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  • 151. Locke, Adam E
    et al.
    Kahali, Bratati
    Berndt, Sonja I
    Justice, Anne E
    Pers, Tune H
    Day, Felix R
    Powell, Corey
    Vedantam, Sailaja
    Buchkovich, Martin L
    Yang, Jian
    Croteau-Chonka, Damien C
    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.
    Ferreira, Teresa
    Gustafsson, Stefan
    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
    Mägi, Reedik
    Randall, Joshua C
    Winkler, Thomas W
    Wood, Andrew R
    Workalemahu, Tsegaselassie
    Faul, Jessica D
    Smith, Jennifer A
    Hua Zhao, Jing
    Zhao, Wei
    Chen, Jin
    Fehrmann, Rudolf
    Hedman, Åsa K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Karjalainen, Juha
    Schmidt, Ellen M
    Absher, Devin
    Amin, Najaf
    Anderson, Denise
    Beekman, Marian
    Bolton, Jennifer L
    Bragg-Gresham, Jennifer L
    Buyske, Steven
    Demirkan, Ayse
    Deng, Guohong
    Ehret, Georg B
    Feenstra, Bjarke
    Feitosa, Mary F
    Fischer, Krista
    Goel, Anuj
    Gong, Jian
    Jackson, Anne U
    Kanoni, Stavroula
    Kleber, Marcus E
    Kristiansson, Kati
    Lim, Unhee
    Lotay, Vaneet
    Mangino, Massimo
    Mateo Leach, Irene
    Medina-Gomez, Carolina
    Medland, Sarah E
    Nalls, Michael A
    Palmer, Cameron D
    Pasko, Dorota
    Pechlivanis, Sonali
    Peters, Marjolein J
    Prokopenko, Inga
    Shungin, Dmitry
    Stančáková, Alena
    Strawbridge, Rona J
    Ju Sung, Yun
    Tanaka, Toshiko
    Teumer, Alexander
    Trompet, Stella
    van der Laan, Sander W
    van Setten, Jessica
    Van Vliet-Ostaptchouk, Jana V
    Wang, Zhaoming
    Yengo, Loïc
    Zhang, Weihua
    Isaacs, Aaron
    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
    Attwood, Antony P
    Bandinelli, Stefania
    Barrett, Amy
    Bas, Isabelita N
    Bellis, Claire
    Bennett, Amanda J
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Blagieva, Roza
    Blüher, Matthias
    Böhringer, Stefan
    Bonnycastle, Lori L
    Böttcher, Yvonne
    Boyd, Heather A
    Bruinenberg, Marcel
    Caspersen, Ida H
    Ida Chen, Yii-Der
    Clarke, Robert
    Warwick Daw, E
    de Craen, Anton J M
    Delgado, Graciela
    Dimitriou, Maria
    Doney, Alex S F
    Eklund, Niina
    Estrada, Karol
    Eury, Elodie
    Folkersen, Lasse
    Fraser, Ross M
    Garcia, Melissa E
    Geller, Frank
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Gigante, Bruna
    Go, Alan S
    Golay, Alain
    Goodall, Alison H
    Gordon, Scott D
    Gorski, Mathias
    Grabe, Hans-Jörgen
    Grallert, Harald
    Grammer, Tanja B
    Gräßler, Jürgen
    Grönberg, Henrik
    Groves, Christopher J
    Gusto, Gaëlle
    Haessler, Jeffrey
    Hall, Per
    Haller, Toomas
    Hallmans, Goran
    Hartman, Catharina A
    Hassinen, Maija
    Hayward, Caroline
    Heard-Costa, Nancy L
    Helmer, Quinta
    Hengstenberg, Christian
    Holmen, Oddgeir
    Hottenga, Jouke-Jan
    James, Alan L
    Jeff, Janina M
    Johansson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Jolley, Jennifer
    Juliusdottir, Thorhildur
    Kinnunen, Leena
    Koenig, Wolfgang
    Koskenvuo, Markku
    Kratzer, Wolfgang
    Laitinen, Jaana
    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
    Sin Lo, Ken
    Lobbens, Stéphane
    Lorbeer, Roberto
    Lu, Yingchang
    Mach, François
    Magnusson, Patrik K E
    Mahajan, Anubha
    McArdle, Wendy L
    McLachlan, Stela
    Menni, Cristina
    Merger, Sigrun
    Mihailov, Evelin
    Milani, Lili
    Moayyeri, Alireza
    Monda, Keri L
    Morken, Mario A
    Mulas, Antonella
    Müller, Gabriele
    Müller-Nurasyid, Martina
    Musk, Arthur W
    Nagaraja, Ramaiah
    Nöthen, Markus M
    Nolte, Ilja M
    Pilz, Stefan
    Rayner, Nigel W
    Renstrom, Frida
    Rettig, Rainer
    Ried, Janina S
    Ripke, Stephan
    Robertson, Neil R
    Rose, Lynda M
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Schumacher, Fredrick R
    Scott, William R
    Seufferlein, Thomas
    Shi, Jianxin
    Vernon Smith, Albert
    Smolonska, Joanna
    Stanton, Alice V
    Steinthorsdottir, Valgerdur
    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.
    Tan, Sian-Tsung
    Tayo, Bamidele O
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tyrer, Jonathan P
    Uh, Hae-Won
    Vandenput, Liesbeth
    Verhulst, Frank C
    Vermeulen, Sita H
    Verweij, Niek
    Vonk, Judith M
    Waite, Lindsay L
    Warren, Helen R
    Waterworth, Dawn
    Weedon, Michael N
    Wilkens, Lynne R
    Willenborg, Christina
    Wilsgaard, Tom
    Wojczynski, Mary K
    Wong, Andrew
    Wright, Alan F
    Zhang, Qunyuan
    Brennan, Eoin P
    Choi, Murim
    Dastani, Zari
    Drong, Alexander W
    Eriksson, Per
    Franco-Cereceda, Anders
    Gådin, Jesper R
    Gharavi, Ali G
    Goddard, Michael E
    Handsaker, Robert E
    Huang, Jinyan
    Karpe, Fredrik
    Kathiresan, Sekar
    Keildson, Sarah
    Kiryluk, Krzysztof
    Kubo, Michiaki
    Lee, Jong-Young
    Liang, Liming
    Lifton, Richard P
    Ma, Baoshan
    McCarroll, Steven A
    McKnight, Amy J
    Min, Josine L
    Moffatt, Miriam F
    Montgomery, Grant W
    Murabito, Joanne M
    Nicholson, George
    Nyholt, Dale R
    Okada, Yukinori
    Perry, John R B
    Dorajoo, Rajkumar
    Reinmaa, Eva
    Salem, Rany M
    Sandholm, Niina
    Scott, Robert A
    Stolk, Lisette
    Takahashi, Atsushi
    Tanaka, Toshihiro
    Van't Hooft, Ferdinand M
    Vinkhuyzen, Anna A E
    Westra, Harm-Jan
    Zheng, Wei
    Zondervan, Krina T
    Heath, Andrew C
    Arveiler, Dominique
    Bakker, Stephan J L
    Beilby, John
    Bergman, Richard N
    Blangero, John
    Bovet, Pascal
    Campbell, Harry
    Caulfield, Mark J
    Cesana, Giancarlo
    Chakravarti, Aravinda
    Chasman, Daniel I
    Chines, Peter S
    Collins, Francis S
    Crawford, Dana C
    Adrienne Cupples, L
    Cusi, Daniele
    Danesh, John
    de Faire, Ulf
    den Ruijter, Hester M
    Dominiczak, Anna F
    Erbel, Raimund
    Erdmann, Jeanette
    Eriksson, Johan G
    Farrall, Martin
    Felix, Stephan B
    Ferrannini, Ele
    Ferrières, Jean
    Ford, Ian
    Forouhi, Nita G
    Forrester, Terrence
    Franco, Oscar H
    Gansevoort, Ron T
    Gejman, Pablo V
    Gieger, Christian
    Gottesman, Omri
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hall, Alistair S
    Harris, Tamara B
    Hattersley, Andrew T
    Hicks, Andrew A
    Hindorff, Lucia A
    Hingorani, Aroon D
    Hofman, Albert
    Homuth, Georg
    Kees Hovingh, G
    Humphries, Steve E
    Hunt, Steven C
    Hyppönen, Elina
    Illig, Thomas
    Jacobs, Kevin B
    Jarvelin, Marjo-Riitta
    Jöckel, Karl-Heinz
    Johansen, Berit
    Jousilahti, Pekka
    Wouter Jukema, J
    Jula, Antti M
    Kaprio, Jaakko
    Kastelein, John J P
    Keinanen-Kiukaanniemi, Sirkka M
    Kiemeney, Lambertus A
    Knekt, Paul
    Kooner, Jaspal S
    Kooperberg, Charles
    Kovacs, Peter
    Kraja, Aldi T
    Kumari, Meena
    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
    Moll, Frans L
    Morris, Andrew D
    Morris, Andrew P
    Murray, Jeffrey C
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J
    Ong, Ken K
    Madden, Pamela A F
    Pasterkamp, Gerard
    Peden, John F
    Peters, Annette
    Postma, Dirkje S
    Pramstaller, Peter P
    Price, Jackie F
    Qi, Lu
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Ridker, Paul M
    Rioux, John D
    Ritchie, Marylyn D
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J
    Saramies, Jouko
    Sarzynski, Mark A
    Schunkert, Heribert
    Schwarz, Peter E H
    Sever, Peter
    Shuldiner, Alan R
    Sinisalo, Juha
    Stolk, Ronald P
    Strauch, Konstantin
    Tönjes, Anke
    Trégouët, David-Alexandre
    Tremblay, Angelo
    Tremoli, Elena
    Virtamo, Jarmo
    Vohl, Marie-Claude
    Völker, Uwe
    Waeber, Gérard
    Willemsen, Gonneke
    Witteman, Jacqueline C
    Zillikens, M Carola
    Adair, Linda S
    Amouyel, Philippe
    Asselbergs, Folkert W
    Assimes, Themistocles L
    Bochud, Murielle
    Boehm, Bernhard O
    Boerwinkle, Eric
    Bornstein, Stefan R
    Bottinger, Erwin P
    Bouchard, Claude
    Cauchi, Stéphane
    Chambers, John C
    Chanock, Stephen J
    Cooper, Richard S
    de Bakker, Paul I W
    Dedoussis, George
    Ferrucci, Luigi
    Franks, Paul W
    Froguel, Philippe
    Groop, Leif C
    Haiman, Christopher A
    Hamsten, Anders
    Hui, Jennie
    Hunter, David J
    Hveem, Kristian
    Kaplan, Robert C
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    Martin, Nicholas G
    März, Winfried
    Melbye, Mads
    Metspalu, Andres
    Moebus, Susanne
    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
    Sattar, Naveed
    Schadt, Eric E
    Schlessinger, David
    Eline Slagboom, P
    Snieder, Harold
    Spector, Tim D
    Thorsteinsdottir, Unnur
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uitterlinden, André G
    Uusitupa, Matti
    van der Harst, Pim
    Walker, Mark
    Wallaschofski, Henri
    Wareham, Nicholas J
    Watkins, Hugh
    Weir, David R
    Wichmann, H-Erich
    Wilson, James F
    Zanen, Pieter
    Borecki, Ingrid B
    Deloukas, Panos
    Fox, Caroline S
    Heid, Iris M
    O'Connell, Jeffrey R
    Strachan, David P
    Stefansson, Kari
    van Duijn, Cornelia M
    Abecasis, Gonçalo R
    Franke, Lude
    Frayling, Timothy M
    McCarthy, Mark I
    Visscher, Peter M
    Scherag, André
    Willer, Cristen J
    Boehnke, Michael
    Mohlke, Karen L
    Lindgren, Cecilia M
    Beckmann, Jacques S
    Barroso, Inês
    North, Kari E
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hirschhorn, Joel N
    Loos, Ruth J F
    Speliotes, Elizabeth K
    Genetic studies of body mass index yield new insights for obesity biology2015Inngår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, nr 7538, s. 197-206Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

  • 152.
    Lytsy, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    A proposal for an additional clinical trial outcome measure assessing preventive effect as delay of events2012Inngår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 27, nr 12, s. 903-909Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Many effect measures used in clinical trials are problematic because they are differentially understood by patients and physicians. The emergence of novel methods such as accelerated failure-time models and quantile regression has shifted the focus of effect measurement from probability measures to time-to-event measures. Such modeling techniques are rapidly evolving, but matching non-parametric descriptive measures are lacking. We propose such a measure, the delay of events, demonstrating treatment effect as a gain in event-free time. We believe this measure to be of value for shared clinical decision-making. The rationale behind the measure is given, and it is conceptually explained using the Kaplan–Meier estimate and the quantile regression framework. A formula for calculation of the delay of events is given. Hypothetical and empirical examples are used to demonstrate the measure. The measure is discussed in relation to other measures highlighting the time effects of preventive treatments. There is a need to further investigate the properties of the measure as well as its role in clinical decision-making.

  • 153.
    Lytsy, Per
    et al.
    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.
    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 folkhälso- och vårdvetenskap, Geriatrik.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Interplay of overweight and insulin resistance on hypertension development2014Inngår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 32, nr 4, s. 834-839Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: Obesity and hypertension are associated, possibly through causal pathways involving insulin resistance and metabolic derangements. We aimed to investigate in a whites sample if overweight or obese persons without insulin resistance are at risk of developing hypertension or blood pressure progression. Methods: In a meta-analysis, using multivariable-adjusted mixed-effects logistic regression models, we investigated the risks of hypertension development and blood pressure progression by combinations of relative weight classes and presence or absence of insulin resistance (defined as highest vs. lower three quartiles using the homeostatic model assessment method) in the Uppsala Longitudinal Study of Adult Men (n = 2322) and the Prospective Investigation of the Vasculature in Uppsala Seniors studies (n = 1066). These two samples, consisting mainly of middle-aged and elderly men, provided 1846 observations for the development of hypertension in normotensive individuals and 4223 observations for progressing to a higher blood pressure stage. Results: During a median of 10 years of follow-up, 884 (47.9%) developed hypertension and 1639 (38.8%) progressed to a higher blood pressure stage. Overweight or obese persons without insulin resistance had an increased risk of hypertension development [odds ratio (OR) 1.46, 95% confidence interval 1.14-1.88] and blood pressure progression (OR 1.32, 1.10-1.59) compared with normal-weight persons without insulin resistance. Conclusion: According to this study, being overweight or obese without insulin resistance increases the risk of hypertension and blood pressure progression. This adds to the evidence that overweight and obesity may be harmful per se, and that overweight and obesity without glucometabolic derangements are not benign conditions.

  • 154.
    Lytsy, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Endothelial function and risk of hypertension and blood pressure progression: the prospective investigation of the vasculature in Uppsala seniors2013Inngår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 31, nr 5, s. 936-939Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES

    Impaired endothelial function is associated with risk of cardiovascular events, possibly via increased blood pressure. We aimed to investigate if impaired endothelial function is associated with risk of hypertension and blood pressure progression in a large community-based sample.

    METHODS

    In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, endothelium-dependent vasodilation (EDV) was measured in resistance arteries using the invasive forearm technique and in conduit arteries using the flow-mediated vasodilation technique (FMD) at age 70, and participants were re-examined after 5 years. We investigated risk of developing hypertension or blood pressure progression in multivariable-adjusted logistic regression models.

    RESULTS

    In 201 out of 506 untreated persons, blood pressure progressed to a higher stage, and among 197 normotensive persons, 87 developed hypertension. Endothelial function, measured with the invasive forearm technique and the brachial ultrasound technique, did not predict either the development of hypertension [EDV: odds ratio (OR) per SD 1.16, 95% confidence interval (CI) 0.84-1.59; FMD: OR per SD 1.00, 95% CI 0.76-1.33) or blood pressure progression (EDV: OR per SD 0.90, 95% CI 0.73-1.11; FMD: OR per SD 1.01, 95% CI 0.84-1.21).

    CONCLUSION

    In this large community-based sample of elderly, impaired endothelial function measured with the invasive forearm technique did not play a major role in the development of hypertension or blood pressure progression. Observed associations between endothelial dysfunction and risk of cardiovascular events are likely mediated through other pathways than hypertension.

  • 155.
    Mahadev, Srihari
    et al.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.
    Laszkowska, Monika
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.
    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).
    Björkholm, Magnus
    Karolinska Univ Hosp, Div Hematol, Dept Med, Stockholm, Sweden;Karolinska Inst, Stockholm, Sweden.
    Lebwohl, Benjamin
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.
    Green, Peter H. R.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.
    Ludvigsson, Jonas F.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA;Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden;Orebro Univ Hosp, Dept Pediat, Orebro, Sweden;Univ Nottingham, Sch Med, Div Epidemiol & Publ Hlth, Nottingham, England.
    Prevalence of Celiac Disease in Patients With Iron Deficiency Anemia-A Systematic Review With Meta-analysis2018Inngår i: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 155, nr 2, s. 374-382.e1Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    BACKGROUND & AIMS: Anemia is common in patients with celiac disease (CD) and a frequent mode of presentation. Guidelines recommend screening patients with iron-deficiency anemia (IDA) for CD. However, the reported prevalence of CD in patients with IDA varies. We performed a systematic review to determine the prevalence of biopsy-verified CD in patients with IDA. METHODS: We performed a systematic review of articles published in PubMed Medline or EMBASE through July 2017 for the term "celiac disease" combined with "anemia" or "iron deficiency." We used fixed-effects inverse variance-weighted models to measure the pooled prevalence of CD. Meta-regression was used to assess subgroup heterogeneity. RESULTS: We identified 18 studies composed of 2998 patients with IDA for inclusion in our analysis. Studies originated from the United Kingdom, United States, Italy, Turkey, Iran, and Israel. The crude unweighted prevalence of CD was 4.8% (n = 143). Using a weighted pooled analysis, we found a prevalence of biopsy-confirmed CD of 3.2% (95% confidence interval = 2.6-3.9) in patients with IDA. However, heterogeneity was high (I-2 = 67.7%). The prevalence of CD was not significantly higher in studies with a mean participant age older or younger than 18 years or in studies with a mixed-sex vs female-predominant (>= 60%) population. On meta-regression, year of publication, female proportion, age at CD testing, and prevalence in the general population were not associated with the prevalence of CD in patients with IDA. In the 8 studies fulfilling all our quality criteria, the pooled prevalence of CD was 5.5% (95% confidence interval = 4.1-6.9). CONCLUSIONS: In a systematic review and meta-analysis, we found that approximately 1 in 31 patients with IDA have histologic evidence of CD. This prevalence value justifies the practice of testing patients with IDA for CD.

  • 156.
    Marklund, Matti
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism. Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia;Univ New South Wales, Fac Med, Sydney, NSW, Australia.
    Wu, Jason H. Y.
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia;Univ New South Wales, Fac Med, Sydney, NSW, Australia.
    Imamura, Fumiaki
    Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England.
    Del Gobbo, Liana C.
    Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.
    Fretts, Amanda
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    de Goede, Janette
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
    Shi, Peilin
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
    Tintle, Nathan
    Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA.
    Wennberg, Maria
    Umea Univ, Dept Publ Hlth & Clin Med, Nutr Res, Umea, Sweden.
    Aslibekyan, Stella
    Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
    Chen, Tzu-An
    Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA.
    Otto, Marcia C. de Oliveira
    Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA.
    Hirakawa, Yoichiro
    Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka, Fukuoka, Japan.
    Eriksen, Helle Hojmark
    Aalborg Univ Hosp, Unit Epidemiol & Biostat, Aalborg, Denmark.
    Kroeger, Janine
    German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany.
    Laguzzi, Federica
    Karolinska Inst, Unit Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Lankinen, Maria
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    Murphy, Rachel A.
    Univ British Columbia, Vancouver, BC, Canada.
    Prem, Kiesha
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
    Samieri, Cecilia
    Univ Bordeaux, INSERM, Bordeaux Populat Hlth Res Ctr, TUMR 1219, Bordeaux, France.
    Virtanen, Jyrki
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    Wood, Alexis C.
    Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA.
    Wong, Kerry
    Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
    Yang, Wei-Sin
    Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei, Taiwan.
    Zhou, Xia
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Baylin, Ana
    Univ Michigan, Sch Publ Hlth, Dept Nutr Sci, Ann Arbor, MI 48109 USA;Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Boer, Jolanda M. A.
    Natl Inst Publ Hlth & Environm, Ctr Nutr Prevent & Hlth Serv, Bilthoven, Netherlands.
    Brouwer, Ingeborg A.
    Vrije Univ, Hlth Sci, Amsterdam, Netherlands.
    Campos, Hannia
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
    Chaves, Paulo H. M.
    Florida Int Univ, Herbert Wertheim Coll Med, Benjamin Leon Geriatr Res & Educ, Miami, FL 33199 USA.
    Chien, Kuo-Liong
    Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei, Taiwan;Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan.
    de Faire, Ulf
    Karolinska Inst, Unit Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Djousse, Luc
    Brigham & Womens Hosp, Boston Vet Affairs Healthcare Syst, Boston, MA 02115 USA.
    Eiriksdottir, Gudny
    Iceland Heart Assoc, Kopavogur, Iceland.
    El-Abbadi, Naglaa
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA;USDA, Jean Mayer Human Nutr Res Ctr, Boston, MA USA.
    Forouhi, Nita G.
    Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England.
    Gaziano, J. Michael
    Brigham & Womens Hosp, Boston Vet Affairs Healthcare Syst, Boston, MA 02115 USA.
    Geleijnse, Johanna M.
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
    Gigante, Bruna
    Karolinska Inst, Unit Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Giles, Graham
    Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
    Guallar, Eliseo
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Div Environm Epidemiol, Baltimore, MD USA.
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.
    Harris, Tamara
    NIA, Bethesda, MD 20892 USA.
    Harris, William S.
    Univ South Dakota, Dept Internal Med, Sanford Sch Med, Sioux Falls, SD USA;OmegaQuant Analyt LLC, Sioux Falls, SD USA.
    Helmer, Catherine
    Univ Bordeaux, INSERM, Bordeaux Populat Hlth Res Ctr, TUMR 1219, Bordeaux, France.
    Hellenius, Mai-Lis
    Karolinska Univ Hosp, Karolinska Inst, Cardiol Unit, Dept Med, Stockholm, Sweden.
    Hodge, Allison
    Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
    Hu, Frank B.
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Jacques, Paul F.
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA;USDA, Jean Mayer Human Nutr Res Ctr, Boston, MA USA.
    Jansson, Jan-Hakan
    Umea Univ, Dept Publ Hlth & Clin Med, Res Unit Skelleftea, Umea, Sweden.
    Kalsbeek, Anya
    Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA.
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Sch Clin Med, Cambridge, England.
    Koh, Woon-Puay
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Duke NUS Med Sch, Singapore, Singapore.
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland.
    Leander, Karin
    Karolinska Inst, Unit Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Lin, Hung-Ju
    Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Luben, Robert
    Univ Cambridge, Dept Publ Hlth & Primary Care, Sch Clin Med, Cambridge, England.
    Luo, Juhua
    Indiana Univ, Dept Epidemiol & Biostat, Bloomington, IN USA.
    McKnight, Barbara
    Univ Washington, Dept Biostat, Sch Publ Hlth, Seattle, WA 98195 USA.
    Mursu, Jaakko
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    Ninomiya, Toshiharu
    Kyushu Univ, Grad Sch Med Sci, Dept Epidemiol & Publ Hlth, Fukuoka, Fukuoka, Japan.
    Overvad, Kim
    Aarhus Univ, Dept Publ Hlth, Sect Epidemiol, Aarhus, Denmark;Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark.
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Study, Seattle, WA USA;Univ Washington, Dept Epidemiol, Cardiovasc Hlth Study, Seattle, WA 98195 USA;Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Study, Seattle, WA 98195 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Rimm, Eric
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Schulze, Matthias B.
    German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany.
    Siscovick, David
    New York Acad Med, New York, NY USA.
    Nielsen, Michael Skjelbo
    Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark.
    Smith, Albert, V
    Iceland Heart Assoc, Kopavogur, Iceland.
    Steffen, Brian T.
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
    Steffen, Lyn
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Sun, Qi
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Tsai, Michael Y.
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
    Tunstall-Pedoe, Hugh
    Univ Dundee, Cardiovasc Epidemiol Unit, Inst Cardiovasc Res, Dundee, Scotland.
    Uusitupa, Matti I. J.
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    van Dam, Rob M.
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
    Veenstra, Jenna
    Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA.
    Verschuren, W. M. Monique
    Natl Inst Publ Hlth & Environm, Ctr Nutr Prevent & Hlth Serv, Bilthoven, Netherlands;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
    Wareham, Nick
    Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England.
    Willett, Walter
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Woodward, Mark
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia;Univ New South Wales, Fac Med, Sydney, NSW, Australia;Univ Dundee, Cardiovasc Epidemiol Unit, Inst Cardiovasc Res, Dundee, Scotland;Univ Oxford, George Inst Global Hlth, Oxford, England.
    Yuan, Jian-Min
    Univ Pittsburgh, Div Canc Control & Populat Sci, UPMC Hillman Canc, Pittsburgh, PA 15260 USA;Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
    Micha, Renata
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
    Lemaitre, Rozenn N.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    Mozaffarian, Dariush
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies2019Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, nr 21, s. 2422-2436Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background:

    Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

    Methods:

    We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).

    Results:

    In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15198 incident cardiovascular events occurred among 68659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.

    Conclusions:

    In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

  • 157.
    Masiha, Said
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Inflammatory markers are associated with left ventricular hypertrophy and diastolic dysfunction in a population-based sample of elderly men and women2013Inngår i: Journal of Human Hypertension, ISSN 0950-9240, E-ISSN 1476-5527, Vol. 27, nr 1, s. 13-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Markers of inflammation have previously been related to left ventricular (LV) hypertrophy (LVH) in uremic and hypertensive patients. The present study investigated inflammatory markers in relation to LV geometry and diastolic function in a population of elderly persons. In the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (1016 men and women 70 years of age), echocardiograms to determine relative wall thickness (RWT), LV mass index (LVMI) and the E/A-ratio were obtained. Based on RWT and LVMI, four geometric subgroups were defined; normal, concentric remodeling, eccentric and concentric LVH. In all, 10 circulating inflammatory markers were measured. Higher levels of high sensitive C-reactive protein (hsCRP) and E-selectin were seen in the three abnormal geometry groups than in the normal group adjusting for gender, body mass index, systolic and diastolic blood pressure and use of antihypertensive medication. Higher level of inter-cellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1) and P-selectin were only seen in concentric LVH. Levels of tumor necrosis factor-alpha, interleukin-6, l-selectin, monocyte chemotactic protein-1 and leukocyte count did not differ between the LV groups. l-selectin and hsCRP were related to the E/A-ratio. The adhesion molecules; E-selectin, ICAM-1, VCAM-1, P-selectin and hsCRP were elevated in elderly persons with abnormal LV geometry, especially in concentric LVH, after adjusting for hypertension and obesity. l-selectin and hsCRP were related to LV diastolic function. Further studies are motivated to investigate a pathogenetic role of inflammation for abnormal LV geometry and function.

  • 158.
    Masiha, Said
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    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).
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Left ventricular geometric patterns and adaptations to hemodynamics are similar in elderly men and women2011Inngår i: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 11, s. 25-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Common conditions such as obesity and hypertension result in hemodynamic alterations that will induce remodeling of the left ventricle (LV). However, differences between the genders in the relationship of hemodynamics to LV geometry are not well known. The present study aims to investigate differences between the genders in this respect, in a sample of elderly persons. Methods: Echocardiography and Doppler was performed in a population-based sample aged 70 - The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 922). Hemodynamic patterns obtained by echocardiography and Doppler were evaluated in relation to four LV geometric groups (normal, concentric remodeling, eccentric hypertrophy and concentric hypertrophy). Results: No significant difference between the genders was observed regarding the prevalence of the LV geometric groups. Mean values of most evaluated echocardiography and Doppler variables differed between men and women, such as LA, IVS, LVEDD and IVRT, but the relationship of hemodynamic variables to LV geometric groups did not differ between the genders. Conclusions: Although mean values of many echocardiographic variables differed between men and women, the LV geometric adaptations to a given hemodynamic load appear similar in both genders.

  • 159.
    Mendelson, Michael M.
    et al.
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;Boston Univ, Sch Med, Boston, MA 02118 USA.;Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Marioni, Riccardo E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Joehanes, Roby
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.;Harvard Med Sch, Hebrew SeniorLife, Boston, MA USA..
    Liu, Chunyu
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.;Boston Univ, Dept Biostat, Boston, MA USA..
    Hedman, Åsa K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Aslibekyan, Stella
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA..
    Demerath, Ellen W.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Guan, Weihua
    Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA..
    Zhi, Degui
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA..
    Yao, Chen
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Huan, Tianxiao
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Willinger, Christine
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Chen, Brian
    NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Courchesne, Paul
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Multhaup, Michael
    Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA..
    Lrvin, Marguerite R.
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA..
    Cohain, Ariella
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Bressler, Jan
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    North, Kari
    Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA..
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Gustafsson, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Shah, Sonia
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    McRae, Allan F.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Harris, Sarah E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH8 9YL, Midlothian, Scotland..
    Gibson, Jude
    Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil, Edinburgh EH8 9YL, Midlothian, Scotland..
    Redmond, Paul
    Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland..
    Coriey, Janie
    Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland..
    Murphy, Lee
    Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil, Edinburgh EH8 9YL, Midlothian, Scotland..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9YL, Midlothian, Scotland..
    Kleinbrink, Erica
    Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.;Wayne State Univ, Dept Neurol, Detroit, MI USA..
    Lipovich, Leonard
    Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.;Wayne State Univ, Dept Neurol, Detroit, MI USA..
    Visscher, Peter M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Wray, Naomi R.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Krauss, Ronald M.
    Childrens Hosp Oakland Res Inst, Oakland, CA USA..
    Fallin, Daniele
    Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA..
    Feinberg, Andrew
    Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA..
    Absher, Devin M.
    HudsonAlpha Inst Biotechnol, Huntsville, AL USA..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Univ Texas Houston, Brown Fdn Inst Mol Med, Houston, TX USA..
    Pankow, James S.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Fox, Caroline
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Arnett, Donna K.
    Univ Kentucky, Coll Publ Hlth, Lexington, KY USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Liang, Liming
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA..
    Levy, Daniel
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Deary, Lan J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland..
    Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach2017Inngår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, nr 1, artikkel-id e1002215Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. Methods and Findings We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination. Conclusions We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.

  • 160.
    Michaelsson, H.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Exercise and risk of atrial fibrillation - a systematic review and network meta-analysis2014Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, s. 729-729Artikkel i tidsskrift (Fagfellevurdert)
  • 161.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Baron, John A
    Snellman, Greta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. 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 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.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Blomhoff, Rune
    Wolk, Alicja
    Garmo, Hans
    Regional Oncologic Center, Uppsala University, Uppsala.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Melhus, Håkan
    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 farmakologi.
    Plasma vitamin D and mortality in older men: a community-based prospective cohort study2010Inngår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 92, nr 4, s. 841-848Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Vitamin D status is known to be important for bone health but may also affect the development of several chronic diseases, including cancer and cardiovascular diseases, which are 2 major causes of death. Objective: We aimed to examine how vitamin D status relates to overall and cause-specific mortality. Design: The Uppsala Longitudinal Study of Adult Men, a community-based cohort of elderly men (mean age at baseline: 71 y; n = 1194), was used to investigate the association between plasma 25-hydroxyvitamin D [25(OH)D] and mortality. Total plasma 25(OH)D was determined with HPLC atmospheric pressure chemical ionization mass spectrometry. Proportional hazards regression was used to compute hazard ratios (HRs). Results: During follow-up (median: 12.7 y), 584 (49%) participants died. There was a U-shaped association between vitamin D concentrations and total mortality. An approximately 50% higher total mortality rate was observed among men in the lowest 10% (<46 nmol/L) and the highest 5% (>98 nmol/L) of plasma 25(OH)D concentrations compared with intermediate concentrations. Cancer mortality was also higher at low plasma concentrations (multivariable-adjusted HR: 2.20; 95% CI: 1.44, 3.38) and at high concentrations (HR: 2.64; 95% CI: 1.46, 4.78). For cardiovascular death, only low (HR: 1.89; 95% CI: 1.21, 2.96) but not high (HR: 1.33; 95% CI: 0.69, 2.54) concentrations indicated higher risk. Conclusions: Both high and low concentrations of plasma 25(OH)D are associated with elevated risks of overall and cancer mortality. Low concentrations are associated with cardiovascular mortality.

  • 162.
    Mohammadi, H.
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Ohm, J.
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Discacciati, A.
    Karolinska Inst, Inst Environm Med, Unit Biostat, Stockholm, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Hambraeus, K.
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden.
    Jernberg, T.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Svensson, P.
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Abdominal obesity associates to incident atherosclerotic cardiovascular disease after myocardial infarction2017Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, nr Suppl. 1, s. 237-238, artikkel-id P1121Artikkel i tidsskrift (Annet vitenskapelig)
  • 163.
    Morales Salinas, Alberto
    et al.
    Cardioctr Ernesto Che Guevara, Santa Clara, Cuba.
    Coca, Antonio
    Univ Barcelona, Hosp Clin IDIBAPS, Unidad Hipertens & Riesgo Vasc, Barcelona, Spain.
    Olsen, Michael H.
    Univ Southern Denmark, Holbaek Hosp, Dept Internal Med, Odense, Denmark.;Univ Southern Denmark, Odense Univ Hosp, Ctr Individualized Med Arterial Dis CIMA, Odense, Denmark.
    Sanchez, Ramiro A.
    Hosp Univ, Fdn Favaloro, Hipertens Arterial & Unidad Metabol, Buenos Aires, DF, Argentina.
    Sebba-Barroso, Weimar K.
    Univ Fed Goias, Hypertens League, Jatai, Brazil.
    Kones, Richard
    Cardiometab Res Inst, Houston, TX USA.
    Bertomeu-Martinez, Vicente
    Hosp Univ San Juan, Alicante, Spain.
    Sobrino, Javier
    Fundacio Hosp EsperitSt, Barcelona, Spain.
    Alcocer, Luis
    Inst Mexicano Salud Cardiovasc, Mexico City, DF, Mexico.
    Pineiro, Daniel J.
    Univ Buenos Aires, Buenos Aires, DF, Argentina.
    Lanas, Fernando
    Univ La Frontera, Temuco, Chile.
    Machado, Carlos A.
    Minist Salud, Muncipal Hlth Off, Campos Do Jordao, Brazil.
    Aguirre-Palacios, Fernando
    Clin Kennedy, Guayaquil, Ecuador.
    Ortellado, Jose
    Minist Salud, Asuncion, Paraguay.
    Perez, Gonzalo
    Clin Olivos, Buenos Aires, DF, Argentina.
    Sabio, Rodrigo
    Hospital de Alta Complejidad, Santa Cruz, Argentina.
    Landrove, Orlando
    Minist Salud Pabl, Havana, Cuba.
    Rodriguez-Leyva, Delfin
    Univ Med Holguin, Holguin, Cuba.
    Duenas-Herrera, Alfredo
    Inst Cardiol & Cirugia Cardiovasc, Havana, Cuba.
    Rodriguez Portelles, Ayelen
    Univ Med Holguin, Holguin, Cuba.
    Parra-Carrillo, Jose Z.
    Univ Guadalajara, Guadalajara, Jalisco, Mexico.
    Piskorz, Daniel L.
    Sanatorio Britanico, Inst Cardiol, Rosario, Argentina.
    Bryce-Moncloa, Alfonso
    CARDIOGOLF Lima, Lima, Peru.
    Waisman, Gabriel
    Hosp Italiano Buenos Aires, Buenos Aires, DF, Argentina.
    Yano, Yuichiro
    Univ Mississippi, Med Ctr, University, MS 38677 USA.
    Ventura, Hector
    Univ Queensland, Sch Med, Ochsner Clin Sch, Dept Cardiovasc Dis,John Ochsner Heart & Vasc Ins, New Orleans, LA USA.
    Orias, Marcelo
    Sanatorio Allende & Univ Nacl Cordoba, Cordoba, Argentina.
    Prabhakaran, Dorairaj
    Publ Hlth Fdn India, Gurgaon, Haryana, India.;Ctr Chron Dis Control, Gurgaon, Haryana, India.
    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).
    Wang, Jiguang
    Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Shanghai Inst Hypertens, Shanghai, Peoples R China.
    Burrell, Louise M.
    Univ Melbourne, Austin Health, Dept Med, Melbourne, Vic, Australia.
    Schutte, Alta E.
    North West Univ, Hypertens Africa Res Team, Unit Hypertens & Cardiovasc Dis, South African Med Res Council, Potchefstroom, South Africa.
    Lopez-Jaramillo, Patricio
    Univ Santander, Fdn Oftalmol Santander, Res Inst, Bucaramanga, Colombia.;Univ Santander, Med Sch, Bucaramanga, Ecuador.;Univ Tecnol Equinoccial, Fac Med Eugenio Espejo, Quito, Ecuador.
    Barbosa, Eduardo
    H Moinhos Vento Porto Alegre, Porto Alegre, RS, Brazil.
    Redon, Josep
    Univ Valencia, Valencia, Spain.
    Weber, Michael A.
    Division of Cardiovascular Medicine, State University of New York, Downstate College of Medicine, New York.
    Lavie, Carl J.
    Univ Queensland, Sch Med, Ochsner Clin Sch, Dept Cardiovasc Dis,John Ochsner Heart & Vasc Ins, New Orleans, LA USA.
    Ramirez, Agustin
    Hosp Univ, Fdn Favaloro, Hipertens Arterial & Unidad Metabol, Buenos Aires, DF, Argentina.; Univ Favaloro, CONICET, Inst Med Traslac Trasplante & Bioingn, Buenos Aires, DF, Argentina.
    Ordunez, Pedro
    Pan Amer Hlth Org, Dept Noncommun Dis & Mental Hlth, Washington, DC USA.
    Yusuf, Salim
    Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Hamilton, ON, Canada.
    Zanchetti, Alberto
    Univ Milan, Ist Auxol Italiano, Ctr Interuniv Fisiol Clin & Ipertens, Milan, Italy.
    Clinical Perspective on Antihypertensive Drug Treatment in Adults With Grade 1 Hypertension and Low-to-Moderate Cardiovascular Risk: An International Expert Consultation2017Inngår i: Current problems in cardiology, ISSN 0146-2806, E-ISSN 1535-6280, Vol. 42, nr 7, s. 198-225Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Hypertension is a leading risk factor for disease burden globally. An unresolved question is whether grade 1 hypertension (140-159/90-99 mm Hg) with low (cardiovascular mortality < 1% at 10 years) to moderate (cardiovascular mortality ≥ 1% and <5% at 10 years) absolute total cardiovascular risk (CVR) should be treated with antihypertensive agents. A virtual international consultation process was undertaken to summarize the opinions of select experts. After holistic analysis of all epidemiological, clinical, psychosocial, and public health elements, this consultation process reached the following consensus in hypertensive adults aged < 80 years: (1) The question of whether drug treatment in grade 1 should be preceded by a period of some weeks or months during which only lifestyle measures are recommended cannot be evidence based, but the consensus opinion is to have a period of lifestyle alone reserved only to patients with grade 1 "isolated" hypertension (grade 1 uncomplicated hypertension with low absolute total CVR, and without other major CVR factors and risk modifiers). (2) The initiation of antihypertensive drug therapy in grade 1 hypertension with moderate absolute total CVR should not be delayed. (3) Men ≥ 55 years and women ≥ 60 years with uncomplicated grade 1 hypertension should automatically be classified within the moderate absolute total CVR category, even in the absence of other major CVR factors and risk modifiers. (4) Statins should be considered along with blood-pressure lowering therapy, irrespective of cholesterol levels, in patients with grade 1 hypertensive with moderate CVR.

  • 164. Morris, Andrew P
    et al.
    Le, Thu H
    Wu, Haojia
    Akbarov, Artur
    van der Most, Peter J
    Hemani, Gibran
    Smith, George Davey
    Mahajan, Anubha
    Gaulton, Kyle J
    Nadkarni, Girish N
    Valladares-Salgado, Adan
    Wacher-Rodarte, Niels
    Mychaleckyj, Josyf C
    Dueker, Nicole D
    Guo, Xiuqing
    Hai, Yang
    Haessler, Jeffrey
    Kamatani, Yoichiro
    Stilp, Adrienne M
    Zhu, Gu
    Cook, James P
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Blanton, Susan H
    de Borst, Martin H
    Bottinger, Erwin P
    Buchanan, Thomas A
    Cechova, Sylvia
    Charchar, Fadi J
    Chu, Pei-Lun
    Damman, Jeffrey
    Eales, James
    Gharavi, Ali G
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Heath, Andrew C
    Ipp, Eli
    Kiryluk, Krzysztof
    Kramer, Holly J
    Kubo, Michiaki
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lindgren, Cecilia M
    Lu, Yingchang
    Madden, Pamela A F
    Montgomery, Grant W
    Papanicolaou, George J
    Raffel, Leslie J
    Sacco, Ralph L
    Sanchez, Elena
    Stark, Holger
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Taylor, Kent D
    Xiang, Anny H
    Zivkovic, Aleksandra
    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. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, Stanford Univ, Stanford Cardiovasc Inst, Stanford, USA; Stanford Univ, Stanford Diabet Res Ctr, Stanford, USA.
    Martin, Nicholas G
    Whitfield, John B
    Cai, Jianwen
    Laurie, Cathy C
    Okada, Yukinori
    Matsuda, Koichi
    Kooperberg, Charles
    Chen, Yii-Der Ida
    Rundek, Tatjana
    Rich, Stephen S
    Loos, Ruth J F
    Parra, Esteban J
    Cruz, Miguel
    Rotter, Jerome I
    Snieder, Harold
    Tomaszewski, Maciej
    Humphreys, Benjamin D
    Franceschini, Nora
    Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies2019Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, nr 1, artikkel-id 29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

  • 165.
    Mubanga, Mwenya
    et al.
    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.
    Egenvall, Agneta
    Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Magnusson, Patrik K
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA..
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Dog ownership and Cardiovascular Risk Factors: a nationwide prospective register-based cohort study2019Inngår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, artikkel-id 23447Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To study the association between dog ownership and cardiovascular risk factors.

    Design A nationwide register–based cohort study and a cross-sectional study in a subset.

    Setting A cohort of 2 026 865 participants was identified from the Register of the Total Population and linked to national registers for information on dog ownership, prescribed medication, hospital admissions, education level, income and country of birth. Participants were followed from 1 October, 2006, to the end of the study on 31 December, 2012, assessing medication for a cardiovascular risk factor, emigration and death. Cross-sectional associations were further assessed in 10 110 individuals from the TwinGene study with additional adjustment for professional level, employment status, Charlson comorbidity index, disability and tobacco use.

    Participants All Swedish residents aged 45–80 years on 1 October, 2006.

    Main outcome measures Initiation of medication for hypertension, dyslipidaemia and diabetes mellitus.

    Results After adjustment for confounders, the results indicated slightly higher likelihood of initiating antihypertensive (HR, 1.02; 95% CI, 1.01 to 1.03) and lipid-lowering treatment (HR, 1.02; 95% CI, 1.01 to 1.04) in dog owners than in non-owners, particularly among those aged 45–60 years and in those owning mixed breed or companion/toy breed dogs. No association of dog ownership with initiation of treatment for diabetes was found in the overall analysis (HR, 0.98; 95% CI, 0.95 to 1.01). Sensitivity analyses in the TwinGene cohort indicated confounding of the association between dog ownership and prevalent treatment for hypertension, dyslipidaemia and diabetes mellitus, respectively, from factors not available in the national cohort, such as employment status and non cardiovascularchronic disease status.

    Conclusions In this large cohort study, dog ownership was associated with a minimally higher risk of initiation of treatment for hypertension and dyslipidaemia implying that the previously reported lower risk of cardiovascular mortality among dog owners in this cohort is not explained by reduced hypertension and dyslipidaemia. These observations may suffer from residual confounding despite access to multiple important covariates, and future studies may add valuable information.

  • 166.
    Möller, Christina Ström
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Häggström, Jonas
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Wiberg, Bernice
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sundström, Johan
    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.
    Age and follow-up time affect the prognostic value of the ECG and conventional cardiovascular risk factors for stroke in adult men2007Inngår i: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 61, nr 8, s. 704-712Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To explore whether the predictive power of mid-life ECG abnormalities and conventional cardiovascular risk factors for future stroke change over a 30-year follow-up period, and whether a repeated examination improves their predictive power. DESIGN AND SETTING: Longitudinal population-based study. PARTICIPANTS: 2,322 men aged 50 years, with a follow-up period of 30 years. 1,221 subjects were re-examined at age 70 years MAIN OUTCOME MEASURE: Risk for fatal and non-fatal stroke during three decades of follow-up. Investigations included resting ECG and traditional cardiovascular risk factors. RESULTS: When measured at age 50 years, ST segment depression and T wave abnormalities, together with ECG-left ventricular hypertrophy, were of importance only during the first 20 years, but regained importance when re-measured at age 70 years. Blood pressure was a significant predictor for stroke over all three decades of follow-up. In elderly people only, there is evidence that apolipoprotein A1 may protect from future stroke. CONCLUSION: Mid-life values for blood pressure and ECG abnormalities retain their predictive value over long follow-up periods even though they improved in predictive power when re-measured in elderly people. Despite lower prevalence, ECG abnormalities had greater impact at age 50 years than at age 70 years. By contrast, apolipoprotein A1 was protective for future stroke only at age 70 years.

  • 167.
    Möller, Christina Ström
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Zethelius, Björn
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundström, Johan
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Lind, Lars
    Institutionen för medicinska vetenskaper.
    Impact of follow-up time and re-measurement of the electrocardiogram and conventional cardiovascular risk factors on their predictive value for myocardial infarction.2006Inngår i: J Intern Med, ISSN 0954-6820, Vol. 260, nr 1, s. 22-30Artikkel i tidsskrift (Fagfellevurdert)
  • 168. Neovius, Kristian
    et al.
    Rasmussen, Finn
    Sundstrom, 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).
    Neovius, Martin
    Forecast of future premature mortality as a result of trends in obesity and smoking: nationwide cohort simulation study2010Inngår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 25, nr 10, s. 703-709Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In many countries obesity has increased dramatically during the last decades, while there has been a parallel decrease in smoking. The objective of the present study was to estimate the net effect on premature mortality of these trends. A simulation model was developed to estimate the expected number of deaths between ages 19-56 years for cohorts of young men (n = 50,000), depending on inputs of obesity and smoking prevalence. The model was populated with nationwide data of Swedish men performing mandatory military conscription tests between 1969 and 2005. Risk equations for all cause mortality with smoking and obesity status as predictors were developed based on the 1969-1970 conscription cohort (n = 45,920; 2,897 deaths, median follow-up 38 years). It was found that between 1969 and 2005, the prevalence of smoking decreased from 58.6 to 23.2%, while overweight increased from 5.7 to 15.6% and obesity from 0.8 to 5.5%. As a result of these trends, a 14% (CI95% 6, 21%) reduction of premature deaths between ages 19 and 56 years was forecasted for men aged 19 year in 2004-2005 compared to men aged 19 years in 1969-1970 (2,679 vs. 3,116 deaths). However, one-third of the survival benefit from reduced smoking during the period was offset due to the parallel increase in obesity. This study shows that despite large increases in overweight and obesity, a continued decline in premature deaths among Swedish males is expected due to reduced smoking during the last four decades.

  • 169.
    Neovius, Martin
    et al.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden.
    Bruze, Gustaf
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden.
    Jacobson, Peter
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden.
    Sjoholm, Kajsa
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden.
    Johansson, Kari
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden.
    Granath, Fredrik
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Naslund, Ingmar
    Orebro Univ, Fac Med & Hlth, Dept Surg, Orebro, Sweden.
    Marcus, Claude
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Ottosson, Johan
    Orebro Univ, Fac Med & Hlth, Dept Surg, Orebro, Sweden.
    Peltonen, Markku
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
    Carlsson, Lena M. S.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden.
    Risk of suicide and non-fatal self-harm after bariatric surgery: results from two matched cohort studies2018Inngår i: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 6, nr 3, s. 197-207Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Bariatric surgery reduces mortality, but might have adverse effects on mental health. We assessed the risk of suicide and self-harm after bariatric surgery compared with non-surgical obesity treatment. Methods Suicide and non-fatal self-harm events retrieved from nationwide Swedish registers were examined in two cohorts. The non-randomised, prospective Swedish Obese Subjects (SOS) study compared bariatric surgery (n=2010; 1369 vertical-banded gastroplasty, 376 gastric banding, and 265 gastric bypass) with usual care (n=2037; recruitment 1987-2001). The second cohort consisted of individuals from the Scandinavian Obesity Surgery Registry (SOReg; n=20 256 patients who had gastric bypass) matched to individuals treated with intensive lifestyle modification (n=16 162; intervention 2006-13) on baseline BMI, age, sex, education level, diabetes, cardiovascular disease, history of self-harm, substance misuse, antidepressant use, anxiolytics use, and psychiatric health-care contacts. Findings During 68 528 person-years (median 18; IQR 14-21) in the SOS study, suicides or non-fatal self-harm events were higher in the surgery group (n=87) than in the control group (n=49; adjusted hazard ratio [aHR] 1.78, 95% CI 1.23-2.57; p=0.0021); of these events, nine and three were suicides, respectively (3.06, 0.79-11.88; p=0.11). In analyses by primary procedure type, increased risk of suicide or non-fatal self-harm was identified for gastric bypass (3.48, 1.65-7.31; p=0.0010), gastric banding (2.43, 1.23-4.82; p=0.011), and vertical-banded gastroplasty (2.25, 1.37-3.71; p=0.0015) compared with controls. Out of nine deaths by suicide in the SOS surgery group, five occurred after gastric bypass (two primary and three converted procedures). During 149 582 person-years (median 3.9; IQR 2.8-5.2), more suicides or non-fatal self-harm events were reported in the SOReg gastric bypass group (n=341) than in the intensive lifestyle group (n=84; aHR 3.16, 2.46-4.06; p<0.0001); of these events, 33 and five were suicides, respectively (5.17, 1.86-14.37; p=0.0017). In SOS, substance misuse during follow-up was recorded in 48% (39/81) of patients treated with surgery and 28% (13/47) of controls with non-fatal self-harm events (p=0.023). Correspondingly, substance misuse during follow-up was recorded in 51% (162/316) of participants in the SOReg gastric bypass group and 29% (23/80) of participants in the intensive lifestyle group with non-fatal self-harm events (p=0.0003). The risk of suicide and self-harm was not associated with poor weight loss outcome. Interpretation Bariatric surgery was associated with suicide and non-fatal self-harm. However, the absolute risks were low and do not justify a general discouragement of bariatric surgery. The findings indicate a need for thorough preoperative psychiatric history assessment along with provision of information about increased risk of self-harm following surgery. Moreover, the findings call for postoperative surveillance with particular attention to mental health.

  • 170. Neovius, Martin
    et al.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Rasmussen, Finn
    Combined effects of overweight and smoking in late adolescence on subsequent mortality: nationwide cohort study2009Inngår i: BMJ. British Medical Journal (International Ed.), ISSN 0959-8146, E-ISSN 0959-535X, Vol. 338, s. b496-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To investigate the combined effects on adult mortality of overweight and smoking in late adolescence. DESIGN: Record linkage study with Cox proportional hazard ratios adjusted for muscle strength, socioeconomic position, and age. SETTING: Swedish military service conscription register, cause of death register, and census data. PARTICIPANTS: 45 920 Swedish men (mean age 18.7, SD 0.5) followed for 38 years. MAIN OUTCOME MEASURES: Body mass index (underweight (BMI <18.5), normal weight (18.5-24.9), overweight (25-29.9), and obesity (>or=30)), muscle strength, and self reported smoking (non-smoker, light smoker (1-10 cigarettes/day), heavy smoker (>10/day)) at mandatory military conscription tests in 1969-70. All cause mortality. RESULTS: Over 1.7 million person years, 2897 men died. Compared with normal weight men (incidence rate 17/10 000 person years, 95% confidence interval 16 to 18), risk of mortality was increased in overweight (hazard ratio 1.33, 1.15 to 1.53; incidence rate 23, 20 to 26) and obese men (hazard ratio 2.14, 1.61 to 2.85; incidence rate 38, 27 to 48), with similar relative estimates in separate analyses of smokers and non-smokers. No increased risk was detected in underweight men (hazard ratio 0.97, 0.86 to 1.08; incidence rate 18, 16 to 19), though extreme underweight (BMI <17) was associated with increased mortality (hazard ratio 1.33, 1.07 to 1.64; incidence rate 24, 19 to 29). The relative excess risk due to interaction between BMI and smoking status was not significant in any stratum. Furthermore, all estimates of interaction were of small magnitude, except for the combination of obesity and heavy smoking (relative excess risk 1.5, -0.7 to 3.7). Compared with non-smokers (incidence rate 14, 13 to 15), risk was increased in both light (hazard ratio 1.54, 1.41 to 1.70; incidence rate 15, 14 to 16) and heavy smokers (hazard ratio 2.11, 1.92 to 2.31; incidence rate 26, 24 to 27). CONCLUSIONS: Regardless of smoking status, overweight and obesity in late adolescence increases the risk of adult mortality. Obesity and overweight were as hazardous as heavy and light smoking, respectively, but there was no interaction between BMI and smoking status. The global obesity epidemic and smoking among adolescents remain important targets for intensified public health initiatives.

  • 171.
    Nerpin, Elisabet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Riserus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Jobs, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Oxidativ stress och inflammation.
    Ingelsson, Erik
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men: a cross-sectional study2012Inngår i: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 5, nr 1, s. 537-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

     BACKGROUND: The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Accordingly, we aimed at investigating the associations between estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and markers of different inflammatory pathways and oxidative stress in a community based cohort of elderly men.

    FINDINGS: Cystatin C-based GFR, ACR, and biomarkers of cytokine-mediated inflammation (interleukin-6, high-sensitivity C-reactive protein[CRP], serum amyloid A[SAA]), cyclooxygenase-mediated inflammation (urinary prostaglandin F2alpha [PGF2alpha]), and oxidative stress (urinary F2 isoprostanes) were assessed in the Uppsala Longitudinal Study of Adult Men(n = 647, mean age 77 years).

    RESULTS: In linear regression models adjusting for age, BMI, smoking, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and treatment with statins, ACE-inhibitors, ASA, and anti-inflammatory agents, eGFR was inversely associated with CRP, interleukin-6, and SAA (beta-coefficient -0.13 to -0.19, p < 0.001 for all), and positively associated with urinary F2-isoprostanes (beta-coefficient 0.09, p = 0.02). In line with this, ACR was positively associated with CRP, interleukin-6, and SAA (beta- coefficient 0.09-0.12, p < 0.02 for all), and negatively associated with urinary F2-isoprostanes (beta-coefficient -0.12, p = 0.002). The associations were similar but with lower regression coefficients in a sub-sample with normal eGFR (>60 ml/min/1.73 m2, n = 514), with the exception that F2-isoprostane and SAA were no longer associated with eGFR.

    CONCLUSION: Our data indicate that cytokine-mediated inflammation is involved in the early stages of impaired kidney function in the elderly, but that cyclooxygenase-mediated inflammation does not play a role at this stage. The unexpected association between higher eGFR/lower albuminuria and increased F2-isoprostanes in urine merits further studies.

  • 172.
    Nerpin, Elisabet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ingelsson, Erik
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Jobs, Elisabeth
    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, Biokemisk struktur och funktion.
    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 folkhälso- och vårdvetenskap, Geriatrik.
    Association between glomerular filtration rate and endothelial function in an elderly community cohort2012Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, nr 1, s. 242-246Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Endothelial dysfunction is prevalent among individuals with chronic kidney disease. However, the association between glomerular filtration rate and endothelial function in the community is unclear and needs to be investigated in the general population.

    METHODS: In the community-based Prospective Investigation of the Vasculature of Uppsala Seniors study (PIVUS, n = 952, mean age 70, women 49.3%), we investigated cross-sectional associations between estimated cystatin C-based glomerular filtration rate (eGFR), and 3 measures representing different aspects of endothelial function (endothelial-dependent vasodilation [EDV], endothelial independent vasodilatation [EIDV], and flow-mediated dilatation [FMD]). We also performed pre-specified sub-group analyses in participants with normal eGFR (>60 ml/min/1.73 m(2)).

    RESULTS: In the whole cohort, 10 ml/min/1.73 m(2) higher eGFR was associated with 3% higher EDV (p = 0.001) and 2% higher EIDV (p = 0.007), adjusted for age and sex. The associations were attenuated and no longer statistically significant after adjusting for established cardiovascular risk factors. In participants with eGFR >60 ml/min/1.73 m(2), 10 ml higher eGFR was associated with 2% higher EDV (p = 0.04) after adjusting for sex and age. eGFR was not associated to FMD in any model or sub-sample.

    CONCLUSION: This community-based study suggests that eGFR is associated with endothelial function also in persons with normal kidney function, but that this association is largely explained by confounding by established cardiovascular risk factors. Thus, our data do not support the notion of a direct causal interplay between renal and vascular function prior to the development of CKD.

  • 173.
    Nerpin, Elisabet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Högskolan Dalarna-Medicinsk vetenskap.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Andrén, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Jobs, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Högskolan Dalarna Medicinsk vetenskap.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    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 folkhälso- och vårdvetenskap, Geriatrik. Högskolan Dalarna Medicinsk vetenskap.
    The association between glomerular filtration rate and left ventricular function in two independent community-based cohorts of elderly2014Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, nr 11, s. 2069-2074Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The cardiorenal syndrome, the detrimental bi-directional interplay between symptomatic heart failure and chronic kidney disease, is a major clinical challenge. Nonetheless, it is unknown if this interplay begins already at an asymptomatic stage. Therefore we investigated whether the glomerular filtration rate (GFR) is associated with left ventricular function in participants free from clinical heart failure and with a left ventricular ejection fraction (LVEF) > 40% and with pre-specified sub-group analyses in individuals with a GFR > 60 mL/min/m(2). Two independent community-based cohorts were used; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 911; 50% women; mean age: 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 538; mean age: 71 years). We investigated cross-sectional association between cystatin C-based GFR (estimated glomerular function [eGFR]) and systolic (LVEF), diastolic- (isovolumic relaxation time [IVRT]) and global left ventricular function (myocardial performance index [MPI]) determined by echocardiography. In both PIVUS and ULSAM, higher eGFR was significantly associated with higher LVEF (P = 0.004 [PIVUS] and P = 0.005 [ULSAM]). In PIVUS, higher eGFR was significantly associated with lower IVRT (P = 0.001) and MPI (P = 0.006), in age- and sex-adjusted models. After further adjustment for cardiovascular risk factors, the association between higher eGFR and higher LVEF was still statistically significant (P = 0.008 [PIVUS] and P = 0.02 [ULSAM]). In PIVUS, the age- and sex-adjusted association between eGFR and left ventricular function was similar in participants with eGFR > 60 mL/min/m(2). Our data suggest that the interplay between kidney and heart function begins prior to the development of symptomatic heart failure and kidney disease.

  • 174.
    Nerpin, Elisabet
    et al.
    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.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    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).
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jobs, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Jobs, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk virologi.
    Hallan, Stein
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    The combined contribution of albuminuria and glomerular filtration rate to the prediction of cardiovascular mortality in elderly men2011Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, nr 9, s. 2820-2827Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Cardiovascular risk prediction is particularly important in the primary prevention of cardiovascular disease (CVD). Yet, data on whether the combined addition of albuminuria and estimated glomerular filtration rate (eGFR) improves cardiovascular risk prediction in individuals without CVD in the community is scarce.

    METHODS: We investigated associations between urinary albumin excretion rate (UAER), cystatin C-based eGFR and cardiovascular mortality in a community-based cohort of elderly men (ULSAM study; n = 1113, mean age 71 years, 208 cardiovascular deaths, median follow-up 12.9 years) with prespecified analyses in participants without CVD (n = 649, 86 cardiovascular deaths).

    RESULTS: Using multivariable Cox regression, higher UAER and lower eGFR were associated with increased risk for cardiovascular mortality independently of established cardiovascular risk factors in the whole sample and in men without CVD at baseline [subsample without CVD: UAER; hazard ratio (HR) per 1 SD 1.26, 95% confidence interval (CI) 1.05-1.51, P = 0.01; eGFR: HR per 1 SD 0.74, 95% CI 0.59-0.92, P = 0.007]. Analyses of model discrimination, calibration, reclassification and global fit suggested that UAER and eGFR also add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent CVD. Interestingly, established cutoffs used to diagnose microalbuminuria (UAER > 20 μg/min) and chronic kidney disease Stage 3 (eGFR < 60 mL/min/1.73m(2)), appeared less suitable for cardiovascular risk prediction [integrated discrimination improvement (IDI) 0.006, P = 0.11], while cutoffs UAER > 6 μg/min and eGFR < 45 mL/min/1.73m(2) significantly improved IDI (0.047, P < 0.001).

    CONCLUSIONS: UAER and eGFR improved cardiovascular risk prediction beyond established cardiovascular risk factors, suggesting that these kidney biomarkers may be useful in predicting cardiovascular death in elderly men.

  • 175. Nerpin, Elisabet
    et al.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jobs, Magnus
    Larsson, Anders
    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.
    Arnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort2008Inngår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, nr 8, s. 1550-1555Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR. RESEARCH DESIGN AND METHODS: We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C-based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years. RESULTS: Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69-1.68]; P < 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n = 443; P < 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR <50 ml/min per 1.73 m(2)) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40-0.84]; P < 0.004). CONCLUSIONS: Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality.

  • 176.
    Ng, Winda L.
    et al.
    Karolinska Inst, Dept Med, Solna, Clin Epidemiol Unit, Stockholm, Sweden.;Baker Heart & Diabet Inst, Clin Diabet & Epidemiol, Melbourne, Vic, Australia.;Deakin Univ, Fac Hlth, Sch Hlth & Social Dev, Geelong, Vic, Australia.;Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia..
    Peeters, Anna
    Deakin Univ, Fac Hlth, Sch Hlth & Social Dev, Geelong, Vic, Australia.;Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia..
    Näslund, Ingmar
    Univ Orebro, Fac Med & Hlth, Dept Surg, Orebro, Sweden..
    Ottosson, Johan
    Univ Orebro, Fac Med & Hlth, Dept Surg, Orebro, Sweden..
    Johansson, Kari
    Karolinska Inst, Dept Med, Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Marcus, Claude
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Shaw, Jonathan E.
    Baker Heart & Diabet Inst, Clin Diabet & Epidemiol, Melbourne, Vic, Australia.;Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia..
    Bruze, Gustaf
    Karolinska Inst, Dept Med, Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Neovius, Martin
    Karolinska Inst, Dept Med, Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Change in Use of Sleep Medications After Gastric Bypass Surgery or Intensive Lifestyle Treatment in Adults with Obesity2017Inngår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 25, nr 8, s. 1451-1459Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To examine the change in use of hypnotics and/or sedatives after gastric bypass surgery or intensive lifestyle modification in adults with obesity.

    Methods: Adults with obesity who underwent gastric bypass surgery or initiated intensive lifestyle modification between 2007 and 2012 were identified through the Scandinavian Obesity Surgery Registry and a Swedish commercial weight loss database. The two cohorts were matched on BMI, age, sex, education, history of hypnotics and/or sedatives use, and treatment year (surgery n = 20,626; lifestyle n = 11,973; 77% women, mean age 41 years, mean BMI 41 kg/m(2)). The proportion of participants with filled hypnotics and/or sedatives prescriptions was compared yearly for 3 years.

    Results: In the matched treatment cohorts, 4% had filled prescriptions for hypnotics and/or sedatives during the year before treatment. At 1 year follow-up, following an average weight loss of 37 kg and 18 kg in the surgery and intensive lifestyle cohorts, respectively, this proportion had increased to 7% in the surgery cohort but remained at 4% in the intensive lifestyle cohort (risk ratio 1.7; 95% CI: 1.4-2.1); at 2 years, the proportion had increased to 11% versus 5% (risk ratio 2.0; 95% CI: 1.7-2.4); and at 3 years, it had increased to 14% versus 6% (risk ratio 2.2; 95% CI: 1.9-2.6).

    Conclusions: Gastric bypass surgery was associated with increased use of hypnotics and/or sedatives compared with intensive lifestyle modification.

  • 177.
    Nilsen, Tom
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Serum calprotectin levels in elderly males and females without bacterial or viral infections2014Inngår i: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 47, nr 12, s. 1065-1068Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Calprotectin is released from activated leukocytes and calprotectin can thus be used as a marker for leukocyte activation. Faeces calprotectin is not only used as a marker for inflammatory bowel disease but can also be used to detect leukocyte activation in other body fluids. The aim of the present study was to study serum calprotectin levels in non-infected elderly individuals to establish reference intervals for the marker.

    METHODS: Serum calprotectin was analyzed by immunoturbidimetry in 75year old females and males without known infections. Individuals with CRP>20mg/L were excluded as this could indicate a subclinical infection. The calprotectin levels in the remaining 713 individuals were used to calculate reference values for this population. The Spearman rank correlations between calprotectin and 27 other laboratory biomarkers were also investigated.

    RESULTS: There was a strong positive Spearman rank correlation between calprotectin and CRP (p<0.000001) and alkaline phosphatase (p<0.000001). There were also significant negative correlations between calprotectin and ApoA1 and direct HDL-cholesterol.

    CONCLUSIONS: The reference interval for serum-calprotectin for all study subjects was 0.3-2.6mg/L. Leukocyte alkaline phosphatase contributes to serum alkaline phosphatase levels.

  • 178.
    Nowak, C.
    et al.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden.
    Carlsson, A. C.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden.
    Östgren, C. J.
    Linkoping Univ, Linkoping, Sweden.
    Nyström, F. H.
    Linkoping Univ, Linkoping, Sweden.
    Alam, M.
    Dalarna Univ, Falun, Sweden.
    Feldreich, T. R.
    Dalarna Univ, Falun, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Roig, J. J. Carrero
    Karolinska Inst, Solna, Sweden.
    Leppert, Jerzy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Hedberg, Pär O.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Cordeiro, A. C.
    Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ingelsson, E.
    Stanford Univ, Sch Med, Stanford, CA 94305 USA.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Arnlöv, J.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc NVS, Huddinge, Sweden;Dalarna Univ, Falun, Sweden.
    Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes2018Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, s. S65-S65Artikkel i tidsskrift (Annet vitenskapelig)
  • 179.
    Nowak, Christoph
    et al.
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden.
    Carlsson, Axel C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden.
    Östgren, Carl Johan
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Nyström, Fredrik H.
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Alam, Moudud
    Dalarna Univ, Sch Technol & Business Studies Stat, Falun, Sweden.
    Feldreich, Tobias
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Carrero, Juan-Jesus
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Leppert, Jerzy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Hedberg, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Henriksen, Egil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Cordeiro, Antonio C.
    Dante Pazzanese Inst Cardiol, Dept Hypertens & Nephrol, Sao Paulo, Brazil.
    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
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ärnlöv, Johan
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc NVS, Alfred Nobels Alle 23, SE-14183 Huddinge, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden.
    Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes2018Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, nr 8, s. 1748-1757Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims/hypothesis Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. Methods We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. Results Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (+/- SD) of 6.4 +/- 2.3 years. We replicated associations (< 5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit alpha (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. Conclusions/interpretation We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event.

  • 180.
    Nowak, Christoph
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Hetty, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Castillejo-Lopez, Casimiro
    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, Stockholm, Sweden.
    Cook, Naomi L.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Broeckling, Corey D.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
    Prenni, Jessica E.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
    Shen, Xia
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 8691Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Insulin resistance (IR) predisposes to type 2 diabetes and cardiovascular disease but its causes are incompletely understood. Metabolic challenges like the oral glucose tolerance test (OGTT) can reveal pathogenic mechanisms. We aimed to discover associations of IR with metabolite trajectories during OGTT. In 470 non-diabetic men (age 70.6 +/- 0.6 years), plasma samples obtained at 0, 30 and 120 minutes during an OGTT were analyzed by untargeted liquid chromatography-mass spectrometry metabolomics. IR was assessed with the hyperinsulinemic-euglycemic clamp method. We applied age-adjusted linear regression to identify metabolites whose concentration change was related to IR. Nine trajectories, including monounsaturated fatty acids, lysophosphatidylethanolamines and a bile acid, were significantly associated with IR, with the strongest associations observed for medium-chain acylcarnitines C10 and C12, and no associations with L-carnitine or C2-, C8-, C14- or C16-carnitine. Concentrations of C10-and C12-carnitine decreased during OGTT with a blunted decline in participants with worse insulin resistance. Associations persisted after adjustment for obesity, fasting insulin and fasting glucose. In mouse 3T3-L1 adipocytes exposed to different acylcarnitines, we observed blunted insulin-stimulated glucose uptake after treatment with C10-or C12-carnitine. In conclusion, our results identify medium-chain acylcarnitines as possible contributors to IR.

  • 181.
    Nowak, Christoph
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    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 USA.;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA.;Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden..
    Brandmaier, Stefan
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Munich, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany..
    Tukiainen, Taru
    Univ Helsinki, FIMM, Helsinki, Finland..
    Broeckling, Corey D.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden..
    Prenni, Jessica E.
    Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA..
    Wang-Sattler, Rui
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Munich, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany.;German Ctr Diabet Res DZD, Munich, Germany..
    Peters, Annette
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany.;German Ctr Diabet Res DZD, Munich, Germany.;Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany..
    Meitinger, Thomas
    Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany..
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Gieger, Christian
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Munich, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany.;German Ctr Diabet Res DZD, Munich, Germany..
    Ripatti, Samuli
    Univ Helsinki, FIMM, Helsinki, Finland.;Univ Helsinki, Fac Med, Publ Hlth, Helsinki, Finland.;Wellcome Trust Sanger Inst, Hinxton, England..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Stockholm, Sweden..
    Sundström, Johan
    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 Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Effect of Insulin Resistance on Monounsaturated Fatty Acid Levels: A Multi-cohort Non-targeted Metabolomics and Mendelian Randomization Study2016Inngår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 12, nr 10, artikkel-id e1006379Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or beta-cell responsiveness (disposition index) during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613) followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330), we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining "gold standard" measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development.

  • 182.
    Nowak, Christoph
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sundstrom, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Type 2 diabetes, glycaemic traits and cardiovascular disease: a Mendelian Randomization studyManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Type 2 diabetes (T2D) and its hallmarks insulin resistance, impaired insulin secretion, and hyperglycaemia affect over 400 million persons worldwide and are associated with raised cardiovascular risk, but their causal role has been difficult to dissect due to overlap between risk factors. We used Mendelian randomization analysis, which utilises genetic polymorphisms associated with a risk factor, to assess causal effects of T2D, insulin resistance, insulin secretion, and fasting glucose on mortality, ischaemic stroke, and coronary artery disease (CAD) risk in 120,091 adults in the UK Biobank and in the CARDIoGRAMplusC4D consortium (63,746 cases of CAD and 130,681 controls). We found evidence for a causal effect of T2D on raised CAD risk (odds ratio (OR) per doubling in the odds of T2D, 1.07, 95% confidence interval (CI) 1.05 – 1.09, P = 1.2 x 10-9) and for a causal effect of impaired insulin secretion on the risk of CAD (OR per SD-unit decrease, 1.14, 95% CI 1.06 – 1.22, P = 0.002). The genetic score for insulin resistance was associated with increased coronary artery disease risk; however, sensitivity analysis indicated that the instrument might not be appropriate to use for robust causal inference testing. Our results support previous reports of a causal role of T2D and impaired insulin secretion in coronary artery disease and point to a complex relationship between variants affecting insulin resistance and cardiovascular outcomes.

  • 183.
    Nowak, Christoph
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Sundstrom, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Ganna, Andrea
    Massachusetts General Hospital, Harvard Medical School and Broad Institute, Boston, Massachusetts.
    Shen, Xia
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm , Sweden.
    Broeckling, Corey D.
    Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, Colorado, USA.
    Prenni, Jessica
    Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, Colorado, USA.
    Berne, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. School of Health and Social Studies, Dalarna University, Falun, Sweden.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA.
    Metabolite profiles during an oral glucose tolerance test reveal new associations with clamp-measured insulin sensitivityManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Impaired insulin sensitivity (IS) is a major risk factor for cardiovascular disease and type 2 diabetes. Metabolomic profiling during an oral glucose tolerance test (OGTT) can reveal early pathogenic alterations in healthy individuals. Our aim was to identify IS biomarkers and gain new pathophysiologic insights by applying untargeted metabolomics to repeated OGTT plasma samples in association with a hyperinsulinemic-euglycemic clamp assessment. We studied 192 metabolites identified by non-targeted liquid chromatography/mass spectrometry in plasma samples taken at 0, 30, and 120 min during an OGTT in 470 non-diabetic 71-yr-old men. Insulin sensitivity was associated with 35 metabolites at one or more time points in multivariable-adjusted linear regression. The trajectories of nine metabolites during the OGTT were related to IS, six of which (oleic and palmitoleic acid, decanoyl- and dodecanoylcarnitine, deoxycholate-glycine and hexose) showed no associations with IS in the baseline fasting state. The strongest effects were detected for medium-chain acylcarnitines, which increased between 30-120 min in insulin-resistant individuals compared to those with normal IS. In this large community sample, we identified novel associations between clamp-measured IS and metabolite profiles that became apparent only after an oral glucose challenge. Associations of differential medium-chain acylcarnitine and monounsaturated fatty acid trajectories with IS provide new insights into the pathogenesis of insulin resistance.

  • 184.
    Nowak, Christoph
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    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.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Protein Biomarkers for Insulin Resistance and Type 2 Diabetes Risk in Two Large Community Cohorts2016Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, nr 1, s. 276-284Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Insulin resistance (IR) is a precursor of type 2 diabetes (T2D), and improved risk prediction and understanding of the pathogenesis are needed. We used a novel high-throughput 92-protein assay to identify circulating biomarkers for HOMA of IR in two cohorts of community residents without diabetes (n = 1,367) (mean age 73 ± 3.6 years). Adjusted linear regression identified cathepsin D and confirmed six proteins (leptin, renin, interleukin-1 receptor antagonist [IL-1ra], hepatocyte growth factor, fatty acid-binding protein 4, and tissue plasminogen activator [t-PA]) as IR biomarkers. Mendelian randomization analysis indicated a positive causal effect of IR on t-PA concentrations. Two biomarkers, IL-1ra (hazard ratio [HR] 1.28, 95% CI 1.03-1.59) and t-PA (HR 1.30, 1.02-1.65) were associated with incident T2D, and t-PA predicted 5-year transition to hyperglycemia (odds ratio 1.30, 95% CI 1.02-1.65). Additional adjustment for fasting glucose rendered both coefficients insignificant and revealed an association between renin and T2D (HR 0.79, 0.62-0.99). LASSO regression suggested a risk model including IL-1ra, t-PA, and the Framingham Offspring Study T2D score, but prediction improvement was nonsignificant (difference in C-index 0.02, 95% CI -0.08 to 0.12) over the T2D score only. In conclusion, proteomic blood profiling indicated cathepsin D as a new IR biomarker and suggested a causal effect of IR on t-PA.

  • 185.
    Ohm, J.
    et al.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden;Karolinska Univ Hosp, Dept Emergency Med, Stockholm, Sweden.
    Hjemdahl, P.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden;Karolinska Univ Hosp, Clin Pharmacol Unit, Stockholm, Sweden.
    Discacciati, A.
    Karolinska Inst, Inst Environm Med, Unit Biostat, Stockholm, Sweden.
    Hambraeus, K.
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden.
    Jernberg, T.
    Danderyds Univ Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.
    Skoglund, P. H.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden;Karolinska Univ Hosp, Dept Emergency Med, Stockholm, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Svensson, P.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden;Karolinska Univ Hosp, Dept Emergency Med, Stockholm, Sweden.
    Low density lipoprotein cholesterol levels at first follow-up after acute myocardial infarction predicts recurrent atherosclerotic cardiovascular disease events poorly2017Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, s. 29-30Artikkel i tidsskrift (Annet vitenskapelig)
  • 186.
    Ohm, J.
    et al.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Emergency Med, Stockholm, Sweden..
    Skoglund, P. H.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Emergency Med, Stockholm, Sweden..
    Discacciati, A.
    Karolinska Inst, Inst Environm Med, Unit Biostat, Stockholm, Sweden..
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hambraeus, K.
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden..
    Jernberg, T.
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden..
    Svensson, P.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Emergency Med, Stockholm, Sweden..
    Low socioeconomic status is associated with recurrent atherosclerotic cardiovascular disease event in a population with stable coronary heart disease2016Inngår i: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, s. 33-33Artikkel i tidsskrift (Fagfellevurdert)
  • 187.
    Ohm, Joel
    et al.
    Karolinska Univ Hosp, Funct Emergency Med Solna, Stockholm, Sweden;Karolinska Inst, Dept Med Solna, Stockholm, Sweden.
    Hjemdahl, Paul
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden;Karolinska Univ Hosp, Dept Clin Pharmacol, Stockholm, Sweden.
    Skoglund, Per H.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden;Stiftelsen Stockholms Sjukhem, Ctr Palliat Care, Stockholm, Sweden.
    Discacciati, Andrea
    Karolinska Inst, Inst Environm Med, Unit Biostat, Stockholm, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Hambraeus, Kristina
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Stockholm, Sweden.
    Svensson, Per
    Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden;Soder Sjukhuset, Dept Cardiol, Stockholm, Sweden.
    Lipid levels achieved after a first myocardial infarction and the prediction of recurrent atherosclerotic cardiovascular disease2019Inngår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 296, s. 1-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Low density lipoprotein cholesterol (LDL-C) goals post-myocardial infarction (MI) are debated, and the significance of achieved blood lipid levels for predicting a first recurrent atherosclerotic cardiovascular disease (rASCVD) event post-MI is unclear.

    Methods: This was a cohort study on first-ever MI survivors aged <= 76 years attending 4-14 week revisits throughout Sweden 2005-2013. Personal-level data was collected from SWEDEHEART and linked national registries. Exposures were quintiles of LDL-C, high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TGs) at the revisit. Group level associations with rASCVD (nonfatal MI or coronary heart disease death or fatal or nonfatal ischemic stroke) were estimated in Cox regression models. Predictive capacity was estimated by differences in C-statistic, integrated discriminatory improvement, and net reclassification improvement when adding each blood lipid to a validated risk prediction model.

    Results: 25,643 patients, 96.9% on statin therapy, were followed during a mean of 4.1 years. rASCVD occurred in 2173 patients (8.5%). For LDL-C and TC, moderate associations with rASCVD were observed only in the 5th vs. the lowest (referent) quintiles. For TGs and HDL-C increased risks were observed in quintiles 3-5 vs. the lowest. Minor predictive improvements were observed when lipid fractions were added to the risk model but the discrimination overall was poor (C-statistics < 0.6).

    Conclusions: Our data question the importance of LDL-C levels achieved at first revisit post-MI for decisions on continued treatment intensity considering the weak association with rASCVD observed in this post-MI cohort.

  • 188.
    Ohm, Joel
    et al.
    Karolinska Inst, Funct Area Emergency Med Solna, Karolinska Univ Hosp, S-17176 Stockholm, Sweden;Karolinska Inst, Dept Med Solna, S-17176 Stockholm, Sweden.
    Skoglund, Per H.
    Karolinska Inst, Funct Area Emergency Med Solna, Karolinska Univ Hosp, S-17176 Stockholm, Sweden;Karolinska Inst, Dept Med Solna, S-17176 Stockholm, Sweden.
    Discacciati, Andrea
    Karolinska Inst, Unit Biostat, Inst Environm Med, Stockholm, Sweden.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Hambraeus, Kristina
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Stockholm, Sweden.
    Svensson, Per
    Karolinska Inst, Funct Area Emergency Med Solna, Karolinska Univ Hosp, S-17176 Stockholm, Sweden;Karolinska Inst, Dept Med Solna, S-17176 Stockholm, Sweden.
    Socioeconomic status predicts second cardiovascular event in 29,226 survivors of a first myocardial infarction2018Inngår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 25, nr 9, s. 985-993Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Risk assessment post-myocardial infarction needs improvement, and risk factors derived from general populations apply differently in secondary prevention. The prediction of subsequent cardiovascular events post-myocardial infarction by socioeconomic status has previously been poorly studied. Design Swedish nationwide cohort study. Methods A total of 29,226 men and women (27%), 40-76 years of age, registered at the standardised one year revisit after a first myocardial infarction in the secondary prevention quality registry of SWEDEHEART 2006-2014. Personal-level data on socioeconomic status measured by disposable income and educational level, marital status, and the primary endpoint, first recurrent event of atherosclerotic cardiovascular disease, defined as non-fatal myocardial infarction or coronary heart disease death or fatal or non-fatal stroke were obtained from linked national registries. Results During the mean 4.1-year follow-up, 2284 (7.8%) first recurrent manifestations of atherosclerotic cardiovascular disease occurred. Both socioeconomic status indicators and marital status were associated with the primary endpoint in multivariable Cox regression models. In a comprehensively adjusted model, including secondary preventive treatment, the hazard ratio for the highest versus lowest quintile of disposable income was 0.73 (95% confidence interval 0.62-0.83). The association between disposable income and first recurrent manifestation of atherosclerotic cardiovascular disease was stronger in men as was the risk associated with being unmarried (tests for interaction P<0.05). Conclusions Among one year survivors of a first myocardial infarction, first recurrent manifestation of atherosclerotic cardiovascular disease was predicted by disposable income, level of education and marital status. The association between disposable income and first recurrent manifestation of atherosclerotic cardiovascular disease was independent of secondary preventive treatment but further study on causal pathways is needed.

  • 189.
    Oldgren, Jonas
    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).
    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. Uppsala Univ, Uppsala Clin Res Ctr, Dept Med Sci, Uppsala, Sweden.
    Response by Oldgren and Sundström to Letter Regarding Article, "Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study"2018Inngår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 137, nr 21, s. 2313-2313Artikkel i tidsskrift (Annet vitenskapelig)
  • 190.
    Oldgren, Jonas
    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.
    Wallentin, Lars
    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.
    Alexander, John H
    James, Stefan
    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.
    Jönelid, Birgitta
    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.
    Steg, Gabriel
    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, Kardiovaskulär epidemiologi.
    New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis2013Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, nr 22, s. 1670-1680Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting.

    Methods and results

    All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7-14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59-0.84], but increased clinically significant bleeding (HR: 1.79; 1.54-2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80-0.95), but more than doubled the bleeding (HR: 2.34; 2.06-2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies.

    Conclusion

    In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with dual antiplatelet therapy.

  • 191. Ostgren, C. J.
    et al.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Svennblad, Bodil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lohm, L.
    Nilsson, P. M.
    Johansson, G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Associations of HbA1c and educational level with risk of cardiovascular events in 32871 drug-treated patients with Type2 diabetes: a cohort study in primary care2013Inngår i: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 30, nr 5, s. E170-E177Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims To explore the association of HbA1c and educational level with risk of cardiovascular events and mortality in patients with Type2 diabetes. Methods A cohort of 32871 patients with Type2 diabetes aged 35years and older identified by extracting data from electronic patient records for all patients who had a diagnosis of Type2 diabetes and had glucose-lowering agents prescribed between 1999 and 2009 at 84 primary care centres in Sweden. Associations of mean HbA1c levels and educational level with risks of cardiovascular events and all-cause mortality were analysed. Results The associations of HbA1c with risk of all-cause and cardiovascular mortality were J-shaped, with the lowest risk observed for cardiovascular mortality at an HbA1c level of 51mmol/mol (6.8%) for subjects on oral agents and 56mmol/mol (7.3%) in insulin-treated patients. The lowest risk observed for all-cause mortality was at an HbA1c level of 51mmol/mol (6.8%) for subjects on oral agents and 56mmol/mol (7.3%) in insulin-treated patients. There was an increased risk for cardiovascular death [hazard ratio1.6 (1.22.1), P=0.0008] at the lowest HbA1c decile for subjects in the low education category. For subjects with higher education there was no evident J curve for cardiovascular death [hazard ratio1.2 (0.81.6), P=0.3873]. Conclusions Our results lend support to the recent American Diabetes Association/ European Association for the Study of Diabetes position statement that emphasizes the importance of additional factors, including the propensity for hypoglycaemia, which should influence HbA1c targets and treatment choices for individual patients. 

  • 192. Paige, Ellie
    et al.
    Barrett, Jessica
    Pennells, Lisa
    Sweeting, Michael
    Willeit, Peter
    Di Angelantonio, Emanuele
    Gudnason, Vilmundur
    Nordestgaard, Børge G
    Psaty, Bruce M
    Goldbourt, Uri
    Best, Lyle G
    Assmann, Gerd
    Salonen, Jukka T
    Nietert, Paul J
    Verschuren, W M Monique
    Brunner, Eric J
    Kronmal, Richard A
    Salomaa, Veikko
    Bakker, Stephan J L
    Dagenais, Gilles R
    Sato, Shinichi
    Jansson, Jan-Håkan
    Willeit, Johann
    Onat, Altan
    de la Cámara, Agustin Gómez
    Roussel, Ronan
    Völzke, Henry
    Dankner, Rachel
    Tipping, Robert W
    Meade, Tom W
    Donfrancesco, Chiara
    Kuller, Lewis H
    Peters, Annette
    Gallacher, John
    Kromhout, Daan
    Iso, Hiroyasu
    Knuiman, Matthew
    Casiglia, Edoardo
    Kavousi, Maryam
    Palmieri, Luigi
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Davis, Barry R
    Njølstad, Inger
    Couper, David
    Danesh, John
    Thompson, Simon G
    Wood, Angela
    Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.2017Inngår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 186, nr 8, s. 899-907Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative mean values of repeated measurements and summary measures from longitudinal modeling of the repeated measurements were compared with models using measurements from a single time point. Risk discrimination (C-index) and net reclassification were calculated, and changes in C-indices were meta-analyzed across studies. Compared with the single-time-point model, the cumulative means and longitudinal models increased the C-index by 0.0040 (95% confidence interval (CI): 0.0023, 0.0057) and 0.0023 (95% CI: 0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared with the single-time-point model, overall net reclassification improvements were 0.0369 (95% CI: 0.0303, 0.0436) for the cumulative-means model and 0.0177 (95% CI: 0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction.

  • 193.
    Pennells, Lisa
    et al.
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Kaptoge, Stephen
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Wood, Angela
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Sweeting, Mike
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Zhao, Xiaohui
    Univ Cambridge, Dept Physiol Dev & Neurosci, Downing St, Cambridge CB2 3EG, England.
    White, Ian
    UCL, MRC Clin Trials Unit, 90 High Holborn, London WC1V 6LJ, England.
    Burgess, Stephen
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England;Univ Cambridge, Cambridge Inst Publ Hlth, MRC Biostat Unit, Forvie Site,Robinson Way, Cambridge CB2 0SR, England.
    Willeit, Peter
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England;Med Univ Innsbruck, Dept Neurol & Neurosurg, Anichstra 35, A-6020 Innsbruck, Austria.
    Bolton, Thomas
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Moons, Karel G. M.
    Univ Med Ctr Utrecht, Julius Ctr, Res Program Methodol, Epidemiol Methodol, Heidelberglaan 100, NL-3584 Utrecht, Netherlands.
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Julius Ctr, Res Program Cardiovasc Epidemiol, Dept Epidemiol, Heidelberglaan 100, NL-3584 Utrecht, Netherlands;ProspectEPIC, Utrecht, Netherlands.
    Selmer, Randi
    Norwegian Inst Publ Hlth, Div Epidemiol, Postboks 222 Skoyen, N-0213 Oslo, Norway.
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England;EPICNOR, London, England;RANCHO, Utrecht, Netherlands.
    Gudnason, Vilmundur
    Iceland Heart Assoc, Hjartavernd Holtasmari 1, IS-201 Kopavogur, Iceland;Univ Iceland, Fac Med, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland.
    Assmann, Gerd
    Assmann Fdn Prevent, Gronowskistr 33, D-48161 Munster, Germany;PROCAM, Newton, MA USA.
    Amouyel, Philippe
    Inst Pasteur, 1 Rue Professeur Calmette, F-59019 Lille, France;PRIME, Newton, MA USA.
    Salomaa, Veikko
    Nat Inst Hlth & Welf, Mannerheimintie 166, Helsinki 00271, Finland;KAREL72, Isa Town, Bahrain.
    Kivimaki, Mika
    UCL, Dept Epidemiol & Publ Hlth, 1-19 Torrington Pl, London WC1E 7HB, England;WHITE I, Viana Do Castelo, Portugal.
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Dept Clin Med, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
    Blaha, Michael J.
    Johns Hopkins Univ Hosp, Ciccarone Ctr Prevent Heart Dis, 1800 Orleans St, Baltimore, MD 21287 USA.
    Kuller, Lewis H.
    Univ Pittsburgh, Dept Epidemiol, 200 Lothrop St, Pittsburgh, PA 15212 USA;MRFIT, Utrecht, Netherlands.
    Brenner, Hermann
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Neuenheimer Feld 581, D-69120 Heidelberg, Germany;Heidelberg Univ, Grabengasse 1, D-69117 Heidelberg, Germany;WCWC, Viana Do Castelo, Portugal.
    Gillum, Richard F.
    Howard Univ, Coll Med, Dept Med, 2041 Georgia Ave, Washington, DC 20060 USA;NHANES III, Utrecht, Netherlands.
    Meisinger, Christa
    German Res Ctr Environm Hlth, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany;MONICA KORA2, Karachi, Pakistan;MONICA KORA3, Karachi, Pakistan.
    Ford, Ian
    Univ Glasgow, Inst Hlth & Wellbeing, Boyd Orr Bldg,Univ Ave, Glasgow G12 8QQ, Lanark, Scotland;WOSCOPS, Viana Do Castelo, Portugal.
    Knuiman, Matthew W.
    Univ Western Australia, Sch Populat & Global Hlth, Fac Hlth & Med Sci, 35 Stirling Highway, Perth, WA 6009, Australia;BHS, London, England.
    Rosengren, Annika
    Univ Gothenburg, Sahlgrenska Acad, Medicinaregatan 3, S-41390 Gothenburg, Sweden;Sahlgrens Univ Hosp, Wallenberg Lab, Bla Stradket 5, S-41345 Gothenburg, Sweden;GOT043, Belfast, Antrim, North Ireland;MOSWEGOT, Utrecht, Netherlands.
    Lawlor, Debbie A.
    Univ Bristol, Dept Social Med, Bristol BS8 2PR, Avon, England.
    Volzke, Henry
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Ellernholzstr 1-2, D-17489 Greifswald, Germany.
    Cooper, Cyrus
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Tremona Rd, Southampton SO16 6YD, Hants, England.
    Ibanez, Alejandro Marin
    San Jose Norte Hlth Ctr, 16 Lugar Santuario Cabanas, Zaragoza 50013, Spain.
    Casiglia, Edoardo
    Univ Padua, Dept Med, 2 Via Giustiniani, I-35128 Padua, Italy;CASTEL, New York, NY USA.
    Kauhanen, Jussi
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, 1 Yliopistonranta, Kuopio, Finland.
    Cooper, Jackie A.
    UCL, Ctr Cardiovasc Genet, 5 Univ St, London WC1E 6JF, England;NPHSII, Utrecht, Netherlands.
    Rodriguez, Beatriz
    Univ Hawaii, Dept Geriatr Med, 1960 East West Rd, Honolulu, HI 96822 USA;HONOL, Tokyo, Japan.
    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, Klinisk epidemiologi.
    Barrett-Connor, Elizabeth
    Univ Calif San Diego, 9500 Gilman Dr, La Jolla, CA 92093 USA.
    Dankner, Rachel
    Gertner Inst Epidemiol & Hlth Policy Res, Sheba Med Ctr, Unit Cardiovasc Epidemiol, IL-52621 Tel Hashomer, Israel;Tel Aviv Univ, Sch Publ Hlth, Sackler Fac Med, Dept Epidemiol & Prevent Med, IL-69978 Tel Aviv, Israel.
    Nietert, Paul J.
    Med Univ South Carolina, Dept Publ Hlth Sci, 135 Cannon St, Charleston, SC 29425 USA;CHARL, Greenville, SC USA.
    Davidson, Karina W.
    Columbia Univ Irving Med Ctr, Dept Med, 622 West 168th St, New York, NY 10032 USA.
    Wallace, Robert B.
    Univ Iowa, Coll Publ Hlth, 145 N Riverside Dr, Iowa City, IA 52242 USA.
    Blazer, Dan G.
    Duke Univ, Med Ctr, Dept Surg, 2301 Erwin Rd, Durham, NC 27707 USA.
    Bjorkelund, Cecilia
    Univ Gothenburg, Dept Publ Hlth & Community Med, Medicinaregatan 16, S-41390 Gothenburg, Sweden;GOTOW, Belfast, Antrim, North Ireland.
    Donfrancesco, Chiara
    ISS, Dysmetabol & Aging Associated Dis, Dept Cardiovasc, 299 Viale Regina Elena, I-00161 Rome, Italy;FINE IT, Heidelberg, Germany.
    Krumholz, Harlan M.
    Yale Sch Med, 1 Church St, New Haven, CT 06510 USA.
    Nissinen, Aulikki
    Nat Inst Hlth & Welf, Mannerheimintie 166, Helsinki 00271, Finland;FINE FIN, Heidelberg, Germany.
    Davis, Barry R.
    Univ Texas Houston, Sch Publ Hlth, Dept Biostat, 1200 Pressler St, Houston, TX 77030 USA.
    Coady, Sean
    NHLBI, Div Cardiovasc Sci, 31 Ctr Dr, Bethesda, MD 20892 USA.
    Whincup, Peter H.
    St Georges Univ London, Populat Hlth Res Inst, Cranmer Terrace, London SW17 0RE, England;BRHS, Bridgewater, MA USA.
    Jorgensen, Torben
    Res Ctr Prevent & Hlth, 5 Oster Farimagsgade, DK-1014 Copenhagen, Denmark;Univ Copenhagen, Dept Publ Hlth, 5 Oster Farimagsgade, DK-1014 Copenhagen, Denmark;Aalborg Univ, Fredrik Bajers Vej 5, DK-9100 Aalborg, Denmark.
    Ducimetiere, Pierre
    Univ Paris 05, Fac Med, 12 Rue Ecole Med, F-75006 Paris, France.
    Trevisan, Maurizio
    CUNY, Sch Med, City Coll New York, 160 Convent Ave, New York, NY 10031 USA;RIFLE, Utrecht, Netherlands.
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, Jan Waldenstroms Gata 35, S-20502 Malmo, Sweden.
    Crespo, Carlos J.
    Portland State Univ, Sch Community Hlth, 506 SW Mill St, Portland, OR 97201 USA;PRHHP, Newton, MA USA.
    Meade, Tomw.
    London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, Keppel St, London WC1E 7HT, England.
    Visser, Marjolein
    Vrije Univ Amsterdam, VU Univ, Med Ctr, Dept Hlth Sci, De Boelelaan 1085, NL-1081 Amsterdam, Netherlands;LASA, Karachi, Pakistan.
    Kromhout, Daan
    Univ Grogingen, Univ Med Ctr Groningen, Dept Epidemiol, Hanzepl 1, NL-9713 Groningen, Netherlands.
    Kiechl, Stefan
    Med Univ Innsbruck, Dept Neurol & Neurosurg, Anichstra 35, A-6020 Innsbruck, Austria.
    Daimon, Makoto
    Yamagata Univ, Fac Med, 1-4-12 Kojirakawa Machi, Yamagata 9908560, Japan.
    Price, Jackie F.
    Univ Edinburgh, Old Med Sch, Usher Inst Populat Hlth Sci & Informat, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland.
    de la Camara, Agustin Gomez
    Hosp 12 Octubre, Dept Clin Res, Av Cordoba, E-28041 Madrid, Spain;DRECE, Madrid, Spain.
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Albinusdreef 2, NL-2333 Leiden, Netherlands.
    Lamarche, Benoit
    Univ Laval, Pavillon Ferdinand Vandry,2440 Hochelaga, Quebec City, PQ G1V 0A6, Canada.
    Onat, Altan
    Istanbul Univ, Cerrahpasa Fac Med, Dept Cardiol, TR-34452 Istanbul, Turkey.
    Simons, Leon A.
    UNSW, Fac Med, Sydney, NSW 2052, Australia.
    Kavousi, Maryam
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Doctor Molewaterpl 40, NL-3015 Rotterdam, Netherlands.
    Ben-Shlomo, Yoav
    Univ Bristol, Bristol Neurosci, Queens Rd, Bristol BS8 1QU, Avon, England;CAPS, Oxford, England.
    Gallacher, John
    Univ Oxford, Warneford Hosp, Dept Psychiat, Warneford Lane, Oxford OX3 7JX, England;CAPS, Oxford, England.
    Dekker, Jacqueline M.
    Vrije Univ Amsterdam, Med Ctr, Inst Hlth & Care Res, De Boelelaan 1085, NL-1081 Amsterdam, Netherlands.
    Arima, Hisatomi
    Kyushu Univ, Nishi Ku, 744 Motooka, Fukuoka, Fukuoka 8190395, Japan.
    Shara, Nawar
    MedStar Hlth Res Inst, Dept Biostat & Bioinformat, 6525 Belcrest Rd, Hyattsville, MD 20782 USA.
    Tipping, RobertW.
    Merck, Clin Biostat, 2000 Galloping Hill Rd, Kenilworth, NJ 07033 USA.
    Roussel, Ronan
    INSERM, Ctr Rech Cordeliers, 15 Rue Ecole Med, F-57006 Paris, France.
    Brunner, Eric J.
    UCL, Inst Epidemiol & Hlth, 1-19 Torrington Pl, London WC1E 7HB, England;WHITE II, Viana Do Castelo, Portugal.
    Koenig, Wolfgang
    Tech Univ Munich, Deutsches Herzzentrum Munchen, 21 Arcisstr, D-80333 Munich, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Biedersteiner Str 29, D-80802 Munich, Germany;MONICA KORA2, Karachi, Pakistan;MONICA KORA3, Karachi, Pakistan.
    Sakurai, Masaru
    Kanazawa Med Univ, Dept Social & Environm Med, 1-1 Daigaku, Uchinada, Ishikawa 9200293, Japan.
    Pavlovic, Jelena
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Doctor Molewaterpl 40, NL-3015 Rotterdam, Netherlands.
    Gansevoort, Ron T.
    Univ Grogingen, Univ Med Ctr Groningen, Dept Internal Med, Hanzeplein 1, NL-9713 Groningen, Netherlands.
    Nagel, Dorothea
    Univ Munich, Klinikum Univ Munchen, 15 Marchioninistr, D-81377 Munich, Germany;GRIPS, Tokyo, Japan.
    Goldbourt, Uri
    Tel Aviv Univ, Sch Publ Hlth, Sackler Fac Med, Dept Epidemiol & Prevent Med, IL-69978 Tel Aviv, Israel.
    Barr, Elizabeth L. M.
    Baker Heart & Diabet Inst, Clin Diabet & Epidemiol, 75 Commercial Rd, Melbourne, Vic 3004, Australia.
    Palmieri, Luigi
    ISS, Dysmetabol & Aging Associated Dis, Dept Cardiovasc, 299 Viale Regina Elena, I-00161 Rome, Italy;CUORE, Madrid, Spain.
    Njolstad, Inger
    Univ Tromso, Dept Publ Hlth, Hansine Hansens Veg 18, Tromso, Norway.
    Sato, Shinichi
    Chiba Prefectural Inst Publ Hlth, Chuo Ku, 666-2 Nito No Machi, Chiba 2608715, Japan;IKNS, Isa Town, Bahrain.
    Verschuren, W. M. Monique
    Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis, Antonie Leeuwenhoeklaan 9, NL-3721 Bilthoven, Netherlands;MCVDRFP, Karachi, Pakistan;MORGEN, Utrecht, Netherlands.
    Varghese, Cherian V.
    WHO, Noncommunicable Dis Disabil Violence & Injury Pre, 20 Ave Appia, CH-1211 Geneva 27, Switzerland.
    Graham, Ian
    Univ Dublin, Coll Green, Trinity Coll Dublin, Sch Med, Dublin 2, Ireland.
    Onuma, Oyere
    WHO, Noncommunicable Dis Disabil Violence & Injury Pre, 20 Ave Appia, CH-1211 Geneva 27, Switzerland.
    Greenland, Philip
    Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 420 East Super St, Chicago, IL 60611 USA.
    Woodward, Mark
    Univ Oxford, George Inst Global Hlth, 75 George St, Oxford OX1 2BQ, England;Univ New South Wales, George Inst Global Hlth, 1 King St Newtown, Sydney, NSW 2042, Australia.
    Ezzati, Majid
    Imperial Coll London, Sch Publ Hlth, Fac Med, Norfolk Pl,St Marys Campus, London W2 1PG, England.
    Psaty, Bruce M.
    Univ Washington, Cardiovasc Hlth Res Unit, 1730 Minor Ave, Seattle, WA 98101 USA;CHS, Inver Grove Hts, MN USA.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, 126 Univ Pl, Glasgow G12 8TA, Lanark, Scotland;MIDFAM, Karachi, Pakistan;WOSCOPS, Viana Do Castelo, Portugal.
    Jackson, Rod
    Univ Auckland, Fac Med & Hlth Sci, 261 Morrin Rd, Auckland, New Zealand.
    Ridker, Paul M.
    Harvard Med Sch, Brigham & Womens Hosp, 900 Commonwealth Ave, Boston, MA 02215 USA;USPHS2, Viana Do Castelo, Portugal;WHS, Viana Do Castelo, Portugal.
    Cook, Nancy R.
    Harvard Med Sch, Brigham & Womens Hosp, 900 Commonwealth Ave, Boston, MA 02215 USA.
    D'Agostino, Ralph B., Sr.
    Boston Univ, Math & Stat Dept, 111 Cummington Mall, Boston, MA 02215 USA;FRAM, Boston, MA USA;FRAMOFF, Boston, MA USA.
    Thompson, Simon G.
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Di Angelantonio, Emanuele
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Tipping, Robert W.
    AFTCAPS, Benn, Germany.
    Simpson, Lara M.
    ALLHAT, Bethesda, MD USA.
    Pressel, Sara L.
    ALLHAT, Bethesda, MD USA.
    Couper, David J.
    ARIC, Chapel Hill, NC USA.
    Nambi, Vijay
    ARIC, Chapel Hill, NC USA.
    Matsushita, Kunihiro
    ARIC, Chapel Hill, NC USA.
    Folsom, Aaron R.
    ARIC, Chapel Hill, NC USA.
    Shaw, Jonathan E.
    AUSDIAB, Melbourne, Vic, Australia.
    Magliano, Dianna J.
    AUSDIAB, Melbourne, Vic, Australia.
    Zimmet, Paul Z.
    AUSDIAB, Melbourne, Vic, Australia.
    Wannamethee, S. Goya
    BRHS, Bridgewater, MA USA.
    Willeit, Johann
    BRUN, Bridgewater, MA USA.
    Santer, Peter
    BRUN, Bridgewater, MA USA.
    Egger, Georg
    BRUN, Bridgewater, MA USA.
    Casas, Juan Pablo
    BWHHS, London, England.
    Amuzu, Antointtte
    BWHHS, London, England.
    Tikhonoff, Valerie
    CASTEL, New York, NY USA.
    Sutherland, Susan E.
    CHARL, Greenville, SC USA.
    Cushman, Mary
    CHS, Inver Grove Hts, MN USA.
    Sogaard, Anne Johanne
    CONOR, Tromso, Norway.
    Haheim, Lise Lund
    CONOR, Tromso, Norway.
    Ariansen, Inger
    CONOR, Tromso, Norway.
    Tybjaerg-Hansen, Anne
    COPEN, Copenhagen, Denmark.
    Jensen, Gorm B.
    COPEN, Copenhagen, Denmark.
    Schnohr, Peter
    COPEN, Copenhagen, Denmark.
    Giampaoli, Simona
    CUORE, Madrid, Spain;FINE IT, Heidelberg, Germany.
    Vanuzzo, Diego
    CUORE, Madrid, Spain.
    Panico, Salvatore
    CUORE, Madrid, Spain.
    Balkau, Beverley
    DESIR, Madrid, Spain.
    Bonnet, Fabrice
    DESIR, Madrid, Spain.
    Marre, Michel
    DESIR, Madrid, Spain.
    Herrera, Miguel Angel Rubio
    DRECE, Madrid, Spain.
    Friedlander, Yechiel
    McCallum, John
    McLachlan, Stela
    EAS, Gothenburg, Sweden.
    Guralnik, Jack
    EPESEBOS, London, England;EPESEIOW, Baltimore, MD USA;EPESENCA, Oxford, England;EPESENHA, New York, NY USA.
    Phillips, Caroline L.
    EPESEBOS, London, England.
    Wareham, Nick
    EPICNOR, London, England.
    Schottker, Ben
    ESTHER, Heidelberg, Germany.
    Saum, Kai-Uwe
    ESTHER, Heidelberg, Germany.
    Holleczek, Bernd
    ESTHER, Heidelberg, Germany.
    Tolonen, Hanna
    FINE FIN, Heidelberg, Germany.
    Jousilahti, Pekka
    FINRISK 92 97, Heidelberg, Germany.
    Harald, Kennet
    FINRISK 92 97, Heidelberg, Germany.
    Massaro, Joseph M.
    FRAM, Boston, MA USA;FRAMOFF, Boston, MA USA.
    Pencina, Michael
    FRAM, Boston, MA USA;FRAMOFF, Boston, MA USA.
    Vasan, Ramachandran
    FRAM, Boston, MA USA;FRAMOFF, Boston, MA USA.
    Kayama, Takamasa
    Kato, Takeo
    Oizumi, Toshihide
    Jespersen, Jorgen
    Moller, Lars
    Bladbjerg, Else Marie
    Chetrit, A.
    GOH, Belfast, Antrim, North Ireland.
    Wilhelmsen, Lars
    GOT043, Belfast, Antrim, North Ireland.
    Lissner, Lauren
    GOTOW, Belfast, Antrim, North Ireland.
    Dennison, Elaine
    HCS, Tokyo, Japan.
    Kiyohara, Yutaka
    Ninomiya, Toshiharu
    Doi, Yasufumi
    Nijpels, Giel
    Stehouwer, Coen D. A.
    Kazumasa, Yamagishi
    IKNS, Isa Town, Bahrain.
    Iso, Hiroyasu
    IKNS, Isa Town, Bahrain.
    Vartiainen, Erkki
    FINRISK 92 97, Heidelberg, Germany;KAREL72, Isa Town, Bahrain.
    Kurl, Sudhir
    KIHD, Karachi, Pakistan.
    Tuomainen, Tomi-Pekka
    KIHD, Karachi, Pakistan.
    Salonen, Jukka T.
    KIHD, Karachi, Pakistan.
    Deeg, Dorly J. H.
    LASA, Karachi, Pakistan.
    Nilsson, Peter M.
    Hedblad, Bo
    Melander, Olle
    De Boer, Ian H.
    DeFilippis, Andrew Paul
    Watt, Graham
    MIDFAM, Karachi, Pakistan.
    Verschuren, Monique
    Tverdal, Aage
    NCS, Utrecht, Netherlands.
    Kirkland, Susan
    NSHS, Newton, MA USA.
    Shimbo, Daichi
    NSHS, Newton, MA USA.
    Shaffer, Jonathan
    NSHS, Newton, MA USA.
    Bakker, Stephan J. L.
    PREVEND, Newton, MA USA.
    van der Harst, Pim
    PREVEND, Newton, MA USA.
    Hillege, Hans L.
    PREVEND, Newton, MA USA.
    Dallongeville, Jean
    PRIME, Newton, MA USA.
    Schulte, Helmut
    PROCAM, Newton, MA USA.
    Trompet, Stella
    PROSPER, Newton, MA USA.
    Smit, Roelof A. J.
    PROSPER, Newton, MA USA.
    Stott, David J.
    PROSPER, Newton, MA USA.
    Despres, Jean-Pierre
    Cantin, Bernard
    Dagenais, Gilles R.
    Laughlin, Gail
    RANCHO, Utrecht, Netherlands.
    Wingard, Deborah
    RANCHO, Utrecht, Netherlands.
    Aspelund, Thor
    REYK, Reykjavik, Iceland.
    Eiriksdottir, Gudny
    REYK, Reykjavik, Iceland.
    Gudmundsson, Elias Freyr
    Ikram, Arfan
    van Rooij, Frank J. A.
    Franco, Oscar H.
    Rueda-Ochoa, Oscar L.
    Muka, Taulant
    Glisic, Marija
    Tunstall-Pedoe, Hugh
    Howard, Barbara V.
    Zhang, Ying
    Jolly, Stacey
    Davey-Smith, George
    Can, Gunay
    Yuksel, Husniye
    Nakagawa, Hideaki
    Morikawa, Yuko
    Miura, Katsuyuki
    Ingelsson, Martin
    ULSAM, Viana Do Castelo, Portugal.
    Giedraitis, Vilmantas
    ULSAM, Viana Do Castelo, Portugal.
    Gaziano, J. Michael
    USPHS2, Viana Do Castelo, Portugal.
    Shipley, Martin
    WHITE I, Viana Do Castelo, Portugal;WHITE II, Viana Do Castelo, Portugal.
    Arndt, Volker
    WCWC, Viana Do Castelo, Portugal.
    Cook, Nancy
    WHS, Viana Do Castelo, Portugal.
    Geleijnse, Johanna M.
    ZUTE, Viana Do Castelo, Portugal.
    Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies2019Inngår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 40, nr 7, s. 621-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.

    Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.

    Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.

  • 194.
    Pethrus, Carl-Martin
    et al.
    Karolinska Institutet, Department of Medicine Solna, Clinical Epidemiology Unit.
    Johansson, Kari
    Karolinska Institutet, Department of Medicine Solna, Clinical Epidemiology Unit.
    Neovius, Kristian
    Cyclo AB, Stockholm.
    Reutfors, Johan
    Karolinska Institutet, Department of Medicine Solna, Clinical Epidemiology Unit.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Neovius, Martin
    Karolinska Institutet, Department of Medicine Solna, Clinical Epidemiology Unit.
    Suicide and all-cause mortality in Swedish deployed military veterans: a population-based matched cohort study2017Inngår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, nr 9, artikkel-id e014034Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate suicide and mortality risk in deployed military veterans versus non-deployed comparators who had gone through military conscription testing.

    Design: Population-based matched cohort study.

    Setting: Sweden.

    Participants: Participants were identified from the Military Service Conscription Register and deployment status from the Swedish Military Information Personnel Register. Of 1.9 million conscripts, 21 721 had deployed at some time between 1990 and 2013 (deployed military veterans). Non-deployed comparators were matched to deployed military veterans in two ways: (1) by cognitive ability, psychological assessment, mental health, body mass index, sex, birth-year and conscription-year (carefully matched), with further adjustment for exercise capacity and suicide attempt history; and (2) by sex, birth-year and conscription-year (age-and sex-matched).

    Main outcome: Suicide retrieved from the Swedish National Patient and Causes of Death Register until 31 December 2013.

    Results: During a median follow-up of 12 years, 39 and 211 deaths by suicide occurred in deployed military veterans (n=21 627) and carefully matched non-deployed comparators (n=107 284), respectively (15 vs 16/100 000 person-years; adjusted HR (aHR) 1.07; 95% CI 0.75 to 1.52; p=0.72) and 329 in age-and sex-matched non-deployed comparators (n=108 140; 25/100 000 person-years; aHR 0.59; 95% CI 0.42 to 0.82; p=0.002). There were 284 and 1444 deaths by suicide or attempted suicides in deployed military veterans and carefully matched non-deployed comparators, respectively (109 vs 112; aHR 0.99; 95% CI 0.88 to 1.13; p=0.93) and 2061 in age-and sex-matched non-deployed comparators (158; aHR 0.69; 95% CI 0.61 to 0.79; p<0.001). The corresponding figures for all-cause mortality for carefully matched non-deployed comparators were 159 and 820 (61 vs 63/100 000 person-years; aHR 0.97; 95% CI 0.82 to 1.15; p=0.71) and 1289 for age-and sex-matched non-deployed comparators (98/100 000 person-years; aHR 0.62; 95% CI 0.52 to 0.73; p<0.001).

    Conclusion: Deployed military veterans had similar suicide and mortality risk as non-deployed comparators after accounting for psychological, psychiatric and physical factors. Studies of mental health in deployed veterans need to adjust for more factors than age and sex for comparisons to be meaningful.

  • 195. Pewsner, D
    et al.
    Juni, P
    Egger, M
    Battaglia, M
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Bachmann, LM
    Accuracy of electrocardiography in diagnosis of left ventricular hypertrophy in arterial hypertension: systematic review2007Inngår i: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 335, nr 7622, s. 711-714CArtikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To review the accuracy of electrocardiography in screening for left ventricular hypertrophy in patients with hypertension. DESIGN: Systematic review of studies of test accuracy of six electrocardiographic indexes: the Sokolow-Lyon index, Cornell voltage index, Cornell product index, Gubner index, and Romhilt-Estes scores with thresholds for a positive test of > or =4 points or > or =5 points. DATA SOURCES: Electronic databases ((Pre-)Medline, Embase), reference lists of relevant studies and previous reviews, and experts. STUDY SELECTION: Two reviewers scrutinised abstracts and examined potentially eligible studies. Studies comparing the electrocardiographic index with echocardiography in hypertensive patients and reporting sufficient data were included. DATA EXTRACTION: Data on study populations, echocardiographic criteria, and methodological quality of studies were extracted. DATA SYNTHESIS: Negative likelihood ratios, which indicate to what extent the posterior odds of left ventricular hypertrophy is reduced by a negative test, were calculated. RESULTS: 21 studies and data on 5608 patients were analysed. The median prevalence of left ventricular hypertrophy was 33% (interquartile range 23-41%) in primary care settings (10 studies) and 65% (37-81%) in secondary care settings (11 studies). The median negative likelihood ratio was similar across electrocardiographic indexes, ranging from 0.85 (range 0.34-1.03) for the Romhilt-Estes score (with threshold > or =4 points) to 0.91 (0.70-1.01) for the Gubner index. Using the Romhilt-Estes score in primary care, a negative electrocardiogram result would reduce the typical pre-test probability from 33% to 31%. In secondary care the typical pre-test probability of 65% would be reduced to 63%. CONCLUSION: Electrocardiographic criteria should not be used to rule out left ventricular hypertrophy in patients with hypertension.

  • 196.
    Roos, Vendela
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Elmstahl, Solve
    Lund Univ, Malmo Univ Hosp, Dept Hlth Sci, Div Geriatr Med, Malmo, Sweden..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.;.
    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.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Alterations in Multiple Lifestyle Factors in Subjects with the Metabolic Syndrome Independently of Obesity2017Inngår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, nr 3, s. 118-123Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Many lifestyle factors have been associated with the metabolic syndrome (MetS). However, most of these studies have not considered the potential impact of obesity and have often only investigated one lifestyle factor at the time. We aimed to investigate the interplay between body mass index (BMI) and MetS with respect to multiple lifestyle factors. Methods: BMI and MetS [National Cholesterol Education Program (NCEP)/Adult Treatment Panel III criteria] were assessed in a sample of 18,880 subjects aged 45-75 years from the population-based EpiHealth study. Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m(2), overweight/BMI 25-30 kg/m(2), and obesity/BMI > 30 kg/m(2)) and MetS status (+/-, NCEP criteria). A wide range of lifestyle factors related to physical activity, smoking, alcohol, sleep quality, working conditions, quality of life and stress, and eating patterns were assessed using a questionnaire. Results: Prevalent MetS (23% in the sample) was associated with less physical activity (P < 0.0001), more TV watching (P < 0.0001), more years of smoking (P < 0.0001), lower education level (P = 0.007), and experiencing a poor general quality of life (P < 0.0001). These lifestyle factors were all associated with MetS, independently of each other and independently of BMI. Similar results were generated when number of MetS components and presence/absence of individual MetS components were used as outcomes. Conclusions: This cross-sectional study identified alterations in a number of lifestyle factors associated with MetS independently of each other and independently of BMI. Future longitudinal studies are needed to assess causal and temporal relationships between lifestyle factors and MetS development.

  • 197.
    Roos, Vendela
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Elmstahl, Solve
    Lund Univ, Malmo Univ Hosp, Div Geriatr Med, Dept Hlth Sci, Malmo, Sweden..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    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).
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Metabolic Syndrome Development During Aging with Special Reference to Obesity Without the Metabolic Syndrome2017Inngår i: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518, Vol. 15, nr 1, s. 36-43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Obesity and its associated metabolic complications continue to increase worldwide. We investigated the development of metabolic syndrome (MetS) during aging in relation to body mass index (BMI) and exercise habits. We assigned special emphasis to the metabolic stability in individuals with obesity, but without MetS, a condition often referred to as metabolically healthy obesity. Materials and Methods: Cross-sectional analysis was carried out in a sample of 19,129 men and women aged 45-75 years from the EpiHealth study. In addition, longitudinal analyses were carried out in the ULSAM study (2322 men at baseline followed from age 50 to age 77) and in the PIVUS study (1016 men and women at baseline followed from age 70 to age 80). Participants were categorized into six groups according to BMI category (normal weight/BMI <25 kg/m(2), overweight/BMI 25-30 kg/m(2), and obesity/BMI >30 kg/m(2)) and MetS status (+/-, National Cholesterol Education Program criteria). Results: MetS prevalence and number of MetS components increased with age in all three samples. The PIVUS study showed that high baseline BMI, low baseline physical activity, and increasing BMI during follow-up were related to increasing MetS prevalence and increasing numbers of MetS components during follow-up. One-third to half of individuals initially belonging to the obesity without MetS category acquired MetS during aging. Conclusions: MetS prevalence increased during aging, especially in individuals with high BMI, low level of physical activity, and weight gain. Obesity without MetS was not a stable condition over time as many of those individuals gained metabolic disturbances during aging.

  • 198.
    Roy, Abhik
    et al.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA..
    Laszkowska, Monika
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA..
    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.
    Lebwohl, Benjamin
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA..
    Green, Peter H. R.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA..
    Kämpe, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Autoimmunitet. Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, S-17177 Stockholm, Sweden..
    Ludvigsson, Jonas F.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.;Karolinska Inst, Karolinska Univ Hosp, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.;Orebro Univ Hosp, Dept Paediat, Orebro, Sweden.;Univ Nottingham, Sch Med, Div Epidemiol & Publ Hlth, Nottingham, England..
    Prevalence of Celiac Disease in Patients with Autoimmune Thyroid Disease: A Meta-Analysis2016Inngår i: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 26, nr 7, s. 880-890Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Several screening studies have indicated an increased prevalence of celiac disease (CD) among individuals with autoimmune thyroid disease (ATD), but estimates have varied substantially. Objective: The aim of this study was to examine the prevalence of CD in patients with ATD. Method: A systematic review was conducted of articles published in PubMed Medline or EMBASE until September 2015. Non-English papers with English-language abstracts were also included, as were research abstracts without full text available when relevant data were included in the abstract. Search terms included "celiac disease'' combined with "hypothyroidism'' or "hyperthyroidism'' or "thyroid disease.'' Fixed-effects inverse variance-weighted models were used. Meta-regression was used to examine heterogeneity in subgroups. Results: A pooled analysis, based on 6024 ATD patients, found a prevalence of biopsy-confirmed CD of 1.6% [ confidence interval (CI) 1.3-1.9%]. Heterogeneity was large (I-2 = 70.7%). The prevalence was higher in children with ATD (6.2% [ CI 4.0-8.4%]) than it was in adults (2.7%) or in studies examining both adults and children (1.0%). CD was also more prevalent in hyperthyroidism (2.6% [ CI 0.7-4.4%]) than it was in hypothyroidism (1.4% [ CI 1.0-1.9%]). Conclusions: About 1/62 patients with ATD have biopsy-verified CD. It is argued that patients with ATD should be screened for CD, given this increased prevalence.

  • 199.
    Ruge, Toralph
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden; Karolinska Inst, Dept Med, Stockholm, Sweden.
    Carlsson, Axel C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA USA.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    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 folkhälso- och vårdvetenskap.
    Larsson, Anders
    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.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Huddinge, Sweden.
    Circulating endostatin and the incidence of heart failure.2018Inngår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, nr 5, s. 244-249Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Circulating levels of endostatin are elevated in many underlying conditions leading to heart failure such as hypertension, diabetes, chronic kidney disease and ischemic heart disease. Yet, the association between endostatin and the incidence of heart failure has not been reported previously in the community.

    Design: We investigated the longitudinal association between serum endostatin levels and incident heart failure in two community-based cohorts of elderly: Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 966; mean age 70 years, 51% women, 81 events, mean follow-up 10 years) and Uppsala Longitudinal Study of Adult Men (ULSAM, n = 747 men; mean age 78 years, 98 heart failure events, mean follow-up 8 years). We also investigated the cross-sectional association between endostatin and echocardiographic left ventricular systolic function and diastolic function (ejection fraction and E/A-ratio, respectively).

    Results: Higher serum endostatin was associated with an increased risk for heart failure in both cohorts after adjustment for established heart failure risk factors, glomerular filtration rate and N-terminal pro-brain natriuretic peptide (NT-proBNP) (PIVUS: multivariable hazard ratio (HR) per 1-standard deviation (SD) increase, HR 1.46 (95%CI, 1.17-1.82, p < .001); ULSAM: HR 1.29 (95%CI, 1.00-1.68, p < .05). In cross-sectional analyses at baseline, higher endostatin was significantly associated with both worsened left ventricular systolic and diastolic function in both cohorts.

    Conclusion: Higher serum endostatin was associated with left ventricular dysfunction and an increased heart failure risk in two community-based cohorts of elderly. Our findings encourage further experimental studies that investigate the role of endostatin in the development of heart failure.

  • 200.
    Rönnemaa, E
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Zethelius, B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundelöf, J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Sundström, J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Degerman-Gunnarsson, M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Berne, C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lannfelt, L
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Kilander, L
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Impaired insulin secretion increases the risk of Alzheimer disease2008Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 71, nr 14, s. 1046-47Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Subjects with diabetes are reported to have an increased risk of dementia and cognitive impairment. However, the underlying causes remain unknown. We investigated the longitudinal associations between midlife insulin secretion, glucose metabolism, and the subsequent development of Alzheimer disease (AD) and dementia. METHODS: The population-based Uppsala Longitudinal Study of Adult Men started 1970 when the 2,322 participants were 50 years old. Investigation at baseline included determinations of acute insulin response and glucose tolerance using the IV glucose tolerance test and Homeostasis Model Assessment insulin resistance index. During a median follow up of 32 years, 102 participants were diagnosed with AD, 57 with vascular dementia, and 394 with any dementia or cognitive impairment. Associations were analyzed using Cox proportional hazard models. RESULTS: A low insulin response at baseline was associated with a higher cumulative risk of AD (hazard ratio for 1 SD decrease, 1.31; 95% CI, 1.10-1.56) also after adjustment for age, systolic blood pressure, body mass index, serum cholesterol, smoking, education level, and insulin resistance. This association was stronger in subjects without the APOE epsilon4 allele. Impaired glucose tolerance increased the risk of vascular dementia (hazard ratio for 1 SD decrease, 1.45; 95% CI, 1.05-2.00) but not AD. Impaired insulin secretion, glucose intolerance, and estimates of insulin resistance were all associated with higher risk of any dementia and cognitive impairment. CONCLUSIONS: In this longitudinal study, impaired acute insulin response at midlife was associated with an increased risk of Alzheimer disease (AD) up to 35 years later suggesting a causal link between insulin metabolism and the pathogenesis of AD.

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