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  • 1.
    Andersson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Lundblad, Dan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Escher, Stefan A
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Diabetes mellitus, high BMI and low education level predict sudden cardiac death within 24 hours of incident myocardial infarction2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 17, p. 1814-1820Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: More than half of cardiovascular mortality occurs outside the hospital, mainly due to consistently low survival rates from out-of-hospital cardiac arrest.

    METHODS: This is a prospective, nested, case-control study derived from the Västerbotten Intervention Programme and the World Health Organization's Multinational Monitoring of Trends and Determinants in Cardiovascular Disease study in northern Sweden (1986-2006). To determine predictors for sudden cardiac death risk factors for cardiovascular disease were compared between incident myocardial infarction with sudden cardiac death (n = 363) and survivors of incident myocardial infarction (n = 1998) using multivariate logistic regression analysis.

    RESULTS: Diabetes had the strongest association with sudden cardiac death out of all evaluated risk factors (odds ratio (OR) 1.83, 95% confidence interval (CI) 1.30-2.59), followed by low education (OR 1.55, 95% CI 1.19-2.01), high body mass index (OR 1.05, 95% CI 1.02-1.08) and male sex (OR 1.42, 95% CI 1.001-2.01).

    CONCLUSIONS: The pattern of risk factors for incident myocardial infarction is different among survivors and those who die within 24 hours. The risk factors that contribute the most to death within 24 hours are diabetes mellitus, high body mass index and low education level, and can be addressed at both the public health level and by general practitioners.

  • 2. Ashar, Foram N.
    et al.
    Mitchell, Rebecca N.
    Albert, Christine M.
    Newton-Cheh, Christopher
    Brody, Jennifer A.
    Mueller-Nurasyid, Martina
    Moes, Anna
    Meitinger, Thomas
    Mak, Angel
    Huikuri, Heikki
    Junttila, M. Juhani
    Goyette, Philippe
    Pulit, Sara L.
    Pazoki, Raha
    Tanck, MichaelW.
    Blom, Marieke T.
    Zhao, XiaoQing
    Havulinna, Aki S.
    Jabbari, Reza
    Glinge, Charlotte
    Tragante, Vinicius
    Escher, Stefan A.
    Chakravarti, Aravinda
    Ehret, Georg
    Coresh, Josef
    Li, Man
    Prineas, Ronald J.
    Franco, Oscar H.
    Kwok, Pui-Yan
    Lumley, Thomas
    Dumas, Florence
    McKnight, Barbara
    Rotter, Jerome I.
    Lemaitre, Rozenn N.
    Heckbert, Susan R.
    O'Donnell, Christopher J.
    Hwang, Shih-Jen
    Tardif, Jean-Claude
    VanDenburgh, Martin
    Uitterlinden, Andre G.
    Hofman, Albert
    Stricker, Bruno H. C.
    de Bakker, Paul I. W.
    Franks, Paul W.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Asselbergs, Folkert W.
    Halushka, Marc K.
    Maleszewski, Joseph J.
    Tfelt-Hansen, Jacob
    Engstrom, Thomas
    Salomaa, Veikko
    Virmani, Renu
    Kolodgie, Frank
    Wilde, Arthur A. M.
    Tan, Hanno L.
    Bezzina, Connie R.
    Eijgelsheim, Mark
    Rioux, John D.
    Jouven, Xavier
    Kääb, Stefan
    Psaty, Bruce M.
    Siscovick, David S.
    Arking, Dan E.
    Sotoodehnia, Nona
    A comprehensive evaluation of the genetic architecture of sudden cardiac arrest2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 44, p. 3961-+Article in journal (Refereed)
    Abstract [en]

    Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA.

    Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk.

    Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.

  • 3. Burgess, Stephen
    et al.
    Thompson, Simon G
    Andrews, G
    Samani, N J
    Hall, A
    Whincup, P
    Morris, R
    Lawlor, D A
    Davey Smith, G
    Timpson, N
    Ebrahim, S
    Ben-Shlomo, Y
    Davey Smith, G
    Timpson, N
    Brown, M
    Ricketts, S
    Sandhu, M
    Reiner, A
    Psaty, B
    Lange, L
    Cushman, M
    Hung, J
    Thompson, P
    Beilby, J
    Warrington, N
    Palmer, L J
    Nordestgaard, B G
    Tybjaerg-Hansen, A
    Zacho, J
    Wu, C
    Lowe, G
    Tzoulaki, I
    Kumari, M
    Sandhu, M
    Yamamoto, J F
    Chiodini, B
    Franzosi, M
    Hankey, G J
    Jamrozik, K
    Palmer, L
    Rimm, E
    Pai, J
    Psaty, B
    Heckbert, S
    Bis, J
    Anand, S
    Engert, J
    Collins, R
    Clarke, R
    Melander, O
    Berglund, G
    Ladenvall, P
    Johansson, L
    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.
    Hingorani, A
    Humphries, S
    Rimm, E
    Manson, J
    Pai, J
    Watkins, H
    Clarke, R
    Hopewell, J
    Saleheen, D
    Frossard, R
    Danesh, J
    Sattar, N
    Robertson, M
    Shepherd, J
    Schaefer, E
    Hofman, A
    Witteman, J C M
    Kardys, I
    Ben-Shlomo, Y
    Davey Smith, G
    Timpson, N
    de Faire, U
    Bennet, A
    Sattar, N
    Ford, I
    Packard, C
    Kumari, M
    Manson, J
    Lawlor, Debbie A
    Davey Smith, George
    Anand, S
    Collins, R
    Casas, J P
    Danesh, J
    Davey Smith, G
    Franzosi, M
    Hingorani, A
    Lawlor, D A
    Manson, J
    Nordestgaard, B G
    Samani, N J
    Sandhu, M
    Smeeth, L
    Wensley, F
    Anand, S
    Bowden, J
    Burgess, S
    Casas, J P
    Di Angelantonio, E
    Engert, J
    Gao, P
    Shah, T
    Smeeth, L
    Thompson, S G
    Verzilli, C
    Walker, M
    Whittaker, J
    Hingorani, A
    Danesh, J
    Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables2010In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 29, no 12, p. 1298-1311Article in journal (Refereed)
    Abstract [en]

    Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes.

  • 4.
    Byhamre, Marja Lisa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Gustafsson, Per E.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hammarström, Anne
    Department of Public Health and Caring Sciences, Uppsala University, Sweden.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Snus use during the life-course and risk of the metabolic syndrome and its components2017In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 45, no 8, p. 733-740Article in journal (Refereed)
    Abstract [en]

    Objective: We aimed to investigate the association between life-course exposure to snus and prevalence of the metabolic syndrome and its components in adulthood.

    Design and method: Tobacco habits at baseline (age 16) and three follow-ups (ages 21, 30 and 43) were assessed among 880 participants in a population-based cohort in Northern Sweden. Presence of the metabolic syndrome at age 43 was ascertained using the International Diabetes Federation criteria. Odds ratios and CIs for risk of the metabolic syndrome and its components by snus use at 16, 21, 30 and 43 years were calculated using logistic regression. Cumulative snus use was defined as number of life periods (1-4) with current snus use.

    Results: At age 43, 164 participants (18.6%) were current snus users. We found no association between exclusive snus use at the ages of 16, 21, 30 and 43 years and the metabolic syndrome at age 43 years. Snus use (among non-smokers) was associated with raised triglycerides and high blood pressure in crude analysis, but not in multivariable models. There was no association between cumulative snus use and risk of the metabolic syndrome. Cumulative snus use was associated with central obesity, raised triglycerides and impaired fasting glucose/diabetes mellitus type 2 in crude analyses, but not after adjustments.

    Conclusion: The health consequences of snus exposure from adolescence to mid-adulthood do not seem to include increased risk of the metabolic syndrome or its components. The cardio-metabolic risk of dual exposure to snus and cigarettes may warrant further attention.

  • 5. Carlsson, Axel C.
    et al.
    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.
    Ruge, Toralph
    Larsson, Anders
    Arnlov, Johan
    Levels of soluble tumor necrosis factor receptor 1 and 2, gender, and risk of myocardial infarction in Northern Sweden2018In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 272, p. 41-46Article in journal (Refereed)
    Abstract [en]

    Background and aims: Soluble receptors for tumor necrosis factor alpha (sTNFR1 and sTNFR2) have been associated with cardiovascular diseases, and some evidence points towards a difference in associated risk between men and women. We aimed to study the association between sTNFR1 and sTNFR2 and incident myocardial infarctions (MI) and to explore the influence of established cardiovascular risk factors in men and women.& para;& para;Methods: We conducted a nested case control study in three large Swedish cohorts, including 533 myocardial infarction cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated.& para;& para;Results: An association between circulating sTNFR1 and sTNFR2 and an increased risk for MI was found when comparing cases and controls. The odds ratios were significant after adjustment for established cardiovascular risk factors and C-reactive protein in women (OR 1.44, 95% CI 1.08-1.93 for TNFR1, and 1.61, 95% CI 1.11-2.34 for TNFR2), but was abolished in men. Women with a combination of elevated CRP and values in the upper quartile of TNFR1 or TNFR2 had a 5-fold higher risk of myocardial infarction versus those with normal CRP and values in the lower three quartiles of TNFR1 or TNFR2.& para;& para;Conclusions: As the risk estimates for TNFR1 and TNFR2 were higher and remained significant after adjustments for established cardiovascular risk factors in women but not in men, a potential role for TNFR1 and TNFR2 in identifying women with a higher MI risk is possible. The future clinical role of TNFR1 and TNFR2 in combination with CRP to identify high risk patients for coronary heart disease has yet to be determined. 

  • 6. Carrasquilla, German D.
    et al.
    Chiavenna, Chiara
    Bottai, Matteo
    Magnusson, Patrik K.
    Santacatterina, Michele
    Wolk, Alicja
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Engstrom, Gunnar
    Borgfeldt, Christer
    Pedersen, Nancy L.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Berglund, Anita
    Leander, Karin
    The association between menopausal hormone therapy and coronary heart disease depends on timing of initiation in relation to menopause onset. Results based on pooled individual participant data from The Combined Cohorts of Menopausal Women - Studies of Register Based Health Outcomes in Relation to Hormonal Drugs (COMPREHEND) study2015In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 22, no 12, p. 1373-1373Article in journal (Other academic)
  • 7. Carrasquilla, German D.
    et al.
    Frumento, Paolo
    Berglund, Anita
    Borgfeldt, Christer
    Bottai, Matteo
    Chiavenna, Chiara
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Engström, Gunnar
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Magnusson, Patrik K.
    Nilsson, Peter M.
    Pedersen, Nancy L.
    Wolk, Alicja
    Leander, Karin
    Postmenopausal hormone therapy and risk of stroke: A pooled analysis of data from population-based cohort studies2017In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, no 11, article id e1002445Article in journal (Refereed)
    Abstract [en]

    Background: Recent research indicates a favourable influence of postmenopausal hormone therapy (HT) if initiated early, but not late, on subclinical atherosclerosis. However, the clinical relevance of timing of HT initiation for hard end points such as stroke remains to be determined. Further, no previous research has considered the timing of initiation of HT in relation to haemorrhagic stroke risk. The importance of the route of administration, type, active ingredient, and duration of HT for stroke risk is also unclear. We aimed to assess the association between HT and risk of stroke, considering the timing of initiation, route of administration, type, active ingredient, and duration of HT.

    Methods and findings: Data on HT use reported by the participants in 5 population-based Swedish cohort studies, with baseline investigations performed during the period 1987-2002, were combined in this observational study. In total, 88,914 postmenopausal women who reported data on HT use and had no previous cardiovascular disease diagnosis were included. Incident events of stroke (ischaemic, haemorrhagic, or unspecified) and haemorrhagic stroke were identified from national population registers. Laplace regression was employed to assess crude and multivariable-adjusted associations between HT and stroke risk by estimating percentile differences (PDs) with 95% confidence intervals (CIs). The fifth and first PDs were calculated for stroke and haemorrhagic stroke, respectively. Crude models were adjusted for age at baseline only. The final adjusted models included age at baseline, level of education, smoking status, body mass index, level of physical activity, and age at menopause onset. Additional variables evaluated for potential confounding were type of menopause, parity, use of oral contraceptives, alcohol consumption, hypertension, dyslipidaemia, diabetes, family history of cardiovascular disease, and cohort. During a median follow-up of 14.3 years, 6,371 first-time stroke events were recorded; of these, 1,080 were haemorrhagic. Following multivariable adjustment, early initiation (<5 years since menopause onset) of HT was associated with a longer stroke-free period than never use (fifth PD, 1.00 years; 95% CI 0.42 to 1.57), but there was no significant extension to the time period free of haemorrhagic stroke (first PD, 1.52 years; 95% CI -0.32 to 3.37). When considering timing as a continuous variable, the stroke-free and the haemorrhagic stroke-free periods were maximal if HT was initiated approximately 0-5 years from the onset of menopause. If single conjugated equine oestrogen HT was used, late initiation of HT was associated with a shorter stroke-free (fifth PD, -4.41 years; 95% CI -7.14 to -1.68) and haemorrhagic stroke-free (first PD, -9.51 years; 95% CI -12.77 to -6.24) period than never use. Combined HT when initiated late was significantly associated with a shorter haemorrhagic stroke-free period (first PD, -1.97 years; 95% CI -3.81 to -0.13), but not with a shorter stroke-free period (fifth PD, -1.21 years; 95% CI -3.11 to 0.68) than never use. Given the observational nature of this study, the possibility of uncontrolled confounding cannot be excluded. Further, immortal time bias, also related to the observational design, cannot be ruled out.

    Conclusions: When initiated early in relation to menopause onset, HT was not associated with increased risk of incident stroke, regardless of the route of administration, type of HT, active ingredient, and duration. Generally, these findings held also for haemorrhagic stroke. Our results suggest that the initiation of HT 0-5 years after menopause onset, as compared to never use, is associated with a decreased risk of stroke and haemorrhagic stroke. Late initiation was associated with elevated risks of stroke and haemorrhagic stroke when conjugated equine oestrogen was used as single therapy. Late initiation of combined HT was associated with haemorrhagic stroke risk.

  • 8.
    Claesson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Birgander, Lisbeth Slunga
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jansson, Jan-Håkan
    Lindahl, B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Burell, G
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mattsson, Cecilia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Cognitive-behavioural stress management does not improve biological cardiovascular risk indicators in women with ischaemic heart disease: a randomized-controlled trial.2006In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 260, no 4, p. 320-331Article in journal (Refereed)
  • 9. Crosby, Jacy
    et al.
    Peloso, Gina M.
    Auer, Paul L.
    Crosslin, David R.
    Stitziel, Nathan O.
    Lange, Leslie A.
    Lu, Yingchang
    Tang, Zheng-zheng
    Zhang, He
    Hindy, George
    Masca, Nicholas
    Stirrups, Kathleen
    Kanoni, Stavroula
    Do, Ron
    Jun, Goo
    Hu, Youna
    Kang, Hyun Min
    Xue, Chenyi
    Goel, Anuj
    Farrall, Martin
    Duga, Stefano
    Merlini, Pier Angelica
    Asselta, Rosanna
    Girelli, Domenico
    Olivieri, Oliviero
    Martinelli, Nicola
    Yin, Wu
    Reilly, Dermot
    Speliotes, Elizabeth
    Fox, Caroline S.
    Hveem, Kristian
    Holmen, Oddgeir L.
    Nikpay, Majid
    Farlow, Deborah N.
    Assimes, Themistocles L.
    Franceschini, Nora
    Robinson, Jennifer
    North, Kari E.
    Martin, Lisa W.
    DePristo, Mark
    Gupta, Namrata
    Andersson Escher, Stefan
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Medicine, Skellefteå Hospital, Skellefteå .
    Van Zuydam, Natalie
    Palmer, Colin N. A.
    Wareham, Nicholas
    Koch, Werner
    Meitinger, Thomas
    Peters, Annette
    Lieb, Wolfgang
    Erbel, Raimund
    Konig, Inke R.
    Kruppa, Jochen
    Degenhardt, Franziska
    Gottesman, Omri
    Bottinger, Erwin P.
    O'Donnell, Christopher J.
    Psaty, Bruce M.
    Ballantyne, Christie M.
    Abecasis, Goncalo
    Ordovas, Jose M.
    Melander, Olle
    Watkins, Hugh
    Orho-Melander, Marju
    Ardissino, Diego
    Loos, Ruth J. F.
    McPherson, Ruth
    Willer, Cristen J.
    Erdmann, Jeanette
    Hall, Alistair S.
    Samani, Nilesh J.
    Deloukas, Panos
    Schunkert, Heribert
    Wilson, James G.
    Kooperberg, Charles
    Rich, Stephen S.
    Tracy, Russell P.
    Lin, Dan-Yu
    Altshuler, David
    Gabriel, Stacey
    Nickerson, Deborah A.
    Jarvik, Gail P.
    Cupples, L. Adrienne
    Reiner, Alex P.
    Boerwinkle, Eric
    Kathiresan, Sekar
    Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 371, no 1, p. 22-31Article in journal (Refereed)
    Abstract [en]

    Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G -> A and IVS3+1G -> T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1x10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8x10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4x10(-6)). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)

  • 10. Crowe, Francesca L
    et al.
    Roddam, Andrew W
    Key, Timothy J
    Appleby, Paul N
    Overvad, Kim
    Jakobsen, Marianne U
    Tjønneland, Anne
    Hansen, Louise
    Boeing, Heiner
    Weikert, Cornelia
    Linseisen, Jakob
    Kaaks, Rudolf
    Trichopoulou, Antonia
    Misirli, Gesthimani
    Lagiou, Pagona
    Sacerdote, Carlotta
    Pala, Valeria
    Palli, Domenico
    Tumino, Rosario
    Panico, Salvatore
    Bueno-de-Mesquita, H Bas
    Boer, Jolanda
    van Gils, Carla H
    Beulens, Joline W J
    Barricarte, Aurelio
    Rodríguez, Laudina
    Larrañaga, Nerea
    Sánchez, Maria-José
    Tormo, María-José
    Buckland, Genevieve
    Lund, Eiliv
    Hedblad, Bo
    Melander, Olle
    Jansson, Jan-Håkan
    Department of Medicine, Skellefteå County Hospital, Skellefteå, Sweden .
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Wareham, Nicholas J
    Slimani, Nadia
    Romieu, Isabelle
    Jenab, Mazda
    Danesh, John
    Gallo, Valentina
    Norat, Teresa
    Riboli, Elio
    Fruit and vegetable intake and mortality from ischaemic heart disease: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heart study.2011In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 32, no 10, p. 1235-1243Article in journal (Refereed)
    Abstract [en]

    AIMS: A higher intake of fruits and vegetables has been associated with a lower risk of ischaemic heart disease (IHD), but there is some uncertainty about the interpretation of this association. The objective was to assess the relation between fruit and vegetable intake and risk of mortality from IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heart study.

    METHODS AND RESULTS: After an average of 8.4 years of follow-up, there were 1636 deaths from IHD among 313 074 men and women without previous myocardial infarction or stroke from eight European countries. Participants consuming at least eight portions (80 g each) of fruits and vegetables a day had a 22% lower risk of fatal IHD [relative risk (RR) = 0.78, 95% confidence interval (CI): 0.65-0.95] compared with those consuming fewer than three portions a day. After calibration of fruit and vegetable intake to account for differences in dietary assessment between the participating centres, a one portion (80 g) increment in fruit and vegetable intake was associated with a 4% lower risk of fatal IHD (RR = 0.96, 95% CI: 0.92-1.00, P for trend = 0.033).

    CONCLUSION: Results from this large observational study suggest that a higher intake of fruits and vegetables is associated with a reduced risk of IHD mortality. Whether this association is causal and, if so, the biological mechanism(s) by which fruits and vegetables operate to lower IHD risks remains unclear.

  • 11. Custodio, Hipolito M
    et al.
    Broberg, Karin
    Wennberg, Maria
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Vessby, Bengt
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Skerfving, Staffan
    Polymorphisms in glutathione-related genes affect methylmercury retention.2004In: Arch Environ Health, ISSN 0003-9896, Vol. 59, no 11, p. 588-95Article in journal (Refereed)
  • 12. 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.

  • 13.
    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.

  • 14. Ekstedt, Bertil
    et al.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience. Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    [No scientific evidence supports vitamin B treatment of patients with cardiovascular diseases]2006In: Lakartidningen, ISSN 0023-7205, Vol. 103, no 45, p. 3464-6Article in journal (Refereed)
  • 15.
    Eliasson, Mats
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Janlert, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Time trends in population cholesterol levels 1986-2004: influence of lipid-lowering drugs, obesity, smoking and educational level. The northern Sweden MONICA study.2006In: J Intern Med, ISSN 0954-6820, Vol. 260, no 6, p. 551-9Article in journal (Refereed)
  • 16.
    Eliasson, Mats
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundblad, Dan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The disparity between long-term survival in patients with and without diabetes following a first myocardial infarction did not change between 1989 and 2006: an analysis of 6,776 patients in the Northern Sweden MONICA Study2011In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 54, no 10, p. 2538-2543Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Long-term survival after myocardial infarction(MI) has improved in the population, but data ondiabetic patients is lacking. We analysed survival for up to18 years after a first MI in patients with or without diabetes

    Methods: The Northern Sweden MONICA MyocardialInfarction Registry was linked to the Cause-of-DeathRegistry for a total of 6,776 patients, 25–64 years of age,with a first MI during 1989–2006. Prehospital deaths wereincluded. Follow-up ended on 30 August 2008.

    Results: Sixteen per cent had diabetes. Median follow-uptime was 6.8 years, and the study included 50,667 patientyears.One third of the non-diabetic patients died vs half ofthe diabetic patients. Median survival for non-diabetic menwas 227 months and for diabetic men 123 months.Corresponding figures for the non-diabetic and diabeticwomen were 222 and 81 months respectively. Men withdiabetes had an age-adjusted HR for all-cause mortality of 1.56 (95% CI 1.39, 1.79) vs men without diabetes. Mortality risk was higher among diabetic women, HR1.97 (1.62, 2.39) (diabetes × sex interaction, p=0.03). Survival increased for three consecutive cohorts and washigher in non-diabetic patients for all durations of follow-upand in all three cohorts. The interaction of diabetes x cohortwas not significant over time (p=0.5) and HRs did notdiffer either.

    Conclusions/interpretation Long-term survival after a firstMI is markedly lower in diabetic patients, especially amongwomen, over an 18-year observation time. Althoughsurvival has improved in diabetic patients, the effect ofdiabetes upon mortality has not diminished.

  • 17. Engeset, Dagrun
    et al.
    Braaten, Tonje
    Teucher, Birgit
    Kühn, Tilman
    Bueno-de-Mesquita, H B
    Leenders, Max
    Agudo, Antonio
    Bergmann, Manuela M
    Valanou, Elisavet
    Naska, Androniki
    Trichopoulou, Antonia
    Key, Timothy J
    Crowe, Francesca L
    Overvad, Kim
    Sonestedt, Emily
    Mattiello, Amalia
    Peeters, Petra H
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, Jan Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Dartois, Laureen
    Li, Kuanrong
    Barricarte, Aurelio
    Ward, Heather
    Riboli, Elio
    Agnoli, Claudia
    Huerta, José María
    Sánchez, María-José
    Tumino, Rosario
    Altzibar, Jone M
    Vineis, Paolo
    Masala, Giovanna
    Ferrari, Pietro
    Muller, David C
    Johansson, Mattias
    Luisa Redondo, M
    Tjønneland, Anne
    Olsen, Anja
    Olsen, Karina Standahl
    Brustad, Magritt
    Skeie, Guri
    Lund, Eiliv
    Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort2015In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 30, no 1, p. 57-70Article in journal (Refereed)
    Abstract [en]

    Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992-1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99 % confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p < 0.000) with fatty fish consumption and total mortality and with total fish consumption and cancer mortality (p = 0.046).

  • 18. Engström, Karin S
    et al.
    Wennberg, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine. Department of Medicine, Skellefteå Hospital, Skellefteå, Sweden.
    Strömberg, Ulf
    Bergdahl, Ingvar A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundh, Thomas
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Rentschler, Gerda
    Vessby, Bengt
    Skerfving, Staffan
    Broberg, Karin
    Evaluation of the impact of genetic polymorphisms in glutathione-related genes on the association between methylmercury or n-3 polyunsaturated long chain fatty acids and risk of myocardial infarction: a case-control study2011In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 10, p. Article nr 33-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, which are present in fish, are protective against myocardial infarction. However, fish also contains methylmercury, which influences the risk of myocardial infarction, possibly by generating oxidative stress. Methylmercury is metabolized by conjugation to glutathione, which facilitates elimination. Glutathione is also an antioxidant. Individuals with certain polymorphisms in glutathione-related genes may tolerate higher exposures to methylmercury, due to faster metabolism and elimination and/or better glutathione-associated antioxidative capacity. They would thus benefit more from the protective agents in fish, such as eicosapentaenoic+docosahexaenoic acid and selenium. The objective for this study was to elucidate whether genetic polymorphisms in glutathione-related genes modify the association between eicosapentaenoic+docosahexaenoic acid or methylmercury and risk of first ever myocardial infarction.

    METHODS: Polymorphisms in glutathione-synthesizing (glutamyl-cysteine ligase catalytic subunit, GCLC and glutamyl-cysteine ligase modifier subunit, GCLM) or glutathione-conjugating (glutathione S-transferase P, GSTP1) genes were genotyped in 1027 individuals from northern Sweden (458 cases of first-ever myocardial infarction and 569 matched controls). The impact of these polymorphisms on the association between erythrocyte-mercury (proxy for methylmercury) and risk of myocardial infarction, as well as between plasma eicosapentaenoic+docosahexaenoic acid and risk of myocardial infarction, was evaluated by conditional logistic regression. The effect of erythrocyte-selenium on risk of myocardial infarction was also taken into consideration.

    RESULTS: There were no strong genetic modifying effects on the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction risk. When eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury were divided into tertiles, individuals with GCLM-588 TT genotype displayed a lower risk relative to the CC genotype in all but one tertile; in most tertiles the odds ratio was around 0.5 for TT. However, there were few TT carriers and the results were not statistically significant. The results were similar when taking plasma eicosapentaenoic+docosahexaenoic acid, erythrocyte-selenium and erythrocyte-mercury into account simultaneously.

    CONCLUSIONS: No statistically significant genetic modifying effects were seen for the association between plasma eicosapentaenoic+docosahexaenoic acid or erythrocyte-mercury and risk of myocardial infarction. Still, our results indicate that the relatively rare GCLM-588 TT genotype may have an impact, but a larger study is necessary for confirmation.

  • 19.
    Eriksson, Marie
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Comparison of blood pressure measurements between an automated oscillometric device and a Hawksley random-zero sphygmomanometer in the northern Sweden MONICA study.2012In: Blood Pressure Monitoring, ISSN 1359-5237, E-ISSN 1473-5725, Vol. 17, no 4, p. 164-170Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Hawksley random-zero sphygmomanometer (random-zero) has been used widely in epidemiological observation studies. This study compares blood pressure measurements using the random-zero with measurements using an automated oscillometric device and suggests a correction of the automated oscillometric measurements to enable comparisons of blood pressure levels over time.

    METHODS: The northern Sweden MONICA population survey 2009 included 1729 participants, 853 men and 876 women, 25-74 years old. Blood pressure was measured using both random-zero and an automated oscillometric device in all participants. The Omron M7 digital blood pressure monitor was used for automated oscillometric measurements. A linear mixed model was used to derive a formula to adjust the automated oscillometric readings.

    RESULTS: Automated oscillometric measurements of systolic blood pressure were generally lower than random-zero measurements in women [oscillometric mean 122.1 mmHg (95% confidence interval: 121.0-123.2) versus random-zero mean 124.4 mmHg (123.5-125.5)], whereas automated oscillometric measurements of systolic blood pressure were generally higher than random-zero measurements in men [oscillometric 131.1 mmHg (130.0-132.2) versus random-zero 129.0 mmHg (127.9-130.1)]. For diastolic blood pressure, automated oscillometric measurements were higher in both women [oscillometric 79.9 mmHg (79.2-80.5) versus random-zero 76.7 mmHg (76.0-77.4)] and men [oscillometric 83.1 mmHg (82.4-83.8) vs. random-zero 81.2 mmHg (80.6-81.9)]. The difference also varied with age and order of measurement. Adjustment of the automated oscillometric measurements using mixed model regression coefficients produced estimates of blood pressure that were close to the random-zero measurements.

    CONCLUSION: Blood pressure measurements using an automated oscillometric device differ from those with random-zero, but the oscillometric measurements can be adjusted, on the basis of sex, age and measurement order, to be similar to the random-zero measurements.

  • 20.
    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.

  • 21.
    Eriksson, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Holmgren, L.
    Janlert, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Medicine, Skellefteå Hospital, Skellefteå.
    Lundblad, Dan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Medicine, Sunderby Hospital, Luleå.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. National Board of Health and Welfare, Stockholm.
    Söderberg, Stefan
    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. Department of Medicine, Sunderby Hospital, Luleå.
    Large improvements in major cardiovascular risk factors in the population of northern Sweden: the MONICA study 1986–20092011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 269, no 2, p. 219-231Article in journal (Refereed)
    Abstract [en]

    Objectives. The incidence of cardiovascular disease has declined rapidly in Sweden since the 1980s. We explored changes in major cardiovascular risk factors in northern Sweden between 1986 and 2009.

    Design. Since 1986, six population surveys have been carried out in northern Sweden using procedures of the World Health Organization MONICA project. The population age range was 25–64 years in 1986 and 1990, and 25–74 years from 1994. Trends were analysed using generalized linear models.

    Results. A total of 10 586 subjects were included in the surveys. Blood pressure decreased by 4.9/3.9 mmHg in women and 1.8/1.5 mmHg in men aged 25–64 years between 1986 and 2009. In men and women aged 65–74 years, the decrease was 12.6/6.1 mmHg between 1994 and 2009. From 1994, the use of blood pressure‐lowering drugs increased, particularly among the older subgroup. The prevalence of smoking halved between 1986 and 2009; 11% of women and 9% of men were smokers in 2009. Cholesterol levels decreased by 0.9 mmol L−1 in the younger age group (25–64 years), and the use of lipid‐lowering agents increased from 1994. Among subjects aged 25–64 years, one in five was obese in 2009, which was twice as many as in 1986, and body mass index (BMI) increased by 1.5 kg m−2, corresponding to an increase in weight of 4 kg. There was no further increase in BMI from 2004. The prevalence of diabetes did not change between 1986 and 2009. The proportion that received a university education increased markedly in all age groups, especially in women, during the study period.

    Conclusions. Significant improvements were observed in major cardiovascular risk factors in northern Sweden between 1986 and 2009.

  • 22. Erzurumluoglu, A Mesut
    et al.
    Liu, Mengzhen
    Jackson, Victoria E
    Barnes, Daniel R
    Datta, Gargi
    Melbourne, Carl A
    Young, Robin
    Batini, Chiara
    Surendran, Praveen
    Jiang, Tao
    Adnan, Sheikh Daud
    Afaq, Saima
    Agrawal, Arpana
    Altmaier, Elisabeth
    Antoniou, Antonis C
    Asselbergs, Folkert W
    Baumbach, Clemens
    Bierut, Laura
    Bertelsen, Sarah
    Boehnke, Michael
    Bots, Michiel L
    Brazel, David M
    Chambers, John C
    Chang-Claude, Jenny
    Chen, Chu
    Corley, Janie
    Chou, Yi-Ling
    David, Sean P
    de Boer, Rudolf A
    de Leeuw, Christiaan A
    Dennis, Joe G
    Dominiczak, Anna F
    Dunning, Alison M
    Easton, Douglas F
    Eaton, Charles
    Elliott, Paul
    Evangelou, Evangelos
    Faul, Jessica D
    Foroud, Tatiana
    Goate, Alison
    Gong, Jian
    Grabe, Hans J
    Haessler, Jeff
    Haiman, Christopher
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Hammerschlag, Anke R
    Harris, Sarah E
    Hattersley, Andrew
    Heath, Andrew
    Hsu, Chris
    Iacono, William G
    Kanoni, Stavroula
    Kapoor, Manav
    Kaprio, Jaakko
    Kardia, Sharon L
    Karpe, Fredrik
    Kontto, Jukka
    Kooner, Jaspal S
    Kooperberg, Charles
    Kuulasmaa, Kari
    Laakso, Markku
    Lai, Dongbing
    Langenberg, Claudia
    Le, Nhung
    Lettre, Guillaume
    Loukola, Anu
    Luan, Jian'an
    Madden, Pamela A F
    Mangino, Massimo
    Marioni, Riccardo E
    Marouli, Eirini
    Marten, Jonathan
    Martin, Nicholas G
    McGue, Matt
    Michailidou, Kyriaki
    Mihailov, Evelin
    Moayyeri, Alireza
    Moitry, Marie
    Müller-Nurasyid, Martina
    Naheed, Aliya
    Nauck, Matthias
    Neville, Matthew J
    Nielsen, Sune Fallgaard
    North, Kari
    Perola, Markus
    Pharoah, Paul D P
    Pistis, Giorgio
    Polderman, Tinca J
    Posthuma, Danielle
    Poulter, Neil
    Qaiser, Beenish
    Rasheed, Asif
    Reiner, Alex
    Renstrom, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Genetic and Molecular Epidemiology Unit, Lund University.
    Rice, John
    Rohde, Rebecca
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Samani, Nilesh J
    Samuel, Maria
    Schlessinger, David
    Scholte, Steven H
    Scott, Robert A
    Sever, Peter
    Shao, Yaming
    Shrine, Nick
    Smith, Jennifer A
    Starr, John M
    Stirrups, Kathleen
    Stram, Danielle
    Stringham, Heather M
    Tachmazidou, Ioanna
    Tardif, Jean-Claude
    Thompson, Deborah J
    Tindle, Hilary A
    Tragante, Vinicius
    Trompet, Stella
    Turcot, Valerie
    Tyrrell, Jessica
    Vaartjes, Ilonca
    van der Leij, Andries R
    van der Meer, Peter
    Varga, Tibor V
    Verweij, Niek
    Völzke, Henry
    Wareham, Nicholas J
    Warren, Helen R
    Weir, David R
    Weiss, Stefan
    Wetherill, Leah
    Yaghootkar, Hanieh
    Yavas, Ersin
    Jiang, Yu
    Chen, Fang
    Zhan, Xiaowei
    Zhang, Weihua
    Zhao, Wei
    Zhao, Wei
    Zhou, Kaixin
    Amouyel, Philippe
    Blankenberg, Stefan
    Caulfield, Mark J
    Chowdhury, Rajiv
    Cucca, Francesco
    Deary, Ian J
    Deloukas, Panos
    Di Angelantonio, Emanuele
    Ferrario, Marco
    Ferrières, Jean
    Franks, Paul W
    Frayling, Tim M
    Frossard, Philippe
    Hall, Ian P
    Hayward, Caroline
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Public Health and Clinical Medicine, Skellefteå Research Unit, Umeå University, Umeå, Sweden..
    Jukema, J Wouter
    Kee, Frank
    Männistö, Satu
    Metspalu, Andres
    Munroe, Patricia B
    Nordestgaard, Børge Grønne
    Palmer, Colin N A
    Salomaa, Veikko
    Sattar, Naveed
    Spector, Timothy
    Strachan, David Peter
    van der Harst, Pim
    Zeggini, Eleftheria
    Saleheen, Danish
    Butterworth, Adam S
    Wain, Louise V
    Abecasis, Goncalo R
    Danesh, John
    Tobin, Martin D
    Vrieze, Scott
    Liu, Dajiang J
    Howson, Joanna M M
    Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci2019In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578Article in journal (Refereed)
    Abstract [en]

    Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

  • 23. Forslund, Ann-Sofie
    et al.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundblad, Dan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderberg, Siv
    A second chance at life: people's lived experiences of surviving out-of-hospital cardiac arrest2017In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 31, no 4, p. 878-886Article in journal (Refereed)
    Abstract [en]

    Background: There is more to illuminate about people's experiences of surviving out-of-hospital cardiac arrest (OHCA) and how such an event affects people's lives over time. Aims: This study aimed to elucidate meanings of people's lived experiences and changes in everyday life during their first year after surviving OHCA. Methods: A qualitative, longitudinal design was used. Eleven people surviving OHCA from northern Sweden agreed to participate and were interviewed 6 and 12 months after the event. A phenomenological hermeneutic interpretation was used to analyse the transcribed texts. Findings: The structural analysis resulted in two themes: (i) striving to regain one's usual self and (ii) a second chance at life, and subthemes (ia) testing the body, (ib) pursuing the ordinary life, (ic) gratitude for help to survival, (iia) regaining a sense of security with one's body, (iib) getting to know a new self, and (iic) seeking meaning and establishing a future. Conclusion: To conclude, we suggest that people experienced meanings of surviving OHCA over time as striving to regain their usual self and getting a second chance at life. The event affected them in many ways and resulted in a lot of emotions and many things to think about. Participants experienced back-and-forth emotions, when comparing their present lives to both their lives before cardiac arrest and those lives they planned for the future. During their first year, participants' daily lives were still influenced by being dead' and returning to life. As time passed, they wanted to resume their ordinary lives and hoped for continued lives filled with meaning and joyous activities.

  • 24.
    Forslund, Ann-Sofie
    et al.
    Department of Research, Norrbotten County Council, Luleå ; Department of Health Science, Division of Nursing, Luleå University of Technology.
    Lundblad, Dan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Medicine, Sunderby Hospital, Luleå.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Medicine, Skellefteå Hospital.
    Zingmark, Karin
    Department of Research, Norrbotten County Council, Luleå ; Department of Health Science, Division of Nursing, Luleå University of Technology.
    Söderberg, Siv
    Department of Health Science, Division of Nursing, Luleå University of Technology.
    Risk factors among people surviving out-of-hospital cardiac arrest and their thoughts about what lifestyle means to them: a mixed methods study2013In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 13, p. 62-Article in journal (Refereed)
    Abstract [en]

    Background: The known risk factors for coronary heart disease among people prior suffering an out-of-hospital cardiac arrest with validated myocardial infarction aetiology and their thoughts about what lifestyle means to them after surviving have rarely been described. Therefore the aim of the study was to describe risk factors and lifestyle among survivors. Methods: An explanatory mixed methods design was used. All people registered in the Northern Sweden MONICA myocardial registry between the year 1989 to 2007 who survived out-of-hospital cardiac arrest with validated myocardial infarction aetiology and were alive at the 28th day after the onset of symptoms (n = 71) were included in the quantitative analysis. Thirteen of them participated in interviews conducted in 2011 and analysed via a qualitative manifest content analysis. Results: About 60% of the people had no history of ischemic heart disease before the out-of-hospital cardiac arrest, but 20% had three cardiovascular risk factors (i.e., hypertension, diabetes mellitus, total cholesterol of more or equal 5 mmol/l or taking lipid lowering medication, and current smoker). Three categories (i.e., significance of lifestyle, modifying the lifestyle to the new life situation and a changed view on life) and seven sub-categories emerged from the qualitative analysis. Conclusions: For many people out-of-hospital cardiac arrest was the first symptom of coronary heart disease. Interview participants were well informed about their cardiovascular risk factors and the benefits of risk factor treatment. In spite of that, some chose to ignore this knowledge to some extent and preferred to live a "good life", where risk factor treatment played a minor part. The importance of the support of family members in terms of feeling happy and having fun was highlighted by the interview participants and expressed as being the meaning of lifestyle. Perhaps the person with illness together with health care workers should focus more on the meaningful and joyful things in life and try to adopt healthy behaviours linked to these things.

  • 25.
    Forslund, Ann-Sofie
    et al.
    The Northern Sweden MONICA Myocardial Registry, Department of Research, Norrbotten County Council, Luleå, Sweden; Division of Nursing, Department of Health Science, Luleå University of Technology, Luleå, Sweden.
    Söderberg, Siv
    Division of Nursing, Department of Health Science, Luleå University of Technology, Luleå, Sweden.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Medicine, Skellefteå Hospital, Skellefteå, Sweden.
    Lundblad, Dan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Medicine, Sunderby Hospital, Luleå, Sweden.
    Trends in incidence and outcome of out-of-hospital cardiac arrest among people with validated myocardial infarction2013In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 20, no 2, p. 260-267Article in journal (Refereed)
    Abstract [en]

    Aims: To describe trends in incidence, outcome, and background characteristics among people who suffered an out-of-hospital cardiac arrest with validated myocardial infarction aetiology (OHCA-V).

    Methods and results: People from the northern Sweden MONICA myocardial registry (1989-2007) with OHCA-V (n = 2977) were divided in two age groups (25-64 and 65-74 years). Both those who were resuscitated outside hospital and those who died before resuscitation was started were included in the study. The younger age group was studied during 1989-2007 and the older group during 2000-2007. The incidence of OHCA-V decreased in both the younger group (men p < 0.0001, women p = 0.04) and the older group (men p < 0.0001, women p < 0.0007, respectively). The proportion with a history of ischaemic heart disease prior to the event decreased (p < 0.0001). The proportion of previous myocardial infarction decreased (p < 0.0001), diabetes mellitus increased (p = 0.001), coronary interventions increased (p < 0.0001), and survival after OHCA-V increased (p < 0.0001) in the younger group but not in the older group. Long-term survival after OHCA-V was better in the younger than in the older group (p = 0.026).

    Conclusion: The incidence of OHCA-V decreased in both sexes. The proportion surviving after OHCA-V was small but increased, and long-term survival (≥28 days) was better in the younger age group. Primary preventive measures may explain most of the improvements. However, the effects of secondary preventive measures cannot be excluded.

  • 26. Forslund, Ann-Sofie
    et al.
    Zingmark, Karin
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundblad, Dan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderberg, Siv
    Meanings of people's lived experiences of surviving an out-of-hospital cardiac arrest, 1 month after the event2014In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 29, no 5, p. 464-471Article in journal (Refereed)
    Abstract [en]

    Background: The out-of-hospital cardiac arrest (OHCA) survival rate has been poor and stable for a long time, but more recent studies describe its increase. However, there are few studies in which people narrate their experiences from surviving. Objective: The aim of this study was to elucidate meanings of people's lived experiences of surviving an OHCA with validated myocardial infarction (MI) etiology, 1 month after the event. Methods: A purposive sample of 2 women and 9 men was interviewed between February 2011 and May 2012. A phenomenological hermeneutical method was used for analysis, which involved 3 steps: naive reading and understanding, structural analysis, and comprehensive understanding. Results: There were 2 themes, (1) returning to life and (2) revaluing life, and five subthemes, (1a) waking up and missing the whole picture, (1b) realizing it was not time to die, (2a) wondering why and seeking explanations, (2b) feeling ambiguous in relations, and (2c) wondering whether life will be the same. All were constructed from the analysis. Conclusions: Surviving an OHCA with validated MI etiology meant waking up and realizing that one had experienced a cardiac arrest and had been resuscitated. These survivors had memory loss and a need to know what had happened during the time they were dead/unconscious. They searched for a reason why they experienced an MI and cardiac arrest and had gone from being "heart-healthy'' to having a lifelong illness. They all had the experience of passing from life to death and back to life again. For the participants, these differences led to a revaluation of what is important in life.

  • 27. Grönlund, Hans
    et al.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wikström, Max
    de Faire, Ulf
    Frostegård, Johan
    Low levels of IgM antibodies against phosphorylcholine predict development of acute myocardial infarction in a population-based cohort from northern Sweden.2009In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 16, no 3, p. 382-386Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Phosphorylcholine (PC) is one important epitope on oxidized low-density lipoprotein that may play an important role by contributing to the atherogenicity of oxidized low-density lipoprotein. IgM antibodies against PC (anti-PC) are present ubiquitously in the population as natural antibodies. We here determine the association between anti-PC and incidence of myocardial infarction (MI). METHODS: We studied 462 incident cases of first events of MI and 888 age-matched and sex-matched controls identified through 13 years of follow-up (1987-1999) of participants in a population-based study from northern Sweden. Relative risks (RRs) with 95% confidence intervals (CIs) of incident MI with adjustments for age, sex, geographical region, hypertension, diabetes, BMI, smoking habits, s-cholesterol and high-sensitivity C-reactive protein were determined. Anti-PC levels were measured by enzyme-linked immunoassay. RESULTS: Low anti-PC values were associated with increased risk of MI. Significant associations were found for values below 26.8 U/ml, corresponding to the lowest 25th percentile, and the highest association was seen below 16.9 U/ml. These results remained almost the same after adjustment for confounding factors (RR crude: 1.56, CI: 1.07-2.28 and RR adjusted: 1.69, CI: 1.09-2.54). CONCLUSION: Low levels of natural IgM anti-PC could play an important role as risk markers for development of MI. Adjustment for common confounders only marginally affected the RR, suggesting that the addition of IgM anti-PC add independent information to the more traditional risk factors.

  • 28.
    Hagg, Lovisa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Cecilia
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    External Validity of the ARISTOTLE Trial in Real-Life Atrial Fibrillation Patients2014In: Cardiovascular Therapeutics, ISSN 1755-5914, Vol. 32, no 5, p. 214-218Article in journal (Refereed)
    Abstract [en]

    Objective

    Our primary objective was to determine the proportion of patients with atrial fibrillation (AF) eligible for enrollment in a randomized controlled trial for a novel oral anticoagulant, the ARISTOTLE trial. A secondary objective was to describe the reasons for trial ineligibility.

    Methods

    We performed a cross-sectional study of an unselected population including 2274 patients in Skelleftea, Sweden with at least one verified episode of AF on or before December 31, 2010. Patients were classified as suitable or unsuitable for anticoagulant treatment according to current guidelines. The enrollment criteria from the ARISTOTLE trial were extracted from the original publication and applied to the population.

    Results

    Among all patients with AF, 1579 were classified as suitable for anticoagulant treatment. Of these, only 658 patients (42%) were eligible for participation in the ARISTOTLE trial. Among the 921 patients ineligible for participation, 498 did not meet the ECG criteria, 272 had psychosocial problems, and in addition, 78 patients were excluded due to both of these criteria.

    Conclusion

    Our study shows that a majority of the patients in an unselected population with AF suitable for anticoagulant treatment were ineligible for participation in the ARISTOTLE trial. The applicability of the ARISTOTLE trial is therefore unknown for a considerable proportion of patients with AF in real life.

  • 29.
    Hallmans, Göran
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Agren, A
    Johansson, G
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, Periodontology.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, JH
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindahl, B
    Rolandsson, Olov
    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.
    Nilsson, M
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Cardiovascular disease and diabetes in the Northern Sweden Health and Disease Study Cohort: evaluation of risk factors and their interactions.2003In: Scandinavian Journal of Public Health. Supplement Links, ISSN 1403-4956, Vol. 61, p. 18-24Article in journal (Refereed)
    Abstract [en]

    The purpose of this paper is, first, to describe the organization, sampling procedures, availability of samples/database, ethical considerations, and quality control program of the Northern Sweden Health and Disease Study Cohort. Secondly, some examples are given of studies on cardiovascular disease and diabetes with a focus on the biomarker programme. The cohort has been positioned as a national and international resource for scientific research.

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

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

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

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

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

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

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

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

  • 32. Hergens, Maria-Pia
    et al.
    Galanti, Rosaria
    Hansson, Jenny
    Fredlund, Peeter
    Ahlbom, Anders
    Alfredsson, Lars
    Bellocco, Rino
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Fransson, Eleonor I
    Hallqvist, Johan
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Knutsson, Anders
    Pedersen, Nancy
    Lagerros, Ylva Trolle
    Ostergren, Per-Olof
    Magnusson, Cecilia
    Use of Scandinavian Moist Smokeless Tobacco (Snus) and the Risk of Atrial Fibrillation.2014In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 25, no 6, p. 872-876Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:: Snus is a smokeless tobacco product, widely used among Swedish men and increasingly so elsewhere. There is debate as to whether snus is an acceptable "harm-reduction" tobacco product. Since snus use delivers a dose of nicotine equivalent to cigarettes, and has been implicated in cardiac arrhythmia because of associations with sudden cardiovascular death, a relation with atrial fibrillation is plausible and important to investigate.

    METHODS:: To assess the relation between use of snus and risk of atrial fibrillation, we carried out a pooled analysis of 7 prospective Swedish cohort studies. In total, 274,882 men, recruited between 1978 and 2004, were followed via the National Patient Register for atrial fibrillation. Primary analyses were restricted to 127,907 never-smokers. Relative risks were estimated using Cox proportional hazard regression.

    RESULTS:: The prevalence of snus use was 25% among never-smokers. During follow-up, 3,069 cases of atrial fibrillation were identified. The pooled relative risk of atrial fibrillation was 1.07 (95% confidence interval = 0.97-1.19) in current snus users, compared with nonusers.

    CONCLUSION:: Findings from this large national pooling project indicate that snus use is unlikely to confer any important increase in risk of atrial fibrillation.

  • 33.
    Hernestål-Boman, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    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.
    Nilsson, Torbjörn K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Individual PAI-1 increase over nine years relates differently in men and women to changes in anthropometric, glycaemic, inflammatory and lipid markers.Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Levels of plasminogen activator inhibitor-1 (PAI-1) is known to correlate to factors related to the metabolic syndrome. We have previously shown that PAI-1 antigen increased by 75% in men and 95% in women over nine years.

    Objective: The aim of this study was to explore relationships between intra-individual changes in PAI-1 and changes in anthropometric measurements, blood pressure, glycaemic, lipid and inflammatory markers, separately for men and women.

    Method: In northern Sweden, 125 men and 116 women were examined first in 1990 and re-examined in 1999 during the morning hours. Changes over time (Δ) were calculated as the value at 1999 minus the value at 1990.

    Results: In men, ΔPAI-1 was significantly correlated to ΔBMI (r =0.33), ΔCRP (r =0.25), Δtriglycerides (r =0.39), Δfasting plasma glucose (r =0.41) and Δ2-hour plasma glucose (r =0.29). In women, ΔPAI-1 was significantly correlated to ΔBMI (r =0.36), Δwaist circumference (r =0.38), Δhip circumference (r =0.27), ΔCRP (r =0.27) and Δtotal cholesterol (r =0.19). The multivariate linear regression analysis showed that ΔPAI-1 was significantly related to Δfasting plasma glucose and ΔCRP in men (R2 for the complete model was 0.31). In women, ΔPAI-1 was significantly related to Δwaist circumference (R2 for the complete model was 0.17).

    Conclusion: We expected that changes in anthropometric, glycaemic, inflammatory and lipid markers would explain a large part of the observed PAI-1 increase. However, the multivariate analysis explained only 20% of the variation in ΔPAI-1 in women and 30% in men. Interestingly, the patterns of components correlating with the changes in PAI-1 differed between sexes.

  • 34.
    Hernestål-Boman, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Individual changes in fibrinolytic factors, von Willebrand factor, and C-reactive protein over a nine-year period.Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Intra-individual changes in haemostatic factor concentrations over time are unknown, in the general population.

    Objective: To describe intra-individual longitudinal changes in tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), tPA/PAI-1 complex, von Willebrand factor (VWF), and C-reactive protein (CRP) over nine years, in different age groups, stratified for sex.

    Methods: The MONICA survey in 1990 examined randomly selected men and women in four age groups (25–64 years) who were re-examined in 1999. A total of 309 individuals donated venous blood samples in Stabilyte tubes for both surveys during the morning hours, after an overnight fast. We analysed tPA activity and antigens of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP.

    Results: Over nine years, in both men and women, we found significant intra-individual increases in the antigen levels of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP (P < 0.001). PAI-1 antigen levels increased by 75% for men and 95% for women. Compared to men, women had a significantly higher CRP increase (0.92 vs. 0.22 mg/L; P = 0.044). The P for trend for mean Δ1999–1990 across age groups showed a significant linear trend for VWF (P = 0.001 for men; P < 0.001 for women), but not for the other studied variables.

    Conclusions: There were intra-individual longitudinal increases in the antigen levels of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP over nine years in both men and women, with PAI-1 showing the highest relative increase. VWF increased significantly across age groups; however, fibrinolytic variables did not.

  • 35.
    Hernestål-Boman, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Long-term stability of fibrinolytic factors stored at -80 degrees C.2010In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 125, no 5, p. 451-456Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Blood samples in epidemiological studies are often stored for several years and analysed at different occasions. The reagent kits are continually modified for better precision and accuracy. Our hypothesis was that epidemiological studies are affected by long-term storage and/or modifications of reagent kits.

    MATERIALS AND METHODS: Plasma samples stored at -80( degrees )C from two populations were used: A case-referent study with samples collected from 1985 to 2000 and analysed 2005 (n=1598) were used to study influence of long-term storage. A cross-sectional study analysed 1990 (n=1558) and re-analysed 2001 (n=78) and 2005 (n=828) was used to study influence of reagent kit modifications. Fibrinolytic analyses included immunoassays of tPA, PAI-1 and tPA-PAI-1 complex and chromogenic substrate assays of the activities of tPA and PAI-1.

    RESULTS: Long-term storage for a median time of 11.6years (range 5 to 20) showed an effect of time on tPA antigen R(2)=0.01, PAI-1 antigen R(2)=0.01 and tPA-PAI-1 complex R(2) = 0.02. Modifications in reagent kits affected the levels of fibrinolytic factors; for tPA antigen the slope coefficients were between 0.72 and 0.95 (R(2) 0.47 - 0.75), whereas tPA activity showed an agreement with slope coefficients 1.06 to 1.09 (R(2) 0.67 - 0.93).

    CONCLUSIONS: This study showed that long-term storage affects fibrinolytic variables to a negligible extent, but modifications in reagent kits introduced an element of bias. We conclude that analysis of samples on a single occasion is preferable to multiple occasions, as storage has negligible effect.

  • 36.
    Hernestål-Boman, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jansson, Jan-Håkan
    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. Department of Medicine, Sunderby Hospital, Luleå, Sweden.
    Eriksson, Jan W
    Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Gothenburg and AstraZeneca R&D, Mölndal, Sweden.
    Lindahl, Bernt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study2012In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 11, p. 152-Article in journal (Refereed)
    Abstract [en]

    Background: Diabetic patients experience stimulated coagulation and dysfibrinolysis, which is associated with an increased risk of cardiovascular events. This imbalance may precede the manifest diagnosis. We investigated whether elevated antigen levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), the tPA/PAI-1 complex, or von Willebrand Factor (VWF) precede type 2 diabetes mellitus (T2DM) diagnosis, and whether this elevation occurs before increased fasting plasma glucose (FPG) or 2-hour plasma glucose (2hPG) in individuals who later develop T2DM.

    Methods: We conducted a prospective incident case-referent study within the Vasterbotten Intervention Programme. Cardiovascular risk factor data as well as FPG and 2hPG and blood samples for future research were collected at a baseline health examination between 1989 and 2000, (n= 28 736). During follow-up in January 2001, 157 cases had developed T2DM. Referents without T2DM were matched for sex, age, and year of participation (n=277). Subgroup analysis was performed for cases with normal baseline glucose levels (FPG <6.1 mmol/L and 2hPG < 8.9 mmol/L) and cases with elevated levels (FPG 6.1-6.9 mmol/L and/or 2hPG 8.9-12.1 mmol/L).

    Results: After adjusting for BMI, family history of diabetes, physical activity, smoking, systolic blood pressure and levels of C-reactive protein and triglycerides, independent associations were found between incident T2DM and elevated levels of tPA (OR=1.54, 95% CI 1.06-2.23), PAI-1 (OR=1.61, 95% CI 1.14-2.28), and tPA/PAI-1 complex (OR=2.45, 95% CI 1.56-3.84). In participants with normal glucose levels, PAI-1 (OR=2.06, 95% CI 1.10 - 3.86) exhibited an independent relationship with incident T2DM after the adjustments.

    Conclusions: Elevated levels of fibrinolytic variables precede the manifestation of T2DM after adjusting for metabolic and cardiovascular risk factors and can be detected several years before changes in glucose tolerance.

  • 37.
    Hultdin, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Thøgersen, Ann Margreth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, T K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Weinehall, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Elevated plasma homocysteine: cause or consequence of myocardial infarction?2004In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 256, no 6, p. 491-498Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To determine whether a first myocardial infarction leads to increased plasma homocysteine concentrations and whether the association between homocysteine and myocardial infarction was greater at follow-up compared with baseline. DESIGN: A population-based, prospective, nested case-referent study. SETTING: Screening took place at the nearest health survey centre in northern Sweden. SUBJECTS: Of more than 36,000 persons screened, 78 developed a first myocardial infarction (average 18 months after sampling). Fifty of these had participated in a follow-up health survey (average 8(1/2) years between surveys) and were sex- and age-matched with 56 referents. MAIN OUTCOME MEASURES: Comparison of plasma homocysteine levels in case and referent subjects before and after development of a first myocardial infarction. RESULTS: No statistically significant difference was found between cases and referents regarding homocysteine at baseline or follow-up. Plasma homocysteine and plasma creatinine increased significantly, and plasma albumin decreased significantly over time. Conditional univariate logistic regression indicated that high homocysteine at follow-up but not baseline was associated with first myocardial infarction (OR 2.49; 95% CI: 1.03-6.02), but the relation disappeared in multivariate analyses including plasma creatinine and plasma albumin. High plasma creatinine remained associated with first myocardial infarction at both baseline (OR 2.94; 95% CI: 1.05-8.21) and follow-up (OR 3.38; 95% CI: 1.21-9.48). CONCLUSION: In this study, first myocardial infarction did not cause increased plasma homocysteine concentration.

  • 38.
    Höglund, Henrik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Forslund, Ann-Sofie
    Lundblad, Dan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Prodromal symptoms and health care consumption prior to out-of-hospital cardiac arrest in patients without previously known ischaemic heart disease2014In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 85, no 7, p. 864-868Article in journal (Refereed)
    Abstract [en]

    Aims: To describe prodromal symptoms and health care consumption prior to an out-of-hospital cardiac arrest (OHCA) in patients without previously known ischaemic heart disease (IHD). Background: The most common lethal event of cardiovascular disease is sudden cardiac death, and the majority occur outside hospital. Little is known about prodromal symptoms and health care consumption associated with OHCAs. Design: Case-crossover study. Methods: Medical records of 403 OHCA cases without previously known IHD, age 25-74 years in the MONICA myocardial registry in Norrbotten County 2000-2008, were reviewed. Presenting symptoms and emergency visits at public primary care facilities and internal medicine clinics in Norrbotten County were analyzed from the week prior to the OHCA and from the same week one year previously, which served as a control week. Unlike most studies we included unwitnessed arrests and those where no cardiopulmonary resuscitation (CPR) was attempted. Results: Emergency visits were more common during the week prior to the OHCA than during the control week, both for visits to primary care (29 vs. 6, p < 0.001) and to internal medicine clinics (16 vs. 0, p < 0.001). Symptoms were more prevalent during the week prior to the OHCA (36.7 vs. 6.7%, p < 0.001). The most prevalent symptoms were chest pain (14.6 vs. 0%, p < 0.001), gastrointestinal symptoms (7.7 vs. 1.2%, p < 0.001) and dyspnoea/peripheral oedema (6.9 vs. 0.2%, p < 0.001). Conclusions: Patients who suffer an OHCA seek health care and present prodromal symptoms significantly more often the week prior to the event than the same week one year earlier.

  • 39.
    Isaksson, Rose-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundblad, Dan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Zingmark, Karin
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Better long-term survival in young and middle-aged women than in men after a first myocardial infarction between 1985 and 2006. An analysis of 8630 patients in the Northern Sweden MONICA Study.2011In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 11, p. 1-Article in journal (Refereed)
    Abstract [en]

    Age-adjusted survival was higher among women than men after a first MI and has improved markedly and equally in both men and women over a 23-year period. This difference was due to lower risk for women to die before reaching hospital.

  • 40.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Central venkateter och malign sjukdom: värdet av trombosprofylax ifrågasätts nu2005In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102, no 26-27, p. 1984-1985Article in journal (Other academic)
    Abstract [sv]

    Kateterrelaterad trombos är vanligt hos patienter med malign sjukdom och central venkateter, och konsekvenserna för patienten kan bli betydande. Nyare studier ifrågasätter nyttan med lågdos warfarin och lågmolekylärt heparin som profylax mot kateterrelaterade tromboser hos dessa patienter.

  • 41.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Molecular Periodontology.
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Åhren, Ann-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    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.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Prevalence of systemic immunoreactivity to Aggregatibacter actinomycetemcomitans leukotoxin in relation to the incidence of myocardial infarction2011In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 11, no 1, p. 55-Article in journal (Refereed)
    Abstract [en]

    Background: Chronic infections and associated inflammatory markers are suggested risk factors for cardiovascular disease (CVD). The proinflammatory cytokine, interleukin (IL)-1, is suggested to play a role in the regulation of local inflammatory responses in both CVD and periodontitis. The leukotoxin from the periodontal pathogen Aggregatibacter actinomycetemcomitans has recently been shown to cause abundant secretion of IL-1 from macrophages. The aim of the present study was to compare the prevalence of systemic immunoreactivity to A. actinomycetemcomitans leukotoxin in myocardial infarction (MI) cases (n=532) and matched controls (n=1000) in a population-based case and referents study in northern Sweden.

    Methods: Capacity to neutralize A. actinomycetemcomitans leukotoxin was analyzed in a bioassay with leukocytes, purified leukotoxin, and plasma. Plasma samples that inhibited lactate-dehydrogenase release from leukotoxin-lysed cells by 50 % were classified as positive.

    Results: Neutralizing capacity against A. actinomycetemcomitans leukotoxin was detected in 53.3% of the plasma samples. The ability to neutralize leukotoxin correlated to increasing age in men (n=1082) but not in women (n=450). There was no correlation between presence of systemic leukotoxin neutralization capacity and the incidence of MI, except for women (n=146). Women with a low neutralizing capacity had a significantly higher incidence of MI than those who had a high neutralizing capacity.

    Conclusions: Systemic immunoreactivity against A. actinomycetemcomitans leukotoxin was found at a high prevalence in the analyzed population of adults from northern Sweden. The results from the present study do not support the hypothesis that systemic leukotoxin-neutralizing capacity can decrease the risk for MI.

  • 42.
    Johansson, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Dahlqvist, Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Andersson, Jonas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Incidence, type of atrial fibrillation and risk factors for stroke: a population-based cohort study2017In: Clinical Epidemiology, ISSN 1179-1349, E-ISSN 1179-1349, Vol. 9, p. 53-62Article in journal (Refereed)
    Abstract [en]

    Purpose: The aims of this study were to estimate the incidence of atrial fibrillation and atrial flutter (AF), to assess the presence of provoking factors and risk factors for stroke and systemic embolism, and to determine the type of AF in patients with first-diagnosed AF. Patients and methods: This cohort study was performed in northern Sweden between January 1, 2011 and December 31, 2012. Diagnosis registries were searched for the International Classification of Diseases-10 code for AF (I48) to identify cases of incident AF. All AF diagnoses were electrocardiogram-verified. Data pertaining to provoking factors, type of AF and presence of risk factors for stroke and systemic embolism according to the CHA(2)DS(2)-VASc score were obtained from medical records. Results: The incidence of AF in the entire population was 4.0 per 1,000 person-years. The incidence was 27.5 per 1,000 person-years in patients aged >= 80 years. A total of 21% of all patients had a provoking factor in association with the first-diagnosed episode of AF. The CHA(2)DS(2)-VASc score was 2 or higher in 81% of the patients. Permanent AF was the most common type of AF (29%). Conclusion: There was a considerable increase in the incidence of AF with age, and a provoking factor was found in one-fifth. The most common type of AF was permanent AF. Four in five patients had a CHA(2)DS(2)-VASc score of 2 or more.

  • 43.
    Johansson, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hägg, Lovisa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Characterization of patients with atrial fibrillation not treated with oral anticoagulants2014In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 32, no 4, p. 226-231Article in journal (Refereed)
    Abstract [en]

    Objective: An underuse of oral anticoagulants (OAC) in patients with atrial fibrillation (AF) has been suggested, as only 50% of all patients with AF receive OAC treatment. Whether this is due to contraindications, lack of an indication to treat, or an expression of underuse is sparsely investigated. This study therefore aimed to characterize individuals without OAC treatment in a real-life population of patients with AF. Design: Retrospective cross-sectional study. The medical records were scrutinized in order to identify the type of AF, risk factors for embolism and bleeding, and other factors of importance for OAC treatment. Setting: The municipalities of Skellefteå and Norsjö, northern Sweden. Subjects: A total of 2274 living residents with at least one verified episode of AF on or before December 31, 2010. Main outcome measures: Prevalence of treatment with OAC and documented reasons to withhold OAC treatment. Results: Among all 2274 patients with AF, 1187 (52%) were not treated with OAC. Of the untreated patients, 19% had no indication or had declined or had experienced adverse effects other than bleeding on warfarin treatment. The most common reason to withhold OAC was presence of risk factors for bleeding, found in 38% of all untreated patients. Furthermore, a documented reason could be identified to withhold OAC in 75%. Conclusions: Among patients with AF without OAC treatment a reason could be identifi ed to withhold OAC in 75%. The underuse of OAC is estimated to be 25%.

  • 44.
    Johansson, Ingegerd
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Public Health and Clinical Medicine, Research Unit Skellefteå, Umeå University, 90187 Umeå, Sweden. .
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Winkvist, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden. .
    Dairy Product Intake and Cardiometabolic Diseases in Northern Sweden: A 33-Year Prospective Cohort Study2019In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 11, no 284Article in journal (Refereed)
    Abstract [en]

    Dairy products are important constituents of most diets, and their association with adverse health outcomes remains a focus. We characterized dairy food intake and examined associations with the incidence of type 2 diabetes (T2D), myocardial infarction (MI) or stroke among 108,065 Swedish men and women. Hazard ratios (HRs) and 95% CIs were estimated using the multivariable Cox proportional hazards models in a population characterized by high milk tolerance. During a mean follow-up of 14.2 years, 11,641 first-time events occurred. Non-fermented milk intake decreased, whereas butter intake increased over the period. For high intake of non-fermented milk, the HR (95% CI) for developing T2D and MI was 1.17 (1.03, 1.34) and 1.23 (1.10, 1.37), respectively, in men. A greater intake of butter, fermented milk, and cheese tended to be associated with a reduced risk of T2D and/or MI. Non-consumers and those who chose low-fat variants of the targeted dairy products had increased risk for T2D, MI, or stroke compared to those in the non-case group. Generally, effect-sizes were small. This prospective study found that non-fermented milk was associated with an increased risk for developing T2D and MI and that subjects abstaining from dairy products or choosing low-fat variants were at greater risk. However, the overall cardiometabolic risk of non-fermented milk intake was judged as low, since the effect sizes were small.

  • 45.
    Johansson, Ingegerd
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Winkvist, Anna
    Dairy intake revisited - associations between dairy intake and lifestyle related cardio-metabolic risk factors in a high milk consuming population2018In: Nutrition Journal, ISSN 1475-2891, E-ISSN 1475-2891, Vol. 17, article id 110Article in journal (Refereed)
    Abstract [en]

    Background: The association between milk and dairy intake and the incidence of cardiometabolic diseases, cancer and mortality has been evaluated in many studies, but these studies have had conflicting results with no clear conclusion on causal or confounding associations. The present study aims to further address this association by cross-sectional and longitudinal evaluation of the associations between exposure to various types of dairy products and metabolic risk markers among inhabitants in northern Sweden while taking other lifestyle factors into account.

    Methods: Respondents in the Vasterbotten Intervention Programme with complete and plausible diet data between 1991 and 2016 were included, yielding 124,934 observations from 90,512 unique subjects. For longitudinal analysis, 27,682 participants with a visit 8-12years after the first visit were identified. All participants completed a validated Food Frequency Questionnaire. Metabolic risk markers, including body mass index (BMI), blood pressure, serum (S) cholesterol and triglycerides, and blood glucose, were measured. Participants were categorized into quintiles by intake of dairy products, and risk (odds ratios, OR) of undesirable levels of metabolic risk markers was assessed in multivariable logistic regression analyses. In longitudinal analyses, intake quintiles were related to desirable levels of metabolic risk markers at both visits or deterioration at follow-up using Cox regression analyses.

    Results: The OR of being classified with an undesirable BMI decreased with increasing quintiles of total dairy, cheese and butter intake but increased with increasing non-fermented milk intake. The OR of being classified with an undesirable S-cholesterol level increased with increasing intake of total dairy, butter and high fat (3%) non-fermented milk, whereas an undesirable S-triglyceride level was inversely associated with cheese and butter intake in women. In longitudinal analyses, increasing butter intake was associated with deterioration of S-cholesterol and blood glucose levels, whereas increasing cheese intake was associated with a lower risk of deterioration of S-triglycerides.

    Conclusions: Confounding factors likely contribute to the demonstrated association between dairy intake and mortality, and other medical conditions and analyses should be stratified by dairy type.

  • 46.
    Johansson, K.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Johansson, L.
    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.
    Nilsson, T. K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    D-dimer is associated with first-ever intracerebral hemorrhage. A prospective ease-control study2018In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 45, p. 213-213Article in journal (Other academic)
  • 47.
    Johansson, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Bylesjö, Ingemar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Nilsson, Torbjörn K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Eliasson, Mats
    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.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Factor XII as a Risk Marker for Hemorrhagic Stroke: A Prospective Cohort Study2017In: Cerebrovascular diseases extra, ISSN 1664-5456, Vol. 7, no 1, p. 84-94Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Coagulation factor XII (FXII) is involved in pathological thrombus formation and is a suggested target of anticoagulants. It is unclear whether FXII levels are correlated with cardiovascular risk factors and whether they are associated with myocardial infarction or ischemic or hemorrhagic stroke. The aim of this study was to investigate the correlation between FXII and cardiovascular risk factors in the general population. We also aimed to study the associations between FXII levels and future myocardial infarction and ischemic and hemorrhagic stroke.

    METHODS: This prospective cohort study measured FXII levels in 1,852 randomly selected participants in a health survey performed in northern Sweden in 1994. Participants were followed until myocardial infarction, stroke, death, or until December 31, 2011.

    RESULTS: During the median follow-up of 17.9 years, 165 individuals were diagnosed with myocardial infarction, 108 with ischemic stroke, and 30 with hemorrhagic stroke. There were weak correlations between FXII and body mass index, cholesterol, and hypertension. There was no association between FXII and myocardial infarction or ischemic stroke, neither in univariable Cox regression analysis nor after adjustment for age, sex, smoking, body mass index, cholesterol, hypertension, and diabetes. In univariable Cox regression analysis, the hazard ratio for the association between FXII levels and hemorrhagic stroke was 1.42 per SD (95% confidence interval: 0.99-2.05). In the multivariable model, higher levels of FXII were associated with increased risk of hemorrhagic stroke (hazard ratio 1.51 per SD; 95% confidence interval: 1.03-2.21).

    CONCLUSION: We found an independent association between FXII levels and the risk of hemorrhagic stroke, but not between FXII levels and ischemic stroke or myocardial infarction.

  • 48.
    Johansson, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Wiklund, Per-Gunnar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Nilsson, Torbjörn K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    D-Dimer is associated with first-ever intracerebral hemorrhage: a nested case-control study2018In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 49, no 9, p. 2034-2039Article in journal (Refereed)
    Abstract [en]

    Background and Purpose - Hypertension is the most important risk factor for intracerebral hemorrhage (ICH), but further characterization is needed for groups at high risk of ICH. One way to predict the risk of developing a disease is with plasma biomarkers. This study aimed to investigate the association between the biomarker, D-dimer, and ICH risk.

    Methods - This population-based, nested case-control study was conducted using data from 2 population-based surveys; the Vasterbotten Intervention Programme and MONICA Northern Sweden (Monitoring Trends and Determinants in Cardiovascular Disease). All participants underwent a health examination and blood sampling at baseline before the event. Cases (n=141) were diagnosed with a first-ever ICH between 1985 and March 2007. One or 2 controls (n=255) were matched to each case.

    Results - The median age was 60 years; 39% of participants were women; and the median time from blood sampling to ICH was 5.2 years. When D-dimer was evaluated as a continuous variable, it was significantly associated with ICH. After multivariable adjustment (for hypertension, body mass index, cholesterol levels, diabetes mellitus, and smoking), the odds ratio was 1.36 per SD of D-dimcr (95% CI, 1.05-1.77). When participants were stratified in 3 groups according to time from blood sampling at health examination to ICH, we found that the association between D-dimer levels and ICH was most pronounced in individuals with the shortest time from blood sampling to ICH event (<3.5 years; odds ratio, 1.78; 95% CI, 1.05-3.05).

    Conclusions - High plasma concentrations of D-dimer were associated with increased risk of a future ICH, after adjusting for cardiovascular risk factors. This association was predominantly driven by the cases with the shortest time from blood sampling to ICH event.

  • 49.
    Johansson, Lars
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Torbjörn K
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hemostatic factors as risk markers for intracerebral hemorrhage: a prospective incident case-referent study.2004In: Stroke, ISSN 1524-4628, Vol. 35, no 4, p. 826-30Article in journal (Refereed)
  • 50.
    Johansson, Magdalena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lind, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Fhärm, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Johansson, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Fasting plasma glucose, oral glucose tolerance test, and the risk of first-time venous thromboembolism. A report from the VEINS cohort study2018In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 165, p. 86-94Article in journal (Refereed)
    Abstract [en]

    Introduction: It remains unclear whether high plasma glucose levels are associated with venous thromboembolism (VTE). This study investigated the association between fasting plasma glucose (FPG), oral glucose tolerance test (two-hour post-load plasma glucose (2HPG)), diabetes, and VTE. Materials and methods: The population-based, prospective Venous thromboEmbolism In Northern Sweden (VEINS) cohort study included 108,025 residents of Vasterbotten County in northern Sweden. The participants were aged 30 to 60 years and had no previous VTE events. They were included from 1985 onwards and were followed until a VTE event, death, emigration, or the study end on September 5, 2014. All underwent a health examination that measured weight, height, FPG, and 2HPG and included a questionnaire regarding smoking, education level, and history of diabetes. Potential VTE events were identified by an extensive diagnosis registry search and were validated by reviewing medical records and radiology reports. Results: An objectively verified first-time VTE event was experienced by 2054 participants during 1,496,669 person-years of follow-up. In univariable analysis, there were associations between FPG, 2HPG, diabetes, and the risk of VTE. These associations disappeared after adjustment for potential confounders (age, sex, body mass index, cancer at inclusion, education level, smoking, and hypertension). The adjusted hazard ratios were 1.01 (95% confidence interval 0.83-1.23) for diabetes, 1.01 for each standard deviation of FPG (95% confidence interval 0.97-1.05), and 0.96 for each standard deviation of 2HPG (95% confidence interval 0.91-1.00). Conclusions: There were no independent associations between FPG, 2HPG, diabetes, and future risk of VTE.

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