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  • 1401. Thygesen, Kristian
    et al.
    Mair, Johannes
    Mueller, Christian
    Huber, Kurt
    Weber, Michael
    Plebani, Mario
    Hasin, Yonathan
    Biasucci, Luigi M
    Giannitsis, Evangelos
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Koenig, Wolfgang
    Tubaro, Marco
    Collinson, Paul
    Katus, Hugo
    Galvani, Marcello
    Venge, Per
    Alpert, Joseph S
    Hamm, Christian
    Jaffe, Allan S
    Recommendations for the use of natriuretic peptides in acute cardiac care: A position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no 16, p. 2001-2006Article in journal (Refereed)
  • 1402.
    Tomasdottir, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Friberg, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Risk of stroke in women and men with atrial fibrillation and only one additional CHA2DS2-VASC risk factor2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 69, no 11 Suppl., p. 327-327Article in journal (Refereed)
  • 1403.
    Trasande, Leonardo
    et al.
    New York University (NYU) School of Medicine, New York, New York, USA NYU Wagner School of Public Service, New York, New York, USA Department of Nutrition, NYU Steinhardt School of Culture, Education and Human Development, Food & Public Health, New York, New York, USA NYU College of Global Public Health, New York University, New York, New York, USA.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Population attributable risks and costs of diabetogenic chemical exposures in the elderly2017In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 71, no 2, p. 111-114Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A previous analysis examined the contribution of endocrine disruptor exposures (endocrine-disrupting chemicals, EDCs) to adult diabetes, but was limited to effects of phthalates in middle-aged women and did not simultaneously examine multiple EDCs which are known to coexist in the environment. We therefore endeavoured to quantify potential reductions in diabetes and disease costs that could result from reducing synthetic chemical diabetogenic exposures in the elderly in Europe.

    METHODS: We leveraged the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (∼1000 participants), which has measured exposure to phthalates; dichlorodiphenyltrichloroethylene; polychlorinated biphenyls (PCBs) and perfluoroalkyl substances to examine their independent contribution to diabetes. We estimated risk reductions assuming identical 25% reductions across levels of 4 selected compounds (PCB 153, monoethylphthalate, dichlorodiphenyldichloroethylene and perfluorononanoic acid), and diabetes costs saved in European men and women if diabetogenic exposures are limited.

    RESULTS: Reduction of chemical exposures was associated with a 13% (95% CI 2% to 22%) reduction in prevalent diabetes, compared with 40% resulting from an identical (25%) reduction in body mass index (BMI) in cross-sectional analyses. Extrapolating to Europe, 152 481 cases of diabetes in Europe and €4.51 billion/year in associated costs could be prevented, compared with 469 172 cases prevented by reducing BMI.

    CONCLUSIONS: These findings support regulatory and individual efforts to reduce chemical exposures to reduce the burden and costs of diabetes.

  • 1404.
    Trasande, Leonardo
    et al.
    NYU, Sch Med, New York, NY USA.;NYU, Wagner Sch Publ Serv, New York, NY USA.;NYU, Coll Global Publ Hlth, New York, NY USA..
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Dismissing manufactured uncertainties, limitations and competing interpretations about chemical exposures and diabetes2017In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 71, no 9, p. 942-942Article in journal (Other academic)
  • 1405. Tricoci, P.
    et al.
    Clare, R.
    Leonardi, S.
    White, H. D.
    Moliterno, D. J.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Van De Werf, F.
    Newby, L. K.
    Mahaffey, K. W.
    Armstrong, P. W.
    Prognostic implication of the new peri-PCI (type 4a) myocardial infarction definition according to the third universal definition of myocardial infarction in patients with NSTE ACS2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 138-138Article in journal (Refereed)
  • 1406. Tricoci, P.
    et al.
    Huang, Z.
    White, H. D.
    Van De Werf, F.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Aylward, P.
    Armstrong, P. W.
    Chen, E.
    Moliterno, D. J.
    Harrington, R.
    Clinical characteristics associated with major bleeding in NSTE ACS and the relationship between bleeding risk, ischemic events, and the vorapaxar effect: analysis from the TRACER trial2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 322-322Article in journal (Other academic)
  • 1407. Tricoci, Pierluigi
    et al.
    Chen, Edmond
    Neely, Megan L.
    Warner, Amelia
    Wong, Peggy H.
    Sinnaeve, Peter
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jennings, Lisa K.
    Storey, Robert F.
    Aylward, Phillip E.
    White, Harvey D.
    Van de Werf, Frans
    Armstrong, Paul W.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Valgimigli, Marco
    Harrington, Robert A.
    Strony, John
    Mahaffey, Kenneth W.
    Moliterno, David J.
    CYP2C19 Polymorphism and PON-1 Activity in NSTE ACS: Vorapaxar Effect in Relation to Clopidogrel Metabolism in the TRACER Trial2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 1408. Tricoci, Pierluigi
    et al.
    Huang, Zhen
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Moliterno, David J
    Armstrong, Paul W
    van de Werf, Frans
    White, Harvey D
    Aylward, Philip E
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Chen, Edmond
    Lokhnygina, Yuliya
    Pei, Jinglan
    Leonardi, Sergio
    Rorick, Tyrus L
    Kilian, Ann M
    Jennings, Lisa H K
    Ambrosio, Giuseppe
    Bode, Christoph
    Cequier, Angel
    Cornel, Jan H
    Diaz, Rafael
    Erkan, Aycan
    Huber, Kurt
    Hudson, Michael P
    Jiang, Lixin
    Jukema, J Wouter
    Lewis, Basil S
    Lincoff, A Michael
    Montalescot, Gilles
    Nicolau, José Carlos
    Ogawa, Hisao
    Pfisterer, Matthias
    Prieto, Juan Carlos
    Ruzyllo, Witold
    Sinnaeve, Peter R
    Storey, Robert F
    Valgimigli, Marco
    Whellan, David J
    Widimsky, Petr
    Strony, John
    Harrington, Robert A
    Mahaffey, Kenneth W
    Thrombin-receptor antagonist vorapaxar in acute coronary syndromes2012In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 366, no 1, p. 20-33Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation.

    METHODS:

    In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization.

    RESULTS:

    Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups.

    CONCLUSIONS:

    In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).

  • 1409. Tricoci, Pierluigi
    et al.
    Lokhnygina, Yuliya
    Huang, Zhen
    Van de Werf, Frans
    Cornel, Jan H.
    Chen, Edmond
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Aylward, Philip E.
    Moliterno, David J.
    Jennings, Lisa K.
    White, Harvey D.
    Armstrong, Paul W.
    Harrington, Robert A.
    Strony, John
    Mahaffey, Kenneth W.
    Vorapaxar with or without clopidogrel after non-ST-segment elevation acute coronary syndromes: Results from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome trial2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, no 6, p. 869-877.e1Article in journal (Refereed)
    Abstract [en]

    Background Protease-activated receptor 1 antagonism with vorapaxar represents a novel strategy for platelet inhibition. In TRACER, vorapaxar was compared with placebo plus standard of care among 12,944 patients with non-ST-segment elevation acute coronary syndromes. We anticipated that most patients would have received clopidogrel as part of standard care. We investigated the modification of vorapaxar's effect associated with clopidogrel use over time. Methods The marginal structural model method was used to estimate causal modification of vorapaxar effect by use of clopidogrel over time. The primary outcomes were the composite of cardiovascular death, myocardial infarction, or stroke and Global Use of Strategies to Open Occluded Coronary Arteries moderate or severe bleeding. The event accrual period excluded the time during which clopidogrel was clinically warranted. Results Among 12,887 patients who received study medication, 11,117 (86.3%) received clopidogrel before randomization, of whom 38.5% stopped later in the trial (median time to stoppage 200 days with placebo; interquartile range [IQR] 14-367) (186 days with vorapaxar; IQR 17-366). In total, 1,770 (13.7%) patients were not on clopidogrel at randomization, of whom 47.8% started afterward (median time to start 2 days; IQR 2-4). During the period of event accrual, vorapaxar was associated with a 26% reduction in the composite of cardiovascular death, myocardial infarction, or stroke when used with clopidogrel (hazard ratio [HR] 0.74; 95% CI 0.60-0.91) and a 24% reduction when used without clopidogrel (HR 0.76; 95% CI 0.56-1.02) (interaction; P = .89). The hazard of Global Use of Strategies to Open Occluded Coronary Arteries bleeding with vorapaxar was not significantly different without clopidogrel (HR 1.33; 95% CI 0.81-2.20) or with clopidogrel (HR 1.09; 95% CI 0.76-1.56) (interaction; P = .53). Conclusions We observed no interaction between vorapaxar and clopidogrel after non-ST-segment elevation acute coronary syndromes on efficacy or safety outcomes, supporting a complementary role of protease-activated receptor 1 and P2Y(12) antagonism.

  • 1410.
    Tricoci, Pierluigi
    et al.
    Duke Univ, Duke Clin Res Inst, Durham, NC USA.
    Neely, Megan
    Duke Univ, Duke Clin Res Inst, Durham, NC USA.
    Whitley, Michael J.
    Thomas Jefferson Univ, Dept Med, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA.
    Edelstein, Leonard C.
    Thomas Jefferson Univ, Dept Med, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA.
    Simon, Lukas M.
    Baylor Coll Med, Dept Human & Mol Genet, Houston, TX 77030 USA.
    Shaw, Chad
    Rice Univ, Dept Stat, Houston, TX 77251 USA;Baylor Coll Med, Dept Human & Mol Genet, Houston, TX 77030 USA.
    Fortina, Paolo
    Thomas Jefferson Univ, Canc Genom & Bioinformat Lab, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
    Moliterno, David J.
    Univ Kentucky, Gill Heart Inst, Lexington, KY USA;Univ Kentucky, Div Cardiovasc Med, Lexington, KY USA.
    Armstrong, Paul W.
    Univ Alberta, Div Cardiol, Edmonton, AB, Canada.
    Aylward, Philip
    Flinders Med Ctr, Div Med Cardiac & Crit Care Serv, Bedford Pk, SA, Australia.
    White, Harvey
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.
    Van de Werf, Frans
    Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium.
    Jennings, Lisa K.
    Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA;CirQuest Labs LLC, Memphis, TN USA.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA.
    Mahaffey, Kenneth W.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA.
    Bray, Paul F.
    Univ Utah, Dept Internal Med, Div Hematol & Hematol Malignancies, Salt Lake City, UT 84112 USA;Univ Utah, Mol Med Program, Salt Lake City, UT USA.
    Effects of genetic variation in protease activated receptor 4 after an acute coronary syndrome: Analysis from the TRACER trial2018In: Blood Cells, Molecules & Diseases, ISSN 1079-9796, E-ISSN 1096-0961, Vol. 72, p. 37-43Article in journal (Refereed)
    Abstract [en]

    Variation in platelet response to thrombin may affect the safety and efficacy of PAR antagonism. The Thr120 variant of the common single nucleotide polymorphism (SNP) rs773902 in the protease-activated receptor (PAR) 4 gene is associated with higher platelet aggregation compared to the Ala120 variant. We investigated the relationship between the rs773902 SNP with major bleeding and ischemic events, safety, and efficacy of PAR1 inhibition in 6177 NSTE ACS patients in the TRACER trial. There was a lower rate of GUSTO moderate/severe bleeding in patients with the Thr120 variant. The difference was driven by a lower rate in the smaller homozygous group (recessive model, HR 0.13 [0.02-0.92] P= 0.042). No significant differences were observed in the ischemic outcomes. The excess in bleeding observed with PAR1 inhibition was attenuated in patients with the Thr120 variant, but the interactions were not statistically significant. In summary, lower major bleeding rates were observed in the overall TRACER cohort with the hyperreactive PAR4 Thr120 variant. The increase in bleeding with vorapaxar was attenuated with the Thr120 variant, but we could not demonstrate an interaction with PAR1 inhibition. These findings warrant further exploration, including those of African ancestry where the A allele (Thr120) frequency is similar to 65%.

  • 1411. Tubaro, Marco
    et al.
    Danchin, Nicolas
    Goldstein, Patrick
    Filippatos, Gerasimos
    Hasin, Yonathan
    Heras, Magda
    Jansky, Petr
    Norekval, Tone M
    Swahn, Eva
    Thygesen, Kristian
    Vrints, Christiaan
    Zahger, Doron
    Arntz, Hans R
    Bellou, Abdelouahab
    De La Coussaye, Jean E
    De Luca, Leonardo
    Huber, Kurt
    Lambert, Yves
    Lettino, Maddalena
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    McLean, Scott
    Nibbe, Lutz
    Peacock, William F
    Price, Susanna
    Quinn, Tom
    Spaulding, Christian
    Tatu-Chitoiu, Gabriel
    Van De Werf, Frans
    Pre-Hospital Treatment of STEMI Patients: A Scientific Statement of the Working Group Acute Cardiac Care of the European Society of Cardiology2012In: Revista Española de Cardiología, ISSN 0300-8932, E-ISSN 1579-2242, Vol. 65, no 1, p. 60-70Article in journal (Refereed)
    Abstract [en]

    In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patient's delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patient's baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the eff ectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.

  • 1412.
    Turcot, Valerie
    et al.
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada..
    Lu, Yingchang
    Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Ingram Canc Ctr,Vanderbilt Ep, Nashville, TN 37212 USA.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Highland, Heather M.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.;Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Univ Texas Sch Publ Hlth, Univ Texas MD Anderson Canc Ctr,UTHealth Grad Sch, Houston, TX 77030 USA..
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Justice, Anne E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Fine, Rebecca S.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA..
    Bradfield, Jonathan P.
    Childrens Hosp Philadelphia, Div Human Genet, Ctr Appl Gen, Philadelphia, PA 19104 USA.;Quantinuum Res LLC, San Diego, CA USA..
    Esko, Tonu
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Giri, Ayush
    Vanderbilt Univ, Dept Med, Div Epidemiol, Inst Med & Publ Hlth,Vanderbilt Genet Inst, Nashville, TN USA..
    Graff, Mariaelisa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Guo, Xiuqing
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Hendricks, Audrey E.
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Colorado, Dept Math & Stat Sci, Denver, CO 80202 USA..
    Karaderi, Tugce
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Eastern Mediterranean Univ, Fac Arts & Sci, Dept Biol Sci, Gazimagusa, Cyprus..
    Lempradl, Adelheid
    Max Planck Inst Immunobiol & Epigenet, Freiburg, Germany..
    Locke, Adam E.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO USA..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Marouli, Eirini
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England..
    Sivapalaratnam, Suthesh
    AMC, Dept Vasc Med, Amsterdam, Netherlands.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Young, Kristin L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Alfred, Tamuno
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Gen, St Louis, MO 63110 USA..
    Masca, Nicholas G. D.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Manning, Alisa K.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA USA..
    Medina-Gomez, Carolina
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Mudgal, Poorva
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA..
    Reiner, Alex P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Vedantam, Sailaja
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA..
    Willems, Sara M.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Winkler, Thomas W.
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Aben, Katja K.
    Netherlands Comprehens Canc Org, Utrecht, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Alam, Dewan S.
    York Univ, Sch Kinesiol & Hlth Sci, Fac Hlth, Toronto, ON, Canada..
    Alharthi, Sameer E.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Allison, Matthew
    Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA..
    Amouyel, Philippe
    INSERM, U1167, Lille, France.;Inst Pasteur, U1167, Lille, France.;Univ Lille, U1167, RID AGE Risk Factors & Mol Determinants Aging Rel, Lille, France..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England..
    Auer, Paul L.
    Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA..
    Balkau, Beverley
    Ctr Rech Epidemiol & Sante Populat CESP, U1018, INSERM, Villejuif, France..
    Bang, Lia E.
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Cambridge, Metabol Res Labs, Cambridge, England.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Wellcome Trust MRC Inst Metab Sci, Cambridge, England..
    Bastarache, Lisa
    Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Benn, Marianne
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark..
    Bergmann, Sven
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland.;Swiss Inst Bioinformat, Lausanne, Switzerland..
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Blueher, Matthias
    Univ Leipzig, IFB Adipos Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbrucke DIfE, Dept Epidemiol, Nuthetal, Germany..
    Boerwinkle, Eric
    Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Univ Texas Sch Publ Hlth, Univ Texas MD Anderson Canc Ctr,UTHealth Grad Sch, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Boeger, Carsten A.
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Bots, Michiel L.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Brandslund, Ivan
    Lillebaelt Hosp, Dept Clin Biochem, Vejle, Denmark.;Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark..
    Breen, Gerome
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London, England.;South London & Maudsley Hosp, NIHR Biomed Res Ctr Mental Hlth, London, England..
    Brilliant, Murray H.
    Marshfield Clin Res Inst, Marshfield, WI USA..
    Broer, Linda
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Brumat, Marco
    Univ Trieste, Dept Med Sci, Trieste, Italy..
    Burt, Amber A.
    Univ Washington, Dept Med, Seattle, WA USA..
    Butterworth, Adam S.
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England..
    Campbell, Peter T.
    Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA..
    Cappellani, Stefania
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Carey, David J.
    Geisinger Hlth Syst, Weis Ctr Res, Danville, PA USA..
    Catamo, Eulalia
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Caulfield, Mark J.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London, England..
    Chambers, John C.
    Ealing Gen Hosp, London North West Healthcare NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Chasman, Daniel I.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Chen, Yii-Der I.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Chowdhury, Rajiv
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England..
    Christensen, Cramer
    Lillebaelt Hosp, Med Dept, Vejle, Denmark..
    Chu, Audrey Y.
    NHLBI Framingham Heart Study, Framingham, MA USA.;Merck Sharp & Dohme Ltd, Genet & Pharmacogen, Boston, MA USA..
    Cocca, Massimiliano
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Collins, Francis S.
    NHGRI, US Natl Inst Hlth, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Corley, Janie
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Galbany, Jordi Corominas
    Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Ophthalmol, Nijmegen, Netherlands..
    Cox, Amanda J.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Griffith Univ, Menzies Hlth Inst Queensland, Southport, Qld, Australia..
    Crosslin, David S.
    Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98195 USA..
    Cuellar-Partida, Gabriel
    Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia.;QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    D'Eustacchio, Angela
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Danesh, John
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Dept Med, British Heart Fdn Cambridge Ctr Excellence, Cambridge, England..
    Davies, Gail
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Ctr Mol Med, Dept Genet, Utrecht, Netherlands..
    Groot, Mark C. H.
    Univ Med Ctr Utrecht, Div Lab & Pharm, Dept Clin Chem & Haematol, Utrecht, Netherlands.;Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands..
    Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Dedoussis, George
    Harokopio Univ, Dept Nutr & Dietet, Sch Hlth Sci & Educ, Athens, Greece..
    Demerath, Ellen W.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Heijer, Martin
    Vrije Univ Amsterdam Med Ctr, Dept Internal Med, Amsterdam, Netherlands..
    Hollander, Anneke I.
    Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Ophthalmol, Nijmegen, Netherlands..
    Ruijter, Hester M.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Utrecht, Netherlands..
    Dennis, Joe G.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England..
    Denny, Josh C.
    Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Angelantonio, Emanuele
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England..
    Drenos, Fotios
    UCL, Inst Cardiovasc Sci, London, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Du, Mengmeng
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.;Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA..
    Dube, Marie-Pierre
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.;Univ Montreal, Dept Med, Fac Med, Montreal, PQ, Canada..
    Dunning, Alison M.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England..
    Easton, Douglas F.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.;Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England..
    Edwards, Todd L.
    Vanderbilt Univ, Dept Med, Div Epidemiol, Inst Med & Publ Hlth,Vanderbilt Genet Inst, Nashville, TN USA..
    Ellinghaus, David
    Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany..
    Ellinor, Patrick T.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA USA..
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England..
    Evangelou, Evangelos
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina, Greece..
    Farmaki, Aliki-Eleni
    Harokopio Univ, Dept Nutr & Dietet, Sch Hlth Sci & Educ, Athens, Greece.;Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Farooqi, I. Sadaf
    Univ Cambridge, Metabol Res Labs, Cambridge, England.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Wellcome Trust MRC Inst Metab Sci, Cambridge, England..
    Faul, Jessica D.
    Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA..
    Fauser, Sascha
    Univ Cologne, Dept Ophthalmol, Cologne, Germany..
    Feng, Shuang
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Ferrannini, Ele
    CNR, Inst Clin Physiol, Pisa, Italy.;Univ Pisa, Dept Clin & Expt Med, Pisa, Italy..
    Ferrieres, Jean
    Toulouse Univ, Sch Med, Toulouse, France..
    Florez, Jose C.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA USA..
    Ford, Ian
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Franke, Andre
    Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany..
    Franks, Paul W.
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Umea Univ, Med Unit, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Friedrich, Nele
    Univ Med Greifswald, Inst Clin Chem, Greifswald, Germany.;Univ Med Greifswald, Lab Med, Greifswald, Germany..
    Frikke-Schmidt, Ruth
    Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark..
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Gan, Wei
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Gandin, Ilaria
    AREA Sci Pk, Res Unit, Trieste, Italy..
    Gasparini, Paolo
    Univ Trieste, Dept Med Sci, Trieste, Italy.;IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Gibson, Jane
    Univ Southampton, Fac Nat & Environm Sci, Ctr Biol Sci, Southampton, Hants, England..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gjesing, Anette P.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Gordon-Larsen, Penny
    Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.;Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC USA..
    Gorski, Mathias
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany.;Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany..
    Grabe, Hans-Joergen
    Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany.;German Ctr Neurodegenerat Dis DZNE, Greifswald, Germany..
    Grant, Struan F. A.
    Childrens Hosp Philadelphia, Div Human Genet, Ctr Appl Gen, Philadelphia, PA 19104 USA.;Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Div Endocrinol, Philadelphia, PA 19104 USA..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Griffiths, Helen L.
    Univ Southampton, Fac Med, Clin Neurosci Res Grp, Vis Sci, Southampton, Hants, England..
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA..
    Gudnason, Vilmundur
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Iceland Heart Assoc, Kopavogur, Iceland..
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Haessler, Jeff
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Hakonarson, Hakon
    Childrens Hosp Philadelphia, Div Human Genet, Ctr Appl Gen, Philadelphia, PA 19104 USA.;Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Hammerschlag, Anke R.
    Vrije Univ Amsterdam, Dept Complex Trait Genet, Ctr Neurogen & Cognit Res, Amsterdam Neurosci, Amsterdam, Netherlands..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Harris, Kathleen Mullan
    Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.;Univ N Carolina, Dept Sociol, Chapel Hill, NC USA..
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Hattersley, Andrew T.
    Univ Exeter, Med Sch, Exeter, Devon, England..
    Have, Christian T.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    He, Liang
    Duke Univ, Social Sci Res Inst, Biodemog Aging Res Unit, Durham, NC USA.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Heard-Costa, Nancy L.
    NHLBI Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA..
    Heath, Andrew C.
    Washington Univ, Dept Psychiat, St Louis, MO USA..
    Heid, Iris M.
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany..
    Helgeland, Oyvind
    Haukeland Hosp, Dept Pediat, Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway..
    Hernesniemi, Jussi
    Tampere Univ Hosp, Ctr Heart, Dept Cardiol, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Tampere, Finland.;Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland..
    Hewitt, Alex W.
    Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.;Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Vis Sci, Perth, WA, Australia.;Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas, Australia..
    Holmen, Oddgeir L.
    Norwegian Univ Sci & Technol, NTNU, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, Trondheim, Norway..
    Hovingh, G. Kees
    AMC, Dept Vasc Med, Amsterdam, Netherlands..
    Howson, Joanna M. M.
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England..
    Hu, Yao
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Huang, Paul L.
    Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Huffman, Jennifer E.
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Neurol, Rotterdam, Netherlands.;Erasmus MC, Dept Radiol, Rotterdam, Netherlands..
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Jansson, Jan-Hakan
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Res Unit Skelleftea, Skelleftea, Sweden..
    Jarvik, Gail P.
    Univ Washington, Dept Med, Seattle, WA USA.;Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA..
    Jensen, Gorm B.
    Frederiksberg Univ Hosp, Copenhagen City Heart Study, Frederiksberg, Denmark..
    Jia, Yucheng
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Johansson, Stefan
    Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway.;Haukeland Hosp, Ctr Med Genet & Mol Med, Bergen, Norway..
    Jorgensen, Marit E.
    Univ Southern Denmark, Natl Inst Publ Hlth, Copenhagen, Denmark.;Steno Diabet Ctr Copenhagen, Gentofte, Denmark..
    Jorgensen, Torben
    Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37235 USA.;Aalborg Univ, Fac Med, Aalborg, Denmark.;Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Interunivers Cardiol Inst Netherlands, Utrecht, Netherlands..
    Kahali, Bratati
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA.;Indian Inst Sci, Ctr Brain Res, Bangalore, Karnataka, India..
    Kahn, Rene S.
    Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Kahonen, Mika
    Univ Tampere, Fac Med & Life Sci, Dept Clin Physiol, Tampere, Finland.;Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland..
    Kamstrup, Pia R.
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark..
    Kanoni, Stavroula
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England..
    Kaprio, Jaakko
    Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Karaleftheri, Maria
    Echinos Med Ctr, Echinos, Greece..
    Kardia, Sharon L. R.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Kathiresan, Sekar
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA..
    Kee, Frank
    Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth Res, Belfast, Antrim, North Ireland..
    Kiemeney, Lambertus A.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Kim, Eric
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Kitajima, Hidetoshi
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Komulainen, Pirjo
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.;Univ Eastern Finland, Sch Med, Inst Biomed, Kuopio Campus, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Kooner, Jaspal S.
    Ealing Gen Hosp, London North West Healthcare NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll London, Natl Heart & Lung Inst, Hammersmith Hosp Campus, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Korhonen, Tellervo
    Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Kovacs, Peter
    Univ Leipzig, IFB Adipos Dis, Leipzig, Germany..
    Kuivaniemi, Helena
    Geisinger Hlth Syst, Weis Ctr Res, Danville, PA USA.;Stellenbosch Univ, Fac Med & Hlth Sci, Dept Psychiat, Tygerberg, South Africa.;Stellenbosch Univ, Fac Med & Hlth Sci, Dept Biomed Sci, Div Mol Biol & Human Genet, Tygerberg, South Africa..
    Kutalik, Zoltan
    Swiss Inst Bioinformat, Lausanne, Switzerland.;Lausanne Univ Hosp, Inst Social & Prevent Med, Lausanne, Switzerland..
    Kuulasmaa, Kari
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Lakka, Timo A.
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.;Univ Eastern Finland, Sch Med, Inst Biomed, Kuopio Campus, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Lamparter, David
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland.;Swiss Inst Bioinformat, Lausanne, Switzerland..
    Lange, Ethan M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Lange, Leslie A.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Larson, Eric B.
    Univ Washington, Dept Med, Seattle, WA USA.;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA..
    Lee, Nanette R.
    Univ San Carlos, Dept Anthropol Sociol & Hist, Cebu, Philippines.;Univ San Carlos, USC Off Populat Studies Fdn Inc, Cebu, Philippines..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland..
    Lewis, Cora E.
    Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA..
    Li, Huaixing
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Li, Jin
    Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Lin, Honghuang
    Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA..
    Lin, Keng-Hung
    Taichung Vet Gen Hosp, Dept Ophthalmol, Taichung, Taiwan..
    Lin, Li-An
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Lin, Xu
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindstrom, Jaana
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Linneberg, Allan
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Rigshosp, Dept Clin Expt Res, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Liu, Dajiang J.
    Penn State Univ, Coll Med, Inst Personalized Med, Dept Publ Hlth Sci, Hershey, PA USA..
    Liu, Yongmei
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA..
    Lo, Ken S.
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada..
    Lophatananon, Artitaya
    Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry, W Midlands, England..
    Lotery, Andrew J.
    Univ Southampton, Fac Med, Clin Neurosci Res Grp, Vis Sci, Southampton, Hants, England..
    Loukola, Anu
    Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Lubitz, Steven A.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland..
    Mannisto, Satu
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Marenne, Gaelle
    Wellcome Trust Sanger Inst, Hinxton, England..
    Mazul, Angela L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    McKean-Cowdin, Roberta
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA..
    Medland, Sarah E.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Meidtner, Karina
    German Inst Human Nutr Potsdam Rehbrucke DIfE, Dept Mol Epidemiol, Nuthetal, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Mistry, Vanisha
    Univ Cambridge, Metabol Res Labs, Cambridge, England.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Wellcome Trust MRC Inst Metab Sci, Cambridge, England..
    Mitchell, Paul
    Univ Sydney, Ctr Vis Res, Westmead Millennium Inst Med Res, Sydney, NSW, Australia.;Univ Sydney, Dept Ophthalmol, Sydney, NSW, Australia..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Moilanen, Leena
    Kuopio Univ Hosp, Dept Med, Kuopio, Finland..
    Moitry, Marie
    Univ Strasbourg, Dept Epidemiol & Publ Hlth, Strasbourg, France.;Univ Hosp Strasbourg, Dept Publ Hlth, Strasbourg, France..
    Montgomery, Grant W.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands..
    Moore, Carmel
    Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, INTERVAL Coordinating Ctr, Cambridge, England..
    Mori, Trevor A.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia..
    Morris, Andrew D.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med, Munich, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany..
    Munroe, Patricia B.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London, England..
    Nalls, Mike A.
    NIA, Lab Neurogenet, US Natl Inst Hlth, Bethesda, MD 20892 USA.;Data Tecn Int, Glen Echo, MD USA..
    Narisu, Narisu
    NHGRI, US Natl Inst Hlth, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Nelson, Christopher P.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Nielsen, Sune F.
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark..
    Nikus, Kjell
    Tampere Univ Hosp, Ctr Heart, Dept Cardiol, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Tampere, Finland..
    Njolstad, Pal R.
    Haukeland Hosp, Dept Pediat, Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway..
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark..
    Nyholt, Dale R.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.;Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia..
    O'Connel, Jeffrey R.
    Univ Maryland, Sch Med, Program Personalized & Genom Med, Dept Med, Baltimore, MD 21201 USA..
    O'Donoghue, Michelle L.
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Loohuis, Loes M. Olde
    Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA..
    Ophoff, Roel A.
    Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands.;Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA..
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Packard, Chris J.
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Padmanabhan, Sandosh
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Palmer, Colin N. A.
    Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Med Res Inst, Dundee, Scotland..
    Palmer, Nicholette D.
    Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Pasterkamp, Gerard
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, Utrecht, Netherlands..
    Patel, Aniruddh P.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA..
    Pattie, Alison
    Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Peissig, Peggy L.
    Marshfield Clin Res Inst, Marshfield, WI USA..
    Peloso, Gina M.
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Pennell, Craig E.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA, Australia..
    Perola, Markus
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland..
    Perry, James A.
    Univ Maryland, Sch Med, Program Personalized & Genom Med, Dept Med, Baltimore, MD 21201 USA..
    Perry, John R. B.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Pers, Tune H.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark..
    Person, Thomas N.
    Marshfield Clin Res Inst, Marshfield, WI USA..
    Peters, Annette
    German Ctr Diabet Res, Neuherberg, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Petersen, Eva R. B.
    Lillebaelt Hosp, Dept Clin Immunol & Biochem, Vejle, Denmark..
    Peyser, Patricia A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Pirie, Ailith
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England..
    Polasek, Ozren
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.;Univ Split, Sch Med, Split, Croatia..
    Polderman, Tinca J.
    Vrije Univ Amsterdam, Dept Complex Trait Genet, Ctr Neurogen & Cognit Res, Amsterdam Neurosci, Amsterdam, Netherlands..
    Puolijoki, Hannu
    Cent Hosp Southern Ostrobothnia, Seinajoki, Finland..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland..
    Rasheed, Asif
    Ctr Noncommun Dis, Karachi, Pakistan..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.;Univ Eastern Finland, Sch Med, Inst Biomed, Kuopio Campus, Kuopio, Finland..
    Reilly, Dermot F.
    Merck Sharp & Dohme Ltd, Genet & Pharmacogen, Boston, MA USA..
    Renstrom, Frida
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Umea Univ, Dept Biobank Res, Umea, Sweden..
    Rheinberger, Myriam
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany..
    Ridker, Paul M.
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Rioux, John D.
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.;Univ Montreal, Dept Med, Fac Med, Montreal, PQ, Canada..
    Rivas, Manuel A.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Univ Oxford, Nuffield Dept Clin Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Roberts, David J.
    Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England.;NHS Blood & Transplant Oxford Ctr, Oxford, England.;Univ Oxford, BRC Haematol Theme & Radcliffe Dept Med, Oxford, England..
    Robertson, Neil R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Robino, Antonietta
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Umea Univ, Unit Family Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Ruth, Katherine S.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Saleheen, Danish
    Ctr Noncommun Dis, Karachi, Pakistan.;Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA USA..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Samani, Nilesh J.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Sapkota, Yadav
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Sattar, Naveed
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Schoen, Robert E.
    Univ Pittsburgh, Dept Med, Med Ctr, Pittsburgh, PA USA.;Univ Pittsburgh, Med Ctr, Dept Epidemiol, Pittsburgh, PA USA..
    Schreiner, Pamela J.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Schulze, Matthias B.
    German Inst Human Nutr Potsdam Rehbrucke DIfE, Dept Mol Epidemiol, Nuthetal, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Scott, Robert A.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Segura-Lepe, Marcelo P.
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Shah, Svati H.
    Duke Univ, Duke Mol Physiol Inst, Durham, NC USA..
    Sheu, Wayne H. -H.
    Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrinol & Metab, Taichung, Taiwan.;Natl Def Med Ctr, Sch Med, Taipei, Taiwan.;Natl Yang Ming Univ, Sch Med, Taipei, Taiwan..
    Sim, Xueling
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Slater, Andrew J.
    GlaxoSmithKline, Genet, Target Sci, Res Triangle Pk, NC USA.;OmicSoft Qiagen Co, Cary, NC USA..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Smith, Albert V.
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Iceland Heart Assoc, Kopavogur, Iceland..
    Southam, Lorraine
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Speliotes, Elizabeth K.
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland..
    Stefansson, Kari
    Univ Iceland, Fac Med, Reykjavik, Iceland..
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen E.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Strauch, Konstantin
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.;Amgen Inc, deCODE Genet, Reykjavik, Iceland.;Ludwig Maximilians Univ Munchen, Fac Med, IBE, Chair Genet Epidemiol, Munich, Germany..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Stumvoll, Michael
    Univ Leipzig, IFB Adipos Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Sun, Liang
    Duke Univ, Social Sci Res Inst, Biodemog Aging Res Unit, Durham, NC USA.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Surendran, Praveen
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England..
    Swift, Amy J.
    NHGRI, US Natl Inst Hlth, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Tada, Hayato
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA.;Kanazawa Univ, Kanazawa, Ishikawa, Japan..
    Tansey, Katherine E.
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England.;Cardiff Univ, Coll Biomed & Life Sci, Cardiff, S Glam, Wales..
    Tardif, Jean-Claude
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada..
    Taylor, Kent D.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Thompson, Deborah J.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England..
    Thorleifsson, Gudmar
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, Reykjavik, Iceland..
    Thuesen, Betina H.
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark..
    Toenjes, Anke
    Univ Leipzig, Dept Womens & Child Hlth, Ctr Pediat Res, Leipzig, Germany..
    Tromp, Gerard
    Geisinger Hlth Syst, Weis Ctr Res, Danville, PA USA.;Stellenbosch Univ, Fac Med & Hlth Sci, Dept Biomed Sci, Div Mol Biol & Human Genet, Tygerberg, South Africa..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Tsafantakis, Emmanouil
    Anogia Med Ctr, Anogia, Greece..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;Dasman Diabet Inst, Dasman, Kuwait.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia..
    Tybjaerg-Hansen, Anne
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark..
    Tyrer, Jonathan P.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England..
    Uher, Rudolf
    Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Uusitupa, Matti
    Univ Eastern Finland, Dept Publ Hlth & Clin Nutr, Kuopio, Finland..
    Laan, Sander W.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Utrecht, Netherlands..
    Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Leeuwen, Nienke
    Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands.;Leiden Univ, Med Ctr, Dept Mol Cell Biol, Leiden, Netherlands..
    van Setten, Jessica
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands..
    Vanhala, Mauno
    Cent Hosp Cent Finland, Primary Hlth Care Unit, Jyvaskyla, Finland.;Kuopio Univ Hosp, Primary Hlth Care Unit, Kuopio, Finland..
    Varbo, Anette
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark..
    Varga, Tibor V.
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden..
    Varma, Rohit
    Univ Southern Calif, Dept Ophthalmol, Keck Sch Med, USC Roski Eye Inst, Los Angeles, CA USA..
    Edwards, Digna R. Velez
    Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Genet Inst, Dept Obstet & Gynecol, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Vermeulen, Sita H.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Veronesi, Giovanni
    Univ Insubria, Dept Med & Surg, Res Ctr Epidemiol & Prevent Med, Varese, Italy..
    Vestergaard, Henrik
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Steno Diabet Ctr Copenhagen, Gentofte, Denmark..
    Vitart, Veronique
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Vogt, Thomas F.
    Merck Sharp & Dohme Ltd, Cardiometabol Dis, Kenilworth, NJ USA..
    Voelker, Uwe
    German Ctr Cardiovasc Res DZHK, Partner Site Greifswald, Greifswald, Germany.;Univ Med Greifswald, Interfaculty Inst Genet & Funct Gen, Greifswald, Germany..
    Vuckovic, Dragana
    Univ Trieste, Dept Med Sci, Trieste, Italy.;IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Wagenknecht, Lynne E.
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA..
    Walker, Mark
    Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle, NSW, Australia..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wang, Feijie
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Wang, Carol A.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA, Australia..
    Wang, Shuai
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Wang, Yiqin
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Ware, Erin B.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.;Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Warren, Helen R.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London, England..
    Waterworth, Dawn M.
    GlaxoSmithKline, Target Sci, Genet, King Of Prussia, PA USA..
    Wessel, Jennifer
    Indiana Univ, Dept Epidemiol, Fairbanks Sch Publ Hlth, Diabet Translat Res Ctr, Indianapolis, IN 46204 USA.;Indiana Univ, Dept Med, Fairbanks Sch Publ Hlth, Diabet Translat Res Ctr, Indianapolis, IN 46204 USA.;Indiana Univ, Sch Med, Indianapolis, IN USA..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    Willer, Cristen J.
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Witte, Daniel R.
    Danish Diabet Acad, Odense, Denmark.;Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark..
    Wood, Andrew R.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Wu, Ying
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Yaghootkar, Hanieh
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Yao, Jie
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Yao, Pang
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Yerges-Armstrong, Laura M.
    Univ Maryland, Sch Med, Program Personalized & Genom Med, Dept Med, Baltimore, MD 21201 USA.;GlaxoSmithKline, King Of Prussia, PA USA..
    Young, Robin
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Glasgow, Glasgow, Lanark, Scotland..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Hinxton, England..
    Zhan, Xiaowei
    Univ Texas Southwestern Med Ctr Dallas, Dept Clin Sci, Quantitat Biomed Res Ctr, Ctr Genet Host Def, Dallas, TX 75390 USA..
    Zhang, Weihua
    Ealing Gen Hosp, London North West Healthcare NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Zhao, Wei
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.;Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA USA..
    Zhou, Wei
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Zondervan, Krina T.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Nuffield Dept Obstet & Gynaecol, Endometriosis CaRe Ctr, Oxford, England..
    Rotter, Jerome I.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Pospisilik, John A.
    Max Planck Inst Immunobiol & Epigenet, Freiburg, Germany..
    Rivadeneira, Fernando
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, Div Stat Gen, St Louis, MO 63110 USA..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Lettre, Guillaume
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.;Univ Montreal, Dept Med, Fac Med, Montreal, PQ, Canada..
    North, Kari E.
    Dept Epidemiol, Chapel Hill, NC USA.;Carolina Ctr Genome Sci, Chapel Hill, NC USA..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England..
    Hirschhorn, Joel N.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA..
    Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity2018In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 1, p. 26-+Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

  • 1413.
    Tängdén, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Eriksson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Cars, Otto
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Radical reduction of cephalosporin use at a tertiary hospital after educational antibiotic intervention during an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae2011In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 66, no 5, p. 1161-1167Article in journal (Refereed)
    Abstract [en]

    Objectives: During an outbreak of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae at our hospital, we performed an educational antibiotic intervention aimed at reducing prescriptions of second- and third-generation cephalosporins and preventing increased use of fluoroquinolones and carbapenems. In this report, we describe the implementation strategy used and evaluate the intervention effect according to Cochrane recommendations. Methods: New recommendations for empirical intravenous antibiotic treatment were communicated to prescribers throughout the hospital by infectious diseases physicians working with Strama (the Swedish strategic programme against antibiotic resistance). No restrictive measures were used. The intervention effect was analysed with interrupted time series (ITS) regression analysis of local and national monthly antibiotic sales data. Results: A radical immediate and sustained reduction was demonstrated for the cephalosporins targeted in the intervention, whereas consumption of piperacillin/tazobactam and penicillin G increased substantially. Fluoroquinolone and carbapenem use was essentially unchanged. The ESBL outbreak subsided and no increased resistance to piperacillin/tazobactam was detected in K. pneumoniae, Escherichia coli or Pseudomonas aeruginosa blood isolates during the 2.5 year follow-up. Conclusions: Our study clearly demonstrates that an educational intervention can have an immediate and profound effect on antibiotic prescription patterns at a large tertiary hospital. ITS regression analysis of local and national antibiotic sales data was valuable to readily assess the immediate and sustained effects of the intervention.

  • 1414.
    Ueda, Peter
    et al.
    Karolinska Inst, Dept Med, Clin Epidemiol Div, Eugeniahemmet T2, S-17176 Stockholm, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alfredsson, Joakim
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden;Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Linkoping, Sweden.
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden.
    Omerovic, Elmir
    Sahlgrens Univ Hosp, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden.
    Persson, Jonas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden.
    Ravn-Fischer, Annica
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden.
    Tornvall, Per
    Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden.
    Svennblad, Bodil
    Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Pfizer AB, Sollentuna, Sweden.
    External Validation of the DAPT Score in a Nationwide Population2018In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 72, no 10, p. 1069-1078Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The dual antiplatelet therapy (DAPT) score guides decisions on DAPT duration after coronary stenting by simultaneously predicting ischemic and bleeding risk. OBJECTIVES This study sought to assess the performance of the DAPT score in a nationwide real-world population. METHODS The study used register data in Sweden (2006 to 2014) and followed 41,101 patients who had undergone 12 months of event-free DAPT, from months 12 to 30 after stenting. Risk of myocardial infarction (MI) or stent thrombosis, major adverse cardiovascular and cerebrovascular events (MACCE) (MI, stroke, and all-cause death), and fatal or major bleeding were compared according to DAPT score. RESULTS The score had a discrimination of 0.58 (95% confidence interval [CI]: 0.56 to 0.60) for MI or stent thrombosis, 0.54 (95% CI: 0.53 to 0.55) for MACCE, and 0.49 (95% CI: 0.45 to 0.53) for fatal or major bleeding. Risk of MI or stent thrombosis was significantly increased at scores of >= 3 while MACCE risk followed a J-shaped pattern and increased at scores of >= 4. Absolute differences in fatal or major bleeding risk were small between scores. Event rates of ischemic and bleeding outcomes in patients with high (>= 2) and low (< 2) scores differed compared to the DAPT Study from which the score was derived; fatal or major bleeding rates were approximately one-half of those in the placebo arm of the DAPT Study. CONCLUSIONS In a nationwide population, the DAPT score did not adequately discriminate ischemic and bleeding risk, the relationship between score and ischemic risk did not correspond to the suggested decision rule for extended DAPT, and risk of bleeding was lower compared with the DAPT Study. The score and its decision rule may not be generalizable to real-world populations.

  • 1415. Ueland, T.
    et al.
    Aukrust, P.
    Michelsen, A.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Himmelmann, A.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Storey, R.
    Kontny, F.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Secreted wingless (Wnt) antagonists and risk prediction in acute coronary syndrome (ACS) a PLATO biomarker substudy2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 318-318Article in journal (Refereed)
  • 1416. Ueland, T.
    et al.
    Michelsen, A.
    Aukrust, P.
    Becker, R.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Storey, R. F.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kontny, F.
    Chemokine (CXC motif) ligand 16 (CXCL16) and osteoprotegerin (OPG) as predictors of outcome in patients with acute coronary syndromes (ACS) a PLATO biomarker substudy2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 486-486Article in journal (Refereed)
  • 1417.
    Ueland, Thor
    et al.
    Univ Oslo, Res Inst Internal Med, Natl Hosp, Oslo, Norway;Univ Oslo, KG Jebsen Inflammatory Res Ctr, Oslo, Norway;Univ Tromso, KG Jebsen Thrombosis Res & Expertise Ctr, Tromso, Norway.
    Åkerblom, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ghukasyan, Tatevik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michelsen, Annika E.
    Univ Oslo, Res Inst Internal Med, Natl Hosp, Oslo, Norway.
    Aukrust, Pål
    Univ Oslo, Res Inst Internal Med, Natl Hosp, Oslo, Norway;Univ Oslo, KG Jebsen Inflammatory Res Ctr, Oslo, Norway;Univ Tromso, KG Jebsen Thrombosis Res & Expertise Ctr, Tromso, Norway;Oslo Univ Hosp, Rikshosp, Sect Clin Immunol & Infect Dis, Oslo, Norway.
    Becker, Richard C.
    Univ Cincinnati, Coll Med, Div Cardiovasc Hlth & Dis, Heart Lung & Vasc Inst, Cincinnati, OH USA.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Himmelmann, Anders
    AstraZeneca Res & Dev, Gothenburg, Sweden.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England.
    Kontny, Frederic
    Stavanger Univ Hosp, Dept Cardiol, Stavanger, Norway;Drammen Heart Ctr, Drammen, Norway.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 2, article id e007009Article in journal (Refereed)
    Abstract [en]

    Background-Elevated levels of osteoprotegerin, a secreted tumor necrosis factor-related molecule, might be associated with adverse outcomes in patients with coronary artery disease. We measured plasma osteoprotegerin concentrations on hospital admission, at discharge, and at 1 and 6months after discharge in a predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Methods and Results-The associations between osteoprotegerin and the composite end point of cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke, and non-coronary artery bypass grafting major bleeding during 1year of follow-up were assessed by Cox proportional hazards models. Event rates of the composite end point per increasing quartile groups at baseline were 5.2%, 7.5%, 9.2%, and 11.9%. A 50% increase in osteoprotegerin level was associated with a hazard ratio (HR) of 1.31 (95% confidence interval [CI], 1.21-1.42) for the composite end point but was not significant in adjusted analysis (ie, clinical characteristics and levels of C-reactive protein, troponin T, NT-proBNP [N-terminal pro-B-type natriuretic peptide], and growth differentiation factor-15). The corresponding rates of non-coronary artery bypass grafting major bleeding were 2.4%, 2.2%, 3.8%, and 7.2%, with an unadjusted HR of 1.52 (95% CI, 1.36-1.69), and a fully adjusted HR of 1.26 (95% CI, 1.09-1.46). The multivariable association between the osteoprotegerin concentrations and the primary end point after 1month resulted in an HR of 1.09 (95% CI, 0.89-1.33); for major bleeding after 1month, the HR was 1.33 (95% CI, 0.91-1.96). Conclusions-In patients with acute coronary syndrome treated with dual antiplatelet therapy, osteoprotegerin was an independent marker of major bleeding but not of ischemic cardiovascular events. Thus, high osteoprotegerin levels may be useful in increasing awareness of increased bleeding risk in patients with acute coronary syndrome receiving antithrombotic therapy.

  • 1418.
    Ueland, Thor
    et al.
    Research Institute of Internal Medicine, National Hospital, University of Oslo, Norway ; K.G. Jebsen Inflammatory Research Center, University of Oslo, Norway ; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Norway .
    Åkerblom, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ghukasyan, Tatevik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michelsen, Annika E
    From the Research Institute of Internal Medicine, National Hospital, University of Oslo, Norway .
    Becker, Richard C
    Division of Cardiovascular Health and Disease, Heart, Lung and Vascular Institute, University of Cincinnati College of Medicine, Ohio, USA.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Himmelmann, Anders
    AstraZeneca Research and Development, Gothenburg, Sweden .
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Storey, Robert F
    Department of Infection, Immunity, and Cardiovascular Disease, University of Sheffield, United Kingdom .
    Kontny, Frederic
    Department of Cardiology, Stavanger University Hospital, Norway ; Drammen Heart Center, Norway .
    Aukrust, Pål
    Research Institute of Internal Medicine, National Hospital, University of Oslo, Norway ; K.G. Jebsen Inflammatory Research Center, University of Oslo, Norway ; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Norway ; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Norway .
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Admission Levels of DKK1 (Dickkopf-1) Are Associated With Future Cardiovascular Death in Patients With Acute Coronary Syndromes2019In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 39, no 2, p. 294-302Article in journal (Refereed)
    Abstract [en]

    Objective- The Wnt/wingless signaling antagonist DKK1 (dickkopf-1) regulates platelet-mediated inflammation and may contribute to plaque destabilization. We hypothesized that DKK1 would be associated with cardiovascular outcomes.

    Approach and Results- We determined DKK1 levels in serum samples obtained before randomization, at discharge, and 1 and 6 months in a subset of 5165 patients with acute coronary syndromes in the PLATO trial (Platelet Inhibition and Patient Outcomes; NCT00391872). The median (interquartile range) DKK1 concentrations were 0.61 (0.20-1.27) ng/mL at baseline and increased during follow-up. The hazard ratio (95% CIs) for the composite end point (cardiovascular death, nonprocedural spontaneous myocardial infarction, or stroke) during 1 year of follow-up, per 50% increase in baseline DKK1 concentration, was 1.06 (1.02-1.10), P=0.0011, and remained significant in fully adjusted analysis with 14 conventional clinical and demographic and 6 biochemical variables, including NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-TnT (high-sensitivity troponin T), and GDF-15 (growth differentiation factor 15; 1.05 [1.00-1.09]; P=0.028). This association was mainly driven by the association with cardiovascular death, where a gradual increase in event rates was observed with increasing quartiles of DKK1 (2.7%, 3.0%, 4.3%, and 5.0%) and remained significant and unmodified in fully adjusted analysis (hazard ratio, 1.10 [1.04-1.17]; P=0.002). Change in DKK1 and levels at 1 month were unrelated to outcomes. A modifying effect of ticagrelor on DKK1 discharge levels was observed but not associated with prognosis.

    Conclusions- In patients with acute coronary syndromes treated with dual antiplatelet treatment, admission DKK1 levels were independently associated with a composite of cardiovascular death, myocardial infarction, or stroke and with cardiovascular death alone.

  • 1419.
    Ungar, Leo
    et al.
    Univ Calif Irvine, Dept Cardiol, Med Ctr, Orange, CA 92668 USA.
    Clare, Robert M.
    Duke Clin Res Inst, Dept Med, Durham, NC 27710 USA.
    Rodriguez, Fatima
    Stanford Univ, Div Cardiovasc Med, Sch Med, Stanford, CA USA.
    Kolls, Bradley J.
    Duke Clin Res Inst, Dept Med, Durham, NC 27710 USA.
    Armstrong, Paul W.
    Univ Alberta, Div Cardiol, Edmonton, AB, Canada.
    Aylward, Philip
    Flinders Univ S Australia, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia;Med Ctr, Adelaide, SA, Australia.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Moliterno, David J.
    Univ Kentucky, Gill Heart Inst, Div Cardiovasc Med, Lexington, KY USA.
    Strony, John
    Johnson & Johnson, New Brunswick, NJ USA.
    Van de Werf, Frans
    Univ Hosp Leuven, Dept Cardiovasc Sci, Leuven, Belgium.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.
    Tricoci, Pierluigi
    Duke Clin Res Inst, Dept Med, Durham, NC 27710 USA.
    Harrington, Robert A.
    Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
    Mahaffey, Kenneth W.
    Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
    Melloni, Chiara
    Duke Clin Res Inst, Dept Med, Durham, NC 27710 USA.
    Stroke Outcomes With Vorapaxar Versus Placebo in Patients With Acute Coronary Syndromes: Insights From the TRACER Trial2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 24, article id e009609Article in journal (Refereed)
    Abstract [en]

    Background

    Vorapaxar, a protease‐activated receptor‐1 antagonist, is approved for secondary prevention of cardiovascular events but is associated with increased intracranial hemorrhage.

    Methods and Results

    TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) was a trial of vorapaxar versus placebo among patients with acute coronary syndrome. Strokes were adjudicated by a central events committee. Of 12 944 patients, 199 (1.5%) had ≥1 stroke during the study period (median follow‐up, 477 days). Four patients had a single stroke of unknown type; 195 patients had ≥1 stroke classified as hemorrhagic or nonhemorrhagic (165 nonhemorrhagic, 28 hemorrhagic, and 2 both). Strokes occurred in 96 of 6473 patients (1.5%) assigned vorapaxar and 103 of 6471 patients (1.6%) assigned placebo. Kaplan‐Meier incidence of stroke for vorapaxar versus placebo was higher for hemorrhagic stroke (0.45% versus 0.14% [hazard ratio, 2.74; 95% confidence interval, 1.22–6.15]), lower but not significantly different for nonhemorrhagic stroke (1.53% versus 1.98% at 2 years [hazard ratio, 0.79; 95% confidence interval, 0.58–1.07]), and similar for stroke overall (1.93% versus 2.13% at 2 years [hazard ratio, 0.94; 95% confidence interval, 0.71–1.24]).

    Conclusions

    Stroke occurred in <2% of patients. Vorapaxar‐assigned patients had increased hemorrhagic stroke but a nonsignificant trend toward lower nonhemorrhagic stroke. Overall stroke frequency was similar with vorapaxar versus placebo.

  • 1420.
    Urban, Philip
    et al.
    La Tour Hosp, Geneva, Switzerland;Cardiovasc European Res Ctr, Massy, France.
    Mehran, Roxana
    Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
    Colleran, Roisin
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.
    Angiolillo, Dominick J.
    Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA.
    Byrne, Robert A.
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.
    Capodanno, Davide
    Ctr Alte Specialita & Trapianti, Cardiothorac Vasc Dept, Catania, Italy;Univ Catania, Azienda Osped Univ Vittorio Emanuele Policlin, Catania, Italy.
    Cuisset, Thomas
    Ctr Hosp Univ Timone, Dept Cardiol, Marseille, France;Aix Marseille Univ, Fac Med, Ctr Rech Cardiovasc & Nutr, Inserm,Inra, Marseille, France.
    Cutlip, Donald
    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Cardiol Div, Boston, MA 02115 USA.
    Eerdmans, Pedro
    DEKRA Certificat BV, Notified Body, Boston, MA USA.
    Eikelboom, John
    McMaster Univ, Dept Med, Hamilton, ON, Canada.
    Farb, Andrew
    US FDA, Silver Spring, MD USA.
    Gibson, C. Michael
    Baim Inst Clin Res, Brookline, MA USA;Harvard Med Sch, Boston, MA 02115 USA.
    Gregson, John
    London Sch Hyg & Trop Med, London, England.
    Haude, Michael
    Lukaskrankenhaus GmbH, Stadt Kliniken Neuss, Neuss, Germany.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kim, Hyo-Soo
    Seoul Natl Univ Hosp, Cardiovasc Ctr, Seoul, South Korea.
    Kimura, Takeshi
    Kyoto Univ, Dept Cardiovasc Med, Grad Sch Med, Kyoto, Japan.
    Konishi, Akihide
    Pharmaceut & Med Devices Agcy, Off Med Devices 1, Tokyo, Japan.
    Laschinger, John
    US FDA, Silver Spring, MD USA.
    Leon, Martin B.
    Columbia Univ, Med Ctr, New York, NY USA;Cardiovasc Res Fdn, New York, NY USA.
    Magee, P. F. Adrian
    US FDA, Silver Spring, MD USA.
    Mitsutake, Yoshiaki
    Pharmaceut & Med Devices Agcy, Off Med Devices 1, Tokyo, Japan.
    Mylotte, Darren
    Univ Hosp, Galway, Ireland;Natl Univ Ireland, Galway, Ireland.
    Pocock, Stuart
    London Sch Hyg & Trop Med, London, England.
    Price, Matthew J.
    Scripps Clin, La Jolla, CA 92037 USA.
    Rao, Sunil V.
    Duke Clin Res Inst, Durham, NC USA.
    Spitzer, Ernest
    Erasmus Univ, Med Ctr, Thoraxctr, Rotterdam, Netherlands;Cardialysis Clin Trial Management & Core Labs, Rotterdam, Netherlands.
    Stockbridge, Norman
    US FDA, Silver Spring, MD USA.
    Valgimigli, Marco
    Univ Bern, Dept Cardiol, Inselspital, Bern, Switzerland.
    Varenne, Olivier
    Hop Cochin, AP HP, Serv Cardiol, Paris, France;Univ Paris 05, Sorbonne Paris Cite, Paris, France.
    Windhoevel, Ute
    Cardiovasc European Res Ctr, Massy, France.
    Yeh, Robert W.
    Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
    Krucoff, Mitchell W.
    Duke Clin Res Inst, Durham, NC USA;Duke Univ, Med Ctr, Durham, NC USA.
    Morice, Marie-Claude
    Cardiovasc European Res Ctr, Massy, France.
    Defining High Bleeding Risk in Patients Undergoing Percutaneous Coronary Intervention: A Consensus Document From the Academic Research Consortium for High Bleeding Risk2019In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 140, no 3, p. 240-261Article in journal (Refereed)
    Abstract [en]

    Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.

  • 1421.
    Urban, Philip
    et al.
    La Tour Hosp, Geneva, Switzerland;Cardiovasc European Res Ctr, Massy, France.
    Mehran, Roxana
    Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
    Colleran, Roisin
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.
    Angiolillo, Dominick J.
    Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA.
    Byrne, Robert A.
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.
    Capodanno, Davide
    Ctr Alte Special & Trapianti, Cardiothoracvasc Dept, Catania, Italy;Univ Catania, Azienda Osped Univ Vittorio Emanuele Policlin, Catania, Italy.
    Cuisset, Thomas
    Aix Marseille Univ, Fac Med, CHU Timone, Dept Cardiol, Marseille, France;Aix Marseille Univ, Fac Med, INSERM, Inra,Ctr Rech Cardiovasc & Nutr, Marseille, France.
    Cutlip, Donald
    Harvard Med Sch, Cardiol Div, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
    Eerdmans, Pedro
    DEKRA Certificat BV, Notified Body, Hamilton, ON, Canada.
    Eikelboom, John
    McMaster Univ, Dept Med, Hamilton, ON, Canada.
    Farb, Andrew
    US FDA, Silver Spring, MD USA.
    Gibson, C. Michael
    Harvard Med Sch, Boston, MA 02115 USA;Baim Inst Clin Res, Brookline, MA USA.
    Gregson, John
    London Sch Hyg & Trop Med, London, England.
    Haude, Michael
    Lukaskrankenhaus GmbH, Stadt Kliniken Neuss, Neuss, Germany.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kim, Hyo-Soo
    Seoul Natl Univ Hosp, Cardiovasc Ctr, Seoul, South Korea.
    Kimura, Takeshi
    Kyoto Univ, Dept Cardiovasc Med, Grad Sch Med, Kyoto, Japan.
    Konishi, Akihide
    Pharmaceut & Med Devices Agcy, Off Med Devices 1, Tokyo, Japan.
    Laschinger, John
    US FDA, Silver Spring, MD USA.
    Leon, Martin B.
    Columbia Univ, Med Ctr, New York, NY USA;Cardiovasc Res Fdn, New York, NY USA.
    Magee, Pf Adrian
    US FDA, Silver Spring, MD USA.
    Mitsutake, Yoshiaki
    Pharmaceut & Med Devices Agcy, Off Med Devices 1, Tokyo, Japan.
    Mylotte, Darren
    Univ Hosp, Galway, Ireland;Natl Univ Ireland, Galway, Ireland.
    Ls, Stuart Pocock
    London Sch Hyg & Trop Med, London, England.
    Price, Matthew J.
    Scripps Clin, La Jolla, CA USA.
    Rao, Sunil, V
    Duke Clin Res Inst, Durham, NC USA.
    Spitzer, Ernest
    Erasmus Univ, Thoraxctr, Med Ctr, Rotterdam, Netherlands;Clin Trial Management & Core Labs, Cardialysis, Rotterdam, Netherlands.
    Stockbridge, Norman
    US FDA, Silver Spring, MD USA.
    Valgimigli, Marco
    Univ Bern, Dept Cardiol, Inselspital, Bern, Switzerland.
    Varenne, Olivier
    Hop Cochin, AP HP, Serv Cardiol, Paris, France;Univ Paris 05, Sorbonne Paris Cite, Paris, France.
    Windhoevel, Ute
    Cardiovasc European Res Ctr, Massy, France.
    Yeh, Robert W.
    Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
    Krucoff, Mitchell W.
    Duke Clin Res Inst, Durham, NC USA;Duke Univ, Med Ctr, Durham, NC USA.
    Morice, Marie-Claude
    Cardiovasc European Res Ctr, Massy, France.
    Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk2019In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 40, no 31, p. 2632-2653Article in journal (Refereed)
    Abstract [en]

    Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.

  • 1422.
    Vaegter, Katarina Kebbon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology. Carl von Linne Clin, Uppsala Sci Pk, Uppsala, Sweden; PCG Clin Serv, Uppsala, Sweden.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala Univ, Uppsala Clin Res Ctr, S-75185 Uppsala, Sweden;Uppsala Univ, Dept Publ Hlth & Caring Sci Geriatr, Uppsala, Sweden.
    Tilly, Johanna
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics. PCG Clin Serv, Uppsala, Sweden.
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Brodin, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology. Carl von Linne Clin, Uppsala Sci Pk, Uppsala, Sweden; PCG Clin Serv, Uppsala, Sweden.
    Holte, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology. Carl von Linne Clin, Uppsala Sci Pk, Uppsala, Sweden; Univ Agr Sci Uppsala, Ctr Reprod Biol Uppsala, Uppsala, Sweden; PCG Clin Serv, Uppsala, Sweden.
    Construction and validation of a prediction model to minimize twin rates at preserved high live birth rates after IVF2019In: Reproductive Biomedicine Online, ISSN 1472-6483, E-ISSN 1472-6491, Vol. 38, no 1, p. 22-29Article in journal (Refereed)
    Abstract [en]

    Research question: Elective single-embryo transfer (eSET) at blastocyst stage is widely used to reduce the frequency of multiple pregnancies after IVF. There are, however, concerns about increased risks for the offspring with prolonged embryo culture. Is it possible to select embryos for transfer at the early cleavage stage and still achieve low twin rates at preserved high live birth rates? Design: A prediction model (PM) was developed to optimize eSET based on variables known 2 days after oocyte retrieval (fresh day 2 embryo transfers; double-embryo transfers 1999-2002 (n=2846) and SET 1999-2003 (n=945); n total=3791). Seventy-five variables were analysed for association with pregnancy chance and twin risk and combined for PM construction. This PM was validated in 2004-2016 including frozen-thawed transfers (FET), to compare cumulative live birth rate (CLBR) and twin rate before (1999-2002 fresh embryo transfers plus FET from the same oocyte retrievals until the end of 2007, n=3495) and after (2004-2011 fresh embryo transfers plus FET from the same oocyte retrievals until the end of 2016, n=11195) implementing the model. Results: The PM was constructed from four independent variables: female age, embryo score, ovarian sensitivity and treatment history. The calibration, i.e. the fit of observed versus predicted results, was excellent both at construction and at validation. Without compromising CLBR, twin rate was reduced from 25.2% to 3.8%, accompanied by profound improvements in perinatal outcome. Conclusion: The results provide the first successful construction, validation and impact analysis of a day 2 transfer PM to reduce multiple pregnancies.

  • 1423.
    Vaegter, Katarina Kebbon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Carl von Linne Clin, Uppsala, Sweden..
    Ghukasyan Lakic, Tatevik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Univ Agr Sci Uppsala, Uppsala, Sweden..
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Berglund, Lars
    Univ Agr Sci Uppsala, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Brodin, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Carl von Linne Clin, Uppsala, Sweden..
    Holte, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Carl von Linne Clin, Uppsala, Sweden.; Center for Reproductive Biology in Uppsala, University of Agricultural Sciences and Uppsala University, Uppsala, Sweden..
    Which factors are most predictive for live birth after in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatments?: Analysis of 100 prospectively recorded variables in 8,400 IVF/ICSI single-embryo transfers2017In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 107, no 3, p. 641-+Article in journal (Refereed)
    Abstract [en]

    Objective: To construct a prediction model for live birth after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and single-embryo transfer (SET) after 2 days of embryo culture. Design: Prospective observational cohort study. Setting: University-affiliated private infertility center. Patient(s): SET in 8,451 IVF/ICSI treatments in 5,699 unselected consecutive couples during 1999-2014. Intervention(s): A total of 100 basal patient characteristics and treatment data were analyzed for associations with live birth after IVF/ICSI (adjusted for repeated treatments) and subsequently combined for prediction model construction. Main Outcome Measure(s): Live birth rate (LBR) and performance of live birth prediction model. Result(s): Embryo score, treatment history, ovarian sensitivity index (OSI; number of oocytes/total dose of FSH administered), female age, infertility cause, endometrial thickness, and female height were all independent predictors of live birth. A prediction model (training data set; n = 5,722) based on these variables showed moderate discrimination, but predicted LBR with high accuracy in subgroups of patients, with LBR estimates ranging from <10% to >40%. Outcomes were similar in an internal validation data set (n = 2,460). Conclusion(s): Based on 100 variables prospectively recorded during a 15-year period, a model for live birth prediction after strict SET was constructed and showed excellent calibration in internal validation. For the first time, female height qualified as a predictor of live birth after IVF/ICSI.

  • 1424. Vaez, Marjan
    et al.
    Dalén, Magnus
    Friberg, Örjan
    Nilsson, Johan
    Frøbert, Ole
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ivert, Torbjörn
    Regional differences in coronary revascularization procedures and outcomes: a nationwide 11-year observational study.2017In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 3, no 3, p. 243-248Article in journal (Refereed)
    Abstract [en]

    Aims: The study investigated whether regional differences in choice of coronary revascularization affected outcomes in Sweden.

    Methods and results: We conducted a prospective nationwide study of outcome in patients undergoing coronary artery bypass grafting (CABG, n = 47 065) or percutaneous coronary intervention (PCI, n = 140 945) from 2001 through 2011, tracked for a median of 5 years. During this period, the proportion of CABG in revascularization procedures decreased nationwide from an average of 38% to 18%e. Three-vessel disease and left main stem coronary artery stenosis were more common among CABG patients than in PCI patients. In both males and females, all-cause mortality was higher in CABG patients than in PCI patients, while repeat PCI was performed more frequently in the PCI group. CABG proportions in 21 counties ranged from 13% to 42% in females and males. The combined outcomes of repeat revascularization, non-fatal acute myocardial infarction, and death during the tracking period was recorded in 151 936 patients without ST-elevation myocardial infarction after PCI (n = 37 820, 36%) and CABG (n = 18 903, 40%). The multivariable adjusted risk of combined outcomes was higher after both PCI and CABG in both females and males in the three quartiles of counties with a smaller proportion of CABG than in the quartile of counties with the highest proportion of CABG. Similar patterns persisted after including only mortality in the analyses.

    Conclusion: There are subgroups of patients who have prognostic benefits of CABG in addition to symptomatic improvement that is well documented with both PCI and CABG.

  • 1425.
    Valgimigli, Marco
    et al.
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.;Erasmus MC, Thoraxctr, Rotterdam, Netherlands..
    Costa, Francesco
    Erasmus MC, Thoraxctr, Rotterdam, Netherlands.;Univ Messina, Dept Clin & Expt Med, Policlin G Martino, Messina, Italy..
    Lokhnygina, Yuliya
    Duke Clin Res Inst, Durham, NC USA..
    Clare, Robert M.
    Duke Clin Res Inst, Durham, NC USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Moliterno, David J.
    Univ Kentucky, Div Cardiovasc Med, Gill Heart Inst, Lexington, KY USA..
    Armstrong, Paul W.
    Univ Alberta, Div Cardiol, Edmonton, AB, Canada..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Aylward, Philip E.
    Flinders Univ S Australia, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.;Med Ctr, Adelaide, SA, Australia..
    Van de Werf, Frans
    Univ Leuven, Dept Cardiol, Leuven, Belgium..
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Mahaffey, Kenneth W.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Tricoci, Pierluigi
    Duke Clin Res Inst, Durham, NC USA..
    Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome: lessons from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) randomized trial2017In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, no 11, p. 804-810Article in journal (Refereed)
    Abstract [en]

    Aims: Dual antiplatelet therapy reduces non-fatal ischaemic events after acute coronary syndrome (ACS) but increases bleeding to a similar extent. We sought to determine the prognostic impact of myocardial infarction (MI) vs. bleeding during an extended follow-up period to gain insight into the trade-off between efficacy and safety among patients after ACS.

    Methods and results: In 12 944 patients with non-ST-segment elevation ACS from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial, we investigated the relative impact of MI and bleeding occurring> 30 days post-ACS and subsequent all-cause mortality. Bleeding was graded according to Bleeding Academic Research Consortium (BARC) criteria. MI was associated with a five-fold increase in mortality. BARC type 2 and 3, but not type 1, bleeding had a significant impact on mortality. MI was associated with a greater risk of mortality compared with BARC 2 [relative risk (RR) 3.5; 95% confidence interval (CI) 2.08-4.77; P< 0.001] and BARC 3a bleeding (RR 2.23; 95% CI 1.36-3.64; P = 0.001), and a risk similar to BARC 3b bleeding (RR 1.37; 95% CI 0.81-2.30; P = 0.242). Risk of death after MI was significantly lower than after BARC 3c bleeding (RR 0.22; 95% CI 0.13-0.36; P< 0.001). MI and bleeding had similar time-associations with mortality, which remained significant for several months, still being higher early after the event.

    Conclusion: In patients treated with antiplatelet therapy after ACS, both MI and bleeding significantly impacted mortality with similar time-dependency. Although BARC 2 and 3a bleeding were less prognostic for death than MI, the risk of mortality was equivalent between BARC 3b bleeding and MI, and was higher following BARC 3c bleeding.

  • 1426. Valgimigli, Marco
    et al.
    Tricoci, Pierluigi
    Huang, Zhen
    Aylward, Philip E.
    Armstrong, Paul W.
    Van de Werf, Frans
    Leonardi, Sergio
    White, Harvey D.
    Widimsky, Petr
    Harrington, Robert A.
    Cequier, Angel
    Chen, Edmond
    Lokhnygina, Yuliya
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Strony, John
    Mahaffey, Kenneth W.
    Moliterno, David J.
    Usefulness and Safety of Vorapaxar in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention (from the TRACER Trial)2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 114, no 5, p. 665-673Article in journal (Refereed)
    Abstract [en]

    The therapeutic potential of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention (PCI) is unknown. This prespecified analysis of a postrandomization subgroup evaluated the effects of vorapaxar compared with placebo among Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) participants undergoing PCI, focusing on the implanted stent type (drug-eluting stent [DES] vs bare-metal stent [BMS]). Among 12,944 recruited patients, 7,479 (57.8%) underwent PCI during index hospitalization, and 3,060 (40.9%) of those patients received exclusively BMS, whereas 4,015 (53.7%) received DES. The median (twenty-fifth, seventy-fifth percentiles) duration of thienopyridine therapy was 133 days (47, 246) with BMS and 221 days (88, 341) with DES. At 2 years among patients undergoing PCI, the primary (cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization) and secondary (cardiovascular death, myocardial infarction, or stroke) end points did not differ between vorapaxar and placebo groups, which was consistent with the treatment effect observed in the overall study population (p value for interaction = 0.540). However, the treatment effect trended greater (p value for interaction = 0.069) and the risk for bleeding in patients taking vorapaxar versus placebo appeared attenuated in BMS-only recipients. After adjustment for confounders, the interaction was no longer significant (p value = 0.301). The covariate that mostly explained the stent-type-by-treatment interaction was the duration of clopidogrel therapy. In conclusion, among patients with PCI, the effect of vorapaxar is consistent with the overall TRACER results. Patients who received a BMS underwent shorter courses of clopidogrel therapy and displayed trends toward greater ischemic benefit from vorapaxar and lesser bleeding risk, compared with patients who received a DES. 

  • 1427. van Diepen, Sean
    et al.
    Roe, Matthew T.
    Lopes, Renato D.
    Stebbins, Amanda
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Newby, L. Kristin
    Moliterno, David J.
    Neumann, Franz-Josef
    Ezekowitz, Justin A.
    Mahaffey, Kenneth W.
    Hochman, Judith S.
    Hamm, Christian W.
    Armstrong, Paul W.
    Theroux, Pierre
    Granger, Christopher B.
    Baseline NT-proBNP and biomarkers of inflammation and necrosis in patients with ST-segment elevation myocardial infarction: insights from the APEX-AMI trial2012In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 34, no 1, p. 106-113Article in journal (Refereed)
    Abstract [en]

    Coronary plaque rupture is associated with a systemic inflammatory response. The relationship between baseline N-terminal pro B-type natriuretic peptide (NT-proBNP), a prognostic marker in patients with acute coronary syndromes, and systemic inflammatory mediators in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) is not well described. Of 5,745 STEMI patients treated with primary PCI in the APEX-AMI trial, we evaluated the relationship between baseline NT-proBNP levels and baseline levels of inflammatory markers and markers of myonecrosis in a subset of 772 who were enrolled in a biomarker substudy. Spearman correlations (r (s)) were calculated between baseline NT-proBNP levels and a panel of ten systemic inflammatory biomarkers. Interleukin (IL)-6, a pro-inflammatory cytokine, was significantly positively correlated with NT-proBNP (r (s) = 0.317, P < 0.001). In a sensitivity analysis excluding all heart failure patients, the correlation between baseline IL-6 and NT-proBNP remained significant (n = 651, r (s) = 0.296, P < 0.001). A positive association was also observed with high sensitivity C-reactive protein (r (s) = 0.377, P < 0.001) and there was a weak negative correlation with the anti-inflammatory cytokine IL-10 (r (s) = -0.109, P = 0.003). No other significant correlations were observed among the other testes inflammatory cytokines and chemokines. In STEMI patients undergoing primary PCI, the pro-inflammatory cytokine IL-6 was modestly correlated with baseline NT-proBNP levels. This relationship remained significant in patients without heart failure. This finding is consistent with pre-clinical and clinical research suggesting that systemic inflammation may influence NT-proBNP expression independently of myocardial stretch.

  • 1428. van Diepen, Sean
    et al.
    Tricoci, Pierluigi
    Podder, Mohua
    Westerhout, Cynthia M
    Aylward, Philip E
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Van de Werf, Frans
    Strony, John
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Moliterno, David J
    White, Harvey D
    Mahaffey, Kenneth W
    Harrington, Robert A
    Armstrong, Paul W
    Efficacy and Safety of Vorapaxar in Non-ST-Segment Elevation Acute Coronary Syndrome Patients Undergoing Noncardiac Surgery2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 12, article id e002546Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Perioperative antiplatelet agents potentially increase bleeding after non-ST-segment elevation (NSTE) acute coronary syndromes (ACS). The protease-activated receptor 1 antagonist vorapaxar reduced cardiovascular events and was associated with increased bleeding versus placebo in NSTE ACS, but its efficacy and safety in noncardiac surgery (NCS) remain unknown. We aimed to evaluate ischemic, bleeding, and long-term outcomes of vorapaxar in NCS after NSTE ACS.

    METHODS AND RESULTS: In the TRACER trial, 2202 (17.0%) patients underwent major or minor NCS after NSTE ACS over 1.5 years (median); continuing study treatment perioperatively was recommended. The primary ischemic end point for this analysis was cardiovascular death, myocardial infarction, stent thrombosis, or urgent revascularization within 30 days of NCS. Safety outcomes included 30-day NCS bleeding and GUSTO moderate/severe bleeding. Overall, 1171 vorapaxar and 1031 placebo patients underwent NCS. Preoperative aspirin and thienopyridine use was 96.8% versus 97.7% (P=0.235) and 89.1% versus 86.1% (P=0.036) for vorapaxar versus placebo, respectively. Within 30 days of NCS, no differences were observed in the primary ischemic end point between vorapaxar and placebo groups (3.4% versus 3.9%; adjusted odds ratio 0.81, 95% CI 0.50 to 1.33, P=0.41). Similarly, no differences in NCS bleeding (3.9% versus 3.4%; adjusted odds ratio 1.41, 95% CI 0.87 to 2.31, P=0.17) or GUSTO moderate/severe bleeding (4.2% versus 3.7%; adjusted odds ratio 1.15, 95% CI, 0.72 to 1.83, P=0.55) were observed. In a 30-day landmarked analysis, NCS patients had a higher long-term risk of the ischemic end point (adjusted hazard ratio 1.62, 95% CI 1.33 to 1.97, P<0.001) and GUSTO moderate/severe bleeding (adjusted hazard ratio 5.63, 95% CI 3.98 to 7.97, P<0.001) versus patients who did not undergo NCS, independent of study treatment.

    CONCLUSION: NCS after NSTE ACS is common and associated with more ischemic outcomes and bleeding. Vorapaxar after NSTE ACS was not associated with increased perioperative ischemic or bleeding events in patients undergoing NCS.