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  • 201.
    Rönnemaa, Elina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundelöf, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Degerman-Gunnarsson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Glucose metabolism and the risk of Alzheimer's disease and dementia: a population-based 12 year follow-up study in 71-year-old men2009Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, nr 8, s. 1504-1510Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS/HYPOTHESIS: Accumulating evidence suggests that diabetes increases the risk of dementia, but few studies have addressed possible mechanisms underlying this relationship. The aim of our study was to investigate the longitudinal association of glucose metabolism, insulin secretion and insulin action with the development of Alzheimer's disease and vascular dementia. METHODS: The Uppsala Longitudinal Study of Adult Men is an ongoing observational study in Sweden in which 1,125 men aged 71 years and free from dementia underwent an OGTT and a euglycaemic insulin clamp between 1990 and 1995. During a median follow-up of 12 years, 257 persons developed dementia or cognitive impairment, of whom 81 had Alzheimer's disease and 26 vascular dementia. Associations were analysed with the Cox proportional hazards method. RESULTS: Low early insulin response to oral glucose challenge, but not low insulin sensitivity, was associated with a higher risk of Alzheimer's disease (HR for 1 SD decrease 1.32; 95% CI 1.02, 1.69) after adjustment for diabetes, blood pressure, body mass index, cholesterol, smoking and educational level. Low insulin sensitivity was associated with a higher risk of vascular dementia (HR for 1 SD decrease 1.55; 95% CI 1.02, 2.35), but not after multiple adjustments. Diabetes increased the risk of any dementia and cognitive impairment by 63%. CONCLUSIONS/INTERPRETATION: In this community-based study, low early insulin response was associated with increased risk of subsequent Alzheimer's disease, whereas low insulin sensitivity was not. Vascular dementia was not related to early insulin response. We suggest that glucometabolic disturbances are linked differentially to the pathogenesis of these two main dementia subtypes.

  • 202. Sabale, U.
    et al.
    Bodegard, J.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Svennblad, Bodil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Oestgren, C. J.
    Nilsson, P.
    Johansson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Henriksson, M.
    Association Of Changes In Body Weight With Health Care Costs Among Patients With Newly-Diagnosed Type-2 Diabetes In Sweden2014Inngår i: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 17, nr 7, s. A338-A338Artikkel i tidsskrift (Annet vitenskapelig)
  • 203.
    Sabale, U.
    et al.
    AstraZeneca, Sodertalje, Sweden..
    Bodegard, J.
    AstraZeneca, Sodertalje, Sweden..
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Svennblad, Bodil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ostgren, C.
    Linkoping Univ, Linkoping, Sweden..
    Nilsson, P. M.
    Lund Univ, Malmo, Sweden..
    Johansson, G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ekman, M.
    AstraZeneca, Sodertalje, Sweden..
    Weight change over time and its link to healthcare costs among newly-diagnosed type 2 diabetes patients in Sweden2015Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S26-S27Artikkel i tidsskrift (Annet vitenskapelig)
  • 204.
    Sabale, Ugne
    et al.
    AstraZeneca Nord Balt, SE-15185 Sodertalje, Sweden..
    Bodegard, Johan
    AstraZeneca Nord Balt, SE-15185 Sodertalje, Sweden..
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Ostgren, Carl Johan
    Linkoping Univ, Linkoping, Sweden..
    Nilsson, Peter
    Lund Univ, Malmo, Sweden..
    Johansson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Svennblad, Bodil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Henriksson, Martin
    AstraZeneca Nord Balt, SE-15185 Sodertalje, Sweden..
    Healthcare utilization and costs following newly diagnosed type-2 diabetes in Sweden: A follow-up of 38,956 patients in a clinical practice setting2015Inngår i: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 9, nr 5, s. 330-337Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims: To describe healthcare resource use patterns and estimate healthcare costs of newly diagnosed Type 2 diabetes mellitus (T2DM) patients in Sweden. Methods: Patients with a newly diagnosed T2DM between 1999 and 2009 were identified from 84 Swedish primary care centres. Healthcare resource use data, excluding pharmaceuticals, were extracted from electronic patient records and a national patient register, and reported as per patient mean number of primary care contacts, laboratory tests and hospitalizations. Per patient mean healthcare costs are reported as annual and cumulative costs. Results: During a median (maximum) of 4.6 (9.0) years follow-up; 38,956 patients (183,513 patient years) on average made 81 primary care contacts, was hospitalized 2.14 times, and took 31 laboratory tests. Mean per patient annual healthcare costs were (sic)4128 (95% CI, 4054-4199) the first year after diagnosis, (sic)2708 (95% CI, 2641-2776) the second year, and (sic)3030 (95% CI, 2854-3204) in year 9 (2012 values). Mean per patient cumulative healthcare costs were (sic)26,503 (95% CI, 26,025-26,970) at 9 years of follow-up. Hospitalizations accounted for the majority of healthcare costs. Conclusions: Although newly diagnosed T2DM patients require a substantial amount of healthcare services in primary care, hospitalizations account for the majority of healthcare costs.

  • 205.
    Salam, Abdul
    et al.
    Univ New South Wales, George Inst Global Hlth, Hyderabad, India.
    Atkins, Emily
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Hirakawa, Yoichiro
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.
    Ettehad, Dena
    Univ Oxford, George Inst Global Hlth, 1st Floor,Hayes House,George St, Oxford OX1 2BQ, England.
    Emdin, Connor
    Univ Oxford, George Inst Global Hlth, 1st Floor,Hayes House,George St, Oxford OX1 2BQ, England.
    Neal, Bruce
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.
    Woodward, Mark
    Univ Sydney, Sydney, NSW, Australia.
    Chalmers, John
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.
    Berge, Eivind
    Oslo Univ Hosp, Oslo, Norway.
    Yusuf, Salim
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Rahimi, Kazem
    Univ Oxford, George Inst Global Hlth, 1st Floor,Hayes House,George St, Oxford OX1 2BQ, England.
    Rodgers, Anthony
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.
    Effects of blood pressure lowering on cardiovascular events, in the context of regression to the mean: a systematic review of randomized trials2019Inngår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 37, nr 1, s. 16-23Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Objective: To assess the clinical relevance of regression to the mean for clinical trials and clinical practice. Methods: MEDLINE was searched until February 2018 for randomized trials of BP lowering with over 1000 patient-years follow-up per group. We estimated baseline mean BP, follow-up mean (usual) BP amongst patients grouped by 10 mmHg strata of baseline BP, and assessed effects of BP lowering on coronary heart disease (CHD) and stroke according to these BP levels. Results: Eighty-six trials (349 488 participants), with mean follow-up of 3.7 years, were included. Most mean BP change was because of regression to the mean rather than treatment. At high baseline BP levels, even after rigorous hypertension diagnosis, downwards regression to the mean caused much of the fall in BP. At low baseline BP levels, upwards regression to the mean increased BP levels, even in treatment groups. Overall, a BP reduction of 6/3 mmHg lowered CHD by 14% (95% CI 11-17%) and stroke by 18% (15-22%), and these treatment effects occurred at follow-up BP levels much closer to the mean than baseline BP levels. In particular, more evidence was available in the SBP 130-139 mmHg range than any other range. Benefits were apparent in numerous high-risk patient groups with baseline mean SBP less than 140 mmHg. Conclusion: Clinical practice should focus less on pretreatment BP levels, which rarely predict future untreated BP levels or rule out capacity to benefit from BP lowering in high cardiovascular risk patients. Instead, focus should be on prompt, empirical treatment to maintain lower BP for those with high BP and/or high risk.

  • 206. Sarwar, Nadeem
    et al.
    Butterworth, Adam S.
    Freitag, Daniel F.
    Gregson, John
    Willeit, Peter
    Gorman, Donal N.
    Gao, Pei
    Saleheen, Danish
    Rendon, Augusto
    Nelson, Christopher P.
    Braund, Peter S.
    Hall, Alistair S.
    Chasman, Daniel I.
    Tybjaerg-Hansen, Anne
    Chambers, John C.
    Benjamin, Emelia J.
    Franks, Paul W.
    Clarke, Robert
    Wilde, Arthur A. M.
    Trip, Mieke D.
    Steri, Maristella
    Witteman, Jacqueline C. M.
    Qi, Lu
    van der Schoot, C. Ellen
    de Faire, Ulf
    Erdmann, Jeanette
    Stringham, Heather M.
    Koenig, Wolfgang
    Rader, Daniel J.
    Melzer, David
    Reich, David
    Psaty, Bruce M.
    Kleber, Marcus E.
    Panagiotakos, Demosthenes B.
    Willeit, Johann
    Wennberg, Patrik
    Woodward, Mark
    Adamovic, Svetlana
    Rimm, Eric B.
    Meade, Tom W.
    Gillum, Richard F.
    Shaffer, Jonathan A.
    Hofman, Albert
    Onat, Altan
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wassertheil-Smoller, Sylvia
    Mellstrom, Dan
    Gallacher, John
    Cushman, Mary
    Tracy, Russell P.
    Kauhanen, Jussi
    Karlsson, Magnus
    Salonen, Jukka T.
    Wilhelmsen, Lars
    Amouyel, Philippe
    Cantin, Bernard
    Best, Lyle G.
    Ben-Shlomo, Yoav
    Manson, JoAnn E.
    Davey-Smith, George
    de Bakker, Paul I. W.
    O'Donnell, Christopher J.
    Wilson, James F.
    Wilson, Anthony G.
    Assimes, Themistocles L.
    Jansson, John-Olov
    Ohlsson, Claes
    Tivesten, Asa
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Reilly, Muredach P.
    Hamsten, Anders
    Ingelsson, Erik
    Cambien, Francois
    Hung, Joseph
    Thomas, G. Neil
    Boehnke, Michael
    Schunkert, Heribert
    Asselbergs, Folkert W.
    Kastelein, John J. P.
    Gudnason, Vilmundur
    Salomaa, Veikko
    Harris, Tamara B.
    Kooner, Jaspal S.
    Allin, Kristine H.
    Nordestgaard, Borge G.
    Hopewell, Jemma C.
    Goodall, Alison H.
    Ridker, Paul M.
    Holm, Hilma
    Watkins, Hugh
    Ouwehand, Willem H.
    Samani, Nilesh J.
    Kaptoge, Stephen
    Di Angelantonio, Emanuele
    Harari, Olivier
    Danesh, John
    Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies2012Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 379, nr 9822, s. 1205-1213Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling.

    Methods: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6.

    Findings: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes.

    Interpretation: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.

  • 207. Shungin, Dmitry
    et al.
    Winkler, Thomas W
    Croteau-Chonka, Damien C
    Ferreira, Teresa
    Locke, Adam E
    Mägi, Reedik
    Strawbridge, Rona J
    Pers, Tune H
    Fischer, Krista
    Justice, Anne E
    Workalemahu, Tsegaselassie
    Wu, Joseph M W
    Buchkovich, Martin L
    Heard-Costa, Nancy L
    Roman, Tamara S
    Drong, Alexander W
    Song, Ci
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Day, Felix R
    Esko, Tonu
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Kutalik, Zoltán
    Luan, Jian'an
    Randall, Joshua C
    Scherag, André
    Vedantam, Sailaja
    Wood, Andrew R
    Chen, Jin
    Fehrmann, Rudolf
    Karjalainen, Juha
    Kahali, Bratati
    Liu, Ching-Ti
    Schmidt, Ellen M
    Absher, Devin
    Amin, Najaf
    Anderson, Denise
    Beekman, Marian
    Bragg-Gresham, Jennifer L
    Buyske, Steven
    Demirkan, Ayse
    Ehret, Georg B
    Feitosa, Mary F
    Goel, Anuj
    Jackson, Anne U
    Johnson, Toby
    Kleber, Marcus E
    Kristiansson, Kati
    Mangino, Massimo
    Mateo Leach, Irene
    Medina-Gomez, Carolina
    Palmer, Cameron D
    Pasko, Dorota
    Pechlivanis, Sonali
    Peters, Marjolein J
    Prokopenko, Inga
    Stančáková, Alena
    Ju Sung, Yun
    Tanaka, Toshiko
    Teumer, Alexander
    Van Vliet-Ostaptchouk, Jana V
    Yengo, Loïc
    Zhang, Weihua
    Albrecht, Eva
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Arscott, Gillian M
    Bandinelli, Stefania
    Barrett, Amy
    Bellis, Claire
    Bennett, Amanda J
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Blüher, Matthias
    Böhringer, Stefan
    Bonnet, Fabrice
    Böttcher, Yvonne
    Bruinenberg, Marcel
    Carba, Delia B
    Caspersen, Ida H
    Clarke, Robert
    Daw, E Warwick
    Deelen, Joris
    Deelman, Ewa
    Delgado, Graciela
    Doney, Alex S F
    Eklund, Niina
    Erdos, Michael R
    Estrada, Karol
    Eury, Elodie
    Friedrich, Nele
    Garcia, Melissa E
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gigante, Bruna
    Go, Alan S
    Golay, Alain
    Grallert, Harald
    Grammer, Tanja B
    Gräßler, Jürgen
    Grewal, Jagvir
    Groves, Christopher J
    Haller, Toomas
    Hallmans, Goran
    Hartman, Catharina A
    Hassinen, Maija
    Hayward, Caroline
    Heikkilä, Kauko
    Herzig, Karl-Heinz
    Helmer, Quinta
    Hillege, Hans L
    Holmen, Oddgeir
    Hunt, Steven C
    Isaacs, Aaron
    Ittermann, Till
    James, Alan L
    Johansson, Ingegerd
    Juliusdottir, Thorhildur
    Kalafati, Ioanna-Panagiota
    Kinnunen, Leena
    Koenig, Wolfgang
    Kooner, Ishminder K
    Kratzer, Wolfgang
    Lamina, Claudia
    Leander, Karin
    Lee, Nanette R
    Lichtner, Peter
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindström, Jaana
    Lobbens, Stéphane
    Lorentzon, Mattias
    Mach, François
    Magnusson, Patrik K E
    Mahajan, Anubha
    McArdle, Wendy L
    Menni, Cristina
    Merger, Sigrun
    Mihailov, Evelin
    Milani, Lili
    Mills, Rebecca
    Moayyeri, Alireza
    Monda, Keri L
    Mooijaart, Simon P
    Mühleisen, Thomas W
    Mulas, Antonella
    Müller, Gabriele
    Müller-Nurasyid, Martina
    Nagaraja, Ramaiah
    Nalls, Michael A
    Narisu, Narisu
    Glorioso, Nicola
    Nolte, Ilja M
    Olden, Matthias
    Rayner, Nigel W
    Renstrom, Frida
    Ried, Janina S
    Robertson, Neil R
    Rose, Lynda M
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Sennblad, Bengt
    Seufferlein, Thomas
    Sitlani, Colleen M
    Vernon Smith, Albert
    Stirrups, Kathleen
    Stringham, Heather M
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Swertz, Morris A
    Swift, Amy J
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Tayo, Bamidele O
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tomaschitz, Andreas
    Troffa, Chiara
    van Oort, Floor V A
    Verweij, Niek
    Vonk, Judith M
    Waite, Lindsay L
    Wennauer, Roman
    Wilsgaard, Tom
    Wojczynski, Mary K
    Wong, Andrew
    Zhang, Qunyuan
    Hua Zhao, Jing
    Brennan, Eoin P
    Choi, Murim
    Eriksson, Per
    Folkersen, Lasse
    Franco-Cereceda, Anders
    Gharavi, Ali G
    Hedman, Åsa K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hivert, Marie-France
    Huang, Jinyan
    Kanoni, Stavroula
    Karpe, Fredrik
    Keildson, Sarah
    Kiryluk, Krzysztof
    Liang, Liming
    Lifton, Richard P
    Ma, Baoshan
    McKnight, Amy J
    McPherson, Ruth
    Metspalu, Andres
    Min, Josine L
    Moffatt, Miriam F
    Montgomery, Grant W
    Murabito, Joanne M
    Nicholson, George
    Nyholt, Dale R
    Olsson, Christian
    Perry, John R B
    Reinmaa, Eva
    Salem, Rany M
    Sandholm, Niina
    Schadt, Eric E
    Scott, Robert A
    Stolk, Lisette
    Vallejo, Edgar E
    Westra, Harm-Jan
    Zondervan, Krina T
    Amouyel, Philippe
    Arveiler, Dominique
    Bakker, Stephan J L
    Beilby, John
    Bergman, Richard N
    Blangero, John
    Brown, Morris J
    Burnier, Michel
    Campbell, Harry
    Chakravarti, Aravinda
    Chines, Peter S
    Claudi-Boehm, Simone
    Collins, Francis S
    Crawford, Dana C
    Danesh, John
    de Faire, Ulf
    de Geus, Eco J C
    Dörr, Marcus
    Erbel, Raimund
    Eriksson, Johan G
    Farrall, Martin
    Ferrannini, Ele
    Ferrières, Jean
    Forouhi, Nita G
    Forrester, Terrence
    Franco, Oscar H
    Gansevoort, Ron T
    Gieger, Christian
    Gudnason, Vilmundur
    Haiman, Christopher A
    Harris, Tamara B
    Hattersley, Andrew T
    Heliövaara, Markku
    Hicks, Andrew A
    Hingorani, Aroon D
    Hoffmann, Wolfgang
    Hofman, Albert
    Homuth, Georg
    Humphries, Steve E
    Hyppönen, Elina
    Illig, Thomas
    Jarvelin, Marjo-Riitta
    Johansen, Berit
    Jousilahti, Pekka
    Jula, Antti M
    Kaprio, Jaakko
    Kee, Frank
    Keinanen-Kiukaanniemi, Sirkka M
    Kooner, Jaspal S
    Kooperberg, Charles
    Kovacs, Peter
    Kraja, Aldi T
    Kumari, Meena
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Lakka, Timo A
    Langenberg, Claudia
    Le Marchand, Loic
    Lehtimäki, Terho
    Lyssenko, Valeriya
    Männistö, Satu
    Marette, André
    Matise, Tara C
    McKenzie, Colin A
    McKnight, Barbara
    Musk, Arthur W
    Möhlenkamp, Stefan
    Morris, Andrew D
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J
    Ong, Ken K
    Palmer, Lyle J
    Penninx, Brenda W
    Peters, Annette
    Pramstaller, Peter P
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Ridker, Paul M
    Ritchie, Marylyn D
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J
    Saramies, Jouko
    Sarzynski, Mark A
    Schwarz, Peter E H
    Shuldiner, Alan R
    Staessen, Jan A
    Steinthorsdottir, Valgerdur
    Stolk, Ronald P
    Strauch, Konstantin
    Tönjes, Anke
    Tremblay, Angelo
    Tremoli, Elena
    Vohl, Marie-Claude
    Völker, Uwe
    Vollenweider, Peter
    Wilson, James F
    Witteman, Jacqueline C
    Adair, Linda S
    Bochud, Murielle
    Boehm, Bernhard O
    Bornstein, Stefan R
    Bouchard, Claude
    Cauchi, Stéphane
    Caulfield, Mark J
    Chambers, John C
    Chasman, Daniel I
    Cooper, Richard S
    Dedoussis, George
    Ferrucci, Luigi
    Froguel, Philippe
    Grabe, Hans-Jörgen
    Hamsten, Anders
    Hui, Jennie
    Hveem, Kristian
    Jöckel, Karl-Heinz
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    März, Winfried
    Munroe, Patricia B
    Njølstad, Inger
    Oostra, Ben A
    Palmer, Colin N A
    Pedersen, Nancy L
    Perola, Markus
    Pérusse, Louis
    Peters, Ulrike
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Rivadeneira, Fernando
    Saaristo, Timo E
    Saleheen, Danish
    Sinisalo, Juha
    Slagboom, P Eline
    Snieder, Harold
    Spector, Tim D
    Thorsteinsdottir, Unnur
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uitterlinden, André G
    Uusitupa, Matti
    van der Harst, Pim
    Veronesi, Giovanni
    Walker, Mark
    Wareham, Nicholas J
    Watkins, Hugh
    Wichmann, H-Erich
    Abecasis, Goncalo R
    Assimes, Themistocles L
    Berndt, Sonja I
    Boehnke, Michael
    Borecki, Ingrid B
    Deloukas, Panos
    Franke, Lude
    Frayling, Timothy M
    Groop, Leif C
    Hunter, David J
    Kaplan, Robert C
    O'Connell, Jeffrey R
    Qi, Lu
    Schlessinger, David
    Strachan, David P
    Stefansson, Kari
    van Duijn, Cornelia M
    Willer, Cristen J
    Visscher, Peter M
    Yang, Jian
    Hirschhorn, Joel N
    Zillikens, M Carola
    McCarthy, Mark I
    Speliotes, Elizabeth K
    North, Kari E
    Fox, Caroline S
    Barroso, Inês
    Franks, Paul W
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Heid, Iris M
    Loos, Ruth J F
    Cupples, L Adrienne
    Morris, Andrew P
    Lindgren, Cecilia M
    Mohlke, Karen L
    New genetic loci link adipose and insulin biology to body fat distribution2015Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, nr 7538, s. 187-196Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

  • 208. Silventoinen, Karri
    et al.
    Magnusson, Patrik K. E.
    Neovius, Martin
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Batty, G. David
    Tynelius, Per
    Rasmussen, Finn
    Does obesity modify the effect of blood pressure on the risk of cardiovascular disease?: A population-based cohort study of more than one million Swedish men2008Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 118, nr 16, s. 1637-42Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Some studies have suggested that increased blood pressure has a stronger effect on the risk of cardiovascular disease (CVD) in lean persons than in obese persons, although this is not a universal finding. Given the inconsistency of this result, we tested it using a large population-based cohort data set. METHODS AND RESULTS: Systolic and diastolic blood pressures (BPs) and body mass index were measured in 1 145 758 Swedish men born between 1951 and 1976 who were in young adulthood (median age 18.2 years). During the register-based follow-up, which lasted until the end of 2006, 65 611 new CVD events took place, including 6799 myocardial infarctions and 8827 strokes. Hazard ratios (HRs) per 1-SD increase in systolic and diastolic BP were computed within established body mass index categories (underweight, normal, overweight, or obese) with Cox proportional hazards models. The strongest associations of diastolic BP with CVD (HR 1.18), myocardial infarction (HR 1.22), and stroke (HR 1.13) were observed in the obese category. For systolic BP, the strongest associations were observed in the obese category with CVD (HR 1.16) and stroke (HR 1.29) but in the overweight category with myocardial infarction (HR 1.19). We observed statistically significant interactions (P<0.0001) with body mass index for diastolic BP in relation to CVD and for systolic BP in relation to CVD and stroke. CONCLUSIONS: In contrast to the findings of previous studies, we observed a general increase in the magnitude of the association between blood pressure and subsequent CVD with increasing body mass index. Hypertension should not be regarded as a less serious risk factor in obese than in lean or normal-weight persons.

  • 209. Silventoinen, Karri
    et al.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Tynelius, Per
    Eriksson, Johan
    Rasmussen, Finn
    Ethnic differences in blood pressure in young men living in similar environment: a study of international adoptees in Sweden2010Inngår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, nr 7, s. 1393-1399Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To analyze differences in blood pressure in young men with different ethnic backgrounds but living in similar environment. Methods We utilized information on virtually the total Swedish male population born between 1951 and 1987 including 5388 international adoptees, 8834 Swedish adoptees and 1 469 196 Swedish nonadoptees. Systolic blood pressure (SBP), height and weight were measured during conscription examination at the average age of 18.2 years. Results SBP was lower in international adoptees than in native-born Swedes regardless of the geographic area of origin of the adoptees. BMI and height partly explained this difference, but additional adjustment for childhood social position only slightly modified the results. The largest difference was observed in adoptees from the Indian subcontinent when compared with native-born Swedes (-5.21 95% confidence intervals -6.16 to -4.27 when adjusted for height, BMI and childhood social position). Slightly lower SBP was also observed in Swedish adoptees when compared with Swedish nonadoptees. The association between BMI and SBP did not differ between international adoptees and native-born Swedes. Conclusion Our results suggest that international adoptees are not at higher risk for elevated blood pressure in young adulthood than native-born Swedes. Non-white genetic heritage or environmental exposures during pregnancy or in early life specific for adopted children may be associated with lower risk of hypertension. J Hypertens 28: 1393-1399 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

  • 210.
    Soveri, Inga
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Kidney function and discrimination of cardiovascular risk in middle-aged men2009Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 266, nr 4, s. 406-413Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective

    To define the optimal glomerular filtration rate (GFR) cut off for discriminating the risk of myocardial infarction or cardiovascular death.

    Design

    Prospective longitudinal observational study.

    Setting

    A community-based cohort.

    Participants

    A total of 2176 nondiabetic 50-year-old men without cardiovascular disease.

    Methods

    The men were followed until age 70. GFR was estimated at baseline using the Cockcroft–Gault formula. The optimal GFR cut-off points for discriminating risk of a fatal or nonfatal myocardial infarction and cardiovascular death were defined as the GFR levels maximizing integrated discrimination improvement (IDI).

    Main outcome measures

    Fatal or nonfatal myocardial infarction, cardiovascular death.

    Results

    During follow-up, 264 men experienced a fatal or nonfatal myocardial infarction, and 218 died of cardiovascular disease. The IDI-defined optimal GFR cut offs in this study were 98 mL min−1 for discriminating myocardial infarction risk and 92 mL min−1 for discriminating risk of cardiovascular death. In Cox proportional hazard models adjusting for established risk factors, the myocardial infarction risk was substantially higher in men with GFR below versus above 98 mL min−1 [hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.3–2.3, P < 0.001], and the risk of cardiovascular death was doubled in men with GFR below versus above 92 mL min−1 (HR 2.1, 95% CI 1.5–3.0, P < 0.001).

    Conclusion

    The GFR cut-off point for optimal discrimination of cardiovascular risk in the general population may be higher than previously suggested.

  • 211.
    Stenemo, M. Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala Univ, Dept Med Sci, Uppsala, Sweden..
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Proteomic profiling and the risk of heart failure2015Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 17, s. 141-141Artikkel i tidsskrift (Annet vitenskapelig)
  • 212.
    Stenemo, Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ganna, Andrea
    Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA ; Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA ; Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA ; Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nowak, Christoph
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Stockholm, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi. George Inst Global Hlth, Sydney, NSW, Australia.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Broeckling, Corey
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
    Prenni, Jessica
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA ; Colorado State Univ, Dept Hort & Landscape Architecture, Ft Collins, CO 80523 USA.
    Svensson, Per
    Karolinska Inst, Dept Clin Sci & Educ, Dept Cardiol, Sodersjukhuset, Stockholm, Sweden.
    Magnusson, Patrik
    Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA ; Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA ; Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Ärnlöv, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Div Family Med & Primary Care, Stockholm, Sweden ; Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    The metabolites urobilin and sphingomyelin (30:1) are associated with incident heart failure in the general population2019Inngår i: ESC Heart Failure, E-ISSN 2055-5822, Vol. 6, nr 4, s. 764-773Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims: We aimed to investigate whether metabolomic profiling of blood can lead to novel insights into heart failure pathogenesis or improved risk prediction.

    Methods: Mass spectrometry-based metabolomic profiling was performed in plasma or serum samples from three community-based cohorts without heart failure at baseline (total n=3,924; 341 incident heart failure events, median follow-up ranging from 4.6 to 13.9 years). Cox proportional hazards models were applied to assess the association of each of the 206 identified metabolites with incident heart failure in the discovery cohorts Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n=920) and Uppsala Longitudinal Study of Adult Men (ULSAM, n=1,121). Replication was undertaken in the independent cohort TwinGene (n=1,797). We also assessed whether metabolites could improve the prediction of heart failure beyond established risk factors (age, sex, body mass index, low-density lipoprotein- and high-density lipoprotein-cholesterol, triglycerides, lipid medication, diabetes, systolic and diastolic blood pressure, blood pressure medication, glomerular filtration rate, smoking status, and myocardial infarction prior to or during follow-up).

    Results: Higher circulating urobilin and lower sphingomyelin (30:1) were associated with incident heart failure in age- and sex-adjusted models in the discovery and replication sample. The hazard ratio (HR) for urobilin in the replication cohort was estimated to 1.29 per SD unit, 95% confidence interval (CI) 1.03-1.63) and for sphingomyelin (30:1) to 0.72 (95% CI 0.58-0.89). Results remained similar after further adjustment for established heart failure risk factors in meta-analyses of all three cohorts. Urobilin concentrations were inversely associated with left ventricular ejection fraction at baseline in the PIVUS cohort (β= -0.70 (95% CI -1.03-(-0.38)). No improvement in risk prediction was observed when adding the two top metabolites (C-index 0.787 (95% CI 0.752-0.823)) or nine Lasso-selected metabolites (0.790 (95% CI 0.754-0.826)) to a modified Atherosclerosis Risk in Communities (ARIC) heart failure risk score model (0.780 (95% CI 0.745-0.816)).

    Conclusions: Our metabolomics study identified associations of circulating levels of the heme breakdown product urobilin, and sphingomyelin (30:1), a cell membrane component involved in signal transduction and apoptosis, with incident heart failure.

  • 213.
    Stenemo, Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nowak, Christoph
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ärnlöv, Johan
    Dalarna University, School of Health and Social Studies, Falun; Karolinska Institutet, Care Science and Society, Department of Neurobiology, Division of Family Medicine and Primary Care .
    Circulating proteins as predictors of incident heart failure in the elderly2018Inngår i: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 20, nr 1, s. 55-62Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims

    To identify novel risk markers for incident heart failure using proteomic profiling of 80 proteins previously associated with cardiovascular pathology.

    Methods and results

    Proteomic profiling (proximity extension assay) was performed in two community‐based prospective cohorts of elderly individuals without heart failure at baseline: the Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS, n = 901, median age 70.2 (interquartile range 70.0–70.3) years, 80 events]; and the Uppsala Longitudinal Study of Adult Men [ULSAM, n = 685, median age 77.8 (interquartile range 76.9–78.1) years, 90 events]. Twenty‐nine proteins were associated with incident heart failure in the discovery cohort PIVUS after adjustment for age and sex, and correction for multiple testing. Eighteen associations replicated in ULSAM. In pooled analysis of both cohorts, higher levels of nine proteins were associated with incident heart failure after adjustment for established risk factors: growth differentiation factor 15 (GDF‐15), T‐cell immunoglobulin and mucin domain 1 (TIM‐1), tumour necrosis factor‐related apoptosis‐inducing ligand receptor 2 (TRAIL‐R2), spondin‐1 (SPON1), matrix metalloproteinase‐12 (MMP‐12), follistatin (FS), urokinase‐type plasminogen activator surface receptor (U‐PAR), osteoprotegerin (OPG), and suppression of tumorigenicity 2 (ST2). Of these, GDF‐15, U‐PAR, MMP‐12, TRAIL‐R2, SPON1 and FS were associated with worsened echocardiographic left ventricular systolic function at baseline, while only TIM‐1 was positively associated with worsened diastolic function (P < 0.02 for all).

    Conclusion

    Proteomic profiling identified several novel associations between proteins involved in apoptosis, inflammation, matrix remodelling, and fibrinolysis with incident heart failure in elderly individuals. Our results encourage additional studies investigating the underlying mechanisms and the clinical utility of our findings.

  • 214.
    Ström Möller, Christina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    T wave abnormalities, high body mass index, current smoking and high lipoprotein (a) levels predict the development of major abnormal Q/QS patterns 20 years later: A population-based study2006Inngår i: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 6, nr 6, s. 10-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Most studies on risk factors for development of coronary heart disease (CHD) have been based on the clinical outcome of CHD. Our aim was to identify factors that could predict the development of ECG markers of CHD, such as abnormal Q/QS patterns, ST segment depression and T wave abnormalities, in 70-year-old men, irrespective of clinical outcome. METHODS: Predictors for development of different ECG abnormalities were identified in a population-based study using stepwise logistic regression. Anthropometrical and metabolic factors, ECG abnormalities and vital signs from a health survey of men at age 50 were related to ECG abnormalities identified in the same cohort 20 years later. RESULTS: At the age of 70, 9% had developed a major abnormal Q/QS pattern, but 63% of these subjects had not been previously hospitalized due to MI, while 57% with symptomatic MI between age 50 and 70 had no major Q/QS pattern at age 70. T wave abnormalities (Odds ratio 3.11, 95% CI 1.18-8.17), high lipoprotein (a) levels, high body mass index (BMI) and smoking were identified as significant independent predictors for the development of abnormal major Q/QS patterns. T wave abnormalities and high fasting glucose levels were significant independent predictors for the development of ST segment depression without abnormal Q/QS pattern. CONCLUSION: T wave abnormalities on resting ECG should be given special attention and correlated with clinical information. Risk factors for major Q/QS patterns need not be the same as traditional risk factors for clinically recognized CHD. High lipoprotein (a) levels may be a stronger risk factor for silent myocardial infarction (MI) compared to clinically recognized MI.

  • 215.
    Sundelöf, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Irizarry, Michael C
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Rönnemaa, Elina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gunnarsson, Malin Degerman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hyman, Bradley T
    Basun, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Plasma β Amyloid and the Risk of Alzheimer Disease and Dementia in Elderly Men: A Prospective, Population-Based Cohort Study2008Inngår i: Archives of Neurology, ISSN 0003-9942, E-ISSN 1538-3687, Vol. 65, nr 2, s. 256-63Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Beta amyloid (Abeta) protein accumulates in the brains of individuals with Alzheimer disease (AD) and is detectable in cerebrospinal fluid and plasma. OBJECTIVE: To examine plasma levels of Abeta peptides Abeta(40) and Abeta(42) as predictors of incident AD and other types of dementia. DESIGN: Prospective, population-based cohort study. SETTING: The Uppsala Longitudinal Study of Adult Men. PARTICIPANTS: Plasma Abeta(40) and Abeta(42) levels were analyzed as predictors of incident AD in 1045 men at age 70 years and 680 men at age 77 years using Cox proportional hazards analyses. Alzheimer disease and other types of dementia were diagnosed by standardized screening, clinical evaluation, and medical record review. MAIN OUTCOME MEASURES: Hazard ratios of AD (primary outcome) and vascular dementia or other dementia (secondary outcomes) according to baseline levels of plasma Abeta(40) and Abeta(42). RESULTS: From the age of 77 years at baseline, 46 individuals developed AD at follow-up (median, 5.3 years). A low plasma Abeta(40) level at age 77 years was associated with higher incidence of AD. The multivariate-adjusted hazard ratio was 4.87 (95% confidence interval, 1.63-14.6) for the lowest Abeta(40) tertile compared with the highest tertile. On follow-up from age 70 years at baseline (median, 11.2 years), 82 individuals developed AD. Plasma Abeta(40) and Abeta(42) levels measured at age 70 years were not significantly associated with incident AD. CONCLUSIONS: Low plasma Abeta(40) levels predicted incident AD in elderly men independently of potential confounders. Plasma Abeta(42) levels were not significantly associated with AD incidence. The clinical value of Abeta measurement in plasma remains to be established in future studies.

  • 216.
    Sundelöf, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundstrom, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hansson, Oskar
    Eriksdotter-Jönhagen, Maria
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Degerman-Gunnarsson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Minthon, Lennart
    Blennow, Kaj
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Basun, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Cystatin C Levels are Positively Correlated with both Aβ42 and Tau Levels in Cerebrospinal Fluid in Persons with Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls2010Inngår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 21, nr 2, s. 471-478Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cystatin C is suggested to be involved in neurodegeneration and the development of Alzheimer's disease (AD) by binding to soluble amyloid-beta (Abeta) peptides. Studies of cystatin C levels in cerebrospinal fluid (CSF) in relation to risk of AD are conflicting and relations between cystatin C, Abeta42, and tau levels in CSF in AD, mild cognitive impairment (MCI), and healthy controls are unknown. The objective of this study was to investigate cystatin C, Abeta42, and tau levels in CSF in AD, MCI, and controls. As a secondary aim, the relationships between cystatin C, Abeta42, and tau levels across disease groups were investigated. Cystatin C, Abeta42, total tau, and phosphorylated tau levels in CSF were analyzed by turbidimetry (cystatin C) and xMAP Luminex technology (Abeta and tau) in persons with AD (n=101), MCI (n=84), and healthy control subjects (n=28). Mean cystatin C levels were similar in cases of AD (5.6 mumol/L +/- 1.7), MCI (5.4 mumol/L +/- 1.48), and controls (5.6 mumol/L +/- 1.6). However, CSF cystatin C levels were strongly and positively correlated with total tau and phosphorylated tau levels (r=0.61-0.81, p< 0.0001) and Abeta42 (r=0.35-0.65, p< 0.001) independent of age, gender, and APOE genotype. Mean CSF cystatin C levels did not differ between patients with AD and MCI and healthy controls. Interestingly, cystatin C levels were positively correlated with both tau and Abeta42 levels in CSF independent of age, gender, and APOE genotype.

  • 217.
    Sundelöf, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hansson, Oskar
    Eriksdotter-Jönhagen, Maria
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Degerman-Gunnarsson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Minthon, Lennart
    Blennow, Kaj
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Basun, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Higher Cathepsin B Levels in Plasma in Alzheimer's Disease Compared to Healthy Controls2010Inngår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 22, nr 4, s. 1223-1230Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cathepsin B is suggested to be involved in amyloid-β (Aβ) processing and Alzheimer's disease (AD). Studies of cathepsin B levels in plasma and cerebrospinal fluid (CSF) have not been previously performed. We examined cathepsin B levels in plasma and CSF samples in persons with AD, mild cognitive impairment (MCI), and healthy controls in order to test the hypothesis that cathepsin B levels can discriminate persons with AD or MCI from healthy controls. Cathepsin B, Cystatin C, Aβ1-40 and Aβ1-42, total tau, phosphorylated tau, and albumin levels in plasma and CSF were analyzed by ELISA (Cathepsin B) turbidimetry (cystatin C), xMAP Luminex technology (Aβ1-40 and Aβ1-42 and tau), and Cobas C501 analyzer (albumin) in persons with AD (n=101), MCI (n=84), and healthy control subjects (n=28). Plasma cathepsin B levels were higher in persons with AD compared to healthy controls, both in unadjusted models and in multivariable models adjusting for age, gender, APOE genotype, cystatin C, and albumin levels: Odds ratio (OR) for AD per 1 SD of plasma cathepsin B; 2.04, 95% confidence interval (CI); 1.01-4.14, p= 0.05. There was no difference between diagnostic groups in cathepsin B levels in CSF: OR for AD per 1 SD of CSF cathepsin B; 0.93, 95% CI; 0.37-2.30, p= 0.87. Plasma cathepsin B levels were higher in persons with AD compared to healthy controls whereas there was no difference between diagnostic groups in cathepsin B levels in CSF. Further investigation of cathepsin B as a predictor of AD is warranted.

  • 218.
    Sundelöf, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ärnlöv, J.
    Ingelsson, E.
    Sundström, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Irizarry, M. C.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Rönnemaa, Elina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Degerman-Gunnarsson, Malin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hyman, B. T.
    Basun, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Serum cystatin C and the risk of Alzheimer disease in elderly men2008Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 71, nr 14, s. 1072-1079Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Multiple lines of research suggest that increased cystatin C activity in the brain protects against the development of Alzheimer disease (AD). METHODS: Serum cystatin C levels were analyzed at two examinations of the Uppsala Longitudinal Study of Adult Men, a longitudinal, community-based study of elderly men (age 70 years, n = 1,153 and age 77 years, n = 761, a subset of the age 70 examination). Cox regressions were used to examine associations between serum cystatin C and incident AD. AD cases were identified by cognitive screening and comprehensive medical chart review in all subjects. RESULTS: On follow-up (median 11.3 years), 82 subjects developed AD. At age 70 years, lower cystatin C was associated with higher risk of AD independently of age, APOE4 genotype, glomerular filtration rate, diabetes, hypertension, stroke, cholesterol, body mass index, smoking, education level, and plasma amyloid-beta protein 40 and 42 levels (hazard ratio [HR] for lowest [<1.12 micromol/L] vs highest [>1.30 micromol/L] tertile = 2.67, 95% CI 1.22-5.83, p < 0.02). The results were similar at age 77 years (43 participants developed AD during follow-up). Furthermore, a 0.1-mumol/L decrease of cystatin C between ages 70 and 77 years was associated with a 29% higher risk of incident AD (HR 1.29, 95% CI 1.03-1.63, p < 0.03). CONCLUSIONS: Low levels of serum cystatin C precede clinically manifest Alzheimer disease (AD) in elderly men free of dementia at baseline and may be a marker of future risk of AD. These findings strengthen the evidence for a role for cystatin C in the development of clinical AD.

  • 219.
    Sundstrom, Johan
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap. Institutionen för medicinska vetenskaper.
    Lind, L
    Institutionen för medicinska vetenskaper.
    Andren, B
    Institutionen för medicinska vetenskaper.
    Lithell, Hans
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Left ventricular geometry and function are related to electrocardiographic characteristics and diagnoses1998Inngår i: Clin Physiol, Vol. 18, s. 463-Artikkel i tidsskrift (Fagfellevurdert)
  • 220.
    Sundstrom, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lithell, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Clinical value of the metabolic syndrome for long term prediction of total and cardiovascular mortality: prospective, population based cohort study2006Inngår i: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 332, nr 7546, s. 878-882Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To find out if the presence of the metabolic syndrome increases the risk of subsequent total and cardiovascular mortality, taking into account established risk factors for cardiovascular disease. DESIGN: Prospective cohort study. SETTING: General population. PARTICIPANTS: A community based sample of 2322 men followed since 1970 for a maximum of 32.7 years, investigated at ages 50 and 70. MAIN OUTCOME MEASURES: The relations of the metabolic syndrome defined by the national cholesterol education programme (NCEP) of the US National Heart, Lung, and Blood Institute or criteria of the World Health Organization (WHO) to subsequent total and cardiovascular mortality. RESULTS: When adding the metabolic syndrome to models with established risk factors for cardiovascular disease (smoking, diabetes, hypertension, and serum cholesterol) at age 50, presence of the metabolic syndrome as defined in the NCEP significantly predicted total and cardiovascular mortality (Cox proportional hazard ratios 1.36, 95% confidence interval 1.17 to 1.58; and 1.59, 1.29 to 1.95, respectively). The metabolic syndrome added prognostic information to that of the established risk factors for cardiovascular disease (likelihood ratio tests, P < 0.0001 for both outcomes). Similar results were obtained in a subsample without diabetes or manifest cardiovascular disease. CONCLUSIONS: In a large, community based sample of middle aged men, the presence of the metabolic syndrome according to the definition of the NCEP gave long term prognostic information regarding total and cardiovascular mortality if the status of established risk factors for cardiovascular disease was known. If confirmed this may indicate clinical value in diagnosing the metabolic syndrome.

  • 221.
    Sundstrom, Johan
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Vasan, RS
    Heart Failure With Normal Systolic Function. In: Dec W, Heart Failure: Comprehensive Guide to Diagnosis and Treatment.2005Inngår i: Dec W, Heart Failure: Comprehensive Guide to Diagnosis and Treatment. New York: Marcel Dekker, New York: Marcel Dekker , 2005Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 222.
    Sundström, J.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Useful tests of usefulness of new risk factors: Tools for assessing reclassification and discrimination2011Inngår i: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 39, nr 4, s. 439-441Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    New risk factors for various diseases are suggested at an increasing pace, with promise of clinical usefulness for risk prediction, but almost unvaryingly without formal testing of that property. We propose that a risk factor clinically relevant for risk prediction can be defined as one that correctly alters predicted risk to a clinically relevant extent in persons with a relevant absolute risk, such that it affects clinical decision making. We recommend that investigators who suggest a new risk factor for clinical use investigate if the new risk factor adds capacity to discriminate between persons who will subsequently experience the outcome from those who will not. For that purpose, we provide tools for calculating the net reclassification improvement, NRI, and the integrated discrimination improvement, IDI, using major statistical packages.

  • 223.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Högt diastoliskt tryck varningssignal i yngre åldrar: Systoliskt och diastoliskt blodtryck är olika viktigt för yngre och äldre2012Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 4, s. 146-147Artikkel i tidsskrift (Fagfellevurdert)
  • 224.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Myocardial biomarkers for prediction of cardiovascular disease2009Inngår i: Disease Markers, ISSN 0278-0240, E-ISSN 1875-8630, Vol. 26, nr 5-6, s. 235-246Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The identification of those persons in the population who have the highest risk of future cardiovascular events is important for targeting intensive preventive efforts. This can be reliably done using a handful of long since established risk factors. The unmet need for new molecular biomarkers for prediction of cardiovascular events in the general population is therefore low. In order for a new biomarker to be used clinically for risk prediction, a statistically significant association of levels of the biomarker to adverse outcome is not enough, but the biomarker should also be demonstrated to add discriminative capacity beyond established risk factors. In contrast to the limited value of new biomarkers for risk prediction, their usefulness for unraveling the pathophysiology of cardiovascular disease is large. The myocardium is the source of a vast number of interesting biomarkers, of which a few may be useful for risk prediction in the general population. Two of these, troponin-I and the N-terminal fragment of brain natriuretic peptide, have passed tests of added discriminatory value. Numerous other biomarkers produced by cardiomyocytes or non-cardiomyocytes in the myocardium are promising, and if they are not proven useful for risk prediction, they will unquestionably enhance our understanding of cardiovascular disease.

  • 225.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Troponin and heart failure: an early warning system worth listening to?2009Inngår i: Future cardiology, ISSN 1479-6678, Vol. 5, nr 4, s. 321-324Artikkel i tidsskrift (Fagfellevurdert)
  • 226.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Arima, Hisatomi
    Jackson, Rod
    Turnbull, Fiona
    Rahimi, Kazem
    Chalmers, John
    Woodward, Mark
    Neal, Bruce
    Effects of Blood Pressure Reduction in Mild Hypertension: A Systematic Review and Meta-analysis2015Inngår i: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 162, nr 3, s. 184-191Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Effects of blood pressure reduction in persons with grade 1 hypertension are unclear. Purpose: To investigate whether pharmacologic blood pressure reduction prevents cardiovascular events and deaths in persons with grade 1 hypertension. Data Sources: Trials included in the BPLTTC (Blood Pressure Lowering Treatment Trialists' Collaboration) and trials identified from a previous review and electronic database searches. Study Selection: Patients without cardiovascular disease with blood pressures in the grade 1 hypertension range (140 to 159/90 to 99 mm Hg) who were randomly assigned to an active (antihypertensive drug or more intensive regimen) or control (placebo or less intensive regimen) blood pressure-lowering regimen. Data Extraction: Individual-patient data from BPLTTC trials and aggregate data from other trials were extracted. Risk of bias was assessed for all trials. Data Synthesis: Individual-patient data involved 10 comparisons from trials where most patients had diabetes, and aggregate data involved 3 comparisons from trials of patients without diabetes. The average blood pressure reduction was about 3.6/2.4 mm Hg. Over 5 years, odds ratios were 0.86 (95% CI, 0.74 to 1.01) for total cardiovascular events, 0.72 (CI, 0.55 to 0.94) for strokes, 0.91 (CI, 0.74 to 1.12) for coronary events, 0.80 (CI, 0.57 to 1.12) for heart failure, 0.75 (CI, 0.57 to 0.98) for cardiovascular deaths, and 0.78 (CI, 0.67 to 0.92) for total deaths. Results were similar in secondary analyses. Withdrawal from treatment due to adverse effects was more common in the active groups. Limitation: Blood pressure reductions and numbers of events were small. Conclusion: Blood pressure-lowering therapy is likely to prevent stroke and death in patients with uncomplicated grade 1 hypertension.

  • 227.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Arima, Hisatomi
    Woodward, Mark
    Jackson, Rod
    Karmali, Kunal
    Lloyd-Jones, Donald
    Baigent, Colin
    Emberson, Jonathan
    Rahimi, Kazem
    MacMahon, Stephen
    Patel, Anushka
    Perkovic, Vlado
    Turnbull, Fiona
    Neal, Bruce
    Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data2014Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 384, nr 9943, s. 591-598Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    We aimed to investigate whether the benefits of blood pressure-lowering drugs are proportional to baseline cardiovascular risk, to establish whether absolute risk could be used to inform treatment decisions for blood pressure-lowering therapy, as is recommended for lipid-lowering therapy.

    Methods

    This meta-analysis included individual participant data from trials that randomly assigned patients to either blood pressure-lowering drugs or placebo, or to more intensive or less intensive blood pressure-lowering regimens. The primary outcome was total major cardiovascular events, consisting of stroke, heart attack, heart failure, or cardiovascular death. Participants were separated into four categories of baseline 5-year major cardiovascular risk using a risk prediction equation developed from the placebo groups of the included trials (<11%, 11-15%, 15-21%, >21%).

    Findings

    11 trials and 26 randomised groups met the inclusion criteria, and included 67 475 individuals, of whom 51 917 had available data for the calculation of the risk equations. 4167 (8%) had a cardiovascular event during a median of 4.0 years (IQR 3.4-4.4) of follow-up. The mean estimated baseline levels of 5-year cardiovascular risk for each of the four risk groups were 6 0% (SD 2.0), 12.1% (1.5), 17.7% (1.7), and 26.8% (5.4). In each consecutive higher risk group, blood pressure-lowering treatment reduced the risk of cardiovascular events relatively by 18% (95% CI 7-27), 15% (4-25), 13% (2-22), and 15% (5-24), respectively (p=0.30 for trend). However, in absolute terms, treating 1000 patients in each group with blood pressure-lowering treatment for 5 years would prevent 14 (95% CI 8-21), 20 (8-31), 24 (8-40), and 38 (16-61) cardiovascular events, respectively (p=0.04 for trend). Interpretation Lowering blood pressure provides similar relative protection at all levels of baseline cardiovascular risk, but progressively greater absolute risk reductions as baseline risk increases. These results support the use of predicted baseline cardiovascular disease risk equations to inform blood pressure-lowering treatment decisions.

  • 228.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Björkelund, Cecilia
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Publ Hlth & Community Med Primary Hlth Care, Gothenburg, Sweden.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hansson, Per-Olof
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.
    Högman, Marieann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning.
    Janson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning.
    Koupil, Ilona
    Stockholm Univ, Dept Publ Hlth Sci, Stockholm, Sweden;Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
    Kristenson, Margareta
    Linkoping Univ, Dept Med & Hlth Sci, Div Community Med, Linkoping, Sweden.
    Lagerros, Ylva Trolle
    Karolinska Inst, Dept Med, Unit Clin Epidemiol, Stockholm, Sweden;Karolinska Univ Hosp Huddinge, Dept Endocrinol Metab & Diabet, Huddinge, Sweden.
    Leppert, Jerzy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Lissner, Lauren
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Publ Hlth & Community Med Epidemiol & Social, Gothenburg, Sweden.
    Johansson, Ingegerd
    Umea Univ, Sch Dent, Dept Odontol, Umea, Sweden.
    Ludvigsson, Jonas F.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Orebro Univ, Orebro Univ Hosp, Dept Pediat, Orebro, Sweden.
    Nilsson, Peter M.
    Skane Univ Hosp, Dept Clin Sci, Malmo, Sweden;Lund Univ, Lund, Sweden.
    Olsson, Håkan
    Lund Univ, Dept Clin Sci Canc Epidemiol, Lund, Sweden.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Karlsson, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Rosengren, Annika
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.
    Sandin, Sven
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA;Seaver Autism Ctr Res & Treatment Mt Sinai, New York, NY USA.
    Snäckerström, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Stenbeck, Magnus
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Söderberg, Stefan
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden;Umea Univ, Heart Ctr, Umea, Sweden.
    Weiderpass, Elisabete
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Inst Populat Based Canc Res, Dept Res, Canc Registry Norway, Oslo, Norway;Univ Helsinki, Fac Med, Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland;Univ Tromso, Arctic Univ Norway, Dept Community Med, Tromso, Norway.
    Wanhainen, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
    Wennberg, Patrik
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Fortier, Isabel
    McGill Univ, Res Inst, Hlth Ctr, Montreal, PQ, Canada.
    Heller, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Storgärds, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Svennblad, Bodil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Rationale for a Swedish cohort consortium2019Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, nr 1, s. 21-28Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.

  • 229.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Bruze, Gustaf
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Ottosson, Johan
    Orebro Univ, Fac Med & Hlth, Dept Surg, Orebro, Sweden..
    Marcus, Claude
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Naslund, Ingmar
    Orebro Univ, Fac Med & Hlth, Dept Surg, Orebro, Sweden..
    Neovius, Martin
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Weight Loss and Heart Failure A Nationwide Study of Gastric Bypass Surgery Versus Intensive Lifestyle Treatment2017Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 135, nr 17, s. 1577-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Associations of obesity with incidence of heart failure have been observed, but the causality is uncertain. We hypothesized that gastric bypass surgery leads to a lower incidence of heart failure compared with intensive lifestyle modification in obese people. METHODS: We included obese people without previous heart failure from a Swedish nationwide registry of people treated with a structured intensive lifestyle program and the Scandinavian Obesity Surgery Registry. All analyses used inverse probability weights based on baseline body mass index and a propensity score estimated from baseline variables. Treatment groups were well balanced in terms of weight, body mass index, and most potential confounders. Associations of treatment with heart failure incidence, as defined in the National Patient Register, were analyzed with Cox regression. RESULTS: The 25 804 gastric bypass surgery patients had on average lost 18.8 kg more weight after 1 year and 22.6 kg more after 2 years than the 13 701 lifestyle modification patients. During a median of 4.1 years, surgery patients had lower heart failure incidence than lifestyle modification patients (hazard ratio, 0.54; 95% confidence interval, 0.36-0.82). A 10-kg achieved weight loss after 1 year was related to a hazard ratio for heart failure of 0.77 (95% confidence interval, 0.60-0.97) in both treatment groups combined. Results were robust in sensitivity analyses. CONCLUSIONS: Gastric bypass surgery was associated with approximately one half the incidence of heart failure compared with intensive lifestyle modification in this study of 2 large nationwide registries. We also observed a graded association between increasing weight loss and decreasing risk of heart failure.

  • 230.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Evans, Jane C
    Benjamin, Emelia J
    Levy, Daniel
    Larson, Martin G
    Sawyer, Douglas B
    Siwik, Deborah A
    Colucci, Wilson S
    Sutherland, Patrice
    Wilson, Peter W F
    Vasan, Ramachandran S
    Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures: the Framingham Heart Study.2004Inngår i: Circulation, ISSN 1524-4539, Vol. 109, nr 23, s. 2850-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Plasma levels of matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, are increased in heart failure and in acute coronary syndromes. We investigated cross-sectional relations of plasma MMP-9 to vascular risk factors and echocardiographic left ventricular (LV) measurements. METHODS AND RESULTS: We studied 699 Framingham Study participants (mean age, 57 years; 58% women), free of heart failure and previous myocardial infarction, who underwent routine echocardiography. We examined sex-specific distributions of LV internal dimensions (LVEDD) and wall thickness (LVWT) and sampled persons with both LVEDD and LVWT below the sex-specific median (referent, n=299), with increased LVEDD (LVEDD > or =90th percentile, n=204) and increased LVWT (LVWT > or =90th percentile, n=221) in a 3:2:2 ratio. Plasma MMP-9 was detectable in 138 persons (20%). In multivariable models, increasing heart rate (OR per SD, 1.41; 95% CI, 1.17 to 1.71) and antihypertensive treatment (OR, 1.63; 95% CI, 1.06 to 2.50) were key clinical correlates of detectable plasma MMP-9. In multivariable-adjusted models, detectable plasma MMP-9 was associated with increased LVEDD (OR, 2.84; 95% CI, 1.13 to 7.11), increased LVWT (OR, 2.54; 95% CI, 1.00 to 6.46), and higher LV mass (P=0.06) in men but not in women (OR for increased LVEDD, 1.37; 95% CI, 0.54 to 3.46; for increased LVWT, 0.99; 95% CI, 0.39 to 2.52; P=0.59 for LV mass). CONCLUSIONS: In our community-based sample, detectable plasma MMP-9 levels were associated with increased LV diastolic dimensions and increased wall thickness in men. These observations indicate that plasma MMP-9 level may be a marker for cardiac extracellular matrix degradation, a process involved in LV remodeling.

  • 231.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Evans, Jane C
    Benjamin, Emelia J
    Levy, Daniel
    Larson, Martin G
    Sawyer, Douglas B
    Siwik, Deborah A
    Colucci, Wilson S
    Wilson, Peter W F
    Vasan, Ramachandran S
    Relations of plasma total TIMP-1 levels to cardiovascular risk factors and echocardiographic measures: the Framingham heart study.2004Inngår i: Eur Heart J, ISSN 0195-668X, Vol. 25, nr 17, s. 1509-16Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS: Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key regulator of extracellular matrix degradation. We examined relations of plasma total TIMP-1 to cardiovascular risk factors and echocardiographic left ventricular (LV) structure and function in a community-based sample. METHODS AND RESULTS: We studied 1069 Framingham Heart Study participants (mean age 56 years, 58% women) free of heart failure and previous myocardial infarction. Plasma TIMP-1 was higher in men compared with women, and increased with age, body mass index and total/HDL-cholesterol ratio, but decreased with alcohol intake. Plasma TIMP-1 was also directly related to smoking, diabetes and use of anti-hypertensive treatment. Adjusting for age, sex and height, plasma TIMP-1 was positively associated with LV mass, wall thickness, relative wall thickness, end-systolic diameter, and left atrial diameter and the risk of having increased LV end-diastolic diameter or increased wall thickness, and negatively correlated with fractional shortening. Additional adjustment for clinical covariates attenuated the relations of plasma TIMP-1 to most echocardiographic measures. CONCLUSIONS: In our cross-sectional investigation, plasma total TIMP-1 was related to major cardiovascular risk factors and to indices of LV hypertrophy and systolic dysfunction. This raises the possibility that cardiovascular risk factors may influence cardiovascular remodelling via extracellular matrix degradation, which may be reflected in plasma TIMP-1 levels.

  • 232.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Hedberg, Jakob
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Thuresson, Marcus
    Statisticon AB, Uppsala, Sweden..
    Aarskog, Pernilla
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Johannesen, Kasper Munk
    Linkoping Univ, Linkoping, Sweden..
    Oldgren, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study2017Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 136, nr 13, s. 1183-1192Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: There are increasing concerns about risks associated with aspirin discontinuation in the absence of major surgery or bleeding. We investigated whether long-term low-dose aspirin discontinuation and treatment gaps increase the risk of cardiovascular events.

    METHODS: We performed a cohort study of 601 527 users of low-dose aspirin for primary or secondary prevention in the Swedish prescription register between 2005 and 2009 who were >40 years of age, were free from previous cancer, and had >= 80% adherence during the first observed year of treatment. Cardiovascular events were identified with the Swedish inpatient and cause-of-death registers. The first 3 months after a major bleeding or surgical procedure were excluded from the time at risk.

    RESULTS: During a median of 3.0 years of follow-up, 62 690 cardiovascular events occurred. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37; 95% confidence interval, 1.34-1.41), corresponding to an additional cardiovascular event observed per year in 1 of every 74 patients who discontinue aspirin. The risk increased shortly after discontinuation and did not appear to diminish over time.

    CONCLUSIONS: In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding was associated with a >30% increased risk of cardiovascular events. Adherence to low-dose aspirin treatment in the absence of major surgery or bleeding is likely an important treatment goal.

  • 233.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Cardiac troponin-I and risk of heart failure: a community-based cohort study2009Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 30, nr 7, s. 773-781Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS: We examined if circulating levels of cardiac troponin-I (cTnI) predict subsequent heart failure in the community. METHODS AND RESULTS: Using Cox proportional hazards models, we examined the risk of a first hospitalization for heart failure during a maximum of 11.4 years in a community-based sample of 1089 70-year-old men without heart failure, valvular disease, or electrocardiographic left ventricular hypertrophy. Adjusting for smoking, systolic blood pressure, antihypertensive medication use, diabetes, body mass index, serum cholesterol, and myocardial infarction before baseline or during follow-up, 0.01 microg/L higher cTnI conferred a hazard ratio (HR) of 1.26 (95% confidence interval 1.15-1.38) for subsequent heart failure. Persons with cTnI > or =0.03 microg/L had an HR of 5.25 (2.00-13.77) compared with persons with cTnI <0.01 microg/L. Adjusting additionally for serum NTproBNP attenuated the estimates somewhat [HR 1.22 (1.11-1.34) per 0.01 microg/L of cTnI]. Excluding persons with myocardial infarction before baseline and censoring at time of myocardial infarction during follow-up, 0.01 microg/L higher cTnI was associated with a multivariable-adjusted HR of 1.31 (1.16-1.47) for heart failure. CONCLUSION: In a community-based sample, a direct measure of cardiomyocyte damage, cTnI, indicated a substantially increased risk of heart failure, accounting for other risk factors. Studies investigating the clinical utility of measuring cTnI in asymptomatic individuals are warranted.

  • 234.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Jackson, Rod
    Woodward, Mark
    Baigent, Colin
    Neal, Bruce
    Blood pressure lowering and cardiovascular risk reply2014Inngår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 384, nr 9956, s. 1746-1747Artikkel i tidsskrift (Annet vitenskapelig)
  • 235.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Nowrouzi, Shamim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lytsy, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Socialmedicinsk epidemiologi.
    Marttala, Kerstin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ekman, Inger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Öhagen, Patrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Östlund, Ollie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    The Precision HYpertenSIon Care (PHYSIC) study: a double-blind, randomized, repeated cross-over study2019Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, nr 1, s. 51-58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    High blood pressure is the leading risk factor for premature deaths and a major cost to societies worldwide. Effective blood pressure-lowering drugs are available, but patient adherence to them is low, likely partly due to side effects. To identify patient-specific differences in treatment effects, a repeated cross-over design, where the same treatment contrasts are repeated within each patient, is needed. Such designs have been surprisingly rarely used, given the current focus on precision medicine. The Precision HYpertenSIon Care (PHYSIC) study aims to investigate if there is a consistent between-person variation in blood pressure response to the common blood pressure-lowering drug classes of a clinically relevant magnitude, given the within-person variation in blood pressure. The study will also investigate the between-person variation in side effects of the drugs. In a double-blind, randomized, repeated cross-over trial, 300 patients with mild hypertension will be treated with four blood pressure-lowering drugs (candesartan, lisinopril, amlodipine, and hydrochlorothiazide) in monotherapy, with two of the drugs repeated for each patient. If the study indicates that there is a potential for precision hypertension care, the most promising predictors of blood pressure and side effect response to the drugs will be explored, as will the potential for development of a biomarker panel to rank the suitability of blood pressure-lowering drug classes for individual patients in terms of anticipated blood pressure effects and side effects, with the ultimate goal to maximize adherence. The study follows a protocol pre-registered at ClinicalTrials.gov with the identifier NCT02774460.

  • 236.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap. Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Nyström, Niklas
    Zethelius, Björn
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Andren, Bertil
    Institutionen för medicinska vetenskaper.
    Hales, C N
    Lithell, Hans
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Left ventricular concentric remodeling rather than left ventricular hypertrophy is related to the insulin resistance syndrome in elderly men.2000Inngår i: Circulation, ISSN 1524-4539, Vol. 101, nr 22, s. 2595-600Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Associations between left ventricular (LV) geometry and the insulin resistance syndrome have been found, mostly in small studies of middle-aged hypertensives. The purpose of this study was to elucidate these associations through the use of a large sample of elderly men. METHODS AND RESULTS: We investigated 475 men (157 hypertensives) 71 years of age who were attending a population-based health survey in Uppsala County with echocardiography, oral glucose tolerance test (OGTT), hyperinsulinemic euglycemic clamp, and lipid and 24-hour ambulatory blood pressure monitoring. LV relative wall thickness was significantly related to clamp insulin sensitivity index (r=-0.14), fasting insulin, 32-33 split proinsulin, triglycerides, nonesterified fatty acids, OGTT glucose and insulin levels, waist-to-hip ratio, body mass index, 24-hour blood pressure, and heart rate (r=0.10 to 0.22). Only 24-hour systolic pressure (r=0. 15), OGTT 2-hour insulin (r=-0.10), and heart rate (r=-0.14) were significantly related to LV mass index. Comparing subjects with various LV geometry (normal, concentric remodeling and concentric and eccentric hypertrophy) showed that 24-hour heart rate, OGTT glucose and insulin levels, waist-to-hip ratio, and body mass index were significantly higher (P<0.001 to 0.05) and clamp insulin sensitivity index was significantly lower (P<0.01) in the concentric remodeling geometry group than in the normal LV geometry group. The 24-hour blood pressure was significantly higher in the concentric hypertrophy group than in the normal LV geometry group (P<0.001). CONCLUSIONS: Several components of the insulin resistance syndrome were related to thick LV walls and concentric remodeling but less to LV hypertrophy in this population-based sample of elderly men.

  • 237.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lind, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Valind, Sven
    Institutionen för onkologi, radiologi och klinisk immunologi.
    Holmäng, Agneta
    Björntorp, Per
    Andren, Bertil
    Institutionen för medicinska vetenskaper.
    Waldenström, Anders
    Lithell, Hans
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Myocardial insulin-mediated glucose uptake and left ventricular geometry.2001Inngår i: Blood Press, ISSN 0803-7051, Vol. 10, nr 1, s. 27-32Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Whole-body insulin sensitivity has been shown to be impaired in subjects with increased left ventricular relative wall thickness (RWT) and in hypertensive subjects with left ventricular hypertrophy, but the relation between myocardial insulin sensitivity and RWT or left ventricular mass index (LVMI) in normotension is not known. We measured myocardial and skeletal muscle glucose uptake with [18F]fluorodeoxyglucose and positron emission tomography during hyperinsulinemic euglycemic clamp in nine men with wide ranges of echocardiographic RWT and LVMI. The subjects were male, 72-74 years old, normotensive and free from medication or history of heart disease. RWT correlated inversely with skeletal muscle glucose uptake (r = -0.69, p = 0.04), borderline significantly directly with myocardial glucose uptake (r = 0.62, p = 0.07), and directly with the ratio between myocardial and skeletal muscle glucose uptake (r = 0.77, p = 0.02) during hyperinsulinemic euglycemic clamp. LVMI was not related to insulin-mediated myocardial or skeletal muscle glucose uptake or the ratio between myocardial and skeletal muscle glucose uptake. In conclusion, RWT was inversely related to insulin sensitivity in skeletal muscle and borderline significantly directly related to insulin sensitivity in the myocardium in healthy normotensive elderly men, whereas LVMI was not related to myocardial or skeletal muscle insulin sensitivity.

  • 238.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Andren, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Aro, Antti
    Lithell, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Dyslipidemia and an unfavorable fatty acid profile predict left ventricular hypertrophy 20 years later2001Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 103, nr 6, s. 836-841Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:-Left ventricular hypertrophy (LVH) is a common risk factor for cardiovascular mortality. Causes other than hypertension have not previously been investigated longitudinally. The aim of the present study was to determine hemodynamic, metabolic, and psychosocial predictors at 50 years of age for the prevalence of echocardiographic LVH and geometric subtypes at age 70 by use of a large sample of men from the general population followed up for 20 years. Methods and Results-In 1970 to 1973, all men born from 1920 to 1924 and residing in Uppsala County, Sweden, were invited to participate in a health survey aimed at identifying risk factors for cardiovascular disease. At a reinvestigation 20 years later, echocardiographic left ventricular mass index was determined in 475 subjects. A 1-SD increase in body mass index, systolic or diastolic blood pressure, fasting LDL/HDL cholesterol, serum triglycerides, or the serum cholesterol ester proportion of several saturated fatty acids or oleic acid at age 50 significantly increased the odds of having LVH at age 70 by 27% to 41%, whereas an increase in linoleic acid proportion was protective. Almost all metabolic predictors were independent of ischemic heart disease, valvular disease, and use of antihypertensive medication at age 70. CONCLUSIONS:-Dyslipidemia and indices of a low dietary intake of linoleic acid and high intake of saturated and monounsaturated fats, as well as hypertension and obesity, at age 50 predicted the prevalence of LVH 20 years later in this prospective longitudinal cohort study, thereby suggesting that lipids may be important in the origin of LVH.

  • 239.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lind, Lars
    Institutionen för medicinska vetenskaper.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Zethelius, Björn
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Andren, Bertil
    Institutionen för medicinska vetenskaper.
    Lithell, Hans
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Echocardiographic and electrocardiographic diagnoses of left ventricular hypertrophy predict mortality independently of each other in a population of elderly men.2001Inngår i: Circulation, ISSN 1524-4539, Vol. 103, nr 19, s. 2346-51Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:The increased risk associated with left ventricular hypertrophy (LVH) diagnosed echocardiographically (Echo-LVH) or electrocardiographically (ECG-LVH) is well known, but the clinically relevant question of how much additional prognostic information would be provided by echocardiographically assessing LVH if a subject's ECG-LVH and hypertension status are known has not been addressed. Methods and RESULTS:We investigated whether Echo-LVH and ECG-LVH predicted total and cardiovascular mortality and morbidity independently of each other and of other cardiovascular risk factors by using a population-based sample of 475 men investigated at age 70 with a median follow-up time of 5.2 years. Echocardiographic left ventricular mass index (LVMI) predicted total mortality (hazards ratio [HR] 1.44, 95% CI 1.09 to 1.92, for a 1-SD increase in LVMI) and cardiovascular mortality (HR 2.38, 95% CI 1.52 to 3.73) independently of ECG-LVH and other cardiovascular risk factors. ECG-LVH, defined as Cornell product >244 microV. s, predicted total mortality (HR 2.89, 95% CI 1.41 to 5.96) independently of LVMI and other cardiovascular risk factors. Thus, Echo-LVH and ECG-LVH provided complementary prognostic information, especially in hypertensive subjects. CONCLUSIONS:Echo-LVH and ECG-LVH predict mortality independently of each other and of other cardiovascular risk factors, implying that Echo-LVH and ECG-LVH in part carry different prognostic information. Therefore, to fully assess the increased risk associated with these conditions, both ECG and echocardiography should be performed.

  • 240.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Neovius, M.
    Tynelius, P.
    Rasmussen, F.
    BLOOD PRESSURE IN YOUNG ADULTHOOD AND MORTALITY RISK2010Inngår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, s. E239-E240Artikkel i tidsskrift (Annet vitenskapelig)
  • 241.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Neovius, Martin
    Tynelius, Per
    Rasmussen, Finn
    Association of blood pressure in late adolescence with subsequent mortality: cohort study of Swedish male conscripts2011Inngår i: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 342, s. d643-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To investigate the nature and magnitude of relations of systolic and diastolic blood pressures in late adolescence to mortality. Design Nationwide cohort study. Setting General community in Sweden. Participants Swedish men (n=1 207 141) who had military conscription examinations between 1969 and 1995 at a mean age of 18.4 years, followed up for a median of 24 (range 0-37) years. Main outcome measures Total mortality, cardiovascular mortality, and non-cardiovascular mortality. Results During follow-up, 28 934 (2.4%) men died. The relation of systolic blood pressure to total mortality was U shaped, with the lowest risk at a systolic blood pressure of about 130 mm Hg. This pattern was driven by the relation to non-cardiovascular mortality, whereas the relation to cardiovascular mortality was monotonically increasing (higher risk with higher blood pressure). The relation of diastolic blood pressure to mortality risk was monotonically increasing and stronger than that of systolic blood pressure, in terms of both relative risk and population attributable fraction (deaths that could be avoided if blood pressure was in the optimal range). Relations to cardiovascular and non-cardiovascular mortality were similar, with an apparent risk threshold at a diastolic blood pressure of about 90 mm Hg, below which diastolic blood pressure and mortality were unrelated, and above which risk increased steeply with higher diastolic blood pressures. Conclusions In adolescent men, the relation of diastolic blood pressure to mortality was more consistent than that of systolic blood pressure. Considering current efforts for earlier detection and prevention of risk, these observations emphasise the risk associated with high diastolic blood pressure in young adulthood.

  • 242.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Sheikhi, Reza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Oestgren, Carl J.
    Svennblad, Bodil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Bodegard, Johan
    Nilsson, Peter M.
    Johansson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Blood pressure levels and risk of cardiovascular events and mortality in type-2 diabetes: cohort study of 34 009 primary care patients2013Inngår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 31, nr 8, s. 1603-1610Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective:

    The optimal blood pressure (BP) in persons with type-2 diabetes is debated. We investigated shapes of the associations of SBP and DBP levels with risk of cardiovascular events and mortality in a large primary care-based sample of diabetic patients.

    Methods:

    We investigated all 34009 consecutive cardiovascular disease-free type-2 diabetes patients aged 35 years or older (mean age 64 years) at 84 primary care centers in central Sweden between 1999 and 2008. We followed this cohort until the end of 2009 in national registries for the incidence of major cardiovascular events (a composite endpoint of myocardial infarction, stroke, heart failure, or cardiovascular mortality) or total mortality.

    Results:

    During up to 11 years of follow-up, 6344 patients (18.7%) had a first cardiovascular event, and 6235 died (18.3%). The associations of annually updated SBP and DBP with risk of major cardiovascular events were U-shaped. The lowest risk of cardiovascular events was observed at a SBP of 135-139mmHg and a DBP of 74-76mmHg, and the lowest mortality risk at a SBP of 142-150mmHg and a DBP of 78-79mmHg, in both antihypertensive drug-untreated and drug-treated persons.

    Conclusion:

    In a large primary care-based sample of patients with type-2 diabetes, associations of SBP and DBP with risk of major cardiovascular events and mortality were U-shaped. This may have implications for risk stratification of persons with diabetes.

  • 243.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sullivan, Lisa
    D'Agostino, Ralph B
    Jacques, Paul F
    Selhub, Jacob
    Rosenberg, Irwin H
    Wilson, Peter W F
    Levy, Daniel
    Vasan, Ramachandran S
    Plasma homocysteine, hypertension incidence, and blood pressure tracking: the Framingham Heart Study.2003Inngår i: Hypertension, ISSN 1524-4563, Vol. 42, nr 6, s. 1100-5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Plasma homocysteine is cross-sectionally associated with blood pressure in large, community-based studies. It is unknown whether elevated plasma homocysteine predicts hypertension incidence. We investigated the relations of baseline plasma total homocysteine levels to hypertension incidence and blood pressure tracking in 2104 Framingham Heart Study participants (mean age, 57 years; 58% women), who were free of hypertension, myocardial infarction, heart failure, atrial fibrillation, or renal failure at baseline. Baseline mean+/-SD plasma homocysteine was 10.1+/-3.7 micromol/L. On follow-up 4 years from baseline, 360 persons (17.1%) had developed hypertension, and 878 persons (41.7%) had progressed to a higher blood pressure stage. In unadjusted analyses, a 1-SD higher log homocysteine value was associated with increased odds of developing hypertension (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.05 to 1.32) and increased odds of blood pressure progression (OR, 1.17; 95% CI, 1.07 to 1.27). The relations of plasma homocysteine to the incidence of hypertension or blood pressure progression were statistically nonsignificant in age- and sex-adjusted logistic regression models (OR, 0.98; 95% CI, 0.87 to 1.11 and OR, 1.05; 95% CI, 0.96 to 1.16, respectively) and in multivariable models adjusted for age, sex, body mass index, diabetes, interim weight change, smoking, serum creatinine, baseline blood pressure, and blood pressure category (OR, 0.92; 95% CI, 0.81 to 1.06 and OR, 1.07; 95% CI, 0.97 to 1.18, respectively). In conclusion, we found no major relation of baseline plasma homocysteine levels to hypertension incidence or longitudinal blood pressure progression in a large, community-based cohort of nonhypertensive individuals after adjustment for age, sex, and other important covariates.

  • 244.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Institutionen för folkhälso- och vårdvetenskap.
    Sullivan, Lisa
    D'Agostino, Ralph B
    Levy, Daniel
    Kannel, William B
    Vasan, Ramachandran S
    Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence.2005Inngår i: Hypertension, ISSN 1524-4563, Vol. 45, nr 1, s. 28-33Artikkel i tidsskrift (Fagfellevurdert)
  • 245.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sullivan, Lisa
    Selhub, Jacob
    Benjamin, Emelia J
    D'Agostino, Ralph B
    Jacques, Paul F
    Rosenberg, Irwin H
    Levy, Daniel
    Wilson, Peter W F
    Vasan, Ramachandran S
    Relations of plasma homocysteine to left ventricular structure and function: the Framingham Heart Study.2004Inngår i: Eur Heart J, ISSN 0195-668X, Vol. 25, nr 6, s. 523-30Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS: Hyperhomocysteinaemia is a risk factor for congestive heart failure, especially in women. We investigated if homocysteine promotes left ventricular (LV) remodelling. METHODS AND RESULTS: We examined cross-sectional relations of plasma total homocysteine to echocardiographic LV structure and function in 2697 Framingham Heart Study participants (mean age 58 years, 58% women) free of heart failure and previous myocardial infarction. Adjusting for age and height, plasma homocysteine was positively related to LV mass, wall thickness, and relative wall thickness in women (p=0.0004-0.04), but not in men (p=0.28-0.68). Adjusting additionally for other clinical covariates, the relations of plasma homocysteine to LV mass and wall thickness in women remained statistically significant, but the relation to relative wall thickness became of borderline significance (1.92 g, 0.01 cm, and 0.29% increase, respectively, for a 1-SD increase in ln[homocysteine], p=0.01-0.08). LV mass and wall thickness were higher in the fourth quartile of plasma homocysteine compared to the lower three in all models in women (p=0.0003-0.02), but not in men (p=0.25-0.78). Plasma homocysteine was not related to left atrial size or LV fractional shortening in either sex. CONCLUSION: In our community-based sample, plasma homocysteine was directly related to LV mass and wall thickness in women but not in men.

  • 246.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Vallhagen, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Risk associated with the metabolic syndrome versus the sum of its individual components2006Inngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 29, nr 7, s. 1673-1674Artikkel i tidsskrift (Fagfellevurdert)
  • 247.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Vasan, Ramachandran S.
    Circulating biomarkers of extracellular matrix remodeling and risk of atherosclerotic events2006Inngår i: Current Opinion in Lipidology, ISSN 0957-9672, E-ISSN 1473-6535, Vol. 17, nr 1, s. 45-53Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE OF REVIEW: Disturbances of the synthesis and breakdown of the extracellular matrix of arterial walls have emerged as key features of the atherosclerotic process. Altered levels of circulating extracellular matrix markers have frequently been observed in relation to manifestations of atherosclerotic disease and its risk factors.

    RECENT FINDINGS: Research has been focused on the matrix-degrading metalloproteinases, their tissue inhibitors, and procollagen peptides. The most promising matrix metalloproteinase is matrix metalloproteinase-9, which has been observed to predict rapid coronary artery narrowing, ischemic heart disease incidence, abdominal aortic aneurysm expansion, worse outcome in stroke patients, and cardiovascular death. The use of tissue inhibitors of metalloproteinases for prognostication is uncertain thus far. The procollagen marker with most prognostic potential is the marker for type III collagen turnover rate, the N-terminal propeptide PIIINP, higher levels of which predict an adverse outcome after a myocardial infarction and in chronic heart failure, and portend abdominal aortic aneurysm expansion and risk of rupture. Also, the marker for type I collagen synthesis, the C-terminal propeptide PICP, predicts adverse outcomes following myocardial infarction and in chronic heart failure. Extracellular matrix remodeling is also a promising therapeutic target, being favorably affected by several conventional cardiovascular drugs and select dietary interventions. Synthetic matrix metalloproteinase inhibitors are also under development.

    SUMMARY: Circulating matrix markers have emerged as candidate biomarkers for predicting risk of subsequent atherosclerotic events. Future large longitudinal observational and intervention studies will determine the role of matrix biomarkers in diagnosis and prognostication, and as targets for intervention in cardiovascular diseases.

  • 248.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Institutionen för folkhälso- och vårdvetenskap.
    Vasan, Ramachandran S
    Homocysteine and heart failure: a review of investigations from the Framingham Heart Study.2005Inngår i: Clin Chem Lab Med, ISSN 1434-6621, Vol. 43, nr 10, s. 987-92Artikkel i tidsskrift (Fagfellevurdert)
  • 249.
    Sundström, Johan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Stolare, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Blood Pressure-Independent Relations of Left Ventricular Geometry to the Metabolic Syndrome and Insulin Resistance: A Population-Based Study2008Inngår i: Heart, ISSN 1468-201X, Vol. 94, s. 874-878Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Insulin resistance independently predicts heart failure and coronary disease, and has been related to thick left ventricular walls, mainly in studies of hypertensive samples not fully accounting for the influence of blood pressure. This study investigated whether the metabolic syndrome and insulin resistance are related to left ventricular geometry independently of blood pressure.

    Design: Cross-sectional study.

    Setting: A community-based sample of 820 70-year-old men and women (the Prospective Investigation of the Vasculature in Uppsala Seniors, PIVUS) free from valvular disease, heart failure and myocardial infarction.

    Main outcome measures: Relations of the National Cholesterol Education Program-defined metabolic syndrome and homeostasis model assessment of insulin resistance (HOMA-IR) to echocardiographic left ventricular geometry. Models were adjusted for sex, height, intra-arterial systolic and diastolic blood pressures, and antihypertensive medication.

    Results: Left ventricular mass index was increased in persons with the metabolic syndrome in the total sample (49.7 (SD 13.1) vs 39.7 (SD 11.5) g/m2.7, p<0.001) and in subgroups of normotensive and hypertensive persons, mainly accounted for by an increased relative wall thickness. HOMA-IR was related to left ventricular mass index in the total sample (r = 0.31; p<0.001) and in hypertensive persons, but with borderline significance in normotensive persons. HOMA-IR was related to relative wall thickness in the total sample (r = 0.27; p<0.001), in normotensive and hypertensive persons.

    Conclusions: Left ventricular mass and relative wall thickness were increased in persons with the metabolic syndrome and were related to HOMA-IR in a large population-based sample of men and women of the same age, accounting for covariates including intra-arterial blood pressure levels.

  • 250.
    Svedberg, Niclas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Falun Cent Hosp, Dept Cardiol, S-79182 Falun, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Hållmarker, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Mora Hosp, Dept Med, Mora, Sweden.
    Hambraeus, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Falun Cent Hosp, Dept Cardiol, S-79182 Falun, Sweden.
    Andersen, Kasper
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Long-Term Incidence of Atrial Fibrillation and Stroke Among Cross-Country Skiers Cohort Study of Endurance-Trained Male and Female Athletes2019Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 140, nr 11, s. 910-920Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Studies have revealed a higher incidence of atrial fibrillation among well-trained athletes. We aim to investigate associations of endurance training with incidence of atrial fibrillation and stroke and to establish potential sex differences of such associations in a cohort of endurance trained athletes. Methods: All Swedish skiers (208 654) completing 1 or more races in the 30 to 90 km cross-country skiing event Vasaloppet (1989-2011) and a matched sample (n=527 448) of nonskiers were followed until first event of atrial fibrillation or stroke. Cox regression was used to investigate associations of number of completed races and finishing time with incidence of atrial fibrillation and stroke. Results: Female skiers in Vasaloppet had a lower incidence of atrial fibrillation than did female nonskiers (hazard ratio [HR], 0.55; 95% CI, 0.48-0.64), independent of finishing time and number of races. Male skiers had a similar incidence to that of nonskiers (HR, 0.98; 95% CI, 0.93-1.03). Skiers with the highest number of races or fastest finishing times had the highest incidence. Skiers of either sex had a lower incidence of stroke than did nonskiers (HR, 0.64; 95% CI, 0.60-0.67), independent of the number of races and finishing time. Skiers with atrial fibrillation had higher incidence of stroke than did skiers and nonskiers without atrial fibrillation (men: HR, 2.28; 95% CI, 1.93-2.70; women: HR, 3.51; 95% CI, 2.17-5.68; skiers with atrial fibrillation vs. skiers without atrial fibrillation). After diagnosis of atrial fibrillation, skiers with atrial fibrillation had a lower incidence of stroke (HR, 0.73; 95% CI, 0.50-0.91) and lower mortality compared with nonskiers with atrial fibrillation (HR, 0.57; 95% CI, 0.49-0.65). Conclusions: Female skiers in Vasaloppet had lower incidence of atrial fibrillation and stroke. Male skiers had similar incidence of atrial fibrillation and lower risk of stroke. Men with higher number of races and faster finishing times had the highest incidence of atrial fibrillation. After diagnosis of atrial fibrillation, skiers had lower incidence of stroke and death than did nonskiers with atrial fibrillation. This indicates that although on an individual level atrial fibrillation in well-trained individuals is associated with higher incidence of stroke, on population level, risk of stroke is low and that exercise should not be avoided.

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