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  • 201. Del Gobbo, Liana C.
    et al.
    Imamura, Fumiaki
    Aslibekyan, Stella
    Marklund, Matti
    Virtanen, Jyrki K.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    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 Studies2016In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 176, no 8, p. 1155-1166Article in journal (Refereed)
    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.

  • 202. Devereux, Richard B.
    et al.
    Bang, Casper N.
    Roman, Mary J.
    Palmieri, Vittorio
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    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 Study2015In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 66, no 5, p. 945-953Article in journal (Refereed)
    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.

  • 203. 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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Kee, Frank
    Zeller, Tanja
    Kuulasmaa, Kari
    Blankenberg, Stefan
    Donati, Maria Benedetta
    de Gaetano, Giovanni
    Iacoviello, Licia
    Association of Alcohol Intake with Cardiovascular and Total Mortality2019In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139Article in journal (Other academic)
  • 204. 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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    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 Consortium2019In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 50, no 3, p. 610-617Article in journal (Refereed)
    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.

  • 205.
    Diamant, Ulla-Britt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Long QT syndrome: studies of diagnostic methods2013Doctoral thesis, comprehensive summary (Other academic)
    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.

  • 206.
    Diamant, Ulla-Britt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Jensen, Steen M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Winbo, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stattin, Eva-Lena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Vectorcardiographic recordings of the Q-T interval in a pediatric long Q-T syndrome population2013In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 34, no 2, p. 245-249Article in journal (Refereed)
    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.

  • 207.
    Diamant, Ulla-Britt
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Vahedi, Farzad
    Sahlgrenska Akademin Göteborgs Universitet.
    Winbo, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stattin, Eva-Lena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Jensen, Steen M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bergfeldt, Lennart
    Sahlgrenska Akademin Göteborgs Universitet.
    Electrophysiological phenotype in the LQTS mutations Y111C and R518X in the KCNQ1 gene2013In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, no 10, p. 1423-1432Article in journal (Refereed)
    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.

  • 208.
    Diamant, Ulla-Britt
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Winbo, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stattin, Eva-Lena
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Kesek, Milos
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jensen, Steen M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Two automatic QT algorithms compared with manual measurement in identification of long QT syndrome2010In: Journal of Electrocardiology, ISSN 0022-0736, E-ISSN 1532-8430, Vol. 43, no 1, p. 25-30Article in journal (Refereed)
    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.

  • 209. 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 University, Faculty of Medicine, Department of Biobank Research. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Psaty, Bruce M.
    Siscovick, David S.
    Barroso, Ines
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. 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 study2017In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 356, article id j1000Article in journal (Refereed)
    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.

  • 210.
    Ding, Wenhong
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Survival and functional recovery following valve replacement in patients with severe aortic stenosis2013Doctoral thesis, comprehensive summary (Other academic)
    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.

  • 211.
    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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Predictors of survival after aortic valve replacement in patients with low-flow and high-gradient aortic stenosis2009In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 11, no 9, p. 897-902Article in journal (Refereed)
    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.

  • 212.
    Ding, Wen-hong
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lam, Yat-yin
    Kaya, Mehmet G
    Li, Wei
    Chung, Robin
    Pepper, John R
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Echocardiographic predictors of left ventricular functional recovery following valve replacement surgery for severe aortic stenosis.2008In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 128, no 2, p. 178-84Article in journal (Refereed)
    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.

  • 213.
    Ding, Wen-Hong
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lam, Yat-Yin
    Pepper, John R
    Kaya, Mehmet G
    Li, Wei
    Chung, Robin
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Early and long-term survival after aortic valve replacement in septuagenarians and octogenarians with severe aortic stenosis.2010In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 141, no 1, p. 24-31Article in journal (Refereed)
    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.

  • 214.
    Ding, Wenhong
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Zhao, Ying
    Watt, Astrid
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nilsson, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Weintar, Reidar
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ruck, Andreas
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Early effect of TAVI on left ventricular function in severe aortic stenosis: trans-apical vs. trans-femoral approachManuscript (preprint) (Other academic)
  • 215. Dini, Frank Lloyd
    et al.
    Bajraktari, Gani
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. 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 Unit2018In: Heart Failure: From Research to Clinical Practice: vol 3 / [ed] Islam, Shahidul, Springer Publishing Company, 2018, p. 145-159Chapter in book (Refereed)
    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.

  • 216.
    Djekic, Demir
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Replication of LC-MS untargeted lipidomics results in patients with calcific coronary disease: an interlaboratory reproducibility study2015Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 217.
    Djekic, Demir
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Novo, Mehmed
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Metabolomics in atherosclerosis2015In: International Journal of Cardiology Metabolic & Endocrine, E-ISSN 2214-7624, Vol. 8, p. 26-30Article in journal (Refereed)
    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.

  • 218. Djekic, Demir
    et al.
    Pinto, Rui
    Repsilber, Dirk
    Hyotylainen, Tuulia
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. 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 disease2019In: Vascular Health and Risk Management, ISSN 1176-6344, E-ISSN 1178-2048, Vol. 15, p. 123-135Article in journal (Refereed)
    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.

  • 219.
    Djekic, Demir
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Pinto, Rui
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Bioinformatics for Life Sciences (BILS).
    Vorkas, Panagiotis A
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Replication of LC-MS untargeted lipidomics results in patients with calcific coronary disease: an interlaboratory reproducibility study2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 222, p. 1042-1048Article in journal (Refereed)
    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.

  • 220. 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 University, Faculty of Social Sciences, Department of Psychology. 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 Individuals2017In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 28, no 4, p. 619-626Article in journal (Refereed)
    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.

  • 221. Du, Xiaoyang
    et al.
    Khamitova, Adina
    Kyhlstedt, Mattias
    Sun, Sun
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. 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 review2018In: IJC Heart & Vasculature, ISSN 2352-9067, Vol. 19, p. 90-97Article, review/survey (Refereed)
    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.

  • 222. Duranton, Flore
    et al.
    Palma, Alfonso
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wauthier, Michel
    Torres, Armando
    Argilés, Angel
    Blood Pressure Seasonality in Hemodialysis Patients from Five European Cities of Different Latitudes2018In: Kidney and Blood Pressure Research, ISSN 1420-4096, E-ISSN 1423-0143, Vol. 43, no 5, p. 1529-1538Article in journal (Refereed)
    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.

  • 223. 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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    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 Cholangitis2019In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 114, no 7, p. 1101-1108Article in journal (Refereed)
    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.

  • 224. Einarsen, Eigir
    et al.
    Cramariuc, Dana
    Lønnebakken, Mai T
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    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)2017In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 119, no 7, p. 1082-1087Article in journal (Refereed)
    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.

  • 225.
    Ekblom, Kim
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Oxidants and antioxidants in cardiovascular disease2010Doctoral thesis, comprehensive summary (Other academic)
    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.

  • 226.
    Ekblom, Kim
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Van Guelpen, Bethany
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wiklund, Per-Gunnar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Iron stores and HFE genotypes are not related to increased risk of ischemic stroke.: a prospective nested case-referent study2007In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 24, no 5, p. 405-411Article in journal (Refereed)
    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.

  • 227.
    Ekblom, Kim
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Iron stores and HFE genotypes are not related to increased risk of first-time myocardial infarction: a prospective nested case-referent study2011In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 150, no 2, p. 169-172Article in journal (Refereed)
    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.

  • 228.
    Ekblom, Kim
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Jansson, Jan-Håkan
    Medicinkliniken, Skellefteå lasarett.
    Osterman, Pia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Plasma Bilirubin and UGT1A1*28 Are Not Protective Factors Against First-Time Myocardial Infarction in a Prospective, Nested Case–Referent Setting2010In: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, no 3, p. 340-347Article in journal (Refereed)
    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.

  • 229.
    Ekblom, Kim
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Lars
    Medicinkliniken, Skellefteå lasarett.
    Osterman, Pia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wiklund, Per-Gunnar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Bilirubin and UGT1A1*28, are not associated with lower risk for ischemic stroke in a prospective nested case-referent settingArticle in journal (Refereed)
    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.

  • 230. Ekbom, Tord
    et al.
    Linjer, Erland
    Hedner, Thomas
    Lanke, Jan
    De Faire, Ulf
    Wester, Per-Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dahlöf, Björn
    Scherstén, Bengt
    Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP-hypertension-2.2004In: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 13, no 3, p. 137-143Article in journal (Refereed)
    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.

  • 231.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Bäcklund, Tomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Heart centrum, Umeå universitet.
    Natural angioplasty as a mechanical effect of exercise2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, no 3, p. 3083-3085Article in journal (Refereed)
  • 232. Ekström, Mattias
    et al.
    Söderberg, Stefan
    Tornvall, Per
    Acute Systemic Inflammation is Unlikely to Affect Adiponectin and Leptin Synthesis in Humans2015In: Frontiers in cardiovascular medicine, ISSN 2297-055X, Vol. 2Article in journal (Refereed)
    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.

  • 233.
    Eliasson, Mats
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Lundqvist, R.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Comparison of trends in cardiovascular risk factors between two regions with and without a community and primary care prevention programme2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, p. 76-76Article in journal (Other academic)
  • 234.
    Eliasson, Mats
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Lundqvist, Robert
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Comparison of trends in cardiovascular risk factors between two regions with and without a community and primary care prevention programme2018In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 25, no 6, p. 1765-1772Article in journal (Refereed)
    Abstract [en]

    Background The effect of primary prevention of cardiovascular disease is debated. The Västerbotten Intervention Programme (VIP) is an individual and community-based public health programme that comprises the whole county of Västerbotten (VB). In the neighbouring county of Norrbotten (NB), no programmes have been implemented.

    Method Between 1994 and 2014, five surveys were performed in the two counties on persons aged 40 to 75 years within the Northern Sweden MONICA Study. The number of subjects participating was 6600 (75.4%). We compared time trends in risk factors between the two counties using regression models including age, county and year of survey. To test whether time trends differed between counties, the interaction between county and year was included in the models.

    Results Systolic blood pressure declined in both counties, and the decline was faster in Västerbotten than in Norrbotten ( p = 0.043 for interaction county*year). Diastolic blood pressure declined in VB but increased in NB ( p < 0.001). Cholesterol levels declined at a similar rate in both counties whereas body mass index increased in both counties. Fasting glucose decreased in VB ( p = 0.003) and increased in NB. The prevalence of regular smokers decreased faster in VB than in NB ( p = 0.01). Trend in waist and hip circumference, known diabetes, having an academic degree, being physically inactive or 10 year cardiovascular mortality according to SCORE did not differ.

    Conclusion Blood pressure, glucose and smoking improved at a faster rate in the county with a community and primary care-based intervention than in the county without such an intervention.

  • 235. El-Maasarany, Shirley H
    et al.
    Elazab, Eman E B
    Jensen, Steen
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    A-V nodal artery anatomy and relations to the posterior septal space and its contents2010In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 141, no 1, p. 92-98Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIM: Radiofrequency catheter ablation treats resistant nodal re-entrant tachycardia but carries a risk to AV conduction system and its vessels. We aimed to study the origin of the A-V nodal artery (AVNA) and its course within the posterior septal space (PSS). METHODS: Twenty embalmed human hearts of both sexes (16 males) age, 25-60 years, were dissected to study the PPS and its arteries down to their destination. RESULTS: The PSS is a four sided pyramidal space, at the crux of the heart, with its base made of the pericardium. It is made of four; right upper and lower and left upper and lower walls corresponding to the right atrium and ventricle and left atrium and ventricle, respectively. The right coronary artery (RCA) crossed the base from the right to the left angle, to lie inferior and adherent to the terminal part of the coronary sinus (CS). The posterior interventricular artery, the ventricular branches of the RCA, the middle cardiac vein and the ventricular veins, all crossed the base of the space to their final destination. AVNA originated from either the RCA itself or one of its branches. Double AVNA was encountered in 14 specimens with the upper artery larger and passed between the right and left atria and the lower artery smaller and crossed the space adjacent to the right ventricle. CONCLUSIONS: These findings highlight the importance of the PSS and its structural relations, in particular to the AVNA, that should be considered during various interventional procedures.

  • 236. Engström, Karin
    et al.
    Engström, Karl Gunnar
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Hazards with electrocautery-induced decomposition of fatty acids: in view of lipid embolization2010In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 44, no 5, p. 307-312Article in journal (Refereed)
    Abstract [en]

    Electrocautery induces a profound fatty-acid fragmentation to form short-chained compounds. The chemical and toxic nature of these compounds remains to be determined, including their clinical implications at blood recycling in cardiac surgery.

  • 237. Ericsson, M.
    et al.
    Hellström Ängerud, Karin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå University, Faculty of Medicine, Department of Nursing.
    Sederholm Lawesson, S.
    Swahn, E.
    Stromberg, A.
    Isaksson, R. M.
    Brännström, Margareta
    Umeå University, Faculty of Medicine, Department of Nursing.
    First medical contact in the pre-hospital phase of a myocardial infarction, the interaction between callers and tele-nurses impacts action and level of care2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, p. 1120-1120Article in journal (Other academic)
    Abstract [en]

    Background: Pre-hospital delay in myocardial infarction (MI) patients' is of great concern. The total ischemic time, i.e., between symptom onset and reperfusion therapy is the most important factor to achieve best possible outcome. One reason for patient delay is choice of first medical Contact (FMC), still not everyone contact the emergency medical services. A previous Swedish cross-sectional multicentre study found that every fifth patient with an evolving ST elevated MI (STEMI) contacted an advisement tele-nurse intended for non-life-threatening situations as FMC. This caused a median difference in delay of 38 min from symptom onset to diagnosis. Advisement tele-nursing is an expanding actor in the Swedish healthcare system, as in some other Western nations.

    Purpose: The aim was to explore the communication between tele-nurses and callers when MI patients called a national health advisement number as FMC.

    Method: This study had a qualitative approach. We received access to 30 authentic calls. The recordings lasted between 0:39 minutes to 16:44 minutes, transcribed verbatim and analysed with content analysis. The following questions were applied to the transcript: (1) How do the callers communicate their symptom and context (2) How do the tele-nurses respond and which level of care was directed (3) Do the callers get an advice and what action do they take.

    Result: One third of the callers were female, aged 46–89 years, six were diagnosed with NSTEMI and 24 with STEMI. All tele-nurses were females. The calls followed a structure of three phases, opening-, orienting- and end-phase. The first phase was non-interfered, where the caller communicated their context and/or symptoms and tele-nurses adopt an active listening position, followed by two interactive phases. Four categories defined the interaction in the communication, indecisive, irrational, distinct or reasoning. The different interactions illustrated how tele-nurses and callers assessed and elaborated upon symptom, context and furthermore expressed the process in the dialogue. Type of interaction was pivotal for progress in the call and had impact on the communicative process either sufficient in reaching a mutual understanding or not. An indecisive or irrational interaction could increase risk of acute care not being recommended. A non explicit explanation, why it is of importance to seek acute care could lead caller to ignore the advice.

    Conclusion: Both communicative and medical skills are needed to identify level of urgency. Our study suggests that the interaction in the communication categorised in four types, indecisive, irrational or distinct or reasoning can mislead level of care directed as well as a disability to express the need of acute care. This knowledge adds new perspective and hopefully will our findings be useful to deepen our knowledge in identifying MI patients and in a broader sense improve educational efforts and diminsh delay.

  • 238.
    Ericsson, M.
    et al.
    Linkoping Univ Hosp, Dept Cardiol, S-58185 Linkoping, Sweden.
    Sederholm-Lawesson, S.
    Linkoping Univ, Dept Cardiol Med & Hlth Sci, Linkoping, Sweden.
    Isaksson, R. M.
    Norrbotten Cty Council, Dept Res, Lulea, Sweden.
    Hellström Ängerud, Karin
    Umeå University, Faculty of Medicine, Department of Nursing. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Logander, E.
    Linkoping Univ Hosp, Dept Cardiol, S-58185 Linkoping, Sweden.
    Swahn, E.
    Linkoping Univ, Dept Cardiol Med & Hlth Sci, Linkoping, Sweden.
    Thylen, I.
    Linkoping Univ, Div Nursing Sci, Dept Med & Hlth Sci, Linkoping, Sweden.
    Differences in symptom presentation in STEMI patients, with or without a previous history of hypertension: a survey report from the SymTime study group2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no Supplement 1, Meeting abstract P5161, p. 908-908Article in journal (Other academic)
  • 239.
    Ericsson, Madelene
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Sjödin, Anna
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Burén, Jonas
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Försämrad hjärtfunktion efter fyra veckors intag av lågkolhydrat/högfettkost hos möss: Kan vi lära av translationell forskning?2017In: Svensk kardiologi, ISSN 1400-5816, no 1, p. 33-35Article in journal (Other (popular science, discussion, etc.))
  • 240.
    Eriksson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Forensic Medicine.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Ahlm, Kristin
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Forensic Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bygren, Lars Olov
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Johansson, Lars Age
    Swedish National Board of Health and Welfare.
    Olofsson, Bert-Ove
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wall, Stig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Accuracy of death certificates of cardiovascular disease in a community intervention in Sweden.2013In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 41, no 8, p. 883-889Article in journal (Refereed)
    Abstract [en]

    Aim: The aim was to investigate the possibility to evaluate the mortality pattern in a community intervention programme against cardiovascular disease by official death certificates.

    Methods: For all deceased in the intervention area (Norsjö), the accuracy of the official death certificates were compared with matched controls in the rest of Västerbotten. The official causes of death were compared with new certificates, based on the last clinical record, issued by three of the authors, and coded by one of the authors, all four accordingly blinded.

    Results: The degree of agreement between the official underlying causes of death in "cardiovascular disease" (CVD) and the re-evaluated certificates was not found to differ between Norsjö and the rest of Västerbotten. The agreement was 87% and 88% at chapter level, respectively, but only 55% and 55% at 4-digit level, respectively. The reclassification resulted in a 1% decrease of "cardiovascular deaths" in both Norsjö and the rest of Västerbotten.

    Conclusions: The disagreements in the reclassification of cause of death were equal but large in both directions. The official death certificates should be used with caution to evaluate CVD in small community intervention programmes, and restricted to the chapter level and total populations.

  • 241. Eriksson, Jonas
    et al.
    Bjerg, Anders
    Lotvall, Jan
    Wennergren, Goran
    Rönnmark, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Toren, Kjell
    Lundback, Bo
    Rhinitis phenotypes correlate with different symptom presentation and risk factor patterns of asthma2011In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 105, no 11, p. 1611-1621Article in journal (Refereed)
    Abstract [en]

    Background: Asthma and rhinitis frequently coexist, but no population study has previously determined the relationship between nasal comorbidities and symptom expression and risk factors of asthma.

    Methods: In 2008, a postal questionnaire on respiratory health was sent to 30 000 randomly selected subjects aged 16-75 years in West Sweden; 29218 could be traced and 18 087 (62%) responded. The questionnaire included questions on asthma, rhinitis, chronic rhinosinusitis, respiratory symptoms and possible determinants.

    Results: Prevalence of allergic rhinitis in asthma was 63.9% and of asthma in allergic rhinitis 19.8%. Prevalence of chronic rhinosinusitis in asthma was 8.4% and of asthma in chronic rhinosinusitis 24.4%. Asthma subjects with chronic rhinitis, or chronic rhinosinusitis, had more symptoms of asthma and bronchitis than those without rhinitis (p < 0.001). There was an obvious trend of higher ORs for various environmental exposures including occupational exposure to dust, gases and fumes (OR 2.32 vs. OR 1.44), visible mould at home (OR 1.72 vs. OR 1.27) and water damage at home (OR 1.82 vs. OR 1.06) for asthma with chronic rhinosinusitis than for asthma with allergic rhinitis. Family history of allergy yielded a higher OR for asthma with allergic rhinitis than with asthma with chronic rhinosinusitis (OR 7.15 vs. OR 4.48).

    Conclusion: Considerable overlap between asthma and nasal comorbidities was documented, confirming a close relationship between nasal disease and asthma. Allergic rhinitis, chronic rhinitis and chronic rhinosinusitis were associated with different risk factor patterns and symptom expression of asthma. Thus, different nasal comorbidities may reflect different phenotypes of asthma. (C) 2011 Elsevier Ltd. All rights reserved.

  • 242.
    Eriksson, Margareta K.
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    A 3-year randomized trial of lifestyle intervention for cardiovascular risk reduction in the primary care setting: the Swedish Björknäs study2009In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, no 4, p. e5195-Article in journal (Refereed)
    Abstract [en]

    Background Successfully transferring the findings of expensive and tightly controlled programmes of intensive lifestyle modification to the primary care setting is necessary if such knowledge is to be of clinical utility. The objective of this study was to test whether intensive lifestyle modification, shown previously in tightly-controlled clinical trials to be efficacious for diabetes risk-reduction among high-risk individuals, can reduce cardiovascular risk factor levels in the primary care setting. 

    Methodology / Principal Findings The Swedish Björknäs study was a randomized controlled trial conducted from 2003 to 2006 with follow-up on cardiovascular risk factors at 3, 12, 24 and 36 months. A total of 151 middle-aged men and women at moderate- to high-risk of cardiovascular disease from northern Sweden were randomly assigned to either an intensive lifestyle intervention (n=75) or control (n=76) group. The intervention was based broadly on the protocol of the Diabetes Prevention Program. The three-month intervention period was administered in the primary care setting and consisted of supervised exercise sessions and diet counselling, followed by regular group meetings during three years. The control group was given general advice about diet and exercise and received standard clinical care. Outcomes were changes in anthropometrics, aerobic fitness, self-reported physical activity, blood pressure, and metabolic traits. At 36 months post-randomisation, intensive lifestyle modification reduced waist circumference (–2.2cm: p=0.001), waist-hip ratio (–0.02: p<0.0001), systolic blood pressure (–4.9mmHg: p=0.036), and diastolic blood pressure (–1.6mmHg: p=0.005), and improved aerobic fitness (5%; p=0.038). Changes in lipid or glucose values did not differ statistically between groups. At 36 months, self-reported time spent exercising and total physical activity had increased more in the intervention group than in the control group (p<0.001).

    Conclusion / Significance  A program of intensive lifestyle modification undertaken in the primary health care setting can favourably influence cardiovascular risk-factor profiles in high-risk individuals.

  • 243.
    Eriksson, Marie
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Van Rompaye, Bart
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Differences in cardiovascular risk factors and socioeconomic status do not explain the increased risk of death after a first stroke in diabetic patients: results from the Swedish Stroke Register2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, no 10, p. 2181-2186Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: This study compared survival rates and causes of death after stroke in diabetic and non-diabetic patients in Sweden. We hypothesised that differences in cardiovascular risk factors, acute stroke management or socioeconomic status (SES) could explain the higher risk of death after stroke in diabetic patients. METHODS: The study included 155,806 first-ever stroke patients from the Swedish Stroke Register between 2001 and 2009. Individual patient information on SES was retrieved from Statistics Sweden. Survival was followed until 2010 (532,140 person-years) with a median follow-up time of 35 months. Multiple Cox regression was used to analyse survival adjusting for differences in background characteristics, in-hospital treatment, SES and year of stroke. Causes of death were analysed using cause-specific proportional hazard models. RESULTS: The risk of death after stroke increased in diabetic patients (HR 1.28, 95% CI 1.25, 1.31), and this risk was greater in younger patients and in women. Differences in background characteristics, cardiovascular risk factors, in-hospital treatment and SES did not explain the increased risk of death after stroke (HR 1.35, 95% CI 1.32, 1.37) after adjustments. Diabetic patients had an increased probability of dying from cerebrovascular disease and even higher probabilities of dying from other circulatory causes and all other causes except cancer. CONCLUSIONS/INTERPRETATION: Differences in cardiovascular risk factors, acute stroke management and SES do not explain the lower survival after stroke in diabetic compared with non-diabetic patients. Diabetic patients are at higher risk of dying from cardiovascular causes and all other causes of death, other than cancer.

  • 244.
    Eriksson, Marie
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Forslund, Ann-Sofi
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Greater decreases in cholesterol levels among individuals with high cardiovascular risk than among the general population: the northern Sweden MONICA study 1994 to 20142016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, no 25, p. 1985-1992Article in journal (Refereed)
    Abstract [en]

    AIM: Decreasing cholesterol levels in Western populations is the main reason for decreasing mortality due to coronary heart disease. Our aim was to analyze trends in cholesterol levels in the population during a period of 20 years in relation to previous cardiovascular disease (CVD), other cardiovascular risk factors, and socioeconomic status.

    METHODS AND RESULTS: A total of 4546 women and 4349 men aged 25-74 years participated in five population-based surveys in the Northern Sweden MONICA Study between 1994 and 2014 (participation rate 76.8-62.5%). Total cholesterol levels decreased from 6.2 mmol/L (95% confidence interval, CI, 6.1-6.2) in 1994 to 5.5 mmol/L (CI 5.4-5.5) in 2014. The decrease was more pronounced in elderly vs. younger participants (1.0 vs. 0.5 mmol/L). In 2014, participants with previous CVD, diabetes, or hypertension had lower cholesterol levels than the general population, whereas their levels were higher or similar to the general population in 1994. The use of lipid-lowering drugs increased markedly and was used by 14.3% in 2014. Previously described differences in cholesterol levels between participants with obesity and normal weight, and between those with and without university education, diminished, or vanished over time.

    CONCLUSION: Cholesterol levels decreased by 0.7 mmol/L over 20 years with no sign of abating. The improvement occurred in all age and gender groups but more prominently among those at high risk of ischaemic heart disease.

  • 245.
    Eriksson, Marie
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Glader, Eva-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Norrving, B.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Post-stroke suicide attempts and completed suicides: A socioeconomic and nationwide perspective2015In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 10, p. 33-33Article in journal (Other academic)
  • 246.
    Eriksson, Marie
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Glader, Eva-Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Norrving, Bo
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Kvalitetsregistret Riksstroke visar på ojämlik strokevård: omedveten diskriminering kanske förklarar en del av skillnaderna2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, article id DR7HArticle in journal (Refereed)
    Abstract [en]

    In this article, results from a series of studies on the relationships between socioeconomic factors and stroke processes (stroke unit care, acute reperfusion treatment, secondary prevention with oral anticoagulants and statins) and outcomes (long-term survival, return to work and risk of suicide and suicide attempts) are summarized. The overall pattern is that acute and secondary prevention interventions and prognosis are better in patients with a high compared with a low level of education, better in people with high than low income, better in people who are cohabitant than single. As to country of birth, a more complex pattern has emerged. Unmeasured confounding may possibly explain part of the difference, but the socioeconomic gradients remain after adjustment for multiple potential confounders, leaving the possibility that there is an element of unconscious discrimination in stroke care.

  • 247.
    Eriksson, Peter
    Umeå University, Faculty of Medicine.
    Cardiac involvement in familial amyloidosis with polyneuropathy1984Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Familial amyloidosis with polyneuropathy (FAP) is a neuropathic form of heredofamilial systemic amyloidosis. Clusters of patients have been reported predominantly from Portugal, Japan and Sweden. The present study examines the involvement of the heart in individuals with the Swedish variety of FAP. During long-term ECG recording in 16 patients, a high frequency of disturbances of sinus node function and atrioventricular conduction were observed. Long-term ECG may help considerably in the evaluation of symptoms attributable to disturbances of heart rhythm in FAP. A retrospective survey of 20 patients with FAP treated with a pacemaker showed that the indication for pacing was advanced atrioventricular block (12 cases), dysfunction of the sinus node (5 cases), and atrial fibrillation with a slow ventricular response (3 cases). All patients experienced the effective relief of symptoms attributable to a slow ventricular rate. The long-term prognosis, however, seemed unaffected by this treatment. Histopathological examination of the sinoatrial (9 cases) and atrioventricular (6 cases) parts of the conduction system showed marked amyloid infiltration in all cases, which may explain the high occurrence of disturbances of cardiac rhythm and conduction. Twelve patients were examined by two-dimensional echocardiography and changes of varying degrees, such as highly refractile myocardial echoes (12 cases) and thickened ventricular walls (8 cases) and valves (7 cases), could be observed. Technetium-99m-pyrophosphate scintigraphy of the same patients revealed abnormal myocardial uptake of the isotope only in four. Echocardiography thus seems to be superior to scintigraphy for non-invasive detection of cardiac involvement in FAP. Myocardial samples from regions producing highly refractile myocardial echoes were obtained at in vitro échocardiographie examination of hearts from FAP autopsy cases. Histological examination showed that the highly refractile echoes corresponded to more or less sharply delineated nodules, containing amyloid and collagen in various amounts. 

  • 248. Erlinge, D.
    et al.
    Omerovic, E.
    Frobert, O.
    Linder, Robert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Danielewicz, M.
    Hamid, M.
    Swahn, E.
    Henareh, L.
    Wagner, H.
    Hårdhammar, P.
    Sjögren, I.
    Stewart, J.
    Grimfjärd, P.
    Jensen, J.
    Aasa, M.
    Robertsson, L.
    Lindroos, P.
    Haupt, J.
    Wikström, H.
    Ulvenstam, A.
    Bhiladvala, P.
    Lindvall, B.
    Lundin, A.
    Tödt, T.
    Ioanes, D.
    Råmunddal, T.
    Kellerth, T.
    Zagozdzon, L.
    Götberg, M.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Angerås, O.
    Östlund, O.
    Lagerqvist, B.
    Held, C.
    Wallentin, L.
    Scherstén, F.
    Eriksson, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Koul, S.
    James, S.
    Bivalirudin versus heparin monotherapy in myocardial infarction2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 12, p. 1132-1142Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y 12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors.

    METHODS In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y(12) inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up.

    RESULTS A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P = 0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P = 0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P = 0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P = 0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P = 0.76).

    CONCLUSIONS Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART Clinical-TrialsRegister.eu number, 2012-005260-10; ClinicalTrials.gov number, NCT02311231.)

  • 249. Erlinge, David
    et al.
    Koul, Sasha
    Eriksson, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Schersten, Fredrik
    Omerovic, Elmir
    Linder, Rikard
    Ostlund, Olof Petter
    Wallentin, Lars
    Frobert, Ole
    James, Stefan
    Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction-a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial)2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 175, p. 36-46Article in journal (Refereed)
    Abstract [en]

    Background The optimal anticoagulant for patients with acute coronary syndrome treated with percutaneous coronary intervention (PCI) has not been validated in current practice of radial approach and pretreatment with potent P2Y12 inhibitors. Several studies have indicated increased bleeding rate and, in some instances, even increased mortality by the routine use of heparin and glycoprotein IIb/IIIa inhibitors compared to bivalirudin. Direct comparison of bivalirudin versus heparin alone has yielded contradictory results depending on study designs. Methods/design The VALIDATE-SWEDEHEART trial is a multicenter, prospective, randomized, registry-based, controlled, and open-label clinical trial in patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing PCI pretreated with ticagrelor, prasugrel, or cangrelor. We hypothesize that bivalirudin is superior to heparin alone in reducing death, myocardial infarction, and major bleeding events at 180 days (primary end point). The trial will enroll 3,000 patients with STEMI and 3,000 patients with non-STEMI undergoing PCI. The trial will use a hybrid registry-based randomized clinical trial design where inclusion, randomization, and baseline data collection are performed using The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry. The primary composite end point (death, myocardial infarction, or major bleeding events at 180 days) will be identified through active screening after 7 and 180 days and adjudicated by a blinded central end point committee. Secondary end points and long-term outcomes will be recorded from national registries. Conclusion The VALIDATE-SWEDEHEART trial is founded on a nationwide clinical registry and uses a hybrid registry-based randomized clinical trial (RRCT) design methodology to evaluate efficacy and safety of bivalirudin as compared to heparin alone for acute coronary syndrome, in a large population receiving contemporary recommended therapies including predominantly radial invasive approach and pretreatment with potent P2Y12 inhibitors.

  • 250. Faggiano, Pompilio
    et al.
    Dasseni, Nicolo
    Gaibazzi, Nicola
    Rossi, Andrea
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. St George University, London, UK; Brunel University, London, UK.
    Pressman, Gregg
    Cardiac calcification as a marker of subclinical atherosclerosis and predictor of cardiovascular events: A review of the evidence2019In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 26, no 11, p. 1191-1204Article, review/survey (Refereed)
    Abstract [en]

    Risk prediction of future atherothrombotic cardiovascular events is currently based on conventional risk factor assessment and the use of validated algorithms, such as the Framingham Risk Score, the Pooled Cohort Equations, and the European SCORE Risk Charts. However, the identification of subclinical organ damage has emerged as a potentially more accurate predictor of individual risk. Several imaging modalities have been proposed for identification of preclinical atherosclerosis. Coronary artery calcification scanning performed using cardiac computed tomography and calculation of the Agatston score is the most commonly used technique in clinical practice for detection of subclinical disease, prognostic stratification of asymptomatic individuals and implementation of preventive strategies. Furthermore, conventional echocardiographic examination may offer an assessment of cardiac calcifications at different sites, such as the mitral apparatus (including annulus, leaflets and papillary muscles), aortic valve and ascending aorta, that are associated with the clinical manifestation of atherosclerotic disease and are predictive of future cardiovascular events. The aim of this paper is to summarize available evidence on the clinical use of cardiac calcification, review the pathogenetic mechanisms involved, including similarities with atherosclerosis, and evaluate its potential for risk stratification and prevention of clinical events in the primary prevention setting.

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