an important risk factor2015In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 109, no 11, p. 1439-1445Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although active tobacco smoking is the main risk factor for COPD, COPD is not uncommon also among never-smokers. Different study locations along with different spirometric definitions of COPD have historically yielded different prevalence estimates of the disease.

    AIM: To study current prevalence and risk factors of COPD among never-smokers in two areas of Sweden.

    METHODS: Data collected in 2008-2012 within the West Sweden Asthma Study and Obstructive Lung Disease in Northern Sweden Studies was pooled. The study population consisted of 1839 subjects who participated in spirometry and interviews. COPD was defined as post-bronchodilator a) FEV1/(F)VC < 0.7, b) FEV1/FVC < 0.7 and c) FEV1/FVC < lower limit of normal.

    RESULTS: Of the 1839 subjects, 967 (52.6%) were never-smokers. Among the never-smoking subjects, the prevalence of COPD according to definitions a-c was 7.7%, 4.9% and 3.0%, respectively. The corresponding prevalence of GOLD grade ≥2 was 2.0%, 1.4% and 1.3%. No significant difference in prevalence between the two study areas was observed. In never-smokers, occupational exposure to gas, dust or fumes (GDF) was significantly associated with both COPD (OR 1.85, 95% CI 1.03-3.33), and GOLD ≥2 (OR 4.51, 1.72-11.9) according to definition a), after adjusting for age, educational level and exposure to passive smoking at work.

    CONCLUSION: Depending on definition, prevalence of COPD among never-smokers was 3.0-7.7%, whereas GOLD ≥2 was present in 1.3-2.0%. Occupational exposure to GDF remained independently and significantly associated with COPD regardless of spirometric definition of the disease.

  • 325.
    Hagström, Linn
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Karp, Kjell
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Impact of age and sex on normal left heart structure and function2017In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 37, no 6, p. 759-766Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Accurate age- and sex-related normal reference values of ventricular structure and function are important to determine the level of dysfunction in patients. The aim of this study therefore was to document normal age range sex-related measurements of LV structural and functional measurements to serve such purpose.

    METHODS: We evaluated left ventricular structure and function in 293 healthy subjects between 20 and 90 years with equally distributed gender. Doppler echocardiography was used including measure of both systolic and diastolic functions.

    RESULTS: Due to systolic LV function, only long axis function correlated with age (r = 0·55, P<0·01) and the correlation was stronger in females. Concerning diastolic function, there was a strong age correlation in all parameters used (r = 0·40-0·74, P<0·001). Due to LV structural changes over age, females showed a larger reduction in end-diastolic volumes, but no or trivial difference in wall thickness after the age of 60 years.

    CONCLUSION: Age is associated with significant normal changes in left ventricular structure and function, which should be considered when deciding on normality. These changes are related to systemic arterial changes as well as body stature, thus reflecting overall body ageing process. Furthermore, normal cardiac ageing in females might partly explain the higher prevalence of heart failure with preserved ejection in females.

  • 326. Hambraeus, Kristina
    et al.
    Held, Claes
    Johansson, Per
    Svennberg, Lars
    Cider, Asa
    James, Stefan
    Lagerqvist, Bo
    Friberg, Orjan
    Nilsson, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    From-Attebring, Mona
    Harnek, Jan
    Jernberg, Tomas
    SWEDEHEART Annual Report 20122014In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 48, no S63, p. 1-129Article in journal (Refereed)
    Abstract [en]

    The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) supports continuous monitoring and improvement of care for coronary artery disease, catheter-based and surgical coronary interventions, secondary prevention as well as catheter based and surgical valve intervention, by providing extensive data on base-line, diagnostic, procedural and outcome variables. Design. This national quality registry collects information from all Swedish hospitals treating patients with acute coronary artery disease and all patients undergoing coronary angiography, catheter-based interventions or heart surgery. Combination with other national mandatory official registries enables complete follow-up of all individuals regarding myocardial infarction, new interventional procedures, death and all-cause hospitalizations. The registry is governed by an independent steering committee and funded by the Swedish National Health care provider. The software is developed by Uppsala Clinical Research Center. Results. The SWEDEHEART Quality Index reflects overall quality of care for coronary artery disease including secondary prevention. In comparison with 2011, an improvement of the index occurred in 2012 overall. There was however, still a wide range in performance between individual centers, emphasizing the need for continuous monitoring of quality of care at a national as well as on a center level.

  • 327.
    Hamoudi, Zainab
    et al.
    Canterbury Christ Church University, Canterbury, UK.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Comparative assessment of non-invasive imaging in detecting coronary artery disease2014In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, no 5, p. 218-225Article, review/survey (Refereed)
    Abstract [en]

    Coronary artery disease (CAD) has an important impact on the morbidity and mortality in the West and health service resources worldwide. It is therefore crucial to accurately diagnose CAD early, in an attempt to limit its burden on patients and society, potentially by optimum risk stratification, accurate diagnosis and management. Invasive coronary angiography (ICA) is the conventional gold standard imaging investigation for the coronary circulation and assessment of disease severity. However, it is an invasive procedure and is associated with risks, although rare. In addition, it detects luminal stenosis but not the functional importance of those anatomical lesions. Therefore, a wide variety of non-invasive imaging developed to evaluate the presence and severity of CAD, including anatomical techniques e.g. coronary CT that assesses coronary stenosis, and quantifies coronary calcium, hence the burden of atherosclerotic plaques and functional imaging e.g. stress echocardiography, nuclear imaging by SPECT and PET and stress CMR. Selection of the most appropriate imaging, therefore, is challenging and requires knowledge of patients' pre-test probability and prevalence of disease, their advantages and limitations, cost and availability. This review attempts to provide an overview of the current supporting evidence of the role of non-invasive imaging in diagnosing CAD, in addition to its prognostic value, limitations and advantages.

  • 328.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Coronary physiology2012In: Core Topics in Cardiac Anesthesi: 2nd Edition / [ed] Jonathan H. Mackay and Joseph E. Arrowsmith, CAMBRIDGE: Cambridge University Press, 2012, 2, p. 22-27Chapter in book (Refereed)
  • 329.
    Haney, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Häggmark, Sören
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Heart-lung interactions during positive pressure ventilation: left ventricular pressure-volume momentary response to airway pressure elevation2001In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 45, no 6, p. 702-709Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Left ventricular (LV) pressure and volume changes are known to occur in response to positive airway pressure (PAP). We aimed to further describe the immediate LV response to increased PAP as demonstrated in successive heart cycles with LV pressure and volume alterations. We postulated that these acute systematic LV events during institution of PAP can follow a distinct pattern that would allow calculation of parameters of systolic function, including end-systolic elastance (Ees) and preload recruitable stroke work (PRSW). We also aimed to examine the relationship of PAP-derived Ees and PRSW to the same parameters derived from vascular occlusion. METHODS: Eight anesthetized adult pigs were studied with invasive circulatory measurements including LV pressure and volume (conductance). The PAP intervention was an airway pressure plateau of 15 cm H2O for 6 s (APP). Venous occlusion was performed by transient balloon inflation in the inferior vena cava (IVCO). Ees and PRSW were derived for each APP and IVCO intervention. RESULTS: Central circulatory variables during APP and IVCO are reported. LV systolic function parameters could be derived from each of the heart-lung interactions during APP sequences. Ees and PRSW derived from APP showed a significant positive bias in relation to those derived from the IVCO sequence. CONCLUSIONS: We conclude that the heart-lung interactions during APP of the magnitude and duration shown here can allow derivation of Ees and PRSW. These parameters are not interchangeable with Ees and PRSW derived from IVCO.

  • 330.
    Hannuksela, Matias
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Familial thoracic aortic aneurysms and dissections: studies on genotype and phenotype2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Thoracic aortic aneurysms and dissections (TAAD) have a genetic component with an estimated 20-25% of the patients having a positive family history. An aneurysm often precedes a dissection. Acute aortic dissections are associated with high mortality and morbidity, even when operated on. Complications due to prophylactic surgery are considerably fewer. Therefore, patients at risk for dissection should be identified, followed-up and evaluated for prophylactic intervention.

    Aims: 1. To establish reference values for ascending (AoA) and descending aortic (AoD) diameters measured by computed tomography. 2. To study the effectiveness of phenotypic cascade screening in families with an inherited form of thoracic aortic aneurysms and dissections (FTAAD) and to address questions that arise when screening for a genetic disorder is applied. 3. To study the agreement of aortic diameters obtained by TTE and MRI and to study aortic stiffness in individuals from families with FTAAD. 4. To perform exome sequencing in order to identify pathogenic sequence variants causing FTAAD, to characterize the phenotype, and to compare thoracic aortic diameter and stiffness in mutation carriers and non-carriers.

    Results: Paper I: The diameter of the thoracic aorta increased by 0.17 mm (0.12 – 0.20 mm) per year. The mean sex-related difference in diameter was 1.99 mm (1.28 – 2.60 mm) with men having larger aortas than women. The mean difference in aortic diameter per unit BMI was 0.27 mm (0.14 – 0.44 mm). Upper normal limits for the AoA can be calculated by the formula D (mm)=31+0.16*age and for the AoD by D (mm)=21+0.16*age.

    Paper II: Of 106 individuals from families with FTAAD but without known thoracic aortic disease, 19 individuals (18%) were identified to have a dilated AoA. The expected number of individuals in this group with an autosomal dominant disease would have been 40 (p<0.0001). In first-degree relatives younger than 40, we found only one individual with a dilated aorta although the expected number of individuals with disease causing mutation would have been 10.

    Paper III: Of 116 individuals investigated, 21 were identified with thoracic aortic dilatation and 95 individuals with normal thoracic aortic diameter. Aortic stiffness increased with age and diameter. The individuals with aortic dilatation were older than those without (49 vs. 37 years, p=0.001) and showed lower aortic elastic properties. The diameters measured by TTE and MRI correlated strongly (r2=0.93). The mean difference in diameters between the two methods was 0.72 mm (95% CI 0.41-1.02) with TTE giving larger diameters than MRI.

    Paper IV: From exome sequencing and segregation analysis, a 2-bp deletion in the MYLK gene (c.3272_3273del) was identified to cause FTAAD. The age and the aortic diameter at dissection or rupture varied in the family members. We did not find any differences in aortic diameter, aortic stiffness, or pulse wave velocity between carriers and non-carriers.

    Conclusions: Thoracic aortic diameter increases with age, and sex and body size are also associated with the diameter. In FTAAD, screening identifies family members with a previously unknown aortic dilatation. However, a normal aortic diameter does not exclude an individual from being a carrier of FTAAD. TTE can be used in follow-up for the ascending aorta. Individuals identified to have a dilated thoracic aorta have increased aortic stiffness compared to individuals with normal thoracic aortic diameter. The MYLK mutation (c.3272_3273del) causes thoracic aortic dissections with variable clinical expression. No differences in aortic stiffness were identified between MYLK mutation carriers and non-carriers.

  • 331.
    Hannuksela, Matias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Aortic stiffness in families with inherited non-syndromic thoracic aortic disease2018In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, no 6, p. 301-307Article in journal (Refereed)
    Abstract [en]

    Background. In families with an inherited form of non-syndromic thoracic aortic disease (TAAD), aortic diameter alone is not a reliable marker for disease occurrence or progression. To identify other parameters of aortic function, we studied aortic stiffness in families with TAAD. We also compared diameter measurements obtained by transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI).

    Methods. Seven families, including 116 individuals, with non-syndromic TAAD, were studied. The aortic diameter was measured by TTE and MRI. Aortic stiffness was assessed as local distensibility in the ascending aorta and as regional and global pulse wave velocity (PWV). Individuals with a dilated thoracic aorta (n = 21) were compared with those without aortic dilatation (n = 95).

    Results. Ascending aortic diameter measured by TTE strongly correlated with the diameter measured by MRI (r2 = 0.93). The individuals with dilated aortas were older than those without dilatation (49 vs 37 years old). Ascending aortic diameter increased and distensibility decreased with increasing age; while, PWV increased with age and diameter. Some young subjects without aortic dilatation showed increased aortic stiffness. Individuals with a dilated thoracic aorta had significantly higher PWV and lower distensibility, measured by MRI than individuals without dilatation.

    Conclusions. Diameters measured with TTE agree with those measured by MRI. Aortic stiffness might be a complementary marker for aortic disease and progression when used with aortic diameter, especially in young individuals.

  • 332.
    Hannuksela, Matias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Lundqvist, Stefan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Thoracic aorta: dilated or not?2006In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 40, no 3, p. 175-178Article in journal (Refereed)
    Abstract [en]

    Objectives: Knowledge of normal aortic diameters is important in the assessment of aortic disease. The aim of this study was to determine normal thoracic aortic diameters.

    Design: 77 patients undergoing computed tomography of the thorax were studied. The diameter of the thoracic aorta was measured at three levels in the ascending aorta and at three levels in the descending aorta. The diameter was studied in relation to age, sex, weight and height.

    Results: We found that aortic diameter is increasing with increasing age. Even sex and BMI influence the aortic diameter but to a lesser extent than age. The upper normal limit for ascending aorta can be calculated with the formula D(mm) = 31 + 0.16*age and for descending aorta with the formula D(mm) = 21 + 0.16*age. Thus a 20-year-old person has an upper normal limit for ascending aorta of 34 mm and an 80-year-old person has a limit of 44 m.

    Conclusions: The thoracic aortic diameter varies with age, sex and body weight and height. The strongest correlation can be seen with age. Age should therefore be taken into consideration when determining whether the thoracic aorta is dilated or not.

  • 333.
    Hannuksela, Matias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Stattin, Eva-Lena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Screening for familial thoracic aortic aneurysms with aortic imaging does not detect all potential aarriers of the disease2015In: Aorta, ISSN 2325-4637, Vol. 3, no 1, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Background: About 20% of patients with thoracic aortic aneurysm or dissection (TAAD) have a first-degree relative with a similar disease. The familial form (FTAAD) of the disease is inherited in an autosomal-dominant pattern. Current guidelines for thoracic aortic disease recommend screening of first-degree relatives of TAAD patients. In known familial disease, screening of both first- and second-degree relatives is recommended. However, the outcomes of such a screening program are unknown.

    Methods: We screened all first- and second-degree relatives in seven families with known FTAAD with echo- cardiography. No underlying gene defect had been detected in these families.

    Results: Of 119 persons investigated, 13 had known thoracic aortic disease. In the remaining 106 cases, we diagnosed 19 additional individuals with a dilated ascending thoracic aorta; for an autosomal-dominant disease, the expected number of individuals in this group would have been 40 (p<0.0001). Further, only one of the 20 first-degree relatives younger than 40 years had a dilated aorta, although the expected number of individuals with a disease-causing mutation would have been 10.

    Conclusions: In most families with TAAD, a diagnosis still relies on measuring the diameter of the thoracic aorta. We show that a substantial number of previously unknown cases of aortic dilatation can be identified by screening family members. It is, however, not possible to consider anyone free of the condition, even if the aortic diameter is normal, especially at a younger age.

  • 334.
    Hannuksela, Matias
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Stattin, Eva-Lena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Nyberg, Peter
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Familära torakala aortaaneurysm och dissektioner: flera former finns2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 9-10, p. 399-403Article in journal (Refereed)
    Abstract [en]

    Thoracic aortic aneurysms and dissections (TAAD) can be divided into three different main categories. 1. Inherited syndromes predisposing to TAAD such as Marfan syndrome, Ehlers-Danlos syndrome type IV and Loeys-Dietz syndrome (less than 5% of all TAAD). 2. Familial TAAD (FTAAD) with more than one affected family member (20 % of all TAAD). Inheritance shows an autosomal dominant pattern and there are no features of known syndromes. 3. Sporadic forms of TAAD with no family history or features of syndromic forms. FTAAD present earlier in life and dissections occur in smaller diameter than in sporadic cases. The underlying genetic cause can be found in about 20 % of the inherited cases. The pathogenesis seems to be an involvement of the transforming growth factor β (TGFβ) signaling pathway or a dysfunction of the smooth muscle cell contraction. The role of β-blockers for aneurysm prevention is uncertain and there are on-going studies comparing angiotensin receptor blockers and β-blockers.

  • 335. Hansson, Jenny
    et al.
    Galanti, Maria Rosaria
    Hergens, Maria-Pia
    Fredlund, Peeter
    Ahlbom, Anders
    Alfredsson, Lars
    Bellocco, Rino
    Engström, Gunnar
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Hallqvist, Johan
    Hedblad, Bo
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Pedersen, Nancy L
    Lagerros, Ylva Trolle
    Östergren, Per-Olof
    Magnusson, Cecilia
    Snus (Swedish smokeless tobacco) use and risk of stroke: Pooled Analyses of Incidence and Survival2014In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 276, no 1, p. 87-95Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Snus is a moist smokeless tobacco product with a high nicotine content. Its use has a short-term effect on the cardiovascular system, but the relationship between snus use and stroke is unclear.

    OBJECTIVE: The aim of this study was to assess the associations between use of snus and incidence of and survival after stroke, both overall and according to subtypes.

    METHODS: Pooled analyses of eight Swedish prospective cohort studies were conducted, including 130 485 men who never smoked. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of incidence and death after diagnosis using Cox proportional hazard regression models, and case fatality and survival using logistic regression and Kaplan-Meier methods, respectively.

    RESULTS: No associations were observed between the use of snus and the risk of overall stroke (HR 1.04, 95% CI 0.92-1.17) or of any of the stroke subtypes. The odds ratio (OR) of 28-day case fatality was 1.42 (95% CI 0.99-2.04) among users of snus who had experienced a stroke, and the HR of death during the follow-up period was 1.32 (95% CI 1.08-1.61).

    CONCLUSION: Use of snus was not associated with the risk of stroke. Hence, nicotine is unlikely to contribute importantly to the pathophysiology of stroke. However, case fatality was increased in snus users, compared to non-users, but further studies are needed to determine any possible causal mechanisms.

  • 336. Hansson, Jenny
    et al.
    Galanti, Maria Rosaria
    Hergens, Maria-Pia
    Fredlund, Peeter
    Ahlbom, Anders
    Alfredsson, Lars
    Bellocco, Rino
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Hallqvist, Johan
    Hedblad, Bo
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Nilsson, Peter
    Pedersen, Nancy
    Trolle Lagerros, Ylva
    Ostergren, Per-Olof
    Magnusson, Cecilia
    Use of snus and acute myocardial infarction: pooled analysis of eight prospective observational studies2012In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 27, no 10, p. 771-779Article in journal (Refereed)
    Abstract [en]

    The use of snus (also referred to as Scandinavian or Swedish moist smokeless tobacco), which is common in Sweden and increasing elsewhere, is receiving increasing attention since considered a tobacco smoke "potential reduction exposure product". Snus delivers a high dose of nicotine with possible hemodynamic effects, but its impact on cardiovascular morbidity and mortality is uncertain. The aim of this study was to investigate whether snus use is associated with risk of and survival after acute myocardial infarction (AMI). Data from eight prospective cohort studies set in Sweden was pooled and reanalysed. The relative risk of first time AMI and 28-day case-fatality was calculated for 130,361 men who never smoked. During 2,262,333 person-years of follow-up, 3,390 incident events of AMI were identified. Current snus use was not associated with risk of AMI (pooled multivariable hazard ratio 1.04, 95 % confidence interval 0.93 to 1.17). The short-term case fatality rate appeared increased in snus users (odds ratio 1.28, 95 % confidence interval 0.99 to 1.68). This study does not support any association between use of snus and development of AMI. Hence, toxic components other than nicotine appear implicated in the pathophysiology of smoking related ischemic heart disease. Case fatality after AMI is seemingly increased among snus users, but this relationship may be due to confounding by socioeconomic or life style factors.

  • 337. Hare, Matthew JL
    et al.
    Magliano, Dianna J
    Zimmet, Paul Z
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Joonas, Noorjehan
    Pauvaday, Vassen
    Larhubarbe, Jose
    Tuomilehto, Jaakko
    Kowlessur, Sudhir
    Alberti, K George MM
    Shaw, Jonathan E
    Glucose-independent ethnic differences in HbA(1c), in people without known diabetes2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 6, p. 1534-1540Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To determine whether glucose-independent differences in HbA(1c) exist between people of African, South Asian, and Chinese ethnicities.

    RESEARCH DESIGN AND METHODS Data from 6,701 people aged 19-78 years, without known diabetes, from Mauritius, and participating in the population-based Non-Communicable Disease Surveys of the main island and the island of Rodrigues were included. Participants were African (n = 1,219 from main island, n = 1,505 from Rodrigues), South Asian (n = 3,820), and Chinese (n = 157). Survey data included HbA(1c), plasma glucose during oral glucose tolerance testing (OGTT), anthropometry, demographics, and medical and lifestyle history.

    RESULTS Mean HbA(1c), after adjustment for fasting and 2-h plasma glucose and other factors known to influence HbA(1c), was higher in Africans from Rodrigues (6.1%) than in South Asians (5.7%, P < 0.001), Chinese (5.7%, P < 0.001), or Africans from the main island of Mauritius (5.7%, P < 0.001). The age-standardized prevalence of diabetes among Africans from Rodrigues differed substantially depending on the diagnostic criteria used [OGTT 7.9% (95% CI 5.8-10.0); HbA(1c) 17.3% (15.3-19.2)]. Changing diagnostic criteria resulted in no significant change in the prevalence of diabetes within the other ethnic groups.

    CONCLUSIONS People of African ethnicity from Rodrigues have higher HbA(1c) than those of South Asian or African ethnicity from the main island of Mauritius for reasons not explained by plasma glucose during an OGTT or traditional factors known to affect glycemia. Further research should be directed at determining the mechanism behind this disparity and its relevance to clinical outcomes.

  • 338. Harnek, Jan
    et al.
    Freter, Wolfgang
    Holm, Peter
    Ioanes, Dan
    James, Stefan
    Nilsson, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ruck, Andreas
    Zagozdzon, Leszek
    Report from the Swedish TAVI register: comparison of two valve types2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 17, p. B262-B263Article in journal (Other academic)
  • 339. Harnek, Jan
    et al.
    Nilsson, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Friberg, Örjan
    James, Stefan
    Lagerqvist, Bo
    Hambraeus, Kristina
    Cider, Åsa
    Svennberg, Lars
    Attebring, Mona From
    Held, Claes
    Johansson, Per
    Jernberg, Tomas
    The 2011 outcome from the Swedish Health Care Registry on Heart Disease (SWEDEHEART)2013In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 47, no S62, p. 1-10Article in journal (Refereed)
  • 340.
    He, Shu-Lan
    et al.
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Tan, Wu-Hong
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Zhang, Zeng-Tie
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Zhang, Feng
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Qu, Cheng-Juan
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
    Lei, Yan-Xia
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Zhu, Yan-He
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Yu, Han-Jie
    Department of Biotechnology, Northwest University, Xi'an, China.
    Xiang, You-Zhang
    Shandong Institute for prevention & Treatment of Endemic Disease, Jinan, China.
    Guo, Xiong
    Key Laboratory of Environment and Gene Related Diseases, Xi'an Jiaotong University, Ministry Education, Xi'an, China; Key Laboratory of Trace Elements and Endemic Diseases, Xi'an Jiaotong University, Ministry of Health, Xi'an, China.
    Mitochondrial-related gene expression profiles suggest an important role of PGC-1alpha in the compensatory mechanism of endemic dilated cardiomyopathy.2013In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 319, no 17, p. 2604-2616, article id 23954821Article in journal (Refereed)
    Abstract [en]

    Keshan disease (KD) is an endemic dilated cardiomyopathy with unclear etiology. In this study, we compared mitochondrial-related gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from 16 KD patients and 16 normal controls in KD areas. Total RNA was isolated, amplified, labeled and hybridized to Agilent human 4 × 44k whole genome microarrays. Mitochondrial-related genes were screened out by the Third-Generation Human Mitochondria-Focused cDNA Microarray (hMitChip3). Quantitative real-time PCR, immunohistochemical and biochemical parameters related mitochondrial metabolism were conducted to validate our microarray results. In KD samples, 34 up-regulated genes (ratios ≥ 2.0) were detected by significance analysis of microarrays and ingenuity systems pathway analysis (IPA). The highest ranked molecular and cellular functions of the differentially regulated genes were closely related to amino acid metabolism, free radical scavenging, carbohydrate metabolism, and energy production. Using IPA, 40 significant pathways and four significant networks, involved mainly in apoptosis, mitochondrion dysfunction, and nuclear receptor signaling were identified. Based on our results, we suggest that PGC-1alpha regulated energy metabolism and anti-apoptosis might play an important role in the compensatory mechanism of KD. Our results may lead to the identification of potential diagnostic biomarkers for KD in PBMCs, and may help to understand the pathogenesis of KD.

  • 341.
    Hedberg, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Stroke after cardiac surgery - hemispheric distribution and survival2013In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 47, no 3, p. 136-144Article in journal (Refereed)
    Abstract [en]

    Objectives. Stroke following cardiac surgery may occur either in association with surgery (early) or occur postoperatively (delayed). The hemispheric distribution of lesions may provide information about embolic routes, which was analyzed here. Design. In 10,809 patients undergoing cardiac surgery, early (n = 223) and delayed stroke (n = 116) were explored. Symptoms and computed tomography findings were evaluated to categorize hemispheric distributions. This was compared with pre- and intra-operative characteristics and survival, using logistic regression and Kaplan-Meier statistics. Results. Early stroke had preponderance for the right rather than the left hemisphere (P = 0.009), whereas delayed stroke had a uniform distribution. Several intraoperative variables predicted the development of bilateral stroke compared with its unilateral counterpart. At multivariable analysis, the use of tranexamic acid was associated with bilateral stroke (P = 0.017), but was also associated with right rather than left-hemispheric stroke (P = 0.001). Bilateral lesions dramatically impaired survival versus those with unilateral lesions (P < 0.001). There was no survival difference between left and right-hemispheric stroke. Conclusions. When stroke, after cardiac surgery, is subdivided into early and delayed forms, it becomes evident that early, but not delayed stroke, demonstrates a hemispheric side difference. The preponderance for right-hemispheric lesions may indicate embolic mechanisms routed via the brachiocephalic trunk.

  • 342.
    Hedberg, Pia
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Lämås, Kristina
    Umeå University, Faculty of Medicine, Department of Nursing.
    Effects of different types of feedback on cardiopulmonary resuscitation skills among nursing students: a pilot study2013In: Journal of Nursing Education and Practice, ISSN 1925-4040, E-ISSN 1925-4059, Vol. 3, no 10, p. 84-90Article in journal (Refereed)
    Abstract [en]

    Background: During the last 20 years there have been different approaches to teaching nurse students cardiopulmonary resuscitation (CPR). Receiving CPR with compressions of adequate depth and frequency, and ventilations of adequate volume improves the chance of survival. The aim of this study was to evaluate effects of different types of feedback on CPR skills among nursing students.

    Methods: A pilot study with an explorative approach including 30 nurse students. Students was randomized in three groups; 1) instructor-led training followed by self-training without feedback, 2) self-training with visual graphic feedback, and 3) self-training with voice advisory manikin (VAM). Outcomes were correct compression deep, frequency, hand position and release, and correct ventilation volume and flow. If performance was correct to 70%, students were considered to have reached approved level. The students also answered questions about theoretical knowledge about CPR.

    Results: In technical skills, group 2 had significant higher level of correct ventilation volume compared with the other group. Both group 1 and 3 did not reach the level of 70% correct performance. Group 1 and 2 had significant higher level of correct deep of compressions compared with group 3 which did not reach the 70% level. There was no difference in performance between groups in other parameters.

    Conclusion: This pilot study suggests that visual graphic feedback is promising and seemed to be more effective than self-training with voice advisory manikin and instructor-led training with followed self-training without feedback.

  • 343.
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hyaluronan, a beneficial glycosaminoglycan that may affect the phenotype of cardiac hypertrophy: a hypothesis2014In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, no 5, p. 226-229Article in journal (Refereed)
    Abstract [en]

    Myocardial hypertrophy contribute to ventricular diastolic dysfunction and can lead to heart failure, arrhythmia and evensudden death. It have been shown that during development of hypertrophy the concentration of the glycosaminoglycanhyaluronan increases. The increased concentration correlates to the increased gene expression of fetal and extracellularmatrix genes that is associated with cardiac remodeling.Moreover it has been shown that high molecular weight hyaluronan depolarize the membrane potential of cells.The increase of hyaluronan in cardiac hypertrophy could hypothetically affect the resting membrane potential incardiomyocytes and thus affect the conduction through the heart.Hypothesis. The role of hyaluronan as a molecule adapting the extracellular matrix when the heart is growing could potentiallydevelop to be harmful to cardiomyocyte resting membrane potential and hence contribute to the risk of arrhythmia.

  • 344.
    Hellman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Hellström, Martin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Engström Laurent, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Aberg, Anna-Maja
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Oliviero, Patricia
    Samuel, Jane-Lise
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Parallel up-regulation of FGF-2 and hyaluronan during development of cardiac hypertrophy in rat2008In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 332, no 1, p. 49-56Article in journal (Refereed)
  • 345.
    Hellman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lång, Kenneth
    Ihse, Elisabet
    Jonasson, Jenni
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Olsson, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Lundgren, Hans-Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Pilebro, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Westermark, Per
    Wixner, Jonas
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
    Transthyretin Glu54Leu - an unknown mutation within the Swedish population associated with amyloid cardiomyopathy and a unique fibril type2019In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, p. 1-5Article in journal (Refereed)
    Abstract [en]

    For the first time, we report of a Swedish family of five individuals with a TTR Glu54Leu (p. Glu74Leu) mutation in the transthyretin gene. This mutation has been previously described a few times in the literature, but no phenotypic or clinical description has been done before. The most common mutation in the Swedish population is TTRVal30Met and is mostly found in the Northern part of Sweden. Interestingly, the TTRGlu54Leu mutation was found in the same endemic area. The main phenotype of the TTR Glu54Leu patients is severe cardiomyopathy, which resulted in heart transplantation for the index person. As previously seen for ATTR amyloidosis patients with mainly cardiomyopathy, the amyloid fibrils consisted of a mixture of full-length and fragmented TTR species. However, western blot analyses detected a previously unrecognized band, indicating that these patients may have a third, so far unrecognized, fibril composition type that is distinct from the usual type A band pattern.

  • 346.
    Hellman, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Molecular & Clinical Sciences Research Institute, St. George University, London; Brunel University, Middlesex, UK.
    Genetic variants in cardiac calcification in Northern Sweden2019In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 98, no 15, article id e15065Article in journal (Refereed)
    Abstract [en]

    Extensive coronary calcification without significant stenosis, described as calcific coronary artery disease (CCAD) may cause abnormal myocardial perfusion and hence generalized ischemia. There is a discrepancy in the expression pattern of CCAD compared to the well-known atherosclerotic disease which raises questions about the exact pathophysiology of coronary calcification and whether there is a genetic etiology for it.

    In this pilot study we studied 3 candidate genes, ectonucleotide pyrophosphatase/phosphodiesterase (ENPP1), ATP Binding Cassette Subfamily C Member 6 (ABCC6), and 5'-Nucleotidase Ecto (NT5E) involved in pyrophosphate (PPi) and inorganic phosphate (Pi) metabolism, which may predispose to coronary arterial or valvular calcification. We studied 70 patients with calcific cardiac disease; 65 with CCAD (age 43-83 years) and 5 with calcific aortic valve disease (CAVD) (age 76-82 years).

    Five DNA variants potentially affecting protein function were found in 6 patients. One variant is a known disease-causing mutation in the ABCC6 gene. Our findings support that disturbances in the PPi and Pi metabolism might influence the development of CCAD and CAVD. However, segregation in the families must first be performed to ascertain any damaging effect of these variants we have found.

    We report 4 new genetic variants potentially related to coronary calcification, through the disturbed Pi and PPi metabolism. The search for direct causative genetic variants in coronary artery and aortic valve calcification must be broadened with other genes particularly those involved with Pi and PPi metabolism.

  • 347.
    Hellström, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Engström-Laurent, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mörner, Stellan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hyaluronan and collagen in human hypertrophic cardiomyopathy: a morphological analysis2012In: Cardiology Research and Practice, ISSN 2090-8016, E-ISSN 2090-0597, Vol. 2012, p. 545219-Article in journal (Refereed)
    Abstract [en]

    The hypertrophic cardiomyopathy (HCM) disease process is not only limited to cardiomyocyte abnormalities but also engages the extracellular matrix. Hyaluronan (HA) and its receptor CD44 are involved in cellular growth and tissue proliferation but have so far been less studied in myocardial hypertrophy. In HCM, collagens are abundant but their histological distribution and relation to hyaluronan have not been described. Material and Methods. Myocardial specimens from 5 patients with symptomatic left ventricular tract obstruction undergoing myectomy due to HCM were processed for histochemistry and immunohistochemistry. Results. HA staining was more intense in HCM patients. The histological distribution of HA was the same in patients and controls, that is, interstitial staining including the space between cardiomyocytes, in fibrous septa, and in the adventitia of intramyocardial blood vessels. CD44 was not detected in the myocardium of patients or controls. Collagen I showed the same general localisation as HA but detailed distribution differed. Conclusions. This is the first study that describes the distribution of hyaluronan in human HCM. HA staining is more intense in HCM patients but without coexpression of its receptor CD44, at least not in the chronic phase of HCM. HA and collagen I have the same localisation.

  • 348.
    Hellström Ängerud, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Internal Medicine, Sunderbyn, Luleå, Sweden.
    Longer pre-hospital delay in first myocardial infarction among patients with diabetes: an analysis of 4266 patients in the Northern Sweden MONICA Study2013In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 13, no 6Article in journal (Refereed)
    Abstract [en]

    Background: Reperfusion therapy reduces both morbidity and mortality in myocardial infarction, but the effectiveness depends on how fast the patient receives treatment. Despite the time-dependent effectiveness of reperfusion therapy, many patients with myocardial infarction have delays in seeking medical care. The aim of this study was to describe pre-hospital delay in a first myocardial infarction among men and women with and without diabetes and to describe the association between pre-hospital delay time and diabetes, sex, age, symptoms and size of residential area as a proxy for distance to hospital.

    Methods: This population based study was based on data from 4266 people aged 25-74 years, with a first myocardial infarction registered in the Northern Sweden MONICA myocardial infarction registry between 2000 and 2008.

    Results: The proportion of patients with delay times >= 2 h was 64% for patients with diabetes and 58% for patients without diabetes. There was no difference in delay time >= 2 h between men and women with diabetes. Diabetes, older age and living in a town or rural areas were factors associated with pre-hospital delay times >= 2 h. Atypical symptoms were not a predictor for pre-hospital delay times >= 2 h, OR 0.59 (0.47; 0.75).

    Conclusions: A higher proportion of patients with diabetes have longer pre-hospital delay in myocardial infarction than patients without diabetes. There are no differences in pre-hospital delay between men and women with diabetes. The largest risk difference for pre-hospital delay >= 2 h is between women with and without diabetes. Diabetes, older age and living in a town or rural area are predictors for pre-hospital delay >= 2 h.

  • 349.
    Hellström Ängerud, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Brulin, Christine
    Umeå University, Faculty of Medicine, Department of Nursing.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Internal Medicine, Sunderbyn, Luleå, Sweden.
    Patients with diabetes are not more likely to have atypical symptoms when seeking care of a first myocardial infarction: an analysis of 4028 patients in the Northern Sweden MONICA Study2012In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, no 7, p. e82-e87Article in journal (Refereed)
    Abstract [en]

    Aim: To describe symptoms of a first myocardial infarction in men and women with and without diabetes.

    Methods: We conducted a population-based study of 4028 people aged 25-74 years, with first myocardial infarction registered in the Northern Sweden Multinational MONItoring of trends and determinants in CArdiovascular disease (MONICA) myocardial infarction registry between 2000 and 2006. Symptoms were classified as typical or atypical according to the World Health Organization MONICA manual.

    Results: Among patients with diabetes, 90.1% reported typical symptoms of myocardial infarction; the corresponding proportion among patients without diabetes was 91.5%. In the diabetes group, 88.8% of women and 90.8% of men had typical symptoms of myocardial infarction. No differences were found in symptoms of myocardial infarction between women with and without diabetes or between men with and without diabetes. Atypical symptoms were more prevalent in the older age groups (> 65 years) than in the younger age groups (< 65 years). The increases were approximately equal among men and women, with and without diabetes. Diabetes was not an independent predictor for having atypical symptoms of myocardial infarction.

    Conclusions: Typical symptoms of myocardial infarction were equally prevalent in patients with and without diabetes and there were no sex differences in symptoms among persons with diabetes. Diabetes was not a predictor of atypical symptoms.

    © 2011 The Authors. Diabetic Medicine© 2011 Diabetes UK.

  • 350.
    Hellström Ängerud, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå University, Faculty of Medicine, Department of Nursing.
    Ericsson, M.
    Isaksson, R. M.
    Sederholm Lawesson, S.
    Thylen, I.
    Swahn, E.
    Differences in symptoms in relation to myocardial infarction type2016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, p. 730-730Article in journal (Other academic)
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