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  • 201. Crowe, F. L.
    et al.
    Key, T. J.
    Appleby, P. N.
    Overvad, K.
    Schmidt, E. B.
    Egeberg, R.
    Tjonneland, A.
    Kaaks, R.
    Teucher, B.
    Boeing, H.
    Weikert, C.
    Trichopoulou, A.
    Ouranos, V.
    Valanou, E.
    Masala, G.
    Sieri, S.
    Panico, S.
    Tumino, R.
    Matullo, G.
    Bueno-de-Mesquita, H. B.
    Boer, J. M. A.
    Beulens, J. W. J.
    van der Schouw, Y. T.
    Quiros, J. R.
    Buckland, G.
    Sanchez, M-J
    Dorronsoro, M.
    Huerta, J. M.
    Moreno-Iribas, C.
    Hedblad, B.
    Jansson, J. H.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Khaw, K-T
    Wareham, N.
    Ferrari, P.
    Illner, A-K
    Chuang, S-C
    Norat, T.
    Danesh, J.
    Riboli, E.
    Dietary fibre intake and ischaemic heart disease mortality: the European Prospective Investigation into Cancer and Nutrition-Heart study2012Ingår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 66, nr 8, s. 950-956Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Evidence from prospective studies is consistent in showing an inverse association between dietary fibre intake and risk of ischaemic heart disease (IHD), but whether dietary fibre from various food sources differ in their effect on IHD risk is less clear. The objective of this study was to assess the associations of total and food sources of dietary fibre with IHD mortality in the European Prospective Investigation into Cancer and Nutrition-Heart study. SUBJECTS/METHODS: Participants were 306 331 men and women from eight European countries. Dietary fibre intake was assessed using centre or country-specific diet questionnaires and calibrated using a 24-h diet recall. RESULTS: After an average follow-up of 11.5 years, there were 2381 IHD deaths among participants without cardiovascular disease at baseline. The calibrated intake of dietary fibre was inversely related with IHD mortality; each 10 g/day was associated with a 15% lower risk (relative risk (RR) 0.85; 95% confidence interval (CI): 0.73-0.99, P = 0.031). There was no difference in the associations of the individual food sources of dietary fibre with the risk of IHD mortality; RR for each 5 g/day higher cereal fibre intake was 0.91 (CI: 0.82-1.01), RR for each 2.5 g/day fruit fibre intake was 0.94 (CI: 0.88-1.01) and RR for each 2.5 g/day vegetable fibre intake was 0.90 (95% CI: 0.76-1.07). CONCLUSION: A higher consumption of dietary fibre is associated with a lower risk of fatal IHD with no clear difference in the association with IHD for fibre from cereals, fruits or vegetables.

  • 202. Csengeri, D.
    et al.
    Spruenker, N. A.
    Di Castelnuovo, A.
    Niiranen, T.
    Söderberg, Stefan
    Umeå University Hospital.
    Magnussen, C.
    Lochen, M. J.
    Kee, F.
    Blankenberg, S.
    Jørgensen, T.
    Kuulasmaa, K.
    Zeller, T.
    Salomaa, V.
    Iacoviello, L.
    Schnabel, R.
    Alcohol consumption and risk of atrial fibrillation - results from the BiomarCaRE Consortium2018Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, s. 902-903Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Atrial fibrillation (AF) is an arrhythmia with high impact on public health. Among modifiable risk factors for the disease the role of alcohol consumption (AC) has remained inconsistent.

    Purpose: To assess the association between AC and incident AF across European cohorts.

    Methods: To study the association between self-reported AC and incident AF in N=107,845 community-based individuals from the BiomarCaRE consortium, 106,915 individuals free of AF at baseline were followed up for AF and stroke after AF. We assessed AC using validated questionnaires. Biomarkers N-terminal pro B-type natriuretic peptide (Nt-proBNP) and high sensitivity troponin I (hsTnI) were measured.

    Results: The median age of individuals was 47.8 years, 48.3% were men. The median of right-winsorized AC was 3 g/day. N=6,055 individuals developed AF (median follow-up time: 13.9 years). In a linear multivariable-adjusted Cox regression analyses, AC was linearly and positively associated with incident AF (Figure), hazard ratio (HR) per g/day 1.009, 95% confidence interval (CI) 1.007- 1.012, P<0.001. For one drink (12g) per day the HR was 1.15, CI 1.12–1.18, P<0.001. There was a high heterogeneity in associations across cohorts.

    No significant interactions of the association by Nt-proBNP and hsTnI were observed. AC was positively related to stroke risk after diagnosis of AF (HR 1.18, 95% CI 1.04–1.34, P=0.012).

    Conclusions: In contrast to other cardiovascular diseases, we did not observe a U-shaped association of alcohol with incident AF in the community, but a rather linearly increasing relation.

  • 203. Dahlen, Torsten
    et al.
    Edgren, Gustaf
    Lambe, Mats
    Hoglund, Martin
    Bjorkholm, Magnus
    Sandin, Fredrik
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Richter, Johan
    Olsson-Stromberg, Ulla
    Ohm, Lotta
    Back, Magnus
    Stenke, Leif
    Cardiovascular Events Associated With Use of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A Population-Based Cohort Study2016Ingår i: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 165, nr 3, s. 161-166Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Tyrosine kinase inhibitors (TKIs) have increased survival dramatically for patients with chronic myeloid leukemia (CML), but continuous administration of these drugs may elicit long-term toxicity. Objective: To investigate the incidence of vascular events in patients with CML treated with first-and second-generation TKIs. Design: Retrospective cohort study using nationwide population-based registries. Setting: Sweden. Patients: All patients diagnosed with chronic-phase CML in Sweden from 2002 to 2012 and treated with a TKI, and 5 age- and sex-matched control individuals per patient. Measurements: Relative risks, expressed as incidence rate ratios comparing patients with control individuals, were calculated. Events per 1000 person-years were assessed in interdrug comparisons. Results: 896 patients, 94.4% with documented TKI treatment, were followed for a median of 4.2 years. There were 54 arterial and 20 venous events in the CML cohort, corresponding to relative risks of 1.5 (95% CI, 1.1 to 2.1) and 2.0 (CI, 1.2 to 3.3), respectively. The event rate for myocardial infarction was higher in patients treated with nilotinib or dasatinib (29 and 19 per 1000 person-years, respectively) than in those receiving imatinib (8 per 1000 person-years), although data are limited and the CIs were wide and overlapped. Among 31 patients treated with a TKI who had myocardial infarction, 26 (84%) had at least 1 major cardiac risk factor diagnosed before the event occurred. Limitations: Patients may have been exposed to multiple TKIs. Data on second-and third-generation TKIs were limited. Conclusion: An increased risk for arterial and venous vascular events was seen in patients with CML treated with a TKI. Further study is needed to determine whether the risk for myocardial infarction increases with second-generation drugs.

  • 204. Dahlström, Ulf
    et al.
    Håkansson, Jan
    Swedberg, Karl
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Adequacy of diagnosis and treatment of chronic heart failure in primary health care in Sweden2009Ingår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 11, nr 1, s. 92-98Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: We performed an observational multicentre study to obtain information of the diagnostic tools and treatments currently used in patients with chronic heart failure (CHF) in primary health care (PHC) in Sweden. Data were collected from 2093 patients in 158 randomly selected PHC centres. METHODS AND RESULTS: The mean age was 79 years. The dominating aetiology of HF was hypertension and/or ischaemic heart disease. Diagnosis was based on symptoms and/or ECG and/or chest X-ray in 69% of the patients. Treatment with a renin-angiotensin system (RAS) blocker was ongoing in 74% of the patients, but only 37% had > or = 50% of the recommended target dose. In 68%, treatment with a beta-blocker (BB) was present, but only 31% had > or = 50% of the recommended target dose. Only 42% of the patients were on treatment with an RAS blocker and a BB and only 20% had > or = 50% of the recommended target dose. CONCLUSION: The diagnostic criteria for CHF according to the European Society of Cardiology were fulfilled in only approximately 30% of the patients. In addition, evidenced-based treatments to reduce morbidity and mortality were markedly underused, particularly regarding dosing. Our findings may reflect the patients' high age and the presence of important co-morbidities.

  • 205. Dalla, Keti
    et al.
    Hallman, Caroline
    Bech-Hanssen, Odd
    Haney, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Ricksten, Sven-Erik
    Strain echocardiography identifies impaired longitudinal systolic function in patients with septic shock and preserved ejection fraction2015Ingår i: Cardiovascular Ultrasound, ISSN 1476-7120, E-ISSN 1476-7120, Vol. 13, artikel-id 30Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Myocardial dysfunction is recognized in sepsis. We hypothesized that mechanical left (LV) and right (RV) ventricular function analysed using 2-dimensional speckle-tracking echocardiography in a cohort of early severe sepsis or septic shock patients, would be different to that of a group of critically ill, non-septic patients.

    Methods: Critically ill adult patients with early, severe sepsis/septic shock (n = 48) and major trauma patients with no sepsis (n = 24) were included retrospectively, as well as healthy controls (n = 16). Standard echocardiographic examinations, including right (RV) left (LV) volumes and mitral, aortic and pulmonary vein Doppler flow profiles, were retrospectively identified and the studies were then reanalysed for assessment of myocardial strain using speckle-tracking echocardiography. Endocardial tracing of the LV was performed in apical four-chamber (4-Ch), two-chamber (2-Ch), apical long-axis (3-Ch) and apical views of RV determining the longitudinal LV and RV free wall strain in each subject.

    Results: In septic patients, heart rate was significantly higher (p = 0.009) and systolic (p < 0.001) and mean arterial pressures (p < 0.001), as well as systemic vascular resistance (p < 0.001) were significantly lower when compared to the non-septic trauma group. Ninety-three per cent of the septic patients and 50 % of the trauma patients were treated with norepinephrine (p < 0.001). LV ejection fraction (LVEF) was lower in the septic patients (p = 0.019). In septic patients with preserved LVEF (>50 %, n = 34), seventeen patients (50 %) had a depressed LV global longitudinal function, defined as a LV global strain > -15 %, compared to two patients (8.7 %) in the non-septic group (p = 0.0014). In septic patients with preserved LVEF, LV global and RV free wall strain were 14 % (p = 0.014) and 17 % lower (p = 0.008), respectively, compared to the non-septic group with preserved LVEF. There were no significant differences between groups with respect to LV end-diastolic or end-systolic volumes, stroke volume, or cardiac output. There were no signs of diastolic dysfunction from the mitral or pulmonary vein Doppler profiles in the septic patients.

    Conclusions: LV and RV systolic function is impaired in critically ill patients with early septic shock and preserved LVEF, as detected by Speckle-tracking 2D echocardiography. Strain imaging may be useful in the early detection of myocardial dysfunction in sepsis.

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  • 206. Damman, Peter
    et al.
    Varenhorst, Christoph
    Koul, Sasha
    Eriksson, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Heart Centre, University Hospital.
    Erlinge, David
    Lagerqvist, Bo
    James, Stefan K.
    Treatment Patterns and Outcomes in Patients Undergoing Percutaneous Coronary Intervention Treated With Prasugrel or Clopidogrel (from the Swedish Coronary Angiography and Angioplasty Registry [SCAAR])2014Ingår i: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 113, nr 1, s. 64-69Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Large real-world registry data are important for understanding the current use and outcomes of novel therapies. The aim of this study was to assess treatment patterns and outcomes in patients who underwent percutaneous coronary intervention (PCI) with prasugrel or clopidogrel. Consecutive patient data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for 2010 and 2011 were used. The study population consisted of all patients with acute coronary syndromes (ACS) and those without ACS who underwent PCI and were treated with prasugrel (with or without a clopidogrel loading dose) or solely with clopidogrel. Outcomes included were 30-day mortality and in-hospital bleeding. In 2010 and 2011, 23,994 patients were treated with clopidogrel during hospitalization for their first PCI during the study period, while 2,142 patients were treated with prasugrel. Prasugrel was mainly used in patients with ST-segment elevation myocardial infarction. Hemorrhagic risk factors such as older age, female gender, and previous stroke were more common in the clopidogrel-treated patients. However, Mehran bleeding risk scores were higher in prasugrel-treated patients. In the ACS group, lower mortality was observed in the prasugrel group compared with the clopidogrel group. Mortality was comparable in patients who underwent elective angiography and PCI. In-hospital bleeding was lower in prasugrel-treated patients. In conclusion, in this real world population of patients who underwent urgent or elective PCI, prasugrel was used mainly in patients with ACS, while it was avoided in patients with characteristics indicating increased bleeding risk. Mortality and bleeding rates were lower with prasugrel than clopidogrel, probably because of patient selection.

  • 207. D'Ascenzi, F.
    et al.
    Cameli, M.
    Iadanza, A.
    Reccia, R.
    Lisi, M.
    Curci, V.
    Sinicropi, G.
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Pierli, C.
    Mondillo, S.
    Left atrial remodeling in patients undergoing transcatheter aortic valve implantation: a speckle tracking prospective study2013Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, nr Supplement: 1, s. 338-338Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background: Aortic Stenosis (AS) results in several Left Ventricular (LV) disturbances as well as progressive Left Atrial (LA) enlargement and dysfunction. Transcatheter Aortic Valve Implantation (TAVI) reverses LV remodelling and improves overall systolic function but its effect on LA function remains undetermined. The aim of this prospective study was toinvestigate the effects of TAVI on LA structure and function.

    Material and methods: We studied thirty-two patients with severe symptomatic AS and high surgical risk who underwent TAVI, using standard and 2-dimensional speckle-tracking echocardiography before, at 40-day and at 3-month follow-up.

    Results: Following TAVI, mean transvalvular gradient reduced (p<0.001). Both LA mean area index and LA mean volume index decreased at 40-day (16.2±6.4 vs. 12.5±2.9 cm2/m2, and 47.3±12.0 vs. 42.8±12.5 mL/m2, respectively, p<0.05) and values remained unchanged at 3 months. The reduction of LA size was accompanied by a significant increase in global PALS (14.4±3.9% vs. 19.1±4.7%, p<0.001) and global PACS (8.4±2.5% vs. 11.0±4.1%, p<0.05) at 3-month. After the procedure, LA stiffness measurements decreased and became significant at 3-month follow up (p<0.001). Pre-procedural trans-aortic mean gradient and pre-procedural LA volume were identified as predictors of global PALSincrease (p<0.0001) while the delta drop in trans-aortic mean gradient as predictors of LA volume index reduction 3 months after TAVI (p<0.0001).

    Conclusion: TAVI is associated with significant recovery of LA structure and function suggesting a reverse cavity remodelling. Such functional recovery is determined by the severity of pre-procedural valve stenosis.

  • 208.
    D'Ascenzi, Flavio
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Atrial function and loading conditions in athletes2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Intensive training is associated with hemodynamic changes that typically induce an enlargement of cardiac chamber. Despite LA dilatation in athletes has been interpreted as a benign adaptation, little evidence is available. The aim of this thesis is to demonstrate that LA size changes in response to alterations in loading conditions and to analyse atrial myocardial function in athletes through the application of novel echocardiographic techniques.

    We found that top-level athletes exhibit a dynamic morphological and functional LA remodelling, induced by training, with an increase in reservoir and conduit volumes, but stable active volume. Training causes an increase in biatrial volumes which is accompanied by normal filling pressures and stiffness. These changes in atrial morphology are not associated with respective electrical changes. Extending the evidence from adult athletes to children, we found that training-induced atrial remodelling can occur in the early phases of the sports career and is associated with a preserved biatrial function. Finally, in a meta-analysis study of the available evidence we demonstrated that atrial function and size are not affected by aging.

    In conclusions, athlete’s heart is characterized by a physiological biatrial enlargement. This adaptation occurs in close association with LV cavity enlargement, is dynamic and reversible. This increase in biatrial size is not intrinsically an expression of atrial dysfunction. Indeed, in athletes the atria are characterized by a preserved reservoir function, normal myocardial stiffness, and dynamic changes in response to different loading conditions.

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  • 209.
    D'Ascenzi, Flavio
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    The impact of aging on left atrial size and function: a systematic review and meta-analysis in healthy subjectsManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background. The cardiovascular system is affected by aging, however conflicting results cloud this relationship and data on LA myocardial function and aging are scanty. The aim of this study was to evaluate the impact of aging on LA size and function in healthy subjects.

    Methods. We conducted a systematic literature search of MEDLINE database. We included only studies evaluating healthy subjects, with age ranged between 18 and 80 years. Parameters were compared among 4 age groups, <30, 30-45, >45-60, >60 years.

    Results. Three hundred twenty-six studies met the inclusion criteria and the final population consisted of 62,821 subjects. LA antero-posterior diameter and LA volume gradually increased with aging, however LA volume index did not differ among groups. LA ejection fraction measured by three-dimensional echocardiography modestly reduced with age (p=0.049), but respective measurements derived by two-dimensional echocardiography did not (p=0.94). LA reservoir function, measured by strain, did not differ among the groups. Left ventricular (LV) size and function were not different among groups, except LV mass index. A decrease in E/A ratio and an increase in E/e’ ratio with advancing age (p<0.0001 and p=0.001, respectively).

    Conclusions. In healthy subjects LA volume index is not influenced while LA antero-posterior diameter and absolute volumes increase with advancing age. Neither LA deformation nor systolic function measures were affected by age. Thus, an increase in LA volume index and a decrease in LA reservoir function should be considered as an expression of pathology rather than part of normal aging.

  • 210. D'Ascenzi, Flavio
    et al.
    Cameli, Matteo
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Iadanza, Alessandro
    Reccia, Rosanna
    Lisi, Matteo
    Curci, Valeria
    Sinicropi, Giuseppe
    Torrisi, Andrea
    Pierli, Carlo
    Mondillo, Sergio
    Left atrial remodelling in patients undergoing transcatheter aortic valve implantation: a speckle-tracking prospective, longitudinal study.2013Ingår i: The International Journal of Cardiovascular Imaging, ISSN 1569-5794, E-ISSN 1875-8312, Vol. 29, nr 8, s. 1717-1724Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aortic stenosis (AS) results in several left ventricular (LV) disturbances as well as progressive left atrial (LA) enlargement and dysfunction. Transcatheter aortic valve implantation (TAVI) reverses LV remodelling and improves overall systolic function but its effect on LA function remains undetermined. The aim of this prospective, longitudinal study was to investigate the effects of TAVI on LA structure and function. We studied thirty-two patients with severe symptomatic AS who underwent TAVI, using standard and 2-dimensional speckle-tracking echocardiography before, at 40-day and at 3-month follow-up. Following TAVI, mean transvalvular gradient decreased (p < 0.001). Both LA area index and LA volume index decreased at 40-day follow-up (16.2 ± 6.4 vs. 12.5 ± 2.9 cm(2)/m(2), and 47.3 ± 12.0 vs. 42.8 ± 12.5 mL/m(2), respectively, p < 0.05) and values remained unchanged at 3 months. The reduction of LA size was accompanied by a significant increase in global peak atrial longitudinal strain (14.4 ± 3.9 vs. 19.1 ± 4.7 %, p < 0.001) and in global peak atrial contraction strain (8.4 ± 2.5 vs. 11.0 ± 4.1 %, p < 0.05) at 3-month follow-up. LA stiffness measurements significantly decreased 3 months after TAVI (0.93 ± 0.59 vs. 0.65 ± 0.37, respectively, p < 0.001). Trans-aortic mean gradient change and pre-procedural LA volume were identified as predictors of global peak atrial longitudinal strain increase (β = -0.41, β = -0.35, respectively, p < 0.0001) while pre-procedural LA volume and trans-aortic mean gradient change as predictor of LA volume index reduction 3 months after TAVI (β = -0.37, β = -0.28, respectively, p < 0.0001). TAVI is associated with significant recovery of LA structure and function suggesting a reverse cavity remodelling. Such functional recovery is primarily determined by the severity of pre-procedural valve stenosis.

  • 211.
    D'Ascenzi, Flavio
    et al.
    Siena, Italy.
    Pelliccia, Antonio
    Rome, Italy.
    Natali, Benedetta Maria
    Siena, Italy.
    Cameli, Matteo
    Siena, Italy.
    Lisi, Matteo
    Siena, Italy.
    Focardi, Marta
    Siena, Italy.
    Padeletti, Margherita
    Siena, Italy.
    Palmitesta, Paola
    Siena, Italy.
    Corrado, Domenico
    Padua, Italy.
    Bonifazi, Marco
    Siena, Italy.
    Mondillo, Sergio
    Siena, Italy.
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. michael.henein@umu.se.
    Training-induced dynamic changes in left atrial reservoir, conduit, and active volumes in professional soccer players2015Ingår i: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 115, nr 8, s. 1715-1723Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although left atrial (LA) enlargement is a recognized component of athlete's heart, dynamic cavity changes occurring during the training period remain to be elucidated. We aimed to investigate the adaptive changes of LA reservoir, conduit, and active volumes in elite athletes vs. controls and their response to different training loads. LA maximum, pre-P, and minimum volumes were assessed in 26 top-level athletes and 23 controls. In athletes, LA volumes were measured at pre-, mid-, end-training, and post-detraining time points using conventional 2D echocardiography. Athletes had larger maximum (27.5 +/- A 3.2 vs. 20.3 +/- A 5.8 mL/m(2), p = 0.001), pre-P (11.5 +/- A 0.9 vs. 9.8 +/- A 2.2 mL/m(2), p = 0.001), and minimum (6.6 +/- A 0.9 vs. 5.0 +/- A 1.2 mL/m(2), p < 0.001) LA indexed volumes, compared with controls. Total and passive emptying volume indices were also larger in athletes compared with controls (18.7 +/- A 3.1 vs. 15.3 +/- A 4.9 mL/m(2), p < 0.05 and 13.8 +/- A 2.9 vs. 10.5 +/- A 4.6 mL/m(2), p < 0.05, respectively), while active emptying volume was similar (p = 0.74). During training, LA maximum (p < 0.0001), pre-P (p < 0.0001), minimum (p < 0.0001), total (p < 0.005), and passive (p < 0.05) emptying volume indices progressively increased, while active emptying volume (p = 0.10) and E/e' ratio (p = 0.32) remained unchanged. After detraining, LA volume measurements were not different from pre-training ones. End-training left ventricular mass index was the only independent predictor of the respective maximum LA volume (beta = 0.74, p < 0.005). Top-level athletes exhibit a dynamic morphological and functional LA remodeling, induced by training, with an increase in reservoir and conduit volumes, but stable active volume. LA remodeling is closely associated with left ventricular adaptation to exercise and both completely regress after detraining.

  • 212. D'Ascenzi, Flavio
    et al.
    Piu, Pietro
    Capone, Valentina
    Sciaccaluga, Carlotta
    Solari, Marco
    Mondillo, Sergio
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Heart Centre, Umeå, Sweden.
    Reference values of left atrial size and function according to age: should we redefine the normal upper limits?2019Ingår i: International Journal of Cardiac Imaging, ISSN 1569-5794, E-ISSN 1875-8312, Vol. 35, nr 1, s. 41-48Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Different cut-offs have been proposed for left atrial (LA) size. Furthermore, conflicting results have been reported about the influence of age on LA size and data on the impact of age on LA myocardial function are scanty. The aim of this study was to derive references values for LA size and function in healthy subjects and to evaluate the impact of age. We conducted a systematic literature search of MEDLINE database. We included only studies evaluating healthy subjects, with age ranged between 18 and 80years. Parameters were compared among four age groups, <30, 30-45, >45-60, >60years. Three hundred twenty-six studies met the inclusion criteria and the final population consisted of 62,821 subjects. LA volume index (LAVi) did not differ among different age groups (p=0.21). The normal upper limit of LAVi was 24mL/m(2). LA reservoir function, measured by strain, did not differ among age groups (38 +/- 3%, 32-43%; p=0.74). Left ventricular (LV) size and function were not different among groups, except LV mass index. A decrease in E/A ratio and an increase in E/e ratio were found with advancing age (p<0.0001 and p=0.001, respectively). In healthy subjects the normal upper limit of LAVi was lower than that recommended and is not influenced by advancing age. Furthermore, also LA function measured by strain was not affected by age. The current reference values of LAVi should be used with caution when applied to healthy subjects.

  • 213.
    D'Ascenzi, Flavio
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Department of Medical Biotechnologies, Division of Cardiology, University of Siena, Siena, Italy.
    Solari, Marco
    Anselmi, Francesca
    Maffei, Silvia
    Focardi, Marta
    Bonifazi, Marco
    Mondillo, Sergio
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Atrial chamber remodelling in healthy pre-adolescent athletes engaged in endurance sports: A study with a longitudinal design. The CHILD study2016Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 223, s. 325-330Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: Previous studies investigated the exercise-induced adaptation of left (LA) and right atrium (RA) in adults, but little is known about respective changes in the growing heart of children. We aimed to longitudinally investigate the effects of endurance training on biatrial remodelling in preadolescent athletes.

    METHODS AND RESULTS: Ninety-four children (57 endurance athletes, 37 sedentary controls; mean age 10.8±0.2 and 10.2±0.2years, respectively) were evaluated at baseline and after 5months by ECG and by two-dimensional, three-dimensional (3D) and speckle-tracking echocardiography. Athletes were trained at least 10h/week. The resting heart rate was lower in athletes (p=0.046) and decreased further after training (p<0.0001). Neither athletes nor controls had ECG evidence for LA or RA enlargement. At baseline, indexed LA volumes did not differ between groups (p=0.14) but indexed RA dimensions were larger in athletes (p=0.007). After 5months, indexed LA volumes increased in athletes but not in controls (p<0.0001, p=0.29; respectively) while indexed RA volumes increased in both groups (p<0.0001, p=0.018; respectively). At the same time, slight differences in biatrial reservoir and contractile function were found either in athletes, as demonstrated by speckle-tracking echocardiography, but 3D-derived LA and RA ejection fraction remained stable in both groups.

    CONCLUSION: Endurance training influences the growing heart of preadolescent athletes with an additive increase in biatrial size, suggesting that morphological adaptations can occur also in the early phases of the sports career. Training-induced remodelling was associated with a preserved biatrial function, supporting the hypothesis of a physiological remodelling.

  • 214. D'Ascenzi, Flavio
    et al.
    Solari, Marco
    Biagi, Michele
    Cassano, Francesco
    Focardi, Marta
    Corrado, Domenico
    Bonifazi, Marco
    Mondillo, Sergio
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    P-wave morphology is unaffected by training-induced biatrial dilatation: a prospective, longitudinal study in healthy athletes2016Ingår i: International Journal of Cardiac Imaging, ISSN 1569-5794, E-ISSN 1875-8312, Vol. 32, nr 3, s. 407-415Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Biatrial enlargement is common in athletes with a further increase occurring after training. P-wave morphology seems to be unaffected by atrial size, however longitudinal data are not available. This study aimed to prospectively investigate whether exercise-induced increase in biatrial size corresponds to electrical changes on 12-lead ECG. Thirty-five athletes were evaluated at the beginning of the training and after 6 months by ECG and standard and speckle-tracking echocardiography. Twenty-three sedentary subjects served as controls. Athletes had greater left atrial (LA) and right atrial (RA) size compared with controls (20.7 ± 4.7 vs. 27.1 ± 6.6 and 17.3 ± 3.8 vs. 23.4 ± 6.3 mL/m2, respectively, p < 0.0001). After 6 months, a further increase in LA and RA size was observed (p < 0.0001 and p = 0.002, respectively). Neither athletes nor controls fulfilled the ECG criteria for RA enlargement and no differences were found for LA enlargement criteria between athletes and controls (2/35, 6 % vs. 0/23, 0 %, p = 0.23). This percentage remained unchanged after training. Biatrial stiffness remained normal in athletes also after training. Training causes an increase in biatrial volumes, with normal filling pressures and normal stiffness. These changes in atrial morphology are not associated with respective electrical changes, suggesting that P-wave morphology is unaffected by training-induced biatrial dilatation in young healthy athletes.

  • 215. De Marco, Marina
    et al.
    Gerdts, Eva
    Casalnuovo, Giuseppina
    Migliore, Teresa
    Wachtell, Kristian
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Medicine, Skellefteå Hospital, Skellefteå, Sweden.
    Dahlöf, Björn
    Olsen, Michael H
    Kizer, Jorge R
    Devereux, Richard B
    de Simone, Giovanni
    Mitral annular calcification and incident ischemic stroke in treated hypertensive patients: the LIFE study2013Ingår i: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 26, nr 4, s. 567-573Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND Fibro-calcification of the mitral annulus (MAC) has been associated with increased risk of ischemic stroke in general populations. This study was performed to assess whether MAC predicts incidence of ischemic stroke in treated hypertensive patients with left ventricular hypertrophy (LVH).

    METHODS Baseline and follow-up clinical and echocardiographic parameters were assessed in 939 hypertensive patients with electrocardiogram (ECG) LVH participating in the Losartan Intervention for Endpoint reduction in hypertension (LIFE) echocardiography substudy (66 +/- 7 years; 42% women; 11% with diabetes) who did not have aortic or mitral valve stenosis or prosthesis.

    RESULTS MAC was found in 458 patients (49%). Patients with MAC were older (68 +/- 7 vs. 65 +/- 7 years); were more often women (47% vs. 37%); had higher baseline systolic blood pressure (BP) (175 +/- 14 vs. 172 +/- 15 mm Hg), left atrial diameter (4.0 +/- 0.5 vs. 3.8 +/- 0.6 cm), and left ventricular mass index (58 +/- 13 vs. 55 +/- 12 g/m(2.7)) and included more patients with proteinuria (30% vs. 21%; all P < 0.01). During a mean follow-up of 4.8 years, 58 participants had an ischemic stroke. Risk of incident ischemic stroke was significantly related to presence of MAC (log rank = 9; P < 0.01). In multivariable Cox regression analysis models, MAC was associated with increased risk of ischemic stroke (hazard ratio = 1.78-2.35), independent of age, baseline or time-varying systolic BR prevalence or incidence of atrial fibrillation, history of previous cerebrovascular disease, and other well-recognized confounders, such as sex, time-varying left ventricular mass, left atrial diameter, and urinary albumin/creatinine ratio (all P < 0.05).

    CONCLUSIONS MAC is common in treated hypertensive patients with ECG LVH and is an independent predictor of incident ischemic stroke.

  • 216. Del Gobbo, Liana C.
    et al.
    Imamura, Fumiaki
    Aslibekyan, Stella
    Marklund, Matti
    Virtanen, Jyrki K.
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Yakoob, Mohammad Y.
    Chiuve, Stephanie E.
    dela Cruz, Luicito
    Frazier-Wood, Alexis C.
    Fretts, Amanda M.
    Guallar, Eliseo
    Matsumoto, Chisa
    Prem, Kiesha
    Tanaka, Tosh
    Wu, Jason H. Y.
    Zhou, Xia
    Helmer, Catherine
    Ingelsson, Erik
    Yuan, Jian-Min
    Barberger-Gateau, Pascale
    Campos, Hannia
    Chaves, Paulo H. M.
    Djousse, Luc
    Giles, Graham G.
    Gomez-Aracena, Jose
    Hodge, Allison M.
    Hu, Frank B.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Khaw, Kay-Tee
    Koh, Woon-Puay
    Lemaitre, Rozenn N.
    Lind, Lars
    Luben, Robert N.
    Rimm, Eric B.
    Riserus, Ulf
    Samieri, Cecilia
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Siscovick, David S.
    Stampfer, Meir
    Steffen, Lyn M.
    Steffen, Brian T.
    Tsai, Michael Y.
    van Dam, Rob M.
    Voutilainen, Sari
    Willett, Walter C.
    Woodward, Mark
    Mozaffarian, Dariush
    omega-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease Pooling Project of 19 Cohort Studies2016Ingår i: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 176, nr 8, s. 1155-1166Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IMPORTANCE The role of omega-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20: 5 omega-3), docosapentaenoic acid (DPA; 22: 5 omega-3), and docosahexaenoic acid (DHA; 22: 6 omega-3) and plant-derived alpha-linolenic acid (ALA; 18: 3 omega-3) for incident CHD. DATA SOURCES A global consortium of 19 studies identified by November 2014. STUDY SELECTION Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue omega-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, omega-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with omega-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the omega-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived omega-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

  • 217. Devereux, Richard B.
    et al.
    Bang, Casper N.
    Roman, Mary J.
    Palmieri, Vittorio
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gerdts, Eva
    Nieminen, Markku S.
    Papademetriou, Vasilios
    Wachtell, Kristian
    Hille, Darcy A.
    Dahlof, Bjorn
    Left Ventricular Wall Stress-Mass-Heart Rate Product and Cardiovascular Events in Treated Hypertensive Patients LIFE Study2015Ingår i: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 66, nr 5, s. 945-953Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the Losartan Intervention for End Point Reduction in Hypertension (LIFE) study, 4.8 years' losartan- versus atenolol-based antihypertensive treatment reduced left ventricular hypertrophy and cardiovascular end points, including cardiovascular death and stroke. However, there was no difference in myocardial infarction (MI), possibly related to greater reduction in myocardial oxygen demand by atenolol-based treatment. Myocardial oxygen demand was assessed indirectly by the left ventricular massxwall stressxheart rate (triple product) in 905 LIFE participants. The triple product was included as time-varying covariate in Cox models assessing predictors of the LIFE primary composite end point (cardiovascular death, MI, or stroke), its individual components, and all-cause mortality. At baseline, the triple product in both treatment groups was, compared with normal adults, elevated in 70% of patients. During randomized treatment, the triple product was reduced more by atenolol, with prevalences of elevated triple product of 39% versus 51% on losartan (both P0.001). In Cox regression analyses adjusting for age, smoking, diabetes mellitus, and prior stroke, MI, and heart failure, 1 SD lower triple product was associated with 23% (95% confidence interval 13%-32%) fewer composite end points, 31% (18%-41%) less cardiovascular mortality, 30% (15%-41%) lower MI, and 22% (11%-33%) lower all-cause mortality (all P0.001), without association with stroke (P=0.34). Although losartan-based therapy reduced ventricular mass more, greater heart rate reduction with atenolol resulted in larger reduction of the triple product. Lower triple product during antihypertensive treatment was strongly, independently associated with lower rates of the LIFE primary composite end point, cardiovascular death, and MI, but not stroke.

  • 218. Di Castelnuovo, Augusto Filippo
    et al.
    Costanzo, Simona
    Bonaccio, Marialaura
    McElduff, Patrick
    Linneberg, Allan
    Salomaa, Veikko
    Mannisto, Satu
    Moitry, Marie
    Ferrieres, Jean
    Dallongeville, Jean
    Thorand, Barbara
    Brenner, Hermann
    Ferrario, Marco
    Tamosiunas, Abdonas
    Njolstad, Inger
    Drygas, Wojciech
    Nikitin, Yuri
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Kee, Frank
    Zeller, Tanja
    Kuulasmaa, Kari
    Blankenberg, Stefan
    Donati, Maria Benedetta
    de Gaetano, Giovanni
    Iacoviello, Licia
    Association of Alcohol Intake with Cardiovascular and Total Mortality2019Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139Artikel i tidskrift (Övrigt vetenskapligt)
  • 219. Di Castelnuovo, Augusto
    et al.
    Veronesi, Giovanni
    Costanzo, Simona
    Zeller, Tanja
    Schnabel, Renate B.
    de Curtis, Amalia
    Salomaa, Veikko
    Borchini, Rossana
    Ferrario, Marco
    Giampaoli, Simona
    Kee, Frank
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Niiranen, Teemu
    Kuulasmaa, Kari
    de Gaetano, Giovanni
    Donati, Maria Benedetta
    Blankenberg, Stefan
    Iacoviello, Licia
    NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) and the Risk of Stroke Results From the BiomarCaRE Consortium2019Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 50, nr 3, s. 610-617Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Purpose: NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a risk factor for atrial fibrillation and a marker of cardiac function used in the detection of heart failure. Given the link between cardiac dysfunction and stroke, NT-proBNP is a candidate marker of stroke risk. Our aim was to evaluate the association of NT-proBNP with stroke and to determine the predictive value beyond a panel of established risk factors. Methods: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe-Consortium, we analyzed data of 58 173 participants (50% men; mean age 52 y) free of stroke from 6 community-based cohorts. NT-proBNP measurements were performed in the central Biomarkers for Cardiovascular Risk Assessment in Europe laboratory. The outcomes considered were total stroke and subtypes of stroke (ischemic/hemorrhagic). Results: During a median follow-up time of 7.9 years, we observed 1550 stroke events (1176 ischemic). Increasing quarters of the NT-proBNP distribution were associated with increasing risk of stroke (P for trend < 0.0001; multivariable Cox regression analysis adjusted for risk factors and cardiac diseases). Individuals in the highest NT-proBNP quarter (NTproBNP > 82.2 pg/mL) had 2-fold (95% CI, 75%-151%) greater risk of stroke than individuals in the lowest quarter (NTproBNP < 20.4 pg/mL). The association remained unchanged when adjusted for interim coronary events during followup, and though it was somewhat heterogeneous across cohorts, it was highly homogenous according to cardiovascular risk profile or subtypes of stroke. The addition of NT-proBNP to a reference model increased the C-index discrimination measure by 0.006 (P=0.0005), yielded a categorical net reclassification improvement of 2.0% in events and 1.4% in nonevents and an integrated discrimination improvement of 0.007. Conclusions: In European individuals free of stroke, levels of NT-proBNP are positively associated with risk of ischemic and hemorrhagic stroke, independently from several other risk factors and conditions. The addition of NT-proBNP to variables of established risk scores improves prediction of stroke, with a medium effect size.

  • 220.
    Diamant, Ulla-Britt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Long QT syndrome: studies of diagnostic methods2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: The Long QT Syndrome (LQTS) is a hereditary heart disease with risk of malignant ventricular arrhythmia and sudden cardiac death. Despite our increased knowledge about genotype and phenotype correlation we still rely on the 12-lead ECG for assessment of the QT interval and the T-wave morphology for diagnosis and risk stratification. Intra- and -inter individual variability in manually QT measurement and, e.g., difficulties in defining the end of the T-wave may impair the diagnosis of LQTS. Increased heterogeneity in ventricular repolarization (VR) may be an important factor in the arrhythmogenicity in cases of LQTS. In a LQTS founder population the same mutation is carried by numerous individuals in many families which provide a unique opportunity to study diagnostic methods, risk assessment, VR and the correlation between genotype and phenotype.

    Methods: Resting 12-lead ECG and vectorcardiogram (VCG) were recorded in 134 LQTS mutation carriers and 121 healthy controls, to investigate the capability and precision in measuring the QT interval. For assessment of the VR, VCG was compared in individuals with mutations in the KCNQ1 and KCNH2 gene. Genealogical and geographic studies were performed in 37 index cases and their relatives to determine if Swedish carriers of the Y111C mutation in the KCNQ1 gene constitute a founder population. To confirm kinship, haplotype analysis was performed in 26 of the 37 index cases. The age and prevalence of the Y111C mutation were calculated in families sharing a common haplotype.

    Results: VCG by automatic measurement of the QT interval provided the best combination of sensitivity (90%) and specificity (89%) in the diagnosis of LQTS. VCG showed no consistent pattern of increased VR heterogeneity among KCNQ1 and KCNH2 mutation carriers. Living carriers of the Y111C mutation shared a common genetic (haplotype), genealogic and geographic origin. The age of the Y111C mutation was approximately 600 years. The prevalence of living carriers of the Y111C mutation in the mid-northern Sweden was estimated to 1:1,500-3,000.

    Conclusion: We have shown that VCG provides a valuable contribution to the diagnosis and risk assessment of LQTS in adults and children. No consistent pattern of increased VR heterogeneity was found among the LQTS mutation carriers. The identified Swedish LQTS founder population will be a valuable source to future LQTS research and may contribute to increase our understanding of LQTS and the correlation of phenotype, genotype and modifying factors.

    Ladda ner fulltext (pdf)
    Avhandling 20130902 Ulla-Britt Diamant
  • 221.
    Diamant, Ulla-Britt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Jensen, Steen M
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Winbo, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stattin, Eva-Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Vectorcardiographic recordings of the Q-T interval in a pediatric long Q-T syndrome population2013Ingår i: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 34, nr 2, s. 245-249Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Measurements of the Q-T interval are less reliable in children than in adults. Identification of superior diagnostic tools is warranted. This study aimed to investigate whether a vectorcardiogram (VCG) recorded from three orthogonal leads (X, Y, Z) according to Frank is superior to a 12-lead electrocardiogram (ECG) in providing a correct long Q-T syndrome (LQTS) diagnosis in children. This LQTS group consisted of 35 genetically confirmed carriers of mutations in the KCNQ1 (n = 29) and KCNH2 (n = 6) genes. The control group consisted of 35 age- and gender-matched healthy children. The mean age was 7 years in the LQTS group and 6.7 years in the control group (range, 0.5-16 years). The corrected Q-T interval (QT(c)) was measured manually (QT(man)) by one author (A.W.). The 12-lead ECG automatic measurements (QT(ECG)) and interpretation (QT(Interpret)) of QT(c) were performed with the Mac5000 (GE Medical System), and the VCG automatic measurements (QT(VCG)) were performed with the Mida1000, CoroNet (Ortivus AB, Sweden). By either method, a QT(c) longer than 440 ms was considered prolonged and indicative of LQTS. Of the 35 children with genetically confirmed LQTS, 30 (86 %) received a correct diagnosis using QT(VCG), 29 (82 %) using QT(man), 24 (69 %) using QT(ECG), and 17 (49 %) using QT(Interpret). Specificity was 0.80 for QT(VCG), 0.83 for QT(man), 0.77 for QT(ECG), and 0.83 for QT(Interpret). The VCG automatic measurement of QT(c) seems to be a better predictor of LQTS than automatic measurement and interpretation of 12-lead ECG.

  • 222.
    Diamant, Ulla-Britt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Vahedi, Farzad
    Sahlgrenska Akademin Göteborgs Universitet.
    Winbo, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stattin, Eva-Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Jensen, Steen M
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Bergfeldt, Lennart
    Sahlgrenska Akademin Göteborgs Universitet.
    Electrophysiological phenotype in the LQTS mutations Y111C and R518X in the KCNQ1 gene2013Ingår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, nr 10, s. 1423-1432Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Long QT syndrome is the prototypical disorder of ventricular repolarization (VR), and a genotype-phenotype relation is postulated. Furthermore, although increased VR heterogeneity (dispersion) may be important in the arrhythmogenicity in long QT syndrome, this hypothesis has not been evaluated in humans and cannot be tested by conventional electrocardiography. In contrast, vectorcardiography allows assessment of VR heterogeneity and is more sensitive to VR alterations than electrocardiography. Therefore, vectorcardiography was used to compare the electrophysiological phenotypes of two mutations in the LQT1 gene with different in vitro biophysical properties, and with LQT2 mutation carriers and healthy control subjects. We included 99 LQT1 gene mutation carriers (57 Y111C, 42 R518X) and 19 LQT2 gene mutation carriers. Potassium channel function is in vitro most severely impaired in Y111C. The control group consisted of 121 healthy subjects. QRS, QT, and T-peak to T-end (Tp-e) intervals, measures of the QRS vector and T vector and their relationship, and T-loop morphology parameters were compared at rest. Apart from a longer heart rate-corrected QT interval (QT heart rate corrected according to Bazett) in Y111C mutation carriers, there were no significant differences between the two LQT1 mutations. No signs of increased VR heterogeneity were observed among the LQT1 and LQT2 mutation carriers. QT heart rate corrected according to Bazett and Tp-e were longer, and the Tp-e-to-QT ratio greater in LQT2 than in LQT1 and the control group. In conclusion, there was a marked discrepancy between in vitro potassium channel function and in vivo electrophysiological properties in these two LQT1 mutations. Together with previous observations of the relatively low risk for clinical events in Y111C mutation carriers, our results indicate need for cautiousness in predicting in vivo electrophysiological properties and the propensity for clinical events based on in vitro assessment of ion channel function alone.

  • 223.
    Diamant, Ulla-Britt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Winbo, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stattin, Eva-Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Kesek, Milos
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Jensen, Steen M
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Two automatic QT algorithms compared with manual measurement in identification of long QT syndrome2010Ingår i: Journal of Electrocardiology, ISSN 0022-0736, E-ISSN 1532-8430, Vol. 43, nr 1, s. 25-30Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Long QT syndrome (LQTS) is an inherited disorder that increases the risk of syncope and malignant ventricular arrhythmias, which may result in sudden death.

    METHODS: We compared manual measurement by 4 observers (QT(manual)) and 3 computerized measurements for QT interval accuracy in the diagnosis of LQTS: 1. QT measured from the vector magnitude calculated from the 3 averaged orthogonal leads X, Y, and Z (QTVCG) and classified using the same predefined QTc cut-points for classification of QT prolongation as in manual measurements; 2. QT measured by a 12-lead electrocardiogram (ECG) program (QTECG) and subsequently classified using the same cut-points as in (1) above; 3. The same QT value as in (2) above, automatically classified by a 12-lead ECG program with thresholds for QT prolongation adjusted for age and sex (QTinterpret). The population consisted of 94 genetically confirmed carriers of KCNQ1 (LQT1) and KCNH2 (LQT2) mutations and a combined control group of 28 genetically confirmed noncarriers and 66 unrelated healthy volunteers.

    RESULTS: QT(VCG) provided the best combination of sensitivity (89%) and specificity (90%) in diagnosing LQTS, with 0.948 as the area under the receiver operating characteristic curve. The evaluation of QT measurement by the 4 observers revealed a high interreader variability, and only 1 of 4 observers showed acceptable level of agreement in LQTS mutation carrier identification (kappa coefficient >0.75).

    CONCLUSION: Automatic QT measurement by the Mida1000/CoroNet system (Ortivus AB, Danderyd, Sweden) is an accurate, efficient, and easily applied method for initial screening for LQTS.

  • 224. Ding, Ming
    et al.
    Huang, Tao
    Bergholdt, Helle K. M.
    Nordestgaard, Borge G.
    Ellervik, Christina
    Qi, Lu
    Frazier-Wood, Alexis C.
    Aslibekyan, Stella
    North, Kari E.
    Voortman, Trudy
    Graff, Mariaelisa
    Smith, Caren E.
    Lai, Chao-Qiang
    Varbo, Anette
    Lemaitre, Rozenn N.
    de Jonge, Ester A. L.
    Fumeron, Frederic
    Corella, Dolores
    Wang, Carol A.
    Tjonneland, Anne
    Overvad, Kim
    Sorensen, Thorkild I. A.
    Feitosa, Mary F.
    Wojczynski, Mary K.
    Kahonen, Mika
    Ahmad, Shafqat
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Psaty, Bruce M.
    Siscovick, David S.
    Barroso, Ines
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hernandez, Dena
    Ferrucci, Luigi
    Bandinelli, Stefania
    Linneberg, Allan
    Sandholt, Camilla Helene
    Pedersen, Oluf
    Hansen, Torben
    Schulz, Christina-Alexandra
    Sonestedt, Emily
    Orho-Melander, Marju
    Chen, Tzu-An
    Rotter, Jerome I.
    Allison, Mathew A.
    Rich, Stephen S.
    Sorli, Jose V.
    Coltell, Oscar
    Pennell, Craig E.
    Eastwood, Peter R.
    Hofman, Albert
    Uitterlinden, Andre G.
    Zillikens, MCarola
    van Rooij, Frank J. A.
    Chu, Audrey Y.
    Rose, Lynda M.
    Ridker, Paul M.
    Viikari, Jorma
    Raitakari, Olli
    Lehtimaki, Terho
    Mikkila, Vera
    Willett, Walter C.
    Wang, Yujie
    Tucker, Katherine L.
    Ordovas, Jose M.
    Kilpelainen, Tuomas O.
    Province, Michael A.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA; Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Arnett, Donna K.
    Tanaka, Toshiko
    Toft, Ulla
    Ericso, Ulrika
    Franco, Oscar H.
    Mozaffarian, Dariush
    Hu, Frank B.
    Chasman, Daniel I.
    Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study2017Ingår i: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 356, artikel-id j1000Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. DESIGN Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. SETTING CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. PARTICIPANTS Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis. MAIN OUTCOME MEASURES The instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. RESULTS Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (beta=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: beta=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). CONCLUSION The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.

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  • 225.
    Ding, Wenhong
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Survival and functional recovery following valve replacement in patients with severe aortic stenosis2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: Aortic stenosis (AS) is the most common heart valve disease in Europe and North America. Age-related calcification of the valve is the commonest cause of acquired AS, especially in patients older than 70 years.Conventional surgical aortic valve replacement (SAVR) and the novel, minimally invasive transcatheter aortic valve implantation (TAVI), effectively preserve left ventricular (LV) function, relieve symptoms and improve survival in patients with severe symptomatic AS. However, patients with impaired LV function may carry significant operative risk, and long recovery time. In addition, such patients might have other comorbidities, and hence adding another challenge. Thus evaluation of ventricular function before and after AVR, as well as critical evaluation of TAVI patients should contribute to better clinical outcome.

    Methods: We studied LV function by conventional echocardiography before and after SAVR in the following groups; (I) 86 patients (aged 71±10 years) with severe AS and LV dysfunction; (II) 112 consecutive elderly AS patients (aged 77±2 years) and compared them with 72 younger patients (aged 60±1 years); (III)66 patients (age 70±2 years, 53 male) who underwent AVR for severe AS with concurrent LV dysfunction; (IV) 89 consecutive patients with symptomatic severeAS who underwent successful TAVI, 45 of whom received trans-apical TAVI (TA)(age 80.8±4.9 year, 26 male) and 44 trans-femoral TAVI (TF) (age 82.9±5.8 year,22 male).The conventional echocardiographic measurements were made according to the guidelines. Severe AS was identified by aortic valve mean pressure gradient >40mmHg or valve area <1.0 cm2. LV systolic dysfunction was identified as ejection fraction (EF) <50%. LV long-axis function was presented by mitral annular plane systolic excursion ( MAPSE ) at lateral wall and septal wall, which were measured from apical four-chamber view. Also from the same view, LV septal and lateral wall deformation using STE as well as global longitudinal systolic strain. The LV systolic twist as the net difference between apical rotation and basal rotation was measured from the parasternal apical and basal short-axis views in the TAVI patients.

    Results: Study I: In the low flow and high gradient group, operative (30-day) mortality was 10%, and peri-operative mortality was associated with lower mean LVEF, higher mitral E:A ratio, peak systolic pulmonary artery pressure (PSPAP), and higher serum creatinine (all p<0.001), NYHA class III–IV, concomitant coronary artery bypass graft (CABG), urgent surgery, and longer bypass-time (all p< 0.05). Mortality at 4 years was 17%. Univariate predictors of 4-year mortality were: lower EF (p<0.001), presence of restrictive LV filling (p<0.001), raised PSPAP (p<0.001) and CABG (p=0.037). However, only EF<40 % (p=0.03), the presence of restrictive LV filling (p=0.033) and raised PSPAP (p<0.01)independently predicted mortality in this group.Study II: Elderly patients had higher NYHA class, more frequent atrial fibrillation (AF), coronary artery disease (CAD), emergency operation and use of bioprosthetic valves. They also had shorter E-wave deceleration time (DT) and larger left atria (LA) (p<0.05 for all). 30-day mortality was 12% vs 4 % (Log Rank x2=3.02, p=0.08) and long term mortality was 18% vs 7% (Log Rank x2=4.38,p=0.04) in the two groups, respectively. Age was not related to mortality after adjustment for other variables. Among all variables, anemia (OR 4.20, CI:1.02–6.86, p=0.04), cardiopulmonary bypass (CPB) time (OR 1.02, CI 1.01–1.04,p<0.01), significant patient prosthesis mismatch (PPM) (OR 5.43, CI 1.04–18.40,p<0.05) were associated with 30-day mortality in elderly patients. Their long-term mortality was related to CBP time (OR 1.02, CI 1.00–1.05, p=0.04),PPM (OR 4.64, CI 1.33–16.11, p=0.02) and raised LA pressure: DT (OR 0.94, CI0.84–0.99, p=0.03) and pulmonary artery systolic pressure (PASP) (OR 1.12, CI1.03–1.19, p<0.001).STUDY III: Following SAVR peak aortic pressure gradient (AOPG) decreased and indexed valve area increased (64±3 to 19±1 mmHg and 0.30±0.01 to 0.89±0.03 cm2/m2, p<0.001 for both). LVEF increased (from 45±1 to 54±2%;p<0.001), LV end diastolic and end-systolic dimensions fell (LVEDD index: from 33±1 to 30±1 mm/m2; and LVESD index: from 27±1 to 20±1 mm/m2; (p<0.01 forboth). LV diastolic dysfunction improved as evidenced by the fall in E/A ratio (from 2.6±0.2 to 1.9±0.4) and prolongation of total filling time; (from 29.2±0.6 to31.4±0.5 s/min, p=0.01 for both). Among all echocardiographic variables, LV dimensions (LVEDD index, OR 0.70, CI 0.52–0.97, p<0.05; LVESD index, OR 0.57, CI 0.40–0.85, p=0.005) were the two independent predictors of post-operative LV functional recovery on multivariate analysis. A cut-off value ofpre-operative LVESD index<=27.5 mm/m2 was 85% sensitive and 72% specific inpredicting intermediate-term recovery of LV function after AVR (AUC, 0.72, p=0.002). STUDY IV: Before TAVI, there was no difference between the two patient groups in gender, age, body surface area (BSA) and baseline LV function. However, left ventricular mass index (LVMi), left atrial volume index (LAVi) and tricuspid regurgitation pressure drop (TRPdrop) were increased in the TA group (p<0.05).One week after TAVI, aortic pressure gradient (AOPG) markedly dropped in thetwo groups (both p<0.001), LVEDD index and LVESD index fell but EF andmyocardial strain remained unchanged. Overall cavity twist reduced (p<0.048).Significant LVESD index reduction was only seen in TF group (p=0.02) with a slight increase in LVEF (p=0.04). Lateral MAPSE increased only in the TF group(p=0.02). LV longitudinal systolic strain remained unchanged in TA patients while apical lateral strain increased in TF group. LV apical rotation fell in the two groups but basal rotation increased only in the TA patients (p=0.02). LAVi reduced in bothgroups and to a greater extent in TF TAVI (p=0.006), as did TRPdrop (p<0.001).

    Conclusion: SAVR and TAVI are two effective treatments for severe AS patients.The severity of pre-operative systolic and diastolic LV dysfunction is the major predictor of mortality following SAVR for low-flow and high gradient AS.Peri-operative AVR survival is encouraging in the elderly. Long term mortality in the elderly is related to PPM, LV diastolic dysfunction and secondary pulmonary hypertension. LV functional recovery was evident in most patients with LV dysfunction after SAVR. A lower prevalence of LV functional recovery in patients with large pre-operative LVESD index might signify the loss of contractile reserveand thus predict post-operative functional recovery. TAVI results in significant early improvement of segmental and overall ventricular function, particularly in patients receiving the trans-femoral approach. The delayed recovery of the trans-apical TAVI group, we studied, might reflect worse pre-procedural diastolic cavity function.

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  • 226.
    Ding, Wen-Hong
    et al.
    Department of Paediatric Cardiology, Beijing Anzhen Hospital, Capital University of Medical Sciences, Beijing, China.
    Lam, Yat-Yin
    Division of Cardiology, Department of Medicine and Therapeutics Prince of Wales Hospital, Li Ka Shing Institute of Health and Sciences, Institute of Vascular Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
    Duncan, Alison
    Royal Brompton Hospital, London, UK.
    Li, Wei
    Royal Brompton Hospital, London, UK.
    Lim, Eric
    Royal Brompton Hospital, London, UK.
    Kaya, Mehmet G
    Department of Cardiology, Erciyes University, Erciyes, Turkey.
    Chung, Robin
    Royal Brompton Hospital, London, UK.
    Pepper, John R
    Royal Brompton Hospital, London, UK.
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Predictors of survival after aortic valve replacement in patients with low-flow and high-gradient aortic stenosis2009Ingår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 11, nr 9, s. 897-902Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: To identify predictors of survival following aortic valve replacement (AVR) in patients with low-flow and high-gradient aortic stenosis (AS).

    METHODS AND RESULTS: Eighty-six patients (aged 71 +/- 10 years) with severe AS [aortic valve mean pressure gradient >40 mmHg or valve area <1.0 cm(2)] and left ventricular (LV) dysfunction [ejection fraction (EF) <50%] underwent AVR. Cox proportional hazards were used to identify independent clinical and echocardiographic predictors of mortality. Operative (30-day) mortality was 10%. Peri-operative mortality was associated with lower mean LVEF, higher mitral E:A ratio, peak systolic pulmonary artery pressure (PSPAP), and serum creatinine (by 12%, 2.3, 28 mmHg, and 74 mmol/L, respectively, all P < 0.001), NYHA class III-IV (100 vs. 65%), concomitant CABG (89 vs. 55%), urgent surgery (78 vs. 35%), and longer bypass-time (by 28 min, all P < 0.05). Mortality at 4 years was 17%. Univariate predictors [hazard ratio (HR)] of 4-year mortality were: lower EF (HR 0.68 per % increase, P < 0.001), presence of restrictive LV filling (HR: 3.52, P < 0.001), raised PSPAP (HR: 1.07, P < 0.001), and CABG (HR: 4.93, P = 0.037). However, only low EF (<40%, HR 0.74, P = 0.030), the presence of restrictive filling (HR 1.77, P = 0.033), and raised PSPAP (>45 mmHg, HR 2.71, P = 0.010) remained as independent predictors after multivariate analysis.

    CONCLUSION: The severity of pre-operative systolic and diastolic LV dysfunction is the major predictor of mortality following AVR for low-flow and high-gradient AS.

  • 227.
    Ding, Wen-hong
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lam, Yat-yin
    Kaya, Mehmet G
    Li, Wei
    Chung, Robin
    Pepper, John R
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Echocardiographic predictors of left ventricular functional recovery following valve replacement surgery for severe aortic stenosis.2008Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 128, nr 2, s. 178-84Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: We aimed to identify the most sensitive echocardiographic measurements that predict recovery of left ventricular function following valve replacement surgery in patients with severe aortic stenosis (AS) and LV dysfunction.

    METHODS: We studied 66 patients (mean age 70+/-2 years, 53 male) who underwent AVR for severe AS with concurrent LV dysfunction between 1998 and 2003 at the Royal Brompton Hospital. Clinical symptoms, co-morbidities and echocardiographic measurements of LV function were recorded before and at a median follow-up of 46 months after AVR. Pre-operative LV systolic dysfunction was defined as LV ejection fraction (EF) <50% and the post-op LV recovery as an increase of EF >10%.

    RESULTS: Following AVR peak aortic pressure gradient decreased and aortic valve area index increased (64+/-3 to 19+/-1 mm Hg and 0.30+/-0.01 to 0.89+/-0.03 cm(2)/m(2), p<0.001 for both). LV EF increased (from 45+/-1 to 54+/-2%; p<0.001) and the LV dimensions fell (LVEDD index: from 33+/-1 to 30+/-1 mm/m(2); and LVESD index: from 27+/-1 to 20+/-1 mm/m(2); p<0.01 for both). LV diastolic dysfunction improved as evidenced by the fall in E/A ratio (from 2.6+/-0.2 to 1.9+/-0.4) and prolongation of total filling time; (from 29.2+/-0.6 to 31.4+/-0.5 s/min, p=0.01 for both). Among all echocardiographic variables, LV dimensions (LVEDD index, OR 0.70, CI 0.52-0.97, p<0.05; LVESD index, OR 0.57, CI 0.40-0.85, p=0.005) were the two independent predictors of post-operative LV functional recovery on multivariate analysis. A cut off value of pre-operative LVESD index=or<27.5 mm/m(2) was 85% sensitive and 72% specific in predicting intermediate-term recovery of LV function after AVR (AUC, 0.72, p=0.002).

    CONCLUSION: LV functional recovery was evident in majority of aortic stenotic patients with LV dysfunction after aortic valve replacement. A lower prevalence of LV functional recovery in patients with large pre-operative LV end systolic dimension index might signify the loss of contractile reserve and thus predict post-operative functional recovery.

  • 228.
    Ding, Wen-Hong
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lam, Yat-Yin
    Pepper, John R
    Kaya, Mehmet G
    Li, Wei
    Chung, Robin
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Early and long-term survival after aortic valve replacement in septuagenarians and octogenarians with severe aortic stenosis.2010Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 141, nr 1, s. 24-31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To evaluate the predictors for mortality following aortic valve replacement (AVR) in elderly patients with aortic stenosis (AS).

    METHODS: 112 consecutive elderly AS patients (aged 77+/-2 years) with AVR between 1998 and 2003 were studied. Clinical and echocardiographic data of LV function were recorded before and 46 months after AVR. Results were compared with 72 younger patients (aged 60+/-1 years). Outcome measures were 30-day and long-term all cause mortalities.

    RESULTS: Elderly patients had higher NYHA class, more frequent atrial fibrillation, coronary artery disease, emergency operation and use of bioprosthetic valves. They also had shorter E-wave deceleration time (DT) and larger left atria (p<0.05 for all). 30-day mortality was 12% vs 4% (Log Rank x(2)=3.02, p=0.08) and long term mortality was 18% vs 7% (Log Rank x(2)=4.38, p=0.04) in two groups respectively. Age was not related to mortality after adjustment for other variables. Among all variables, anemia (OR 4.20, CI: 1.02-6.86, p=0.04), cardiopulmonary bypass (CPB) time (OR 1.02, CI 1.01-1.04, p<0.01), significant prosthesis patient mismatch (PPM) (OR 5.43, CI 1.04-18.40, p<0.05) were associated with 30-day mortality in elderly patients. Their long-term mortality was related to CBP time (OR 1.02, CI 1.00-1.05, p=0.04), PPM (OR 4.64, CI 1.33-16.11, p=0.02) and raised left atrial pressure: DT (OR 0.94, CI 0.84-0.99, p=0.03) and pulmonary arterial systolic pressure (OR 1.12, CI 1.03-1.19, p<0.001).

    CONCLUSION: Peri-operative AVR survival is encouraging. While pre-operative anemia and a longer CBP time determine early mortality, long term mortality is related to PPM, LV diastolic dysfunction and secondary pulmonary hypertension.

  • 229.
    Ding, Wenhong
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Zhao, Ying
    Watt, Astrid
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Nilsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Weintar, Reidar
    Holmgren, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Ruck, Andreas
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Early effect of TAVI on left ventricular function in severe aortic stenosis: trans-apical vs. trans-femoral approachManuskript (preprint) (Övrigt vetenskapligt)
  • 230. Dini, Frank Lloyd
    et al.
    Bajraktari, Gani
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Clinic of Cardiology, University Clinical Centre of Kosova,Prishtina, Kosovo.
    Zara, Cornelia
    Mumoli, Nicola
    Rosa, Gian Marco
    Optimizing Management of Heart Failure by Using Echo and Natriuretic Peptides in the Outpatient Unit2018Ingår i: Heart Failure: From Research to Clinical Practice: vol 3 / [ed] Islam, Shahidul, Springer Publishing Company, 2018, s. 145-159Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    Chronic heart failure (HF) is an important public health problem and is associated with high morbidity, high mortality, and considerable healthcare costs. More than 90% of hospitalizations due to worsening HF result from elevations of left ventricular (LV) filling pressures and fluid overload, which are often accompanied by the increased synthesis and secretion of natriuretic peptides (NPs). Furthermore, persistently abnormal LV filling pressures and a rise in NP circulating levels are well known indicators of poor prognosis. Frequent office visits with the resulting evaluation and management are most often needed. The growing pressure from hospital readmissions in HF patients is shifting the focus of interest from traditionally symptom-guided care to a more specific patient-centered follow-up care based on clinical findings, BNP and echo. Recent studies supported the value of serial NP measurements and Doppler echocardiographic biomarkers of elevated LV filling pressures as tools to scrutinize patients with impending clinically overt HF. Therefore, combination of echo and pulsed-wave blood-flow and tissue Doppler with NPs appears valuable in guiding ambulatory HF management, since they are potentially useful to distinguish stable patients from those at high risk of decompensation.

  • 231.
    Djekic, Demir
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Replication of LC-MS untargeted lipidomics results in patients with calcific coronary disease: an interlaboratory reproducibility study2015Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 232.
    Djekic, Demir
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Nicoll, Rachel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Novo, Mehmed
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Metabolomics in atherosclerosis2015Ingår i: International Journal of Cardiology Metabolic & Endocrine, E-ISSN 2214-7624, Vol. 8, s. 26-30Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is well established that atherosclerotic cardiovascular disease (ACD) is a leading cause of death in the West. There are several predisposing factors for ACD, which can be divided into two groups: firstly modifiable risk factors, including hypertension, dyslipidaemia, type 2 diabetes mellitus, obesity, smoking and a sedentary lifestyle and secondly the unmodifiable risk factors such as age, gender and heredity. Since single biomarkers are unable to provide sufficient information about the biochemical pathways responsible for the disease, there is a need for a holistic approach technology, e.g. metabolomics, that provide sufficiently detailed information about the metabolic status and assay results will be able to guide food, drug and lifestyle optimisation. Rather than investigating a single pathway, metabolomics deal with the integrated identification of biological and pathological molecular pathways. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy are the two most commonly used techniques for metabolite profiling. This detailed review concluded that metabolomics investigations seem to have great potential in identifying small groups of disturbed metabolites which if put together should draw various metabolic routs that lead to the common track pathophysiology. The current evidence in using metabolomics in atherosclerotic cardiovascular disease is also limited and morewell designed studies remain to be established, which might significantly improve the comprehension of atherosclerosis pathophysiology and consequently management.

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  • 233. Djekic, Demir
    et al.
    Pinto, Rui
    Repsilber, Dirk
    Hyotylainen, Tuulia
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Molecular and Clinic Research Institute, St George University, London, UK; Institute of Environment, Health and Physical Sciences, Brunel University, London, UK.
    Serum untargeted lipidomic profiling reveals dysfunction of phospholipid metabolism in subclinical coronary artery disease2019Ingår i: Vascular Health and Risk Management, ISSN 1176-6344, E-ISSN 1178-2048, Vol. 15, s. 123-135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Disturbed metabolism of cholesterol and triacylglycerols (TGs) carries increased risk for coronary artery calcification (CAC). However, the exact relationship between individual lipid species and CAC remains unclear. The aim of this study was to identify disturbances in lipid profiles involved in the calcification process, in an attempt to propose potential biomarker candidates.

    Patients and methods: We studied 70 patients at intermediate risk for coronary artery disease who had undergone coronary calcification assessment using computed tomography and Agatston coronary artery calcium score (CACS). Patients were divided into three groups: with no coronary calcification (NCC; CACS: 0; n=26), mild coronary calcification (MCC; CACS: 1-250; n=27), or severe coronary calcification (SCC; CACS: >250; n=17). Patients' serum samples were analyzed using liquid chromatography-mass spectrometry in an untargeted lipidomics approach.

    Results: We identified 103 lipids within the glycerolipid, glycerophospholipid, sphingolipid, and sterol lipid classes. After false discovery rate correction, phosphatidylcholine (PC)(16:0/20:4) in higher levels and PC(18:2/18:2), PC(36:3), and phosphatidylethanolamine(20:0/18:2) in lower levels were identified as correlates with SCC compared to NCC. There were no significant differences in the levels of individual TGs between the three groups; however, clustering the lipid profiles showed a trend for higher levels of saturated and monounsaturated TGs in SCC compared to NCC. There was also a trend for lower TG (49:2), TG(51:1), TG(54:5), and TG(56:8) levels in SCC compared to MCC.

    Conclusion: In this study we investigated the lipidome of patients with coronary calcification. Our results suggest that the calcification process may be associated with dysfunction in autophagy. The lipidomic biomarkers revealed in this study may aid in better assessment of patients with subclinical coronary artery disease.

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  • 234.
    Djekic, Demir
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Pinto, Rui
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Bioinformatics for Life Sciences (BILS).
    Vorkas, Panagiotis A
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Replication of LC-MS untargeted lipidomics results in patients with calcific coronary disease: an interlaboratory reproducibility study2016Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 222, s. 1042-1048Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Recently a lipidomics approach was able to identify perturbed fatty acyl chain (FAC) and sphingolipid moieties that could stratify patients according to the severity of coronary calcification, a form of subclinical atherosclerosis. Nevertheless, these findings have not yet been reproduced before generalising their application. The aim of this study was to evaluate the reproducibility of lipidomics approaches by replicating previous lipidomic findings in groups of patients with calcific coronary artery disease (CCAD).

    METHODS: Patients were separated into the following groups based on their calcium score (CS); no calcification (CS: 0; n=26), mild calcification (CS: 1-250; n=27) and severe calcification (CS: >250; n=17). Two serum samples were collected from each patient and used for comparative analyses by 2 different laboratories, in different countries and time points using liquid chromatography coupled to mass spectrometry untargeted lipidomics methods.

    RESULTS: Six identical metabolites differentiated patients with severe coronary artery calcification from those with no calcification were found by both laboratories independently. Additionally, relative intensities from the two analyses demonstrated high correlation coefficients. Phosphatidylcholine moieties with 18-carbon FAC were identified in lower intensities and 20:4 FAC in higher intensities in the serum of diseased group. Moreover, 3 common sphingomyelins were detected.

    CONCLUSION: This is the first interlaboratory reproducibility study utilising lipidomics applications in general and specifically in patients with CCAD. Lipid profiling applications in patients with CCAD are very reproducible in highly specialised and experienced laboratories and could be applied in clinical practice in order to spare patients diagnostic radiation.

  • 235. Dragano, Nico
    et al.
    Siegrist, Johannes
    Nyberg, Solja T.
    Lunau, Thorsten
    Fransson, Eleonor I.
    Alfredsson, Lars
    Bjorner, Jakob B.
    Borritz, Marianne
    Burr, Hermann
    Erbel, Raimund
    Fahlen, Goran
    Goldberg, Marcel
    Hamer, Mark
    Heikkila, Katriina
    Joeckel, Karl-Heinz
    Knutsson, Anders
    Madsen, Ida E. H.
    Nielsen, Martin L.
    Nordin, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Oksanen, Tuula
    Pejtersen, Jan H.
    Pentti, Jaana
    Rugulies, Reiner
    Salo, Paula
    Schupp, Juergen
    Singh-Manoux, Archana
    Steptoe, Andrew
    Theorell, Tores
    Vahtera, Jussi
    Westerholm, Peter J. M.
    Westerlund, Hugo
    Virtanen, Marianna
    Zins, Marie
    Batty, G. David
    Kivimaki, Mika
    Effort-Reward Imbalance at Work and Incident Coronary Heart Disease A Multicohort Study of 90,164 Individuals2017Ingår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 28, nr 4, s. 619-626Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Epidemiologic evidence for work stress as a risk factor for coronary heart disease is mostly based on a single measure of stressful work known as job strain, a combination of high demands and low job control. We examined whether a complementary stress measure that assesses an imbalance between efforts spent at work and rewards received predicted coronary heart disease.

    Methods: This multicohort study (the “IPD-Work” consortium) was based on harmonized individual-level data from 11 European prospective cohort studies. Stressful work in 90,164 men and women without coronary heart disease at baseline was assessed by validated effort–reward imbalance and job strain questionnaires. We defined incident coronary heart disease as the first nonfatal myocardial infarction or coronary death. Study-specific estimates were pooled by random effects meta-analysis.

    Results: At baseline, 31.7% of study members reported effort–reward imbalance at work and 15.9% reported job strain. During a mean follow-up of 9.8 years, 1,078 coronary events were recorded. After adjustment for potential confounders, a hazard ratio of 1.16 (95% confidence interval, 1.00–1.35) was observed for effort–reward imbalance compared with no imbalance. The hazard ratio was 1.16 (1.01–1.34) for having either effort–reward imbalance or job strain and 1.41 (1.12–1.76) for having both these stressors compared to having neither effort–reward imbalance nor job strain.

    Conclusions: Individuals with effort–reward imbalance at work have an increased risk of coronary heart disease, and this appears to be independent of job strain experienced. These findings support expanding focus beyond just job strain in future research on work stress.

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  • 236. Drivelegka, Panagiota
    et al.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Angerås, Oskar
    Bergström, Goran
    Schmidt, Caroline
    Jacobsson, Lennart T. H.
    Dehlin, Mats
    Association between serum level of urate and subclinical atherosclerosis: results from the SCAPIS Pilot2020Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 22, nr 1, artikel-id 37Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Hyperuricemia is closely associated with cardiovascular disease (CVD). However, it has not been definitively established whether this association is independent of traditional cardiovascular risk factors (CVRFs) and whether it is gender-dependent. The aim of this study was to investigate in a population-based cohort (age range, 50-64 years) stratified by sex the association between the serum urate (SU) concentration and subclinical atherosclerosis, as reflected in the coronary artery calcification (CAC) score, common carotid intima-media thickness (CIMT), and carotid plaque score.

    Methods: The study involved participants in the Swedish CArdioPulmonary bioImage Study (SCAPIS) Pilot cohort (N = 1040; 48.8% males). This pilot cohort is part of the large population-based SCAPIS with 30,000 participants in the age range of 50-64 years, aimed at improving risk prediction for CVD. Subjects with a self-reported previous history of CVD (N = 68) or gout (N = 3) were excluded. The CAC score was assessed with the Agatston method using computed tomography. CIMT and carotid plaques were quantified by ultrasound. The associations between the SU quartiles and different levels of CAC, CIMT, and carotid plaques were assessed by multivariable logistic regression.

    Results: Age, BMI, education level, smoking, physical activity, hs-CRP, hypertension, and dyslipidemia showed no differences between males and females, while CAC (score > 0) and diabetes were both twice as common in men than in women (58% vs 26% and 8% vs 4%, respectively). Higher SU quartiles were in both sexes associated with BMI, hs-CRP, and the prevalence of hypertension, and in women, they were also associated with the prevalence of dyslipidemia. The three upper quartiles of SU (>308 mu mol/L) were linked to higher CAC scores in men, when adjusting for CVRFs, but not in women. CIMT and carotid plaques showed no correlation to SU in either sex.

    Conclusions: Higher levels of SU are associated with the presence of CAC in men but not in women, whereas SU is not associated with CIMT or carotid plaques in either men or women. This implies that the biological effects of SU differ in men and women or that SU has varying effects on different vascular beds or during the different stages of the atherosclerotic process.

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  • 237. Du, Xiaoyang
    et al.
    Khamitova, Adina
    Kyhlstedt, Mattias
    Sun, Sun
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Department of Learning, Information, Management and Ethics, Karolinska Institutet, Stockholm, Sweden; Synergus AB, Stockholm, Sweden.
    Sengoelge, Mathilde
    Utilisation of real-world data from heart failure registries in OECD countries: a systematic review2018Ingår i: IJC Heart & Vasculature, ISSN 2352-9067, Vol. 19, s. 90-97Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background: Heart failure represents a major public health issue that impacts 26 million people globally. Currently, real-world data represents a key instrument for providing the verification of both internal and external validity, yet there is still a lack of understanding regarding its scope in complementing evidence of treatments for heart failure. This study aims to increase understanding of the utilisation of real-word data from heart failure registries in Organisation for Economic Co-operation and Development (OECD) countries.

    Method: This was a systematic review of existing observational studies from heart failure registries in 35 OECD member countries. Studies from 2000 to March 2017 were identified through electronic databases (MEDLINE (Ovid), EMBASE, Web of Science Core Collection, CINAHL (Ebsco), Cochrane CENTRAL) and appraised according to eligibility criteria.

    Results: Two-hundred and two studies met the inclusion criteria, in which the majority were published from 2013 to 2016. All 202 studies were observational, among which 98% were cohort studies (198). The median sample size of all studies was 5152 (2417 to 32,890) and median study period 55 months (33.0 to 72.0). Swedish heart failure registry had the most publications (24, 12%).

    Conclusion: Since 2000 there has been an upward trend in the number of published observational studies on heart failure registries in OECD countries with increasingly diverse outcomes and advanced statistical methods to improve their validity and reliability. This indicates that the utilisation of real-world data has experienced a significant upsurge in complementing the findings of clinical trials for improved research of heart failure treatments.

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  • 238. Duranton, Flore
    et al.
    Palma, Alfonso
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wauthier, Michel
    Torres, Armando
    Argilés, Angel
    Blood Pressure Seasonality in Hemodialysis Patients from Five European Cities of Different Latitudes2018Ingår i: Kidney and Blood Pressure Research, ISSN 1420-4096, E-ISSN 1423-0143, Vol. 43, nr 5, s. 1529-1538Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Aims: Climate influences the regulation of blood pressure (BP). Our objective was to precisely estimate BP seasonality in hemodialysis (HD) patients from five European cities with marked climate differences. Methods: Stable prevalent HD patients from 5 European facilities (Santa Cruz de Tenerife (Spain), Seville (Spain), Montpellier (France), Ottignies (Belgium), Umea (Sweden)) present over the years 1995-1999 were included in this historical longitudinal observational study. Individual monthly averages of pre-dialysis BP level were computed from all facility BP measurements (>90 000 observations). The association between BP level and location, seasons and meteorological measurements was analyzed by mixed models. Results: 261 patients were included and followed-up for a median duration of 2 years (6903 monthly observations). Pre-dialysis SBP and DBP were minimal in summer (July) and maximal in winter (November and December), and mean changes were respectively 4.2 [3.0;5.4] and 2.0 [1.3;2.7] mmHg. Seasonality was confirmed in 4 locations (P-season <= 0.0010.001 for SBP and DBP), but not in Umea (both P-season >0.05). Seasonal changes in DBP were larger in southern locations (P-interaction =0.02). BP level was associated with climate parameters: in a positive manner with humidity or rainfall, and inversely with sunshine duration or temperature. The effects of temperature and rainfall on DBP varied with latitude (P-interaction <0.02) and were greater in southern locations. Conclusion: BP varies with seasons and climate in different European areas and seasonality can be more important in southern locations. These changes in BP deserve attention as they may be responsible for a significant increase in cardiovascular risk which may be preventable.

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  • 239. Efe, Cumali
    et al.
    Tascilar, Koray
    Henriksson, Ida
    Lytvyak, Ellina
    Alalkim, Fatema
    Trivedi, Hirsh
    Eren, Fatih
    Eliasson, Johanna
    Beretta-Piccoli, Benedetta Terziroli
    Fischer, Janett
    Caliskan, Ali Riza
    Chayanupatkul, Maneerat
    Coppo, Claudia
    Ytting, Henriette
    Purnak, Tugrul
    Muratori, Luigi
    Werner, Mårten
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Muratori, Paolo
    Rorsman, Fredrik
    Onnerhag, Kristina
    Gunsar, Fulya
    Nilsson, Emma
    Heurgue-Berlot, Alexandra
    Guzelbulut, Fatih
    Demir, Nurhan
    Gonen, Can
    Semela, David
    Aladag, Murat
    Kiyici, Murat
    Schiano, Thomas
    Montano-Loza, Aldo
    Berg, Thomas
    Ozaslan, Ersan
    Yoshida, Eric
    Bonder, Alan
    Marschall, Hanns-Ulrich
    Wahlin, Staffan
    Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis2019Ingår i: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 114, nr 7, s. 1101-1108Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.

  • 240. Einarsen, Eigir
    et al.
    Cramariuc, Dana
    Lønnebakken, Mai T
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gohlke-Bärwolf, Christa
    Chambers, John B
    Gerdts, Eva
    Comparison of frequency of ischemic cardiovascular events in patients with aortic stenosis with versus without asymmetric septal hypertrophy (from the SEAS Trial)2017Ingår i: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 119, nr 7, s. 1082-1087Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Asymmetric interventricular septum hypertrophy (ASH) has been associated with increased perioperative morbidity and mortality in patients with severe, symptomatic aortic valve stenosis (AS). Less is known about the prognostic impact of ASH during progression of AS. Clinical, echocardiographic, and outcome data from 1,691 patients with initially asymptomatic, mostly moderate AS, participating in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study was used. ASH was considered present if interventricular septum/posterior wall thickness ratio in end-diastole ≥1.5. The associations of ASH with hazard rate of ischemic cardiovascular events were tested in time-dependent Cox regression analyses. Based on the presence of ASH at study echocardiograms, the study population was grouped in to a no-ASH, nonpersistent ASH, persistent ASH, and new-onset ASH groups. During a median of 4.3 years of follow-up, ASH persisted or developed in 17% of patients. Persistent or new-onset ASH was characterized by higher left ventricular mass index and ejection fraction at baseline (both p <0.05) but not with female gender or hypertension. In time-varying Cox regression analyses adjusting for these confounders, persistent or new-onset ASH was associated with higher hazard rate of ischemic cardiovascular events (hazard rate 1.45; 95% confidence interval 1.09 to 1.91, p = 0.01), in particular coronary artery bypass grafting (hazard rate 1.69; 95% confidence interval 1.17 to 2.47; p = 0.006), whereas no association with increased mortality was found. In conclusion, in patients with AS without diabetes or known renal or cardiovascular disease participating in the SEAS study, persistent or new-onset ASH during progression of AS was associated with higher rate of ischemic cardiovascular events.

  • 241.
    Ekblom, Kim
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Oxidants and antioxidants in cardiovascular disease2010Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background

    Cardiovascular diseases, including myocardial infarction and stroke, are the main reason of death in Sweden and Western Europe. High iron stores are believed to produce oxygen radicals, which is the presumed putative mechanism behind lipid peroxidation, atherosclerosis and subsequent cardiovascular disease. Iron levels are associated with the hemochromatosis associated HFE single nucleotide polymorphisms C282Y and H63D.

    Bilirubin is an antioxidant present in relatively high levels in the human body. Several previous studies have found an association between high bilirubin levels and a lower risk for cardiovascular disease. Bilirubin levels are highly influenced by the common promoter polymorphism TA-insertion UGT1A1*28, the main reason for benign hyperbilirubinemia in Caucasians.

    There is a lack of prospective studies on both the association of iron and bilirubin levels, and the risk for myocardial infarction and ischemic stroke.

    Material and methods

    Iron, transferrin iron saturation, TIBC, ferritin and bilirubin were analyzed and HFE C282Y, HFE H63D and UGT1A1*28 were determined in myocardial infarction and stroke cases, and their double matched referents within the Northern Sweden Health and Disease Study Cohort.

    Results

    There were no associations between iron levels in the upper normal range and risk for myocardial infarction or stroke. No associations were seen for HFE-genotypes, except for a near fivefold increase in risk for myocardial infarction in HFE H63D homozygous women.

    Plasma bilirubin was lower in cases vs. referents both in the myocardial infarction and the stroke cohort. Despite a strong gene-dosage effect on bilirubin levels in both cases and referents, the UGT1A1*28 polymorphism did not influence the risk for myocardial infarction or stroke.

    Conclusion

    High iron stores are not associated with increased risk for neither myocardial infarction, nor stroke. There was no association between UGT1A1*28 and the risk for myocardial infarction or stroke. Consequently data suggests that other factors, which also may lower bilirubin, are responsible for the elevated risk observed in conjunction with lower bilirubin levels.

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  • 242.
    Ekblom, Kim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Stegmayr, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
    Van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    Johansson, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Wiklund, Per-Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Iron stores and HFE genotypes are not related to increased risk of ischemic stroke.: a prospective nested case-referent study2007Ingår i: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 24, nr 5, s. 405-411Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: High iron levels can increase the formation of noxious oxygen radicals, which are thought to contribute to cerebrovascular disease. The aim of this prospective study was to determine if iron status and HFE genotypes constitute risk factors for stroke.

    Methods: First-ever stroke cases (231 ischemic and 42 hemorrhagic) and matched double referents from the population-based Northern Sweden cohorts were studied in a nested case-referent setting.

    Results: For total iron binding capacity, an increased risk of ischemic stroke was seen in the highest quartile (OR 1.80; 95% CI 1.14-2.83; p for trend 0.012). The highest quartile of transferrin iron saturation showed a decreased risk of ischemic stroke in men (OR 0.44; 95% CI 0.22-0.87; p for trend 0.028), but not in women. There was an increased risk of hemorrhagic stroke in the second (OR 4.07; 95% CI 1.09-15.20) and third quartile (OR 4.22; 95% CI 1.08-16.42) of ferritin. Neither quartiles of plasma iron concentrations nor the HFE C282Y and H63D genotypes were associated with ischemic or hemorrhagic stroke.

    Conclusions: Iron stores were not positively related to increased risk of ischemic stroke. Furthermore, HFE genotypes did not influence the risk of ischemic or hemorrhagic stroke. Copyright (c) 2007 S. Karger AG, Basel.

  • 243.
    Ekblom, Kim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Iron stores and HFE genotypes are not related to increased risk of first-time myocardial infarction: a prospective nested case-referent study2011Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 150, nr 2, s. 169-172Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Our objectives were to study the relationship between iron stores, HFE genotypes and the risk for first-ever myocardial infarction.

    Methods: First-ever myocardial infarction cases (n=618) and double matched referents from the Northern Sweden Health and Disease Cohort Study were studied in a prospective nested case-referent setting. Plasma iron, total iron binding capacity, transferrin iron saturation and ferritin were analyzed, as well as several confounders. HFE C282Y and H63D genotypes were determined.

    Results: There was an inverse risk association for myocardial infarction in the highest quartiles of iron (OR 0.68; 95% CI 0.48-0.96) and transferrin iron saturation (OR 0.62; 95% CI 0.42-0.89) in men. This association, however, was lost after adjusting for C-reactive protein. Women homozygous for H63D had a higher risk for myocardial infarction.

    Conclusions: No risk association between high iron stores and first-ever myocardial infarction was found. The higher risk in female H63D homozygotes is probably not related to iron metabolism.

  • 244.
    Ekblom, Kim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Jansson, Jan-Håkan
    Medicinkliniken, Skellefteå lasarett.
    Osterman, Pia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Plasma Bilirubin and UGT1A1*28 Are Not Protective Factors Against First-Time Myocardial Infarction in a Prospective, Nested Case–Referent Setting2010Ingår i: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, nr 3, s. 340-347Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Bilirubin, an effective antioxidant, shows a large variation in levels between individuals and has been positively associated with reduced cardiovascular disease risk. A major reason for the variability is a common promoter polymorphism, UGT1A1*28, which reduces the transcription of the enzyme that conjugates bilirubin, UDP-glucuronosyltransferase 1A1. The aim of the study was to evaluate a possible protective effect of plasma bilirubin and the UGT1A1*28 polymorphism against myocardial infarction in a prospective case-referent setting.

    Methods and Results: 618 subjects with a first-ever myocardial infarction (median event age 60.5 years, median lag time 3.5 years) and 1184 matched referents were studied. Plasma bilirubin was lower in cases vs. referents. Despite a strong gene-dosage effect on bilirubin levels in both cases and referents, the UGT1A1*28 polymorphism did not influence the risk of myocardial infarction. Among multiple other variables, serum iron showed one of the strongest associations with bilirubin levels.

    Conclusion: We found no evidence for a protective effect of the UGT1A1*28 polymorphism against myocardial infarction and consequently neither for bilirubin. The lower bilirubin levels in cases might be caused by decreased production, increased degradation or increased elimination.

  • 245.
    Ekblom, Kim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Marklund, Stefan L
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Lars
    Medicinkliniken, Skellefteå lasarett.
    Osterman, Pia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Wiklund, Per-Gunnar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Bilirubin and UGT1A1*28, are not associated with lower risk for ischemic stroke in a prospective nested case-referent settingArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Bilirubin, an antioxidant, has been associated with reduced cardiovascular disease risk. A major cause of elevated plasma bilirubin is the common UGT1A1*28 promoter polymorphism in the gene of the bilirubin-conjugating enzyme UDP-glucuronosyltransferase-1A1, which reduces transcription by 70%. Earlier studies reporting a protective effect of bilirubin on stroke, have not included analysis of UGT1A1*28. The purpose of this study is to investigate if bilirubin and UGT1A1*28 are protective against ischemic stroke in a prospective case-referent setting.

    Methods: Cases with first-ever ischemic stroke (n=231; median lag time 4.9 years), and 462 matched referents from the The Northern Sweden Health and Disease Study Cohort were included. Plasma bilirubin was measured and UGT1A1*28 was analyzed by fragment analysis.

    Results: Plasma bilirubin was lower in cases than in referents, but the difference reached significance only for women. The UGT1A1*28 polymorphism (allele frequency 30%), showed a strong gene-dose relationship with bilirubin levels both among cases and referents, but was not associated with risk for stroke. Among multiple other variables analysed the strongest correlation with bilirubin was found for plasma iron.

    Conclusions: There was no evidence for a protective effect of the UGT1A1*28 polymorphism against stroke and consequently neither for bilirubin. The findings suggest that other factors influencing the risk for stroke also might affect bilirubin levels.

  • 246. Ekblom-Bak, Elin
    et al.
    Halldin, Mats
    Vikstrom, Max
    Stenling, Andreas
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Gigante, Bruna
    de Faire, Ulf
    Leander, Karin
    Hellenius, Mai-Lis
    Physical activity attenuates cardiovascular risk and mortality in men and women with and without the metabolic syndrome - a 20-year follow-up of a population-based cohort of 60-year-olds2020Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: The purpose of this study was to analyse the association of leisure-time physical activity of different intensities at baseline, and cardiovascular disease incidence, cardiovascular disease mortality and all-cause mortality in a population-based sample of 60-year-old men and women with and without established metabolic syndrome, for more than 20 years of follow-up. A secondary aim was to study which cardiometabolic factors may mediate the association between physical activity and long-term outcomes.

    Methods: A total of 3693 participants (53% women) underwent physical examination and laboratory tests, completed an extensive questionnaire at baseline 1997–1999 and were followed until their death or until 31 December 2017. First-time cardiovascular disease events and death from any cause were ascertained through regular examinations of national registers.

    Results: Metabolic syndrome prevalence was 23.0%. In metabolic syndrome participants, light physical activity attenuated cardiovascular disease incidence (hazard ratio = 0.71; 95% confidence interval 0.50–1.00) compared to sedentary (reference) after multi-adjustment. Moderate/high physical activity was inversely associated with both cardiovascular disease and all-cause mortality, but became non-significant after multi-adjustment. Sedentary non-metabolic syndrome participants had lower cardiovascular disease incidence (0.47; 0.31–0.72) but not significantly different cardiovascular disease (0.61; 0.31–1.19) and all-cause mortality (0.92; 0.64–1.34) compared to sedentary metabolic syndrome participants. Both light and moderate/high physical activity were inversely associated with cardiovascular disease and all-cause mortality in non-metabolic syndrome participants (p<0.05). There were significant variations in several central cardiometabolic risk factors with physical activity level in non-metabolic syndrome participants. Fibrinogen mediated the protective effects of physical activity in non-metabolic syndrome participants.

    Conclusion: Physical activity of different intensities attenuated cardiovascular risk and mortality in 60-year old men and women with metabolic syndrome during a 20-year follow-up.

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  • 247. Ekbom, Tord
    et al.
    Linjer, Erland
    Hedner, Thomas
    Lanke, Jan
    De Faire, Ulf
    Wester, Per-Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Dahlöf, Björn
    Scherstén, Bengt
    Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP-hypertension-2.2004Ingår i: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 13, nr 3, s. 137-143Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To perform a subgroup analysis on those patients in STOP-Hypertension-2 who had isolated systolic hypertension.

    DESIGN AND METHODS: The STOP-Hypertension-2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs (diuretics, beta-blockers) with that of newer ones [angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists]. In all, 6614 elderly patients with hypertension (mean age 76.0 years, range 70-84 years at baseline) were included in STOP-Hypertension-2. In the present subgroup analysis of STOP-Hypertension-2, isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg, in accordance with the Syst-Eur and Syst-China study criteria. In total, 2280 patients in STOP-Hypertension-2 met these criteria. In the study, patients were randomized to one of three treatment groups: "conventional" antihypertensive therapy with beta-blockers or diuretics (atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or fixed-ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily); ACE inhibitors (enalapril 10 mg or lisinopril 10 mg daily); or calcium antagonists (felodipine 2.5 mg or isradipine 2.5 mg daily). Analysis was by intention to treat.

    RESULTS: The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens: 35/13 mmHg in the conventional group (n=717), 34/12 mmHg in the ACE inhibitor group (n = 724), and 35/13 mmHg in the calcium antagonist group (n=708). Prevention of cardiovascular mortality, the primary endpoint of the study, did not differ between the three treatment groups. All stroke events, i.e. fatal and non-fatal stroke together, were significantly reduced by 25% in the newer-drugs group compared with the conventional group (95% CI 0.58-0.97; p=0.027). This difference was attributable to reduction of non-fatal stroke while fatal stroke events did not differ between groups. New cases of atrial fibrillation were significantly increased by 43% (95% CI 1.02-1.99; p=0.037) on "newer" drugs compared with "conventional" therapy, mainly attributable to the calcium antagonists. There were no significant differences between the three treatment groups with respect to the risks of myocardial infarction, sudden death or congestive heart failure.

    CONCLUSIONS: The analysis demonstrated that "newer" therapy (ACE inhibitors/calcium antagonists) was significantly better (25%) than "conventional" (diuretics/beta-blockers) in preventing all stroke in elderly patients with isolated systolic hypertension.

  • 248.
    Eklund, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Bäcklund, Tomas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Heart centrum, Umeå universitet.
    Natural angioplasty as a mechanical effect of exercise2013Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, nr 3, s. 3083-3085Artikel i tidskrift (Refereegranskat)
  • 249. Ekström, Mattias
    et al.
    Söderberg, Stefan
    Tornvall, Per
    Acute Systemic Inflammation is Unlikely to Affect Adiponectin and Leptin Synthesis in Humans2015Ingår i: Frontiers in cardiovascular medicine, ISSN 2297-055X, Vol. 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Adipose tissue (AT), classically thought to be merely an energy store, has been shown to produce inflammatory and metabolically active cytokines. Recently, adiponectin and leptin, adipokines primarily synthesized by adipocytes, have attracted considerable attention because inflammation has been suggested to modulate adipokine levels. However, the regulation of adiponectin and leptin is complex and the knowledge about their synthesis within the early onset of inflammation is poorly understood. The aim of this study was to investigate if the synthesis of adiponectin and leptin is affected during the early phase of an acute systemic inflammation. Eighteen healthy subjects were allocated to vaccination against Salmonella typhi or to a control group, and adiponectin and leptin concentrations measured in plasma during 24 h. Nine patients, without markers of inflammation, undergoing open heart surgery were investigated before and after the operation by analysis of plasma levels and AT gene expression of adiponectin and leptin. Plasma interleukin (IL)-6 concentrations were measured in both cohorts. Plasma levels of IL-6 were doubled after vaccination and increased 30-fold after open heart surgery. Plasma levels of adiponectin and leptin were unchanged after vaccination whereas adiponectin and leptin tended to decrease after surgery. The gene expression of adiponectin and leptin was unaltered in omental and subcutaneous AT after surgery. Despite the use of two models of stimulated in vivo systemic inflammation, we found no evidence of an early regulation of adiponectin and leptin synthesis, indicating that these two adipokines are not key elements in an acute systemic inflammation in humans.

  • 250.
    Eliasson, Mats
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Eriksson, Marie
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Lundqvist, R.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Comparison of trends in cardiovascular risk factors between two regions with and without a community and primary care prevention programme2018Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, s. 76-76Artikel i tidskrift (Övrigt vetenskapligt)
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