Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
Refine search result
12345 1 - 50 of 211
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Aimo, Alberto
    et al.
    Scuola Super Sant Anna, Pisa, Italy.
    Januzzi, James L
    Massachusetts Gen Hosp, Boston, MA, USA; Harvard Clin Res Inst, Boston, MA USA.
    Vergaro, Giuseppe
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Ripoli, Andrea
    Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Latini, Roberto
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Masson, Serge
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Magnoli, Michela
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Anand, Inder S
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN, USA; VA Med Ctr, Dept Cardiol, Minneapolis, MN USA.
    Cohn, Jay N
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN, USA.
    Tavazzi, Luigi
    ES Hlth Sci Fdn, GVM Hosp Care & Res, Cotignola, Italy.
    Tognoni, Gianni
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Gravning, Jørgen
    Oslo Univ Hosp, Dept Cardiol, Ulleval, Norway; Univ Oslo, Ctr Heart Failure Res, Oslo, Norway.
    Ueland, Thor
    Oslo Univ Hosp, Rikshosp, Internal Med Res Inst, Oslo, Norway; Univ Oslo, Fac Med, Oslo, Norway; Univ Tromso, Jebsen Thrombosis Res & Expertise Ctr, Tromso, Norway.
    Nymo, Ståle H
    Oslo Univ Hosp, Rikshosp, Internal Med Res Inst, Oslo, Norway.
    Brunner-La Rocca, Hans-Peter
    Maastricht Univ, Med Ctr, Dept Cardiol, Maastricht, Netherlands.
    Bayes-Genis, Antoni
    Hosp Badalona Germans Trias & Pujol, Badalona, Barcelona, Spain.
    Lupón, Josep
    Hosp Badalona Germans Trias & Pujol, Badalona, Barcelona, Spain.
    de Boer, Rudolf A
    Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
    Yoshihisa, Akiomi
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Takeishi, Yasuchika
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Egstrup, Michael
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
    Gustafsson, Ida
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
    Gaggin, Hanna K
    Massachusetts Gen Hosp, Boston, MA, USA; Harvard Clin Res Inst, Boston, MA, USA.
    Eggers, Kai M.
    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.
    Huber, Kurt
    Wilhelminenspital Stadt Wien, Fac Internal Med, Vienna, Austria; Sigmund Freud Univ, Med Sch, Vienna, Austria.
    Tentzeris, Ioannis
    Wilhelminenspital Stadt Wien, Fac Internal Med, Vienna, Austria; Sigmund Freud Univ, Med Sch, Vienna, Austria.
    Tang, Wai H.W.
    Cleveland Clin, Inst Heart & Vasc, Cleveland, OH, USA.
    Grodin, Justin
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX USA.
    Passino, Claudio
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Emdin, Michele
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Prognostic Value of High-Sensitivity Troponin T in Chronic Heart Failure: An Individual Patient Data Meta-Analysis2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 137, no 3, p. 286-297Article in journal (Refereed)
    Abstract [en]

    Background: Most patients with chronic heart failure have detectable troponin concentrations when evaluated by high-sensitivity assays. The prognostic relevance of this finding has not been clearly established so far. We aimed to assess high-sensitivity troponin assay for risk stratification in chronic heart failure through a meta-analysis approach.

    Methods: Medline, EMBASE, Cochrane Library, and Scopus were searched in April 2017 by 2 independent authors. The terms were “troponin” AND “heart failure” OR “cardiac failure” OR “cardiac dysfunction” OR “cardiac insufficiency” OR “left ventricular dysfunction.” Inclusion criteria were English language, clinical stability, use of a high-sensitivity troponin assay, follow-up studies, and availability of individual patient data after request to authors. Data retrieved from articles and provided by authors were used in agreement with the PRISMA statement. The end points were all-cause death, cardiovascular death, and hospitalization for cardiovascular cause.

    Results: Ten studies were included, reporting data on 11 cohorts and 9289 patients (age 66±12 years, 77% men, 60% ischemic heart failure, 85% with left ventricular ejection fraction <40%). High-sensitivity troponin T data were available for all patients, whereas only 209 patients also had high-sensitivity troponin I assayed. When added to a prognostic model including established risk markers (sex, age, ischemic versus nonischemic etiology, left ventricular ejection fraction, estimated glomerular filtration rate, and N-terminal fraction of pro-B-type natriuretic peptide), high-sensitivity troponin T remained independently associated with all-cause mortality (hazard ratio, 1.48; 95% confidence interval, 1.41–1.55), cardiovascular mortality (hazard ratio, 1.40; 95% confidence interval, 1.33–1.48), and cardiovascular hospitalization (hazard ratio, 1.42; 95% confidence interval, 1.36–1.49), over a median 2.4-year follow-up (all P<0.001). High-sensitivity troponin T significantly improved risk prediction when added to a prognostic model including the variables above. It also displayed an independent prognostic value for all outcomes in almost all population subgroups. The area under the curve–derived 18 ng/L cutoff yielded independent prognostic value for the 3 end points in both men and women, patients with either ischemic or nonischemic etiology, and across categories of renal dysfunction.

    Conclusions: In chronic heart failure, high-sensitivity troponin T is a strong and independent predictor of all-cause and cardiovascular mortality, and of hospitalization for cardiovascular causes, as well. This biomarker then represents an additional tool for prognostic stratification.

  • 2. Alexander, John H.
    et al.
    Becker, Richard C.
    Bhatt, Deepak L.
    Cools, Frank
    Crea, Filippo
    Dellborg, Mikael
    Fox, Keith A. A.
    Goodman, Shaun G.
    Harrington, Robert A.
    Huber, Kurt
    Husted, Steen
    Lewis, Basil S.
    Lopez-Sendon, Jose
    Mohan, Puneet
    Montalescot, Gilles
    Ruda, Mikhail
    Ruzyllo, Witold
    Verheugt, Freek
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial2009In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 119, no 22, p. 2877-2885Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: After an acute coronary syndrome, patients remain at risk of recurrent events. Apixaban, an oral direct factor Xa inhibitor, is a novel anticoagulant that may reduce these events but also poses a risk of bleeding. METHODS AND RESULTS: Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) was a phase 2, double-blind, placebo-controlled, dose-ranging study. Patients (n=1715) with recent ST-elevation or non-ST-elevation acute coronary syndrome were randomized to 6 months of placebo (n=611) or 1 of 4 doses of apixaban: 2.5 mg twice daily (n=317), 10 mg once daily (n=318), 10 mg twice daily (n=248), or 20 mg once daily (n=221). Nearly all patients received aspirin; 76% received clopidogrel. The primary outcome was International Society of Thrombosis and Hemostasis major or clinically relevant nonmajor bleeding. A secondary outcome was cardiovascular death, myocardial infarction, severe recurrent ischemia, or ischemic stroke. At the recommendation of the Data Monitoring Committee, the 2 higher-dose apixaban arms were discontinued because of excess total bleeding. Compared with placebo, apixaban 2.5 mg twice daily (hazard ratio, 1.78; 95% confidence interval, 0.91 to 3.48; P=0.09) and 10 mg once daily (hazard ratio, 2.45; 95% confidence interval, 1.31 to 4.61; P=0.005) resulted in a dose-dependent increase in major or clinically relevant nonmajor bleeding. Apixaban 2.5 mg twice daily (hazard ratio, 0.73; 95% confidence interval, 0.44 to 1.19; P=0.21) and 10 mg once daily (hazard ratio, 0.61; 95% confidence interval, 0.35 to 1.04; P=0.07) resulted in lower rates of ischemic events compared with placebo. The increase in bleeding was more pronounced and the reduction in ischemic events was less evident in patients taking aspirin plus clopidogrel than in those taking aspirin alone. CONCLUSIONS: We observed a dose-related increase in bleeding and a trend toward a reduction in ischemic events with the addition of apixaban to antiplatelet therapy in patients with recent acute coronary syndrome. The safety and efficacy of apixaban may vary depending on background antiplatelet therapy. Further testing of apixaban in patients at risk of recurrent ischemic events is warranted.

  • 3.
    Alexander, Karen P.
    et al.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Weisz, Giora
    Shaare Zedek Med Ctr, Jerusalem, Israel.;Cardiovasc Res Fdn, New York, NY USA..
    Prather, Kristi
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    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.
    Mark, Daniel B.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Anstrom, Kevin J.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Davidson-Ray, Linda
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Witkowski, Adam
    Inst Cardiol, Dept Intervent Cardiol & Angiol, Warsaw, Poland..
    Mulkay, Angel J.
    Holy Name Med Ctr, Hackensack, NJ USA..
    Osmukhina, Anna
    Gilead Sci Inc, Foster City, CA 94404 USA..
    Farzaneh-Far, Ramin
    Gilead Sci Inc, Foster City, CA 94404 USA..
    Ben-Yehuda, Ori
    Cardiovasc Res Fdn, New York, NY USA.;Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY 10027 USA..
    Stone, Gregg W.
    Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY 10027 USA..
    Ohman, E. Magnus
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Durham, NC 27710 USA..
    Effects of Ranolazine on Angina and Quality of Life After Percutaneous Coronary Intervention With Incomplete Revascularization Results From the Ranolazine for Incomplete Vessel Revascularization (RIVER-PCI) Trial2016In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 133, no 1, p. 39-47Article in journal (Refereed)
    Abstract [en]

    Background Angina often persists or returns in populations following percutaneous coronary intervention (PCI). We hypothesized that ranolazine would be effective in reducing angina and improving quality of life (QOL) in incomplete revascularization (ICR) post-PCI patients. Methods and Results In RIVER-PCI, 2604 patients with a history of chronic angina who had ICR post-PCI were randomized 1:1 to oral ranolazine versus placebo; QOL analyses included 2389 randomized subjects. Angina and QOL questionnaires were collected at baseline and months 1, 6, and 12. Ranolazine patients were more likely than placebo to discontinue study drug by month 6 (20.4% versus 14.1%, P<0.001) and 12 (27.2% versus 21.3%, P<0.001). Following qualifying index PCI, the primary QOL outcome (Seattle Angina Questionnaire [SAQ] angina frequency score) improved markedly, but similarly, in the ranolazine and placebo groups, respectively, from baseline (67.324.5 versus 69.724.0, P=0.01) to month 1 (86.6 +/- 18.1 versus 85.8 +/- 18.5, P=0.27) and month 12 (88.4 +/- 17.8 versus 88.5 +/- 17.8, P=0.94). SAQ angina frequency repeated measures did not differ in adjusted analysis between groups post baseline (mean difference 1.0; 95% CI -0.2, 2.2; P=0.11). Improvement in SAQ angina frequency was observed with ranolazine at month 6 among diabetics (mean difference 3.3; 95% CI 0.6, 6.1; P=0.02) and those with more angina (baseline SAQ angina frequency 60; mean difference 3.4; 95% CI 0.6, 6.2; P=0.02), but was not maintained at month 12. Conclusions Despite ICR following PCI, there was no incremental benefit in angina or QOL measures by adding ranolazine in this angiographically-identified population. These measures markedly improved within 1 month of PCI and persisted up to 1 year in both treatment arms. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442038.

  • 4.
    Al-Khatib, Sana M.
    et al.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    Wojdyla, Daniel M.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    Granger, Christopher B.
    Duke Univ, Duke Clin Res Inst, Sch Med, 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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Garcia, David A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Univ Washington, Div Hematol, Seattle, WA 98195 USA..
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). 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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Alexander, John H.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    Vinereanu, Dragos
    Univ Med & Pharm Carol Davila, Univ & Emergency Hosp, Bucharest, Romania..
    Flaker, Gregory C.
    Univ Missouri, Div Cardiol, Columbia, MO USA..
    Hylek, Elaine M.
    Boston Univ, Sch Med, Boston, MA USA..
    Lopes, Renato D.
    Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC USA..
    Duration of Anticoagulation Interruption Before Invasive Procedures and Outcomes in Patients With Atrial Fibrillation: Insights From the ARISTOTLE Trial2022In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 146, no 12, p. 958-960Article in journal (Refereed)
  • 5. An, Xiaojin
    et al.
    Jin, Yi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Guo, Hongnian
    Foo, Shi-Yin
    Cully, Brittany L
    Wu, Jiaping
    Zeng, Huiyan
    Rosenzweig, Anthony
    Li, Jian
    Response gene to complement 32, a novel hypoxia-regulated angiogenic inhibitor.2009In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 120, no 7, p. 617-27Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Response gene to complement 32 (RGC-32) is induced by activation of complement and regulates cell proliferation. To determine the mechanism of RGC-32 in angiogenesis, we examined the role of RGC-32 in hypoxia-related endothelial cell function.

    METHODS AND RESULTS: Hypoxia/ischemia is able to stimulate both angiogenesis and apoptosis. Hypoxia-inducible factor-1/vascular endothelial growth factor is a key transcriptional regulatory pathway for angiogenesis during hypoxia. We demonstrated that the increased RGC-32 expression by hypoxia was via hypoxia-inducible factor-1/vascular endothelial growth factor induction in cultured endothelial cells. However, overexpression of RGC-32 reduced the proliferation and migration and destabilized vascular structure formation in vitro and inhibited angiogenesis in Matrigel assays in vivo. Silencing RGC-32 had an opposing, stimulatory effect. RGC-32 also stimulated apoptosis as shown by the increased apoptotic cells and caspase-3 cleavage. Mechanistic studies revealed that the effect of RGC-32 on the antiangiogenic response was via attenuating fibroblast growth factor 2 expression and further inhibiting expression of cyclin E without affecting vascular endothelial growth factor and fibroblast growth factor 2 signaling in endothelial cells. In the mouse hind-limb ischemia model, RGC-32 inhibited capillary density with a significant attenuation in blood flow. Additionally, treatment with RGC-32 in the xenograft tumor model resulted in reduced growth of blood vessels that is consistent with reduced colon tumor size.

    CONCLUSIONS: We provide the first direct evidence for RGC-32 as a hypoxia-inducible gene and antiangiogenic factor in endothelial cells. These data suggest that RGC-32 plays an important homeostatic role in that it contributes to differentiating the pathways for vascular endothelial growth factor and fibroblast growth factor 2 in angiogenesis and provides a new target for ischemic disorder and tumor therapies.

  • 6.
    Andersen, Kasper
    et al.
    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.
    Hållmarker, Ulf
    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. Department of Internal Medicine, Mora Hospital, Sweden.
    James, Stefan
    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.
    Sundström, Johan
    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.
    Long-Distance Skiing and Incidence of Hypertension: A Cohort Study of 206,889 Participants in a Long-Distance Cross-Country Skiing Event2020In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 141, no 9, p. 743-750Article in journal (Refereed)
    Abstract [en]

    Background: Hypertension is the leading risk factor for death worldwide and high levels of physical activity is associated with lower incidence of hypertension. The associations of excessive levels of exercise and incidence of hypertension is less known. We aim to compare the incidence of hypertension among 206,889 participants in a long-distance cross-country skiing event and 505,542 persons randomly sampled from the general population (matched to the skiers on age sex and place of residence). Methods: Skiers best performance (in per cent of winning time) and number of completed races during the study period were associated to incidence of hypertension after participation in Vasaloppet. Hypertension was defined as prescription of blood pressure-lowering drugs as obtained from the national drug registry. Models were adjusted for sex, age, education and income (total effect). Results: During a median time-of-risk of 8.3 years skiers had lower incidence of hypertension compared to non-skiers (HR 0.59; 95% confidence interval [CI] 0.58-0.60). Among the skiers, better performance (in % of winning time) in Vasaloppet was strongly associated with lower incidence of hypertension (Fastest fifth: HR 0.41; 95% CI 0.39-0.42. Slowest fifth: 0.78 CI 0.75-0.81). The association was near linear and did not differ between sexes. Among the skiers, a weaker association of number of completed races during the study period with incidence of hypertension (1 race: HR 0.63; 95% CI 0.62-0.65.>5 races: HR 0.51; 95% CI 0.50-0.53). A sub-analysis of 10,804 participants including adjustment for lifestyle factors showed similar results. Conclusions: Participation in a long-distance skiing event was associated with 41% lower incidence of hypertension over the next 8 years, compared to non-participation; and the better the performance, the lower the incidence of hypertension. This adds to the list of beneficial effects of intensive training, as hypertension is the leading risk factor of premature death globally.

  • 7.
    Angiolillo, Dominick J.
    et al.
    Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA..
    Rollini, Fabiana
    Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA..
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England..
    Bhatt, Deepak L.
    Brigham & Womens Hosp, Harvard Med Sch, Heart & Vasc Ctr, Boston, MA USA..
    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.
    Schneider, David J.
    Univ Vermont, Cardiovasc Res Inst, Cardiol Unit, Dept Med, Burlington, VT 05405 USA..
    Sibbing, Dirk
    Ludwig Maximilians Univ Munchen, Dept Cardiol, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Berlin, Germany..
    So, Derek Y. F.
    Univ Ottawa, Heart Inst, Div Cardiol, Ottawa, ON, Canada..
    Trenk, Dietmar
    Univ Heart Ctr Freiburg Bad Krozingen, Dept Cardiol & Angiol 2, Freiberg, Germany..
    Alexopoulos, Dimitrios
    Natl & Capodistrian Univ Athens, Dept Cardiol 2, Attikon Univ Hosp, Athens, Greece..
    Gurbel, Paul A.
    Inova Heart & Vasc Inst, Inova Ctr Thrombosis Res & Drug Dev, Falls Church, VA USA..
    Hochholzer, Willibald
    Univ Heart Ctr Freiburg Bad Krozingen, Dept Cardiol & Angiol 2, Freiberg, Germany..
    De Luca, Leonardo
    San Giovanni Evangelista Hosp, Lab Intervent Cardiol, Div Cardiol, Tivoli Rome, Italy.;Mediterranean Acad Assoc Res & Studies Cardiol, Marseille, France.;Aix Marseille Univ, INSERM, UMRS 1076, Marseille, France..
    Bonello, Laurent
    Hop Nord Marseille, AP HP, Dept Cardiol, Marseille, France..
    Aradi, Daniel
    Heart Ctr Balatonfured, Budapest, Hungary.;Semmelweis Univ Budapest, Budapest, Hungary..
    Cuisset, Thomas
    CHU Timone, Dept Cardiol, Marseille, France.;Aix Marseille Univ, Fac Med, Marseille, France..
    Tantry, Udaya S.
    Inova Heart & Vasc Inst, Inova Ctr Thrombosis Res & Drug Dev, Falls Church, VA USA..
    Wang, Tracy Y.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Valgimigli, Marco
    Bern Univ Hosp, Swiss Cardiovasc Ctr Bern, Bern, Switzerland..
    Waksman, Ron
    MedStar Washington Hosp Ctr, Sect Intervent Cardiol, Washington, DC USA..
    Mehran, Roxana
    Icahn Sch Med Mt Sinai, New York, NY USA..
    Montalescot, Gilles
    Sorbonne Univ Paris 6, Hop Pitie Salpetriere, ACTION Study Grp, Paris, France..
    Franchi, Francesco
    Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA..
    Price, Matthew J.
    Scripps Clin, Div Cardiovasc Dis, La Jolla, CA USA..
    International Expert Consensus on Switching Platelet P2Y(12) Receptor-Inhibiting Therapies2017In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 136, no 20, p. 1955-+Article in journal (Refereed)
    Abstract [en]

    Dual antiplatelet therapy with aspirin and a P2Y(12) inhibitor is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes and for those undergoing percutaneous coronary interventions. The availability of different oral P2Y(12) inhibitors (clopidogrel, prasugrel, ticagrelor) has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. The recent introduction of an intravenous P2Y(12) inhibitor (cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. In clinical practice, it is not uncommon to switch P2Y(12) inhibitor, and switching may be attributed to a variety of factors. However, concerns about the safety of switching between these agents have emerged. Practice guidelines have not fully elaborated on how to switch therapies, leaving clinicians with limited guidance on when and how to switch therapies when needed. This prompted the development of this expert consensus document by key leaders from North America and Europe with expertise in basic, translational, and clinical sciences in the field of antiplatelet therapy. This expert consensus provides an overview of the pharmacology of P2Y(12) inhibitors, different modalities and definitions of switching, and available literature and recommendations for switching between P2Y(12) inhibitors.

  • 8.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hambraeus, Kristina
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindahl, Bertil
    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.
    Sundström, Johan
    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.
    Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction2014In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 130, no 4, p. 325-323Article in journal (Refereed)
    Abstract [en]

    Background-Given the indications of increased risk for fatal myocardial infarction (MI) in people who use snus, a moist smokeless tobacco product, we hypothesized that discontinuation of snus use after an MI would reduce mortality risk. Methods and Results-All patients who were admitted to coronary care units for an MI in Sweden between 2005 and 2009 and were <75 years of age underwent a structured examination 2 months after discharge (the baseline of the present study). We investigated the risk of mortality in post-MI snus quitters (n=675) relative to post-MI continuing snus users (n=1799) using Cox proportional hazards analyses. During follow-up (mean 2.1 years), 83 participants died. The mortality rate was 9.7 (95% confidence interval, 5.7-16.3) per 1000 person-years at risk in post-MI snus quitters and 18.7 (14.8-23.6) per 1000 person-years at risk in post-MI continuing snus users. After adjustment for age and sex, post-MI snus quitters had half the mortality risk of post-MI continuing snus users (hazard ratio, 0.51; 95% confidence interval, 0.29-0.91). In a multivariable-adjusted model, the hazard ratio was 0.57 (95% confidence interval, 0.32-1.02). The corresponding estimate for people who quit smoking after MI versus post-MI continuing smokers was 0.54 (95% confidence interval, 0.42-0.69). Conclusions-In this study, discontinuation of snus use after an MI was associated with a nearly halved mortality risk, similar to the benefit associated with smoking cessation. These observations suggest that the use of snus after MI should be discouraged.

  • 9.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hambraeus, Kristina
    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, Center for Clinical Research Dalarna.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindahl, Bertil
    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.
    Sundström, Johan
    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.
    Response to Letter Regarding Article, "Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction"2015In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 131, no 17, p. E423-E423Article in journal (Refereed)
  • 10. Armaganijan, Luciana
    et al.
    Lopes, Renato
    Huang, Zhen
    Tricoci, Pierluigi
    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.
    Van de Werf, Frans
    Armstrong, Paul W.
    Aylward, Philip E.
    White, Harvey D.
    Moliterno, David 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.
    Chen, Edmond
    Harrington, Robert A.
    Strony, John
    Mahaffey, Kenneth W.
    Efficacy and Safety of Vorapaxar in Elderly Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: Insights From the TRACER Trial2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 11. Armstrong, Paul W
    et al.
    Siha, Hany
    Fu, Yuling
    Westerhout, Cynthia M
    Steg, P Gabriel
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Storey, Robert F
    Horrow, Jay
    Katus, Hugo
    Clemmensen, Peter
    Harrington, Robert A
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    ST Elevation Acute Coronary Syndromes in PLATO: Insights from the ECG Substudy2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, no 3, p. 514-521Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Ticagrelor, when compared with clopidogrel, reduced the 12-month risk of vascular death/myocardial infarction (MI) and stroke in patients with ST-elevation acute coronary syndromes (ST-E ACS) intended to undergo primary percutaneous coronary intervention (PCI) in the PLATelet inhibition and patient Outcomes (PLATO) trial. This pre-specified electrocardiogram (ECG) substudy explored whether ticagrelor's association with vascular death and MI within one year would be amplified by: 1) the extent of baseline ST shift; and 2) subsequently associated with less residual ST changes at hospital discharge.

    METHODS AND RESULTS:

    ECGs were evaluated centrally in a core laboratory in 3,122 ticagrelor- and 3,084 clopidogrel-assigned patients having at least 1mm ST-E in two contiguous leads as identified by site investigators on the qualifying ECG. Patients with greater ST-segment shift at baseline had higher rates of vascular death/MI within one year. Amongst those who also had an ECG at hospital discharge (n=4,798), patients with ≥50% ∑ST-deviation (∑ST-dev) resolution had higher event-free survival than those with incomplete resolution (6.4% vs. 8.8%, adjusted hazard ratio 0.69 (0.54-0.88), p=0.003). The extent of ∑ST-dev resolution was similar irrespective of treatment assignment. The benefit of ticagrelor versus clopidogrel on clinical events was consistent irrespective of the extent of baseline ∑ST-dev (p(interaction)=0.728). When stratified according to conventional times from symptom onset i.e. ≤3 hours, 3-6 hours, >6 hours, the extent of baseline ∑ST-dev declined progressively over time. As time from symptom onset increased beyond three hours, the benefit of ticagrelor appeared to be more pronounced; however, the interaction between time and treatment was not significant (p=0.175).

    CONCLUSIONS:

    Ticagrelor did not modify ∑ST-dev resolution at discharge nor was its benefit affected by the extent of baseline ∑ST-dev. These hypothesis-generating observations suggest that the main effects of ticagrelor may not relate to the rapidity or the completeness of acute reperfusion, but rather the prevention of recurrent vascular events by more powerful platelet inhibition or other mechanisms.

  • 12. Bagai, Akshay
    et al.
    Huang, Zhen
    Lokhnygina, Yuliya
    Harrington, Robert A.
    Armstrong, Paul W.
    Strony, John
    Chen, Edmond
    White, Harvey D.
    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.
    Van de Werf, Frans
    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.
    Tricoci, Pierluigi
    Mahaffey, Kenneth W.
    Differential Prognostic Implications of Peak Troponin Level in Acute Coronary Syndrome Treated With and Without Revascularization2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 13. Beck, AW
    et al.
    Sedrakyan, A
    Mao, J
    Venermo, M
    Faizer, R
    Debus, S
    Behrendt, CA
    Scali, S
    Altreuther, M
    Schermerhorn, M
    Beiles, B
    Szeberin, Z
    Eldrup, N
    Danielsson, G
    Thomson, I
    Wigger, P
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Cronenwett, JL
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    International Consortium of Vascular Registries,
    Variations in abdominal aortic aneurysm care: a report from the International consortium of vascular registries2016In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539Article in journal (Refereed)
    Abstract [en]

    Background: This project by the ICVR (International Consortium of Vascular Registries), a collaboration of 11 vascular surgical quality registries, was designed to evaluate international variation in the contemporary management of abdominal aortic aneurysm (AAA) with relation to recommended treatment guidelines from the Society for Vascular Surgery and the European Society for Vascular Surgery.

    Methods: Registry data for open and endovascular AAA repair (EVAR) during 2010 to 2013 were collected from 11 countries. Variations in patient selection and treatment were compared across countries and across centers within countries.

    Results: Among 51 153 patients, 86% were treated for intact AAA (iAAA) and 14% for ruptured AAA. Women constituted 18% of the entire cohort (range, 12% in Switzerland–21% in the United States; P<0.01). Intact AAAs were repaired at diameters smaller than recommended by guidelines in 31% of men (<5.5 cm; range, 6% in Iceland–41% in Germany; P<0.01) and 12% of women with iAAA (<5 cm; range, 0% in Iceland–16% in the United States; P<0.01). Overall, use of EVAR for iAAA varied from 28% in Hungary to 79% in the United States (P<0.01) and for ruptured AAA from 5% in Denmark to 52% in the United States (P<0.01). In addition to the between-country variations, significant variations were present between centers in each country in terms of EVAR use and rate of small AAA repair. Countries that more frequently treated small AAAs tended to use EVAR more frequently (trend: correlation coefficient, 0.51; P=0.14). Octogenarians made up 23% of all patients, ranging from 12% in Hungary to 29% in Australia (P<0.01). In countries with a fee-for-service reimbursement system (Australia, Germany, Switzerland, and the United States), the proportions of small AAA (33%) and octogenarians undergoing iAAA repair (25%) were higher compared with countries with a population-based reimbursement model (small AAA repair, 16%; octogenarians, 18%; P<0.01). In general, center-level variation within countries in the management of AAA was as important as variation between countries.

    Conclusions: Despite homogeneous guidelines from professional societies, significant variation exists in the management of AAA, most notably for iAAA diameter at repair, use of EVAR, and the treatment of elderly patients. ICVR provides an opportunity to study treatment variation across countries and to encourage optimal practice by sharing these results.

    Download full text (pdf)
    fulltext
  • 14.
    Bekwelem, Wobo
    et al.
    Univ Minnesota, Sch Med, Lillehei Heart Inst, Minneapolis, MN 55455 USA.;Univ Minnesota, Sch Med, Div Cardiovasc, Minneapolis, MN 55455 USA..
    Connolly, Stuart J.
    McMaster Univ, Dept Med, Hamilton, ON, Canada..
    Halperin, Jonathan L.
    Mt Sinai Sch Med, New York, NY USA..
    Adabag, Selcuk
    Minneapolis Vet Adm Med Ctr, Div Cardiol, Minneapolis, MN USA..
    Duval, Sue
    Univ Minnesota, Sch Med, Lillehei Heart Inst, Minneapolis, MN 55455 USA.;Univ Minnesota, Sch Med, Div Cardiovasc, Minneapolis, MN 55455 USA..
    Chrolavicius, Susan
    McMaster Univ, Dept Med, Hamilton, ON, Canada..
    Pogue, Janice
    McMaster Univ, Dept Med, Hamilton, ON, Canada..
    Ezekowitz, Michael D.
    Lankenau Inst Med Res, Wynnewood, PA USA..
    Eikelboom, John W.
    McMaster Univ, Dept Med, Hamilton, ON, Canada..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Yusuf, Salim
    McMaster Univ, Dept Med, Hamilton, ON, Canada..
    Hirsch, Alan T.
    Univ Minnesota, Sch Med, Lillehei Heart Inst, Minneapolis, MN 55455 USA.;Univ Minnesota, Sch Med, Div Cardiovasc, Minneapolis, MN 55455 USA..
    Extracranial Systemic Embolic Events in Patients With Nonvalvular Atrial Fibrillation Incidence, Risk Factors, and Outcomes2015In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 132, no 9, p. 796-803Article in journal (Refereed)
    Abstract [en]

    Background Nonvalvular atrial fibrillation is a major cause of thromboembolic events. In comparison with atrial fibrillation-related stroke, extracranial systemic embolic events (SEEs) remain poorly defined. Methods and Results All suspected SEEs reported among 37973 participants of 4 large contemporary randomized clinical trials of anticoagulation in atrial fibrillation were independently readjudicated for clinical and objective evidence of sudden loss of perfusion of a limb or organ. Over 91746 patient-years of follow-up, 221 SEEs occurred in 219 subjects. The SEE incidence was 0.24 of 100 and stroke incidence was 1.92 of 100 patient-years. In comparison with patients with stroke, those with SEE were more often female (56% versus 47%; P=0.01) and had comparable mean age (73.18.5 versus 73.5 +/- 8.8 years; P=0.57) and mean CHADS(2) scores (2.4 +/- 1.3 versus 2.5 +/- 1.2; P=0.33). SEEs more frequently involved the lower extremity (58%) than visceral-mesenteric (31%) or upper extremity (10%). SEE-related care involved clinic assessment alone in 5%, 30% were hospitalized without procedures, 60% underwent endovascular or surgical intervention, and 5% underwent amputation. Within 30 days, 54% of patients recovered fully, 20% survived with deficits, and 25% died. Thirty-day mortality was greater after visceral-mesenteric than lower- or upper-extremity SEE (55%, 17%, and 9%, respectively, P0.0001). The relative risk of death throughout follow-up was 4.33 (95% confidence interval, 3.29-5.70) after SEE versus 6.79 (95% confidence interval, 6.22-7.41) after stroke in comparison with patients without either event. Conclusions SEE constituted 11.5% of clinically recognized thromboembolic events in patients with atrial fibrillation and was associated with high morbidity and mortality. SEE mortality was comparable to that of ischemic stroke and varied by anatomic site.

  • 15.
    Benson, Tyler W.
    et al.
    Univ Cincinnati, Dept Internal Med, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Div Cardiovasc Hlth & Dis, Coll Med, Cincinnati, OH USA..
    Conrad, Kelsey A.
    Univ Cincinnati, Dept Internal Med, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Div Cardiovasc Hlth & Dis, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Pathobiol & Mol Med Grad Program, Coll Med, Cincinnati, OH USA..
    Li, Xinmin S.
    Cleveland Clin, Dept Cardiovasc & Metab Sci, Learner Res Inst, Cleveland, OH USA.;Cleveland Clin, Ctr Microbiome & Human Hlth, Cleveland, OH USA..
    Wang, Zeneng
    Cleveland Clin, Dept Cardiovasc & Metab Sci, Learner Res Inst, Cleveland, OH USA.;Cleveland Clin, Ctr Microbiome & Human Hlth, Cleveland, OH USA..
    Helsley, Robert N.
    Cleveland Clin, Dept Cardiovasc & Metab Sci, Learner Res Inst, Cleveland, OH USA..
    Schugar, Rebecca. C.
    Cleveland Clin, Dept Cardiovasc & Metab Sci, Learner Res Inst, Cleveland, OH USA..
    Coughlin, Taylor M.
    Univ Cincinnati, Dept Internal Med, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Div Cardiovasc Hlth & Dis, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Pathobiol & Mol Med Grad Program, Coll Med, Cincinnati, OH USA..
    Wadding-Lee, Caris
    Univ Cincinnati, Dept Internal Med, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Div Cardiovasc Hlth & Dis, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Pathobiol & Mol Med Grad Program, Coll Med, Cincinnati, OH USA..
    Fleifil, Salma
    Univ Cincinnati, Dept Internal Med, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Div Cardiovasc Hlth & Dis, Coll Med, Cincinnati, OH USA..
    Russell, Hannah M.
    Univ Cincinnati, Dept Internal Med, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Div Cardiovasc Hlth & Dis, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Pathobiol & Mol Med Grad Program, Coll Med, Cincinnati, OH USA..
    Stone, Timothy
    Univ Cincinnati, Dept Environm Hlth, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Div Biostat & Bioinformat, Coll Med, Cincinnati, OH USA..
    Brooks, Michael
    Univ Cincinnati, Dept Internal Med, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Div Cardiovasc Hlth & Dis, Coll Med, Cincinnati, OH USA..
    Buffa, Jennifer A.
    Cleveland Clin, Dept Cardiovasc & Metab Sci, Learner Res Inst, Cleveland, OH USA.;Cleveland Clin, Ctr Microbiome & Human Hlth, Cleveland, OH USA..
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Sangwan, Naseer
    Cleveland Clin, Dept Cardiovasc & Metab Sci, Learner Res Inst, Cleveland, OH USA.;Cleveland Clin, Ctr Microbiome & Human Hlth, Cleveland, OH USA..
    Biddinger, Sudha
    Harvard Med Sch, Boston Childrens Hosp, Div Endocrinol, Boston, MA USA..
    Bhandari, Rohan
    Cleveland Clin, Dept Cardiovasc & Metab Sci, Learner Res Inst, Cleveland, OH USA.;Cleveland Clin, Heart Vasc & Thorac Inst, Dept Cardiovasc Med, Cleveland, OH USA..
    Ademoya, Akiirayi
    Cleveland Clin, Dept Cardiovasc & Metab Sci, Learner Res Inst, Cleveland, OH USA..
    Pascual, Crystal
    Cleveland Clin, Dept Cardiovasc & Metab Sci, Learner Res Inst, Cleveland, OH USA..
    Tang, W. H. Wilson
    Cleveland Clin, Dept Cardiovasc & Metab Sci, Learner Res Inst, Cleveland, OH USA.;Cleveland Clin, Ctr Microbiome & Human Hlth, Cleveland, OH USA.;Cleveland Clin, Heart Vasc & Thorac Inst, Dept Cardiovasc Med, Cleveland, OH USA..
    Tranter, Michael
    Univ Cincinnati, Dept Internal Med, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Div Cardiovasc Hlth & Dis, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Pathobiol & Mol Med Grad Program, Coll Med, Cincinnati, OH USA..
    Cameron, Scott J.
    Cleveland Clin, Dept Cardiovasc & Metab Sci, Learner Res Inst, Cleveland, OH USA.;Cleveland Clin, Heart Vasc & Thorac Inst, Dept Cardiovasc Med, Cleveland, OH USA..
    Brown, J. Mark
    Cleveland Clin, Dept Cardiovasc & Metab Sci, Learner Res Inst, Cleveland, OH USA.;Cleveland Clin, Ctr Microbiome & Human Hlth, Cleveland, OH USA..
    Hazen, Stanley L.
    Cleveland Clin, Dept Cardiovasc & Metab Sci, Learner Res Inst, Cleveland, OH USA.;Cleveland Clin, Ctr Microbiome & Human Hlth, Cleveland, OH USA.;Cleveland Clin, Heart Vasc & Thorac Inst, Dept Cardiovasc Med, Cleveland, OH USA..
    Owens, A. Phillip, III
    Univ Cincinnati, Dept Internal Med, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Div Cardiovasc Hlth & Dis, Coll Med, Cincinnati, OH USA.;Univ Cincinnati, Pathobiol & Mol Med Grad Program, Coll Med, Cincinnati, OH USA..
    Gut Microbiota-Derived Trimethylamine N-Oxide Contributes to Abdominal Aortic Aneurysm Through Inflammatory and Apoptotic Mechanisms2023In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 147, no 14, p. 1079-1096Article in journal (Refereed)
    Abstract [en]

    Background:Large-scale human and mechanistic mouse studies indicate a strong relationship between the microbiome-dependent metabolite trimethylamine N-oxide (TMAO) and several cardiometabolic diseases. This study aims to investigate the role of TMAO in the pathogenesis of abdominal aortic aneurysm (AAA) and target its parent microbes as a potential pharmacological intervention.

    Methods:TMAO and choline metabolites were examined in plasma samples, with associated clinical data, from 2 independent patient cohorts (N=2129 total). Mice were fed a high-choline diet and underwent 2 murine AAA models, angiotensin II infusion in low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice or topical porcine pancreatic elastase in C57BL/6J mice. Gut microbial production of TMAO was inhibited through broad-spectrum antibiotics, targeted inhibition of the gut microbial choline TMA lyase (CutC/D) with fluoromethylcholine, or the use of mice genetically deficient in flavin monooxygenase 3 (Fmo3(-/-)). Finally, RNA sequencing of in vitro human vascular smooth muscle cells and in vivo mouse aortas was used to investigate how TMAO affects AAA.

    Results:Elevated TMAO was associated with increased AAA incidence and growth in both patient cohorts studied. Dietary choline supplementation augmented plasma TMAO and aortic diameter in both mouse models of AAA, which was suppressed with poorly absorbed oral broad-spectrum antibiotics. Treatment with fluoromethylcholine ablated TMAO production, attenuated choline-augmented aneurysm initiation, and halted progression of an established aneurysm model. In addition, Fmo3(-/-) mice had reduced plasma TMAO and aortic diameters and were protected from AAA rupture compared with wild-type mice. RNA sequencing and functional analyses revealed choline supplementation in mice or TMAO treatment of human vascular smooth muscle cells-augmented gene pathways associated with the endoplasmic reticulum stress response, specifically the endoplasmic reticulum stress kinase PERK.

    Conclusions:These results define a role for gut microbiota-generated TMAO in AAA formation through upregulation of endoplasmic reticulum stress-related pathways in the aortic wall. In addition, inhibition of microbiome-derived TMAO may serve as a novel therapeutic approach for AAA treatment where none currently exist.

  • 16.
    Benz, Alexander P.
    et al.
    McMaster Univ, Populat Hlth Res Inst, 237 Barton St East, Hamilton, ON L8L 2X2, Canada..
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Connolly, Stuart J.
    McMaster Univ, Populat Hlth Res Inst, 237 Barton St East, Hamilton, ON L8L 2X2, Canada..
    Eikelboom, John W.
    McMaster Univ, Populat Hlth Res Inst, 237 Barton St East, Hamilton, ON L8L 2X2, Canada..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Biomarker-Based Risk Prediction With the ABC-AF Scores in Patients With Atrial Fibrillation Not Receiving Oral Anticoagulation2021In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 143, no 19, p. 1863-1873Article in journal (Refereed)
    Abstract [en]

    Background: The novel ABC (Age, Biomarkers, Clinical History) scores outperform traditional risk scores for stroke, major bleeding, and death in patients with atrial fibrillation (AF) receiving oral anticoagulation. To refine their utility, the ABC-AF scores needed to be validated in patients not receiving oral anticoagulation.

    Methods: We measured plasma levels of the ABC biomarkers (N-terminal pro-B-type natriuretic peptide, cardiac troponin-T, and growth-differentiation factor 15) to apply the previously developed ABC-AF scores in patients with AF receiving aspirin (n=3195) or aspirin and clopidogrel (n=1110) in 2 large clinical trials. Calibration was assessed by comparing estimated with observed 1-year risks. Cox regression models were used for recalibration. Discrimination was evaluated separately for the aspirin-only and the overall cohort (n=4305).

    Results: The ABC-AF-stroke score yielded a c-index of 0.70 (95% CI, 0.67-0.73) in both cohorts. The ABC-AF-bleeding score had a c-index of 0.76 (95% CI, 0.71-0.81) in the aspirin-only cohort and 0.73 (95% CI, 0.69-0.77) overall. Both scores were superior to risk scores recommended by current guidelines. The ABC-AF-death score yielded a c-index of 0.78 (95% CI, 0.76-0.80) overall. Calibrated in patients receiving oral anticoagulation, the ABC-AF-stroke score underestimated and the ABC-AF-bleeding score overestimated the risk of events in both cohorts. These scores were recalibrated for prediction of absolute event rates in the absence of oral anticoagulation.

    Conclusions: The biomarker-based ABC-AF scores showed better discrimination than traditional risk scores and were recalibrated for precise risk estimation in patients not receiving oral anticoagulation. They can now provide improved decision support on treatment of an individual patient with AF.

  • 17.
    Bergstrom, Goran
    et al.
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Clin Physiol, Gothenburg, Sweden..
    Persson, Margaretha
    Lund Univ, Dept Clin Sci, Malmö, Sweden.;Skane Univ Hosp, Dept Internal Med, Malmö, Sweden..
    Adiels, Martin
    Univ Gothenburg, Inst Med, Sch Publ Hlth & Community Med, Gothenburg, Sweden..
    Bjornson, Elias
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden..
    Bonander, Carl
    Univ Gothenburg, Inst Med, Sch Publ Hlth & Community Med, Gothenburg, Sweden..
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Alfredsson, Joakim
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden..
    Angeras, Oskar
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Cardiol, Gothenburg, Sweden..
    Berglund, Goran
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Blomberg, Anders
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Brandberg, John
    Sahlgrens Acad, Dept Radiol, Inst Clin Sci, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Radiol, Gothenburg, Sweden..
    Borjesson, Mats
    Sahlgrens Acad, Inst Med, Gothenburg, Sweden.;Univ Gothenburg, Ctr Hlth & Performance, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Cederlund, Kerstin
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden..
    Duvernoy, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Olov.Duvernoy@radiol.uu.se.
    Ekblom, Orjan
    Swedish Sch Sport & Hlth Sci GIH, Dept Phys Act & Hlth, Stockholm, Sweden..
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Engvall, Jan E.
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Clin Physiol, Linköping, Sweden.;Linköping Univ, CMIV, Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Fagman, Erika
    Sahlgrens Acad, Dept Radiol, Inst Clin Sci, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Radiol, Gothenburg, Sweden..
    Eriksson, Mats
    Karolinska Univ Hosp Huddinge, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.;Karolinska Univ Hosp Huddinge, Clin Res Ctr, Stockholm, Sweden..
    Erlinge, David
    Lund Univ, Cardiol, Dept Clin Sci Lund, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Fagerberg, Bjorn
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Flinck, Agneta
    Sahlgrens Acad, Dept Radiol, Inst Clin Sci, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Radiol, Gothenburg, Sweden..
    Goncalves, Isabel
    Lund Univ, Dept Clin Sci Malmö, Lund, Sweden..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hjelmgren, Ola
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Reg Vastra Gotaland, Dept Clin Physiol, Gothenburg, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lindqvist, Per
    Umeå Univ, Dept Surg & Perioperat Sci, Umeå, Sweden..
    Ljungberg, Johan
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Magnusson, Martin
    Lund Univ, Dept Clin Sci, Malmö, Sweden.;Skane Univ Hosp, Dept Cardiol, Malmö, Sweden.;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.;North West Univ, Hypertens Africa Res Team HART, Potchefstroom, South Africa..
    Mannila, Maria
    Karolinska Univ Hosp, Dept Cardiol & Clin Genet, Heart & Vasc Theme, Stockholm, Sweden..
    Markstad, Hanna
    Lund Univ, Clin Sci Malmö, Clin Res Ctr, Expt Cardiovasc Res, Malmö, Sweden.;Lund Univ, Ctr Med Imaging & Physiol, Lund, Sweden..
    Mohammad, Moman A.
    Lund Univ, Cardiol, Dept Clin Sci Lund, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden..
    Nystrom, Fredrik H.
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden..
    Ostenfeld, Ellen
    Skane Univ Hosp, Lund, Sweden.;Lund Univ, Dept Clin Sci Lund, Clin Physiol, Lund, Sweden..
    Persson, Anders
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, Dept Radiol, Linköping, Sweden.;Linköping Univ, CMIV, Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Rosengren, Annika
    Sahlgrens Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Sandstrom, Anette
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Sjalander, Anders
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Skold, Magnus C.
    Karolinska Inst, Dept Med Solna, Resp Med Unit, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Resp Med & Allergy, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia..
    Swahn, Eva
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden..
    Soderberg, Stefan
    Umeå Univ, Dept Publ Hlth & Clin Med Med, Umeå, Sweden.;Umeå Univ, Heart Ctr, Umeå, Sweden..
    Toren, Kjell
    Univ Gothenburg, Sch Publ Hlth & Community Med, Occupat & Environm Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Gothenburg, Sweden..
    Ostgren, Carl Johan
    Linköping Univ, Dept Cardiol Hlth Med & Caring Sci, Linköping, Sweden.;Linköping Univ, CMIV, Ctr Med Image Sci & Visualizat, Linköping, Sweden..
    Jernberg, Tomas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population2021In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 144, no 12, p. 916-929Article in journal (Refereed)
    Abstract [en]

    Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population. Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or >= 50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data. Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (>= 50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population. Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.

    Download full text (pdf)
    FULLTEXT01
  • 18.
    Bikdeli, Behnood
    et al.
    Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA USA.;Harvard Med Sch, Brigham & Womens Hosp, Thrombosis Res Grp, Boston, MA USA.;Yale New Haven Hosp, Yale Ctr Outcomes Res & Evaluat, New Haven, CT USA..
    Erlinge, David
    Lund Univ, Lund, Sweden..
    Valgimigli, Marco
    Univ Bern, Univ Hosp Bern, Bern, Switzerland..
    Kastrati, Adnan
    Tech Univ, Deutsch Herzzentrum Munchen, Munich, Germany.;German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Han, Yaling
    Gen Hosp Northern Theater Command, Shenyang, Peoples R China..
    Steg, Philippe Gabriel
    Univ Paris Cite, French Alliance Cardiovasc Trials, Inst Natl Sante & Rech Med, Assistance Publ Hop Paris,U1148, Paris, France.;Imperial Coll, Royal Brompton Hosp, London, England..
    Stables, Rod H.
    Liverpool Heart & Chest Hosp, Liverpool, Merseyside, England.;Univ Liverpool, Liverpool, Merseyside, England..
    Mehran, Roxana
    Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA.;Cardiovasc Res Fdn, New York, NY USA..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Frigoli, Enrico
    Univ Bern, Univ Hosp Bern, Bern, Switzerland..
    Goldstein, Patrick
    Lille Univ Hosp, Lille, France..
    Li, Yi
    Gen Hosp Northern Theater Command, Shenyang, Peoples R China..
    Shahzad, Adeel
    Liverpool Heart & Chest Hosp, Liverpool, Merseyside, England.;Univ Liverpool, Liverpool, Merseyside, England..
    Schuepke, Stefanie
    Tech Univ, Deutsch Herzzentrum Munchen, Munich, Germany.;German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Mehdipoor, Ghazaleh
    Montefiore Med Ctr, Div Nucl Med, Dept Radiol, Bronx, NY USA..
    Chen, Shmuel
    New York Presbyterian Hosp, Weill Cornell Cornell Med Ctr, New York, NY USA..
    Redfors, Bjorn
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Crowley, Aaron
    Genesis Res, Hoboken, NJ USA..
    Zhou, Zhipeng
    Cardiovasc Res Fdn, New York, NY USA..
    Stone, Gregg W.
    Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA..
    Bivalirudin Versus Heparin During PCI in NSTEMI: Individual Patient Data Meta-Analysis of Large Randomized Trials2023In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 148, no 16, p. 1207-1219Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI.

    METHODS: We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized >= 1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding.

    RESULTS: A total of 12155 patients were randomized: 6040 to bivalirudin (52.3% with a post-PCI bivalirudin infusion), and 6115 to heparin (53.2% with planned glycoprotein IIb/IIIa inhibitor use). Thirty-day mortality was not significantly different between bivalirudin and heparin (1.2% versus 1.1%; adjusted odds ratio, 1.24 [95% CI, 0.86-1.79]; P=0.25). Cardiac mortality, reinfarction, and stent thrombosis rates were also not significantly different. Bivalirudin reduced serious bleeding (both access site-related and non-access site-related) compared with heparin (3.3% versus 5.5%; adjusted odds ratio, 0.59; 95% CI, 0.48-0.72; P<0.0001). Outcomes were consistent regardless of use of a post-PCI bivalirudin infusion or routine lycoprotein IIb/IIIa inhibitor use with heparin and during 1-year follow-up.

    CONCLUSIONS: In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites.

  • 19.
    Björklund, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lithell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Different metabolic predictors of white-coat and sustained hypertension over a 20-year follow-up period: a population-based study of elderly men2002In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 106, no 1, p. 63-68Article in journal (Refereed)
    Abstract [en]

    Background The clinical significance of white-coat hypertension is still unclear. Moreover, no study has examined metabolic predictors of white-coat versus sustained hypertension.

    Methods and Results We investigated men (n=602) in a longitudinal population-based cohort who at age 70 years were identified as normotensive, white-coat hypertensive (office blood pressure [BP] ≥140/90 and daytime ambulatory BP <135/85 mm Hg), and sustained hypertensive (office BP ≥140/90 and daytime ambulatory BP ≥135/85 mm Hg). At baseline, when the subjects were aged 50 years, blood glucose, insulin, lipids, and fatty acid composition of the serum cholesterol esters were analyzed. The investigations at age 70 years included determination of insulin sensitivity and target organ damage. At age 50 years, individuals who 20 years later were identified as white-coat hypertensive or sustained hypertensive showed significantly elevated BP, heart rate, and impaired glucose tolerance compared with normotensive subjects but white coat hypertensive subjects were leaner and had a more favorable serum cholesterol ester fatty acid profile than did sustained hypertensive subjects. At age 70 years, both white-coat and sustained hypertensive subjects showed an impaired insulin sensitivity, elevated blood glucose, and increased serum insulin and heart rate compared with normotensive subjects, but left ventricular mass and urinary albumin excretion were increased only in sustained hypertensive subjects.

    Conclusions These findings indicate that although metabolic abnormalities and elevated heart rate were consistent over time in both hypertensive groups, a lower body mass index and more favorable dietary fat composition predicted the development of white-coat as opposed to sustained hypertension over 20 years.

  • 20.
    Björklund, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lithell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Isolated ambulatory hypertension predicts cardiovascular morbidity in elderly men2003In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 107, no 9, p. 1297-302Article in journal (Refereed)
    Abstract [en]

    Background— Little is known about isolated ambulatory hypertension, a state with elevated ambulatory but normal office blood pressure (BP). This study aimed to investigate the prognostic significance of isolated ambulatory hypertension for cardiovascular morbidity in a population of elderly men.

    Methods and Results— At baseline, 24-hour ambulatory BP and metabolic and cardiac risk profiles were evaluated in 578 untreated 70-year-old men, participants of a population-based cohort. Subjects with isolated ambulatory hypertension (office BP <140/90 and daytime BP ≥135/85) and sustained hypertension (office BP ≥140/90 and daytime BP ≥135/85) had increased plasma glucose, body mass index, and echocardiographically determined left ventricular relative wall thickness compared with normotensive subjects (office BP <140/90 and daytime BP <135/85). Seventy-two cardiovascular morbid events (2.37 per 100 person-years at risk) occurred over 8.4 years of follow-up. The prognostic value of isolated ambulatory and sustained hypertension was assessed with Cox proportional hazard regression. Multivariate models adjusting for serum cholesterol, smoking, and diabetes demonstrated that both isolated ambulatory hypertension (hazard ratio [HR], 2.77; 95% CI, 1.15 to 6.68) and sustained hypertension (HR, 2.94; 95% CI, 1.49 to 5.82) were independent predictors of cardiovascular morbidity. In a multivariate model with continuous BP variables, ambulatory daytime systolic BP (HR for 1 SD increase, 1.47; 95% CI, 1.09 to 1.97) was associated with an adverse outcome independently of office systolic BP.

    Conclusions— In the present study, isolated ambulatory hypertension as well as sustained hypertension predicted cardiovascular morbidity. The findings suggest that 24-hour ambulatory BP monitoring may disclose important prognostic information also in subjects characterized as normotensive according to office BP.

  • 21. Bonamy, Anna-Karin Edstedt
    et al.
    Parikh, Nisha I
    Cnattingius, Sven
    Ludvigsson, Jonas F
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Birth characteristics and subsequent risks of maternal cardiovascular disease: effects of gestational age and fetal growth2011In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 124, no 25, p. 2839-2846Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prior studies showing an inverse relationship between low birth weight in offspring and maternal risks of cardiovascular diseases (CVD) are limited by lack of information on gestational age and/or insufficient adjustment for confounders.

    METHODS AND RESULTS: In a nationwide Swedish study, we included information on 923 686 women and their first singleton births between 1983 and 2005. Cox proportional hazards models were used to study associations between gestational length, fetal growth, and maternal incident hospitalization or death from CVD (coronary heart disease, cerebrovascular events, and heart failure). Multivariable adjusted models accounted for birth year, income, education, country of birth, smoking, diabetes mellitus, hypertension, and preeclampsia. The risk of maternal CVD increased with decreasing gestational age whereas the risk increase related to fetal growth appeared to be restricted to very small-for-gestational-age (SGA) infants. Compared with mothers of non-SGA infants born at term, the hazard ratio of CVD ranged from 1.39 (95% confidence interval 1.22-1.58) to 2.57 (95% confidence interval 1.97-3.34) among mothers to moderately and very preterm infants, respectively. There was a significant interaction between preterm birth and fetal growth with respect to mothers' risk of CVD (P<0.001). Among mothers to very SGA infants, the hazard ratio of CVD ranged from 1.38 (95% confidence interval 1.15-1.65) to 3.40 (95% confidence interval 2.26-5.11) in mothers to term and very preterm infants, respectively.

    CONCLUSIONS: Delivery of a preterm or SGA infant is associated with later life maternal hospitalization or death from CVD even after accounting for socioeconomic factors, smoking, and pregnancy-related complications.

  • 22. Calais, Fredrik
    et al.
    Frobert, Ole
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedberg, Pär O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wachtell, Kristian
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Leisure-time Physical Inactivity and Risk of Myocardial Infarction and All-cause Mortality: a Case-control Study2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 23.
    Capodanno, Davide
    et al.
    Univ Catania, Azienda Osped Univ Policlin G Rodolico San Marco, Catania, Italy..
    Mehran, Roxana
    Icahn Sch Med Mt Sinai, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA.;Pharmaceut & Med Devices Agcy, Tokyo, Japan..
    Krucoff, Mitchell W.
    Duke Univ, Med Ctr, Durham, NC USA..
    Baber, Usman
    Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA..
    Bhatt, Deepak L.
    Icahn Sch Med Mt Sinai, Mt Sinai Heart, New York, NY USA..
    Capranzano, Piera
    Univ Catania, Azienda Osped Univ Policlin G Rodolico San Marco, Catania, Italy..
    Collet, Jean-Philippe
    Sorbonne Univ, Hop Pitie Salpetriere, AP HP, ACTION Study Grp,Inst Cardiol, Paris, France..
    Cuisset, Thomas
    Univ Hosp La Timone, Dept Cardiol, Intervent Cardiol Unit, Marseille, France.;Univ Hosp La Timone, Dept Cardiol, Cathlab, Marseille, France..
    De Luca, Giuseppe
    Univ Messina, Div Cardiol, Azienda Osped Univ Policlin G Martino, Messina, Italy.;IRCCS Hosp Galeazzi St Ambrogio, Div Cardiol, Milan, Italy..
    De Luca, Leonardo
    Azienda Osped San Camillo Forlanini, Dept Cardiothorac & Vasc Med & Surg, Div Cardiol, Rome, Italy.;UniCamillus St Camillus Int Univ Hlth Sci, Rome, Italy..
    Farb, Andrew
    US FDA, Silver Spring, MD USA..
    Franchi, Francesco
    Univ Florida, Div Cardiol, Coll Med, Jacksonville, FL USA..
    Gibson, C. Michael
    Baim Inst Clin Res, Boston, MA USA..
    Hahn, Joo-Yong
    Sungkyunkwan Univ, Heart Vasc Stroke Inst, Samsung Med Ctr, Sch Med, Seoul, South Korea..
    Hong, Myeong-Ki
    Yonsei Univ, Severance Hosp, Div Cardiol, Coll Med, Seoul, South Korea..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Kastrati, Adnan
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;Deutsch Zentrum Herz Kreislauf Forsch DZHK, Munich, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany..
    Kimura, Takeshi
    Hirakata Kohsai Hosp, Dept Cardiol, Osaka, Japan..
    Lemos, Pedro A.
    Hosp Israelita Albert Einstein, Sao Paulo, Brazil..
    Lopes, Renato D.
    Duke Univ, Med Ctr, Durham, NC USA..
    Magee, Adrian
    US FDA, Silver Spring, MD USA..
    Matsumura, Ryosuke
    Mochizuki, Shuichi
    Pharmaceut & Med Devices Agcy, Tokyo, Japan..
    O'Donoghue, Michelle L.
    Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA USA..
    Pereira, Naveen L.
    Mayo Clin, Dept Cardiovasc Med, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA..
    Rao, Sunil V.
    NYU Langone Hlth Syst, New York, NY USA..
    Rollini, Fabiana
    Univ Florida, Div Cardiol, Coll Med, Jacksonville, FL USA..
    Shirai, Yuko
    Pharmaceut & Med Devices Agcy, Tokyo, Japan..
    Sibbing, Dirk
    Deutsch Zentrum Herz Kreislauf Forsch DZHK, Munich, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany.;Ludwig Maximilians Univ Munchen, Munich, Germany.;Privatklin Lauterbacher Muhle Ostsee, Seeshaupt, Germany..
    Smits, Peter C.
    Maasstad Hosp, Dept Cardiol, Rotterdam, Netherlands..
    Steg, P. Gabriel
    Univ Paris Cite, AP HP, Paris, France.;INSERM U1148 LVTS, Paris, France.;Inst Univ France, Paris, France..
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, England..
    ten Berg, Jurrien
    Maastricht Univ Med Ctr, Cardiovasc Res Inst Maastricht CARIM, Sch Cardiovasc Dis, Maastricht, Netherlands.;St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands.;Univ Med Ctr Maastricht, Dept Cardiol, Maastricht, Netherlands..
    Valgimigli, Marco
    Univ Svizzera Italiana USI, Cardioctr Inst, Osped Cantonale, Lugano, Switzerland.;Univ Bern, Bern, Switzerland..
    Vranckx, Pascal
    Jessa Ziekenhuis, Dept Cardiol & Crit Care Med, Hasselt, Belgium.;Univ Hasselt, Fac Med & Life Sci, Hasselt, Belgium..
    Watanabe, Hirotoshi
    Hirakata Kohsai Hosp, Dept Cardiol, Osaka, Japan..
    Windecker, Stephan
    Bern Univ Hosp, Dept Cardiol, Inselspital, Bern, Switzerland..
    Serruys, Patrick W.
    Univ Galway, Dept Cardiol, Galway, Ireland..
    Yeh, Robert W.
    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA..
    Morice, Marie-Claude
    ICPS, Paris, France.;CERC, Paris, France..
    Angiolillo, Dominick J.
    Univ Florida, Div Cardiol, Coll Med, Jacksonville, FL USA..
    Defining Strategies of Modulation of Antiplatelet Therapy in Patients With Coronary Artery Disease: A Consensus Document from the Academic Research Consortium2023In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 147, no 25, p. 1933-1944Article in journal (Refereed)
    Abstract [en]

    Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.

  • 24.
    Carnicelli, Anthony P.
    et al.
    Duke Univ, Div Cardiol, Durham, NC USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Hong, Hwanhee
    Duke Univ, Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA..
    Connolly, Stuart J.
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;Populat Hlth Res Inst, Hamilton, ON, Canada..
    Eikelboom, John
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;Populat Hlth Res Inst, Hamilton, ON, Canada..
    Giugliano, Robert P.
    Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.;Thrombolysis Myocardial Infarct Study Grp, Boston, MA USA..
    Morrow, David A.
    Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.;Thrombolysis Myocardial Infarct Study Grp, Boston, MA USA..
    Patel, Manesh R.
    Duke Univ, Div Cardiol, Durham, NC USA.;Duke Univ, 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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Alexander, John H.
    Duke Univ, Div Cardiol, Durham, NC USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Cecilia Bahit, M.
    INECO Neurociencias Orono, Dept Cardiol, Santa Fe, Argentina..
    Benz, Alexander P.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Bohula, Erin A.
    Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.;Thrombolysis Myocardial Infarct Study Grp, Boston, MA USA..
    Chao, Tze-Fan
    Taipei Vet Gen Hosp, Div Cardiol, Taipei, Taiwan..
    Dyal, Leanne
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Ezekowitz, Michael
    Lankenau Inst Med Res, Wynnewood, PA USA..
    A.a. Fox, Keith
    Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland..
    Gencer, Baris
    Geneva Univ Hosp, Div Cardiol, Geneva, Switzerland.;Univ Bern, Inst Primary Hlth Care BIHAM, Bern, Switzerland..
    Halperin, Jonathan L.
    Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA..
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hohnloser, Stefan H.
    Goethe Univ Frankfurt, Dept Cardiol, Frankfurt, Germany..
    Hua, Kaiyuan
    Duke Univ, Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA..
    Hylek, Elaine
    Boston Univ, Dept Med, Sch Med, Boston, MA 02215 USA..
    Toda Kato, Eri
    Kyoto Univ, Dept Cardiol, Kyoto, Japan..
    Kuder, Julia
    Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA..
    Lopes, Renato D.
    Duke Univ, Div Cardiol, Durham, NC USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Mahaffey, Kenneth W.
    Stanford Univ, Sch Med, Dept Med, Stanford Ctr Clin Res, Stanford, CA 94305 USA..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Piccini, Jonathan P.
    Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Ruff, Christian T.
    Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.;Thrombolysis Myocardial Infarct Study Grp, Boston, MA USA..
    Steffel, Jan
    Univ Zurich, Dept Cardiol, Zurich, Switzerland..
    Wojdyla, Daniel
    Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Granger, Christopher B.
    Duke Univ, Div Cardiol, Durham, NC USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: Patient-Level Network Meta-Analyses of Randomized Clinical Trials With Interaction Testing by Age and Sex2022In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 145, no 4, p. 242-255Article in journal (Refereed)
    Abstract [en]

    Background: Direct oral anticoagulants (DOACs) are preferred over warfarin for stroke prevention in atrial fibrillation. Meta-analyses using individual patient data offer substantial advantages over study-level data.

    Methods: We used individual patient data from the COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation) database, which includes all patients randomized in the 4 pivotal trials of DOACs versus warfarin in atrial fibrillation (RE-LY [Randomized Evaluation of Long-Term Anticoagulation Therapy], ROCKET AF [Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation], ARISTOTLE [Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation], and ENGAGE AF-TIMI 48 [Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48]), to perform network meta-analyses using a stratified Cox model with random effects comparing standard-dose DOAC, lower-dose DOAC, and warfarin. Hazard ratios (HRs [95% CIs]) were calculated for efficacy and safety outcomes. Covariate-by-treatment interaction was estimated for categorical covariates and for age as a continuous covariate, stratified by sex.

    Results: A total of 71 683 patients were included (29 362 on standard-dose DOAC, 13 049 on lower-dose DOAC, and 29 272 on warfarin). Compared with warfarin, standard-dose DOACs were associated with a significantly lower hazard of stroke or systemic embolism (883/29 312 [3.01%] versus 1080/29 229 [3.69%]; HR, 0.81 [95% CI, 0.74-0.89]), death (2276/29 312 [7.76%] versus 2460/29 229 [8.42%]; HR, 0.92 [95% CI, 0.87-0.97]), and intracranial bleeding (184/29 270 [0.63%] versus 409/29 187 [1.40%]; HR, 0.45 [95% CI, 0.37-0.56]), but no statistically different hazard of major bleeding (1479/29 270 [5.05%] versus 1733/29 187 [5.94%]; HR, 0.86 [95% CI, 0.74-1.01]), whereas lower-dose DOACs were associated with no statistically different hazard of stroke or systemic embolism (531/13 049 [3.96%] versus 1080/29 229 [3.69%]; HR, 1.06 [95% CI, 0.95-1.19]) but a lower hazard of intracranial bleeding (55/12 985 [0.42%] versus 409/29 187 [1.40%]; HR, 0.28 [95% CI, 0.21-0.37]), death (1082/13 049 [8.29%] versus 2460/29 229 [8.42%]; HR, 0.90 [95% CI, 0.83-0.97]), and major bleeding (564/12 985 [4.34%] versus 1733/29 187 [5.94%]; HR, 0.63 [95% CI, 0.45-0.88]). Treatment effects for standard- and lower-dose DOACs versus warfarin were consistent across age and sex for stroke or systemic embolism and death, whereas standard-dose DOACs were favored in patients with no history of vitamin K antagonist use (P=0.01) and lower creatinine clearance (P=0.09). For major bleeding, standard-dose DOACs were favored in patients with lower body weight (P=0.02). In the continuous covariate analysis, younger patients derived greater benefits from standard-dose (interaction P=0.02) and lower-dose DOACs (interaction P=0.01) versus warfarin.

    Conclusions: Compared with warfarin, DOACs have more favorable efficacy and safety profiles among patients with atrial fibrillation.

  • 25. Connolly, Stuart J.
    et al.
    Reilly, Paul A.
    Pogue, Janice
    Eikelboom, John
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ezekowitz, Michael D.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Yusuf, Salim
    Randomized Comparison of the Effects of Two Doses of Dabigatran Etexilate on Clinical Outcomes Over 4.3 Years: Results of the Rely-Able Double-Blind Randomized Trial2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 126, no 23, p. 2793-2793Article in journal (Other academic)
  • 26. Connolly, Stuart J.
    et al.
    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.
    Ezekowitz, Michael D.
    Eikelboom, John
    Oldgren, Jonas
    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.
    Reilly, Paul A.
    Brueckmann, Martina
    Pogue, Janice
    Alings, Marco
    Amerena, John V.
    Avezum, Alvaro
    Baumgartner, Iris
    Budaj, Andrzej J.
    Chen, Jyh-Hong
    Dans, Antonio L.
    Darius, Harald
    Di Pasquale, Giuseppe
    Ferreira, Jorge
    Flaker, Greg C.
    Flather, Marcus D.
    Franzosi, Maria Grazia
    Golitsyn, Sergey P.
    Halon, David A.
    Heidbuchel, Hein
    Hohnloser, Stefan H.
    Huber, Kurt
    Jansky, Petr
    Kamensky, Gabriel
    Keltai, Matyas
    Kim, Sung Soon
    Lau, Chu-Pak
    Le Heuzey, Jean-Yves
    Lewis, Basil S.
    Liu, Lisheng
    Nanas, John
    Omar, Razali
    Pais, Prem
    Pedersen, Knud E.
    Piegas, Leopoldo S.
    Raev, Dimitar
    Smith, Pal J.
    Talajic, Mario
    Tan, Ru San
    Tanomsup, Supachai
    Toivonen, Lauri
    Vinereanu, Dragos
    Xavier, Denis
    Zhu, Jun
    Wang, Susan Q.
    Duffy, Christine O.
    Themeles, Ellison
    Yusuf, Salim
    The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 3, p. 237-243Article in journal (Refereed)
    Abstract [en]

    Background During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death. 

  • 27.
    Dalgaard, Frederik
    et al.
    Herlev & Gentofte Hosp, Dept Cardiol, Hellerup, Denmark;Duke Univ, Duke Clin Res Inst, Durham, NC USA.
    Mulder, Hillary
    Duke Univ, Duke Clin Res Inst, Durham, NC USA.
    Wojdyla, Daniel M.
    Duke Univ, Duke Clin Res Inst, Durham, NC USA.
    Lopes, Renato D.
    Duke Univ, Duke Clin Res Inst, Durham, NC USA.
    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.
    Alexander, John H.
    Duke Univ, Duke Clin Res Inst, Durham, NC USA.
    De Caterina, Raffaele
    Univ Pisa, Inst Cardiol, Pisa, Italy.
    Washam, Jeffrey B.
    Duke Univ, Duke Clin Res Inst, Durham, NC USA.
    Hylek, Elaine M.
    Boston Univ, Sch Med, Boston, MA 02215 USA.
    Garcia, David A.
    Univ Washington, Sch Med, Seattle, WA USA.
    Gersh, Bernard J.
    Mayo Clin, Coll Med, Rochester, MN 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.
    Granger, Christopher B.
    Duke Univ, Duke Clin Res Inst, Durham, NC USA.
    Al-Khatib, Sana M.
    Duke Univ, Duke Clin Res Inst, Durham, NC USA.
    Patients With Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial2020In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 141, no 1, p. 10-20Article in journal (Refereed)
    Abstract [en]

    Background:

    The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with oral anticoagulants has been associated with an increased risk of bleeding. We investigated the risk of bleeding and major cardiovascular outcomes in patients with atrial fibrillation taking NSAIDs and apixaban or warfarin.

    Methods:

    The ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201) compared apixaban with warfarin in patients with atrial fibrillation at an increased risk of stroke. Patients in ARISTOTLE without severe renal (creatine clearance ≤30 mL/min) or liver disease were included in this analysis (n=17 423). NSAID use at baseline, NSAID use during the trial (incident NSAID use), and never users were described. The primary outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding, gastrointestinal bleeding, heart failure hospitalization, stroke or systemic embolism, and all-cause mortality. NSAID use during the trial, and the interaction between randomized treatment, was analyzed using time-dependent Cox proportional hazards models.

    Results:

    Those with baseline NSAID use (n=832 [4.8%]), incident NSAID use (n=2185 [13.2%]), and never users were similar in median age (age [25th, 75th]; 70 [64, 77] versus 70 [63, 75] versus 70 [62, 76]). Those with NSAID use at baseline and incident NSAID use were more likely to have a history of bleeding than never users (24.5% versus 21.0% versus 15.6%, respectively). During a median follow-up (25th, 75th) of 1.8 (1.4, 2.3) years and when excluding those taking NSAID at baseline, we found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR], 1.61 [95% CI, 1.11–2.33]) and clinically relevant nonmajor bleeding (HR, 1.70 [95% CI, 1.16–2.48]), but not gastrointestinal bleeding. No significant interaction was observed between NSAID use and randomized treatment for any outcome.

    Conclusions:

    A substantial number of patients in the ARISTOTLE trial took NSAIDs. Incident NSAID use was associated with major and clinically relevant nonmajor bleeding, but not with gastrointestinal bleeding. The safety and efficacy of apixaban versus warfarin appeared not significantly to be altered by NSAID use. This study warrants more investigation of the effect of NSAIDs on the outcomes of patients treated with apixaban.

    Clinical Trial Registration:

    URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984.

  • 28. Damask, Amy
    et al.
    Steg, P Gabriel
    Schwartz, Gregory G
    Szarek, Michael
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Badimon, Lina
    Chapman, M John
    Boileau, Catherine
    Tsimikas, Sotirios
    Ginsberg, Henry N
    Banerjee, Poulabi
    Manvelian, Garen
    Pordy, Robert
    Hess, Sibylle
    Overton, John D
    Lotta, Luca A
    Yancopoulos, George D
    Abecasis, Goncalo R
    Baras, Aris
    Paulding, Charles
    Patients with High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit from Alirocumab Treatment in the Odyssey Outcomes Trial2020In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 141, no 8, p. 624-636Article in journal (Refereed)
    Abstract [en]

    Background: Alirocumab, an antibody that blocks proprotein convertase subtilisin/kexin type 9 (PCSK9), was associated with reduced major adverse cardiovascular events (MACE) and death in the ODYSSEY OUTCOMES trial. In this study, higher baseline LDL cholesterol (LDL-C) levels predicted greater benefit from alirocumab treatment. Recent studies indicate high polygenic risk scores (PRS) for coronary artery disease (CAD) identify individuals at higher risk who derive increased benefit from statins. Herein we perform post hoc analyses to determine whether high PRS for CAD identifies higher-risk individuals, independently from baseline LDLC and other known risk factors, who might derive greater benefit from alirocumab treatment. Methods: ODYSSEY OUTCOMES was a randomized, double-blind, placebo-controlled trial comparing alirocumab or placebo in 18,924 patients with acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin treatment. The primary endpoint (MACE) comprised death from CAD, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. A genome-wide PRS for CAD comprising 6,579,025 genetic variants was evaluated in 11,953 patients with available DNA samples. Analysis of MACE risk was performed in placebo treated patients while treatment benefit analysis was performed in all patients. Results: The incidence of MACE in the placebo group was related to PRS for CAD: 17.0% for high PRS patients (>90th percentile) and 11.4% for lower PRS patients (≤90th percentile) (p<0.001); this PRS relationship was not explained by baseline LDL-C or other established risk factors. Both the absolute and relative reduction of MACE by alirocumab compared to placebo was greater in high versus low PRS patients. There was an absolute reduction by alirocumab in high versus low PRS groups of 6.0% and 1.5%, respectively, and relative risk reduction by alirocumab of 37% in the high PRS group (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.46-0.86; p = 0.004) versus 13% reduction in the low PRS group (HR 0.87; 95% CI 0.78-0.98; p=0.022; interaction p = 0.04). Conclusions: A high PRS for CAD is associated with elevated risk for recurrent MACE after ACS, and larger absolute and relative risk reduction with alirocumab treatment, providing an independent tool for risk stratification and precision medicine.

  • 29. Damman, Peter
    et al.
    de Winter, Robbert 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.
    Fox, Keith A
    Letter by Damman et al regarding articles, "Long-term cardiovascular mortality after procedure-related or spontaneous myocardial infarction in patients with non-ST-segment elevation acute coronary syndrome: a collaborative analysis of individual patient data from the FRISC II, ICTUS, and RITA-3 Trials (FIR)" and "American College of Cardiology/American Heart Association/European Society of Cardiology/World Heart Federation universal definition of myocardial infarction classification system and the risk of cardiovascular death: Observations From the TRITON-TIMI 38 Trial (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38)”2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 126, no 9, p. E136-E137Article in journal (Refereed)
  • 30.
    Damman, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    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.
    Fox, Keith A. A.
    Windhausen, Fons
    Hirsch, Alexander
    Clayton, Tim
    Pocock, Stuart J.
    Lagerqvist, Bo
    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.
    Tijssen, Jan G. P.
    de Winter, Robbert J.
    Long-Term Cardiovascular Mortality after Procedure-Related or Spontaneous Myocardial Infarction in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome: A Collaborative Analysis of Individual Patient Data from the FRISC II, ICTUS, and RITA-3 Trials (FIR)2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, no 4, p. 568-576Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    To investigate the long-term prognostic impact of procedure-related and spontaneous myocardial infarction (MI) on cardiovascular mortality in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS).

    METHODS AND RESULTS:

    Five-year follow-up after procedure-related or spontaneous MI was investigated in the individual patient-pooled dataset of the FRISC-II, ICTUS and RITA-3 (FIR) NSTE-ACS trials. The principal outcome was cardiovascular death up to 5 years of follow-up. Cumulative event rates were estimated with the Kaplan-Meier method, hazard ratios (HR) were calculated with time-dependent Cox proportional-hazards models. Adjustments were made for the variables associated with long-term outcomes. Of the 5467 patients, 212 endured a procedure-related MI within 6 months after enrolment. A spontaneous MI occurred in 236 patients within 6 months. The cumulative cardiovascular death rate was 5.2% in patients who endured a procedure-related MI and comparable to patients without a procedure-related MI (HR 0.66, 95%CI: 0.36-1.20, P=0.17). In patients who endured a spontaneous MI within 6 months, the cumulative cardiovascular death rate was 22.2% and higher than patients without a spontaneous MI (HR 4.52, 95%CI: 3.37-6.06, P<0.001). These HRs did not materially alter after risk adjustments.

    CONCLUSIONS:

    Five-year follow-up of NSTE-ACS patients from the three FIR trials showed no association between a procedure-related MI and long-term cardiovascular mortality. In contrast there was a substantially raised long-term mortality after a spontaneous MI.

  • 31. Danad, Ibrahim
    et al.
    Raijmakers, Pieter G.
    Harms, Hendrik J.
    Heymans, Martijn W.
    van Royen, Niels
    Lammertsma, Adriaan A.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    van Rossum, Albert C.
    Knaapen, Paul
    The Relationship Between Anatomical and Functional Coronary Artery Disease Severity and Transmural Myocardial Blood Flow Distribution2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 32. Dans, Antonio L
    et al.
    Connolly, Stuart 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.
    Yang, Sean
    Nakamya, Juliet
    Brueckmann, Martina
    Ezekowitz, Michael
    Oldgren, Jonas
    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.
    Eikelboom, John W
    Reilly, Paul A
    Yusuf, Salim
    Concomitant Use of Antiplatelet Therapy with Dabigatran or Warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY®) Trial2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 127, no 5, p. 634-640Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    RE-LY showed that dabigatran etexilate 150 mg bid (DE150) was superior, and 110 mg bid (DE110) non-inferior to warfarin in preventing stroke and systemic embolism (SSE) in patients with atrial fibrillation (AF). In this subgroup analysis, we assess the efficacy and safety of dabigatran in patients who did and didn't receive concomitant antiplatelets METHODS AND RESULTS: All comparisons used a cox proportional hazards model with adjustments made for risk factors for bleeding. A time dependent analysis was performed when comparing patients with concomitant antiplatelets to those without. 6952 of 18,113 patients (38.4%) received concomitant ASA or clopidogrel at some time during the study. DE110 was non-inferior to warfarin in reducing SSE, whether patients received antiplatelets (HR=0.93; 95%CI: 0.70-1.25) or not (HR=0.87; 95%CI: 0.66-1.15; interaction p=0.738). There were less major bleeds than warfarin in both subgroups (HR=0.82; 95%CI: 0.67-1.00 for patients who used antiplatelets; HR=0.79; 95% CI: 0.64-0.96 for patients who didn't; interaction p=0.794). DE 150 reduced the primary outcome of SSE compared to warfarin. This effect seemed attenuated among patients who used antiplatelets (HR=0.80, 95%CI: 0.59-1.08) compared to those who didn't (HR=0.52, 95%CI: 0.38-0.72; p for interaction=0.058). Major bleeding was similar to warfarin regardless of antiplatelet use (HR=0.93, 95%CI: 0.76-1.12 for patients who used antiplatelets; HR=0.94, 95%CI: 0.78-1.15 for patients who didn't; p for interaction=0.875). In the time dependent analysis, concomitant use of a single antiplatelet seemed to increase the risk of major bleeding (HR=1.60; 95% CI: 1.42, 1.82). Dual antiplatelet seemed to increased this even more (HR=2.31; 95% CI: 1.79, 2.98). The absolute risks were lowest on DE110 compared to DE150 or warfarin.

    CONCLUSIONS:

    Concomitant antiplatelet drugs appeared to increase the risk for major bleeding in RE-LY without affecting the advantages of dabigatran over warfarin. Choosing between DE110 and DE150 requires a careful assessment of characteristics that influence the balance between benefit and harm.

  • 33. Dery, Jean-Pierre P.
    et al.
    Mahaffey, Kenneth
    Tricoci, Pierluigi
    White, Harvey
    Podder, Mohua
    Moliterno, David
    Harrington, Robert
    Chen, Edmond
    Strony, John
    Van de Werf, Frans
    Ziada, Khaled M.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Aylward, Philip
    Armstrong, Paul W.
    Rao, Sunil
    Arterial Access Site and Outcomes in Patients Undergoing Percutaneous Coronary Intervention With and Without Vorapaxar2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 34.
    Eggers, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Persistent cardiac troponin I elevation in stabilized patients after an episode of acute coronary syndrome predicts long-term mortality2007In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 116, no 17, p. 1907-1914Article in journal (Refereed)
    Abstract [en]

    BACKGROUND - In patients with non-ST-elevation acute coronary syndrome, any troponin elevation is associated with an increased risk for cardiovascular events. However, the prevalence and prognostic importance of persistent troponin elevation in stabilized patients after an episode of non-ST-elevation acute coronary syndrome are unknown and were therefore assessed in this study. METHODS AND RESULTS - Cardiac troponin I (cTnI) was measured in 1092 stabilized patients at 6 weeks and 3 and 6 months after enrollment in the FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC-II) trial. cTnI was analyzed with the Access AccuTnI assay with the application of different prognostic cutoffs. Outcomes were assessed through 5 years. Elevated cTnI levels >0.01 μg/L were found in 48% of the study patients at 6 weeks, in 36% at 6 months, and in 26% at all 3 measurements. cTnI elevation was associated with increased age and other cardiovascular high-risk features. The lowest tested cTnI cutoff (0.01 μg/L) was prognostically most useful and was independently predictive of mortality (hazard ratio, 2.1 [95% confidence interval, 1.3 to 3.3]; P=0.001) on multivariable analysis adjusted for cardiovascular risk factors and randomization to an invasive versus noninvasive treatment strategy, whereas it was related to myocardial infarction only on univariate analysis. CONCLUSIONS - Persistent minor cTnI elevation can be detected frequently in patients stabilized after an episode of non-ST-elevation acute coronary syndrome with the use of a sensitive assay. Elevated cTnI levels >0.01 μg/L predict mortality during long-term follow-up. Our results emphasize the importance of further troponin testing in non-ST-elevation acute coronary syndrome patients after hospital discharge.

  • 35. Eikelboom, John W.
    et al.
    Connolly, Stuart J.
    Healey, Jeff S.
    Yang, Sean
    Yusuf, Salim
    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.
    Oldgren, Jonas
    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.
    Ezekowitz, Mike
    Alings, Marco
    Kaatz, Scott
    Hohnloser, Stefan H.
    Diener, Hans-Christoph
    Franzosi, Maria Grazia
    Huber, Kurt
    Reilly, Paul
    Varrone, Jeanne
    Reply to Letters Regarding Article: "Risk of Bleeding With 2 Doses of Dabigatran Compared With Warfarin in Older and Younger Patients With Atrial Fibrillation : An Analysis of the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Trial"2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, no 3, p. E293-E294Article in journal (Refereed)
  • 36. Eikelboom, John W.
    et al.
    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.
    Connolly, Stuart J.
    Ezekowitz, Mike
    Healey, Jeff S.
    Oldgren, Jonas
    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.
    Yang, Sean
    Alings, Marco
    Kaatz, Scott
    Hohnloser, Stefan H.
    Diener, Hans-Christoph
    Franzosi, Maria Grazia
    Huber, Kurt
    Reilly, Paul
    Varrone, Jeanne
    Yusuf, Salim
    Risk of Bleeding With 2 Doses of Dabigatran Compared With Warfarin in Older and Younger Patients With Atrial Fibrillation An Analysis of the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Trial2011In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 123, no 21, p. 2363-2372Article in journal (Refereed)
    Abstract [en]

    Background-Dabigatran 150 and 110 mg twice a day and warfarin are effective for stroke prevention in atrial fibrillation. The purpose of this study was to compare their risks of bleeding in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial. Methods and Results-The RE-LY trial randomized 18 113 patients to receive dabigatran 110 or 150 mg twice a day or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0 for a median follow-up of 2.0 years. Compared with warfarin, dabigatran 110 mg twice a day was associated with a lower risk of major bleeding (2.87% versus 3.57%; P=0.002), whereas dabigatran 150 mg twice a day was associated with a similar risk of major bleeding (3.31% versus 3.57%; P=0.32). There was a significant treatment-by-age interaction, such that dabigatran 110 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in patients aged = 75 years (4.43% versus 4.37%; P=0.89; P for interaction = 75 years (5.10% versus 4.37%; P=0.07; P for interaction = 75 years, intracranial bleeding risk is lower but extracranial bleeding risk is similar or higher with both doses of dabigatran compared with warfarin.

  • 37. Ezekowitz, Michael D.
    et al.
    Kent, Anthony P.
    Pogue, Janice
    Reilly, Paul A.
    Brueckmann, Martina
    Clemens, Andreas
    Yusuf, Salim
    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.
    Connolly, Stuart J.
    RE-LY and RELY-ABLE: Long-term Follow-up of Patients With Non-valvular Atrial Fibrillation Receiving Dabigatran Etexilate for Up to 6.7 Years2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 38.
    Ezekowitz, Michael D.
    et al.
    Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA.;Cardiovasc Res Fdn, New York, NY USA..
    Nagarakanti, Rangadham
    Rutgers Robert Wood Johnson Med Sch, Piscataway, NJ USA.;Electrophysiol Res Fdn, Warren, NJ USA..
    Noack, Herbert
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Brueckmann, Martina
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany.;Heidelberg Univ, Fac Med Mannheim, Mannheim, Germany..
    Litherland, Claire
    Cardiovasc Res Fdn, New York, NY USA..
    Jacobs, Mark
    Albert Einstein Coll Med, New York, NY USA..
    Clemens, Andreas
    Univ Med Ctr Mainz, Ctr Thrombosis & Hemostasis, Mainz, Germany..
    Reilly, Paul A.
    Boehringer Ingelheim Pharmaceut Inc, 90 E Ridge POB 368, Ridgefield, CT 06877 USA..
    Connolly, Stuart J.
    McMaster Univ, Hamilton, ON, Canada..
    Yusuf, Salim
    McMaster Univ, Hamilton, ON, Canada..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Comparison of Dabigatran and Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease The RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulant Therapy)2016In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 134, no 8, p. 589-598Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The RE-LY trial (Randomized Evaluation of Long-Term Anticoagulant Therapy) compared dabigatran 150 and 110 mg twice daily with warfarin in 18 113 patients with atrial fibrillation. Those with prosthetic heart valves, significant mitral stenosis, and valvular heart disease (VHD) requiring intervention were excluded. Others with VHD were included. METHODS: This is a post hoc analysis of the RE-LY trial. RESULTS: There were 3950 patients with any VHD: 3101 had mitral regurgitation, 1179 with tricuspid regurgitation, 817 had aortic regurgitation, 471 with aortic stenosis, and 193 with mild mitral stenosis. At baseline, patients with any VHD had more heart failure, coronary disease, renal impairment, and persistent atrial fibrillation. Patients with any VHD had higher rates of major bleeds (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.16-1.5) but similar stroke or systemic embolism event rates (HR, 1.09; 95% CI, 0.88-1.33). For patients receiving dabigatran 110 mg, major bleed rates were lower than for patients taking warfarin (HR, 0.73; 95% CI, 0.56-0.95 with VHD; HR, 0.84; 95% CI, 0.71-0.99 without VHD), and major bleed rates for dabigatran 150 mg were similar to those for warfarin in patients with VHD (HR, 0.82; 95% CI, 0.64-1.06) or without VHD (HR, 0.98; 95% CI, 0.83-1.15). For dabigatran 150 mg, stroke/systemic embolic event rates were lower compared with warfarin in those with VHD (HR, 0.59; 95% CI, 0.37-0.93) and those without VHD (HR, 0.67; 95% CI, 0.52-0.86), and stroke/systemic embolic event rates were similar for warfarin and dabigatran 110 mg regardless of the presence of VHD (HR, 0.97; 95% CI, 0.65-1.45; and HR, 0.88; 95% CI, 0.70-1.10). Intracranial bleeds and death rates for dabigatran 150 and 110 mg were lower compared with warfarin independently of the presence of VHD. CONCLUSIONS: The presence of any VHD did not influence the comparison of dabigatran with warfarin.

  • 39. Ezekowitz, Michael D.
    et al.
    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.
    Connolly, Stuart J.
    Parekh, Amit
    Chernick, Michael R.
    Pogue, Janice
    Aikens, Timothy H.
    Yang, Sean
    Reilly, Paul A.
    Lip, Gregory Y. H.
    Yusuf, Salim
    Dabigatran and Warfarin in Vitamin K Antagonist-Naive and -Experienced Cohorts With Atrial Fibrillation2010In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 122, no 22, p. 2246-2253Article in journal (Refereed)
    Abstract [en]

    Background-The comparison of anticoagulants dabigatran and warfarin might be most equitable in vitamin K antagonist (VKA)-naive patients. Methods and Results-Warfarin and 2 doses of dabigatran-110 mg BID (D110) and 150 mg BID (D150)-were compared in a balanced population of VKA-naive (<= 62 days of lifetime VKA exposure, with 33% never prescribed a VKA) and VKA-experienced patients with atrial fibrillation (n=18 113). For VKA-naive and -experienced patients assigned warfarin, the time in therapeutic range (international normalized ratio 2.0 to 3.0) was 62% and 67%, respectively, and 61% and 66% for those never and ever prescribed a VKA. In VKA-naive patients, stroke and systemic embolism rates were 1.57%, 1.07%, and 1.69% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.65); D150 was superior (P=0.005). Major bleeding rates were 3.11%, 3.34%, and 3.57% per year, respectively. D110 and D150 were similar to warfarin (P=0.19 and P=0.55). Intracranial bleeding rates were 0.19%, 0.33%, and 0.73% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 and P=0.005). In VKA-experienced patients, stroke and systemic embolism rates were 1.51%, 1.15%, and 1.74% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.32); D150 was superior (P=0.007). Major bleeding rates were 2.66%, 3.30%, and 3.57% per year, respectively. D110 was lower than warfarin (P=0.003); D150 was similar (P=0.41). Intracranial bleeding rates were 0.26%, 0.32%, and 0.79% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 for both). Results were similar for patients never on a VKA. Conclusions-Previous VKA exposure does not influence the benefits of dabigatran at either dose compared with warfarin.

  • 40.
    Fanaroff, Alexander C.
    et al.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Clare, Robert
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Pieper, Karen S.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Mahaffey, Kenneth W.
    Stanford Univ, Sch Med, Stanford Ctr Clin Res, Stanford, CA 94305 USA.
    Melloni, Chiara
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Green, Jennifer B.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA;Duke Univ, Div Endocrinol, Sch Med, Durham, NC USA.
    Alexander, John H.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Jones, W. Schuyler
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Harrison, Robert W.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Mehta, RaJendra H.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Povsic, Thomas J.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Moreira, Humberto G.
    Univ Sao Paulo, Heart Inst InCor, Med Sch, Sao Paulo, Brazil.
    Ai-Khatib, Sana M.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Roe, Matthew T.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Kong, David F.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Mathews, Robin
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Tricoci, Pierluigi
    CSL Behring, King Of Prussia, PA USA.
    Holman, Rury R.
    Univ Oxford, Diabet Trials Unit, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
    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.
    Califf, Robert M.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA;Verily Life Sci, San Francisco, CA USA.
    Alexander, Karen P.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Lopes, Renato D.
    Duke Univ, Sch Med, Div Cardiol, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials: A Pooled Analysis of 9259 Deaths in 9 Trials2019In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 7, p. 863-873Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Modern cardiometabolic clinical trials often include cardiovascular death as a component of a composite primary outcome, requiring central adjudication by a clinical events committee to classify cause of death. However, sometimes the cause of death cannot be determined from available data. The US Food and Drug Administration has indicated that this circumstance should occur only rarely, but its prevalence has not been formally assessed. METHODS: Data from 9 global clinical trials (2009-2017) with long-term follow-up and blinded, centrally adjudicated cause of death were used to calculate the proportion of deaths attributed to cardiovascular, noncardiovascular, or undetermined causes by therapeutic area (diabetes mellitus/pre-diabetes mellitus, stable atherosclerosis, atrial fibrillation, and acute coronary syndrome), region of patient enrollment, and year of trial manuscript publication. Patient-and trial-level variables associated with undetermined cause of death were identified using a logistic model. RESULTS: Across 127 049 enrolled participants from 9 trials, there were 9259 centrally adjudicated deaths: 5012 (54.1%) attributable to cardiovascular causes, 2800 (30.2%) attributable to noncardiovascular causes, and 1447 (15.6%) attributable to undetermined causes. There was variability in the proportion of deaths ascribed to undetermined causes by trial therapeutic area, region of enrollment, and year of trial manuscript publication. On multivariable analysis, acute coronary syndrome or atrial fibrillation trial (versus atherosclerotic vascular disease or diabetes mellitus/pre-diabetes mellitus), longer time from enrollment to death, more recent trial manuscript publication year, enrollment in North America (versus Western Europe), female sex, and older age were associated with greater likelihood of death of undetermined cause. CONCLUSIONS: In 9 cardiometabolic clinical trials with long-term followup, approximately 16% of deaths had undetermined causes. This provides a baseline for quality assessment of clinical trials and informs operational efforts to potentially reduce the frequency of undetermined deaths in future clinical research.

  • 41. Farooq, Vasim
    et al.
    Serruys, Patrick W.
    Bourantas, Christos V.
    Zhang, Yaojun
    Muramatsu, Takashi
    Feldman, Ted
    Holmes, David R.
    Mack, Michael
    Morice, Marie Claude
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Colombo, Antonio
    de Vries, Ton
    Morel, Marie-angele
    Dawkins, Keith D.
    Kappetein, Arie Pieter
    Mohr, Friedrich W.
    Response to Letter Regarding Article, " Quantification of Incomplete Revascularization and Its Association With Five- Year Mortality in the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery ( SYNTAX) Trial: Validation of the Residual SYNTAX Score"2014In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 129, no 8, p. E355-E356Article in journal (Other academic)
  • 42. Farooq, Vasim
    et al.
    Serruys, Patrick W.
    Bourantas, Christos V.
    Zhang, Yaojun
    Muramatsu, Takashi
    Feldman, Ted
    Holmes, David R.
    Mack, Michael
    Morice, Marie Claude
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Colombo, Antonio
    de Vries, Ton
    Morel, Marie-angele
    Dawkins, Keith D.
    Kappetein, Arie-Pieter
    Mohr, Friedrich W.
    Quantification of Incomplete Revascularization and its Association With Five-Year Mortality in the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Trial Validation of the Residual SYNTAX Score2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 2, p. 141-151Article in journal (Refereed)
    Abstract [en]

    Background The residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) Score is an objective measure of the degree and complexity of residual stenosis after percutaneous coronary intervention (PCI). Methods and Results In the randomized PCI cohort of the SYNTAX Trial (n=903), the baseline and residual SYNTAX Scores were calculated. Subjects with a residual SYNTAX Score of 0 were defined as having undergone complete revascularization (CR), and a residual SYNTAX Score >0 as incomplete revascularization (ICR). Five-year clinical outcomes were stratified by CR and ICR (tertiles of the residual SYNTAX Score: >0-4, >4-8, and >8). In the PCI cohort, the mean baseline and residual SYNTAX Scores were 28.4 +/- 11.5 and 4.5 +/- 6.9, respectively. The mean SYNTAX Score (representative of the burden of disease removed by PCI) was 23.8 +/- 10.9. The residual SYNTAX Score was distributed as follows: CR, 0 (n=386, 42.7%); ICR, >0 to 4 (n=184, 20.4%), >4 to 8 (n=167, 18.5%), >8 (n=153, 16.9%). A progressively higher residual SYNTAX Score was shown to be a surrogate marker of increasing clinical comorbidity and anatomic complexity. Subjects with CR or residual SYNTAX Scores 8 had comparable 5-year mortality (CR, 8.5%; residual SYNTAX Score >0-4, 8.7%; >4-8, 11.4%; P=0.60). A residual SYNTAX Score >8 was associated with 35.3% all-cause mortality at 5-years (P<0.001). Stratified analyses in the predefined medical treated diabetic and left main subgroups yielded similar results. Conclusions The residual SYNTAX Score was shown to be a powerful indicator of 5-year mortality in the SYNTAX Trial. The residual SYNTAX Score may aid in determining a reasonable level of revascularization.

  • 43.
    Fohlman, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pauksen, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hyypiä, T.
    Eggertsen, G.
    Ehrnst, A.
    Ilbäck, Nils-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Friman, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Antiviral treatment with WIN 54954 reduces mortality in murine Coxsackie virus B3 myocarditis1996In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 94, no 9, p. 2254-2259Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Coxsackieviruses B (CBVs) are dominant causative agents in myocarditis and are associated with pathogenesis is some cases of dilated cardiomyopathy, a clinical entity with a poor survival without heart transplantation.

    METHODS AND RESULTS: In vitro, the antiviral agent WIN 54 954 was shown to inhibit replication of CBV3 at a minimal inhibitory concentration value of 0.02 mg/L. Administration of WIN 54 954, 100 mg/kg BID PO, beginning on the day of infection resulted in complete protection from enteroviral mortality (P < .01). WIN 54 954 treatment did not abrogate the inflammatory reaction in the myocardium. No difference was found in the expression of surface lymphocyte subset markers. At 3 weeks, macrophages seemed to dominate the inflammatory reaction, regardless of treatment. There was no difference in CBV3 antibody titers, indicating that WIN 54 954 does not interfere with the development of protective immunity. Complement factors C3 and B were synthesized at a higher level during infection and correlated well with the degree of inflammatory reaction.

    CONCLUSIONS: The results show that WIN 54 954 is a potent antiviral agent with a highly significant effect on survival in CBV-induced myocarditis in the A/J mouse if treatment is started early. It is suggested that the reduction in mortality seen with WIN 54 954 administration is due to an inhibitory effect on virus replication in affected organs that does not interfere with cellular or humoral immunity.

  • 44.
    Fukaya, Eri
    et al.
    Stanford Univ, Sch Med, Dept Surg, Div Vasc Surg, Stanford, CA 94305 USA.
    Flores, Alyssa M.
    Stanford Univ, Sch Med, Dept Surg, Div Vasc Surg, Stanford, CA 94305 USA.
    Lindholm, Daniel P
    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.
    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.
    Zanetti, Daniela
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Ingelsson, Erik
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Cardiovasc Inst, Stanford, CA USA.
    Leeper, Nicholas J.
    Stanford Univ, Sch Med, Dept Surg, Div Vasc Surg, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Cardiovasc Inst, Stanford, CA USA.
    Clinical and Genetic Determinants of Varicose Veins Prospective, Community-Based Study of approximate to 500 000 Individuals2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 138, no 25, p. 2869-2880Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Varicose veins are a common problem with no approved medical therapies. Although it is believed that varicose vein pathogenesis is multifactorial, there is limited understanding of the genetic and environmental factors that contribute to their formation. Large-scale studies of risk factors for varicose veins may highlight important aspects of pathophysiology and identify groups at increased risk for disease. METHODS: We applied machine learning to agnostically search for risk factors of varicose veins in 493 519 individuals in the UK Biobank. Predictors were further studied with univariable and multivariable Cox regression analyses (2441 incident events). A genome-wide association study of varicose veins was also performed among 337 536 unrelated individuals (9577 cases) of white British descent, followed by expression quantitative loci and pathway analyses. Because height emerged as a new candidate risk factor, we performed mendelian randomization analyses to assess a potential causal role for height in varicose vein development. RESULTS: Machine learning confirmed several known (age, sex, obesity, pregnancy, history of deep vein thrombosis) and identified several new risk factors for varicose vein disease, including height. After adjustment for traditional risk factors in Cox regression, greater height remained independently associated with varicose veins (hazard ratio for upper versus lower quartile, 1.74; 95% Cl, 1.51-2.01; P<0.0001). A genomewide association study identified 30 new genome-wide significant loci, identifying pathways involved in vascular development and skeletal/ limb biology. Mendelian randomization analysis provided evidence that increased height is causally related to varicose veins (inverse -variance weighted: odds ratio, 1.26; P=2.07x10(-16)). CONCLUSIONS: Using data from nearly a half -million individuals, we present a comprehensive genetic and epidemiological study of varicose veins. We identified novel clinical and genetic risk factors that provide pathophysiological insights and could help future improvements of treatment of varicose vein disease.

  • 45. Galaup, Ariane
    et al.
    Gomez, Elisa
    Souktani, Rachid
    Durand, Melanie
    Cazes, Aurelie
    Monnot, Catherine
    Teillon, Jeremie
    Le Jan, Sébastien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bouleti, Claire
    Briois, Gaelle
    Philippe, Josette
    Pons, Sandrine
    Martin, Valerie
    Assaly, Rana
    Bonnin, Philippe
    Ratajczak, Philippe
    Janin, Anne
    Thurston, Gavin
    Valenzuela, David M.
    Murphy, Andrew J.
    Yancopoulos, George D.
    Tissier, Renaud
    Berdeaux, Alain
    Ghaleh, Bijan
    Germain, Stephane
    Protection Against Myocardial Infarction and No-Reflow Through Preservation of Vascular Integrity by Angiopoietin-Like 42012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, no 1, p. 140-149Article in journal (Refereed)
    Abstract [en]

    Background-Increased permeability, predominantly controlled by endothelial junction stability, is an early event in the deterioration of vascular integrity in ischemic disorders. Hemorrhage, edema, and inflammation are the main features of reperfusion injuries, as observed in acute myocardial infarction (AMI). Thus, preservation of vascular integrity is fundamental in ischemic heart disease. Angiopoietins are pivotal modulators of cell-cell junctions and vascular integrity. We hypothesized that hypoxic induction of angiopoietin-like protein 4 (ANGPTL4) might modulate vascular damage, infarct size, and no-reflow during AMI. Methods and Results-We showed that vascular permeability, hemorrhage, edema, inflammation, and infarct severity were increased in angptl4-deficient mice. We determined that decrease in vascular endothelial growth factor receptor 2 (VEGFR2) and VE-cadherin expression and increase in Src kinase phosphorylation downstream of VEGFR2 were accentuated after ischemia-reperfusion in the coronary microcirculation of angptl4-deficient mice. Both events led to altered VEGFR2/VE-cadherin complexes and to disrupted adherens junctions in the endothelial cells of angptl4-deficient mice that correlated with increased no-reflow. In vivo injection of recombinant human ANGPTL4 protected VEGF-driven dissociation of the VEGFR2/VE-cadherin complex, reduced myocardial infarct size, and the extent of no-reflow in mice and rabbits. Conclusions-These data showed that ANGPTL4 might constitute a relevant target for therapeutic vasculoprotection aimed at counteracting the effects of VEGF, thus being crucial for preventing no-reflow and conferring secondary cardioprotection during AMI.

  • 46. Ganna, Andrea
    et al.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    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.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    1-acyl-sn-glycero-3-phosphocholine Levels are Related to Obesity and Several Markers of Subclinical CV Disease and its Biosynthesis is Associated With Genetic Variants in the 9p21 Region2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 47. Gaziano, Liam
    et al.
    Sun, Luanluan
    Arnold, Matthew
    Bell, Steven
    Cho, Kelly
    Kaptoge, Stephen K
    Song, Rebecca J
    Burgess, Stephen
    Posner, Daniel C
    Mosconi, Katja
    Robinson-Cohen, Cassianne
    Mason, Amy M
    Bolton, Thomas R
    Tao, Ran
    Allara, Elias
    Schubert, Petra
    Chen, Lingyan
    Staley, James R
    Staplin, Natalie
    Altay, Servet
    Amiano, Pilar
    Arndt, Volker
    Ärnlöv, Johan
    Barr, Elizabeth L M
    Björkelund, Cecilia
    Boer, Jolanda M A
    Brenner, Hermann
    Casiglia, Edoardo
    Chiodini, Paolo
    Cooper, Jackie A
    Coresh, Josef
    Cushman, Mary
    Dankner, Rachel
    Davidson, Karina W
    de Jongh, Renate T
    Donfrancesco, Chiara
    Engström, Gunnar
    Freisling, Heinz
    de la Cámara, Agustín Gómez
    Gudnason, Vilmundur
    Hankey, Graeme J
    Hansson, Per-Olof
    Heath, Alicia K
    Hoorn, Ewout J
    Imano, Hironori
    Jassal, Simerjot K
    Kaaks, Rudolf
    Katzke, Verena
    Kauhanen, Jussi
    Kiechl, Stefan
    Koenig, Wolfgang
    Kronmal, Richard A
    Kyrø, Cecilie
    Lawlor, Deborah A
    Ljungberg, Börje
    MacDonald, Conor
    Masala, Giovanna
    Meisinger, Christa
    Melander, Olle
    Moreno Iribas, Conchi
    Ninomiya, Toshiharu
    Nitsch, Dorothea
    Nordestgaard, Børge G
    Onland-Moret, Charlotte
    Palmieri, Luigi
    Petrova, Dafina
    Garcia, Jose Ramón Quirós
    Rosengren, Annika
    Sacerdote, Carlotta
    Sakurai, Masaru
    Santiuste, Carmen
    Schulze, Matthias B
    Sieri, Sabina
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Tikhonoff, Valérie
    Tjønneland, Anne
    Tong, Tammy
    Tumino, Rosario
    Tzoulaki, Ioanna
    van der Schouw, Yvonne T
    Monique Verschuren, W M
    Völzke, Henry
    Wallace, Robert B
    Wannamethee, S Goya
    Weiderpass, Elisabete
    Willeit, Peter
    Woodward, Mark
    Yamagishi, Kazumasa
    Zamora-Ros, Raul
    Akwo, Elvis A
    Pyarajan, Saiju
    Gagnon, David R
    Tsao, Philip S
    Muralidhar, Sumitra
    Edwards, Todd L
    Damrauer, Scott M
    Joseph, Jacob
    Pennells, Lisa
    Wilson, Peter W F
    Harrison, Seamus
    Gaziano, Thomas A
    Inouye, Michael
    Baigent, Colin
    Casas, Juan P
    Langenberg, Claudia
    Wareham, Nick
    Riboli, Elio
    Gaziano, J Michael
    Danesh, John
    Hung, Adriana M
    Butterworth, Adam S
    Wood, Angela M
    Di Angelantonio, Emanuele
    Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses2022In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 146, no 20, p. 1507-1517Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke.

    METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank.

    RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD.

    CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

    Download full text (pdf)
    fulltext
  • 48. Goepfert, C
    et al.
    Sundberg, Christian
    Sevigny, J
    Enjyoji, K
    Hoshi, T
    Csizmadia, E
    Robson, S
    Disordered cellular migration and angiogenesis in cd39-null mice2001In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 104, no 25, p. 3109-3115Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1)/CD39 is the major ectonucleotidase of endothelial cells and monocytes and catalyzes phosphohydrolysis of extracellular nucleoside diphosphates (NDP) and triphosphates (NTP, eg, ATP and UTP). Deletion of cd39 causes perturbations in the hydrolysis of NTP and NDP in the vasculature. Activation of P2 receptors appears to influence endothelial cell chemotactic and mitogenic responses in vitro. Therefore, aberrant regulation of nucleotide P2 receptors may influence angiogenesis in cd39-null mice. Methods and Results- In control mice, implanted Matrigel plugs containing growth factors were rapidly populated by monocyte/macrophages, endothelial cells, and pericytes, with the development of new vessels over days. In cd39-null mice, migrating cells were completely confined to the tissue-Matrigel interface in a clearly stratified manner. Absolute failure of new vessel ingrowth was consistently observed in the mutant mice. Linked to these findings, chemotaxis of cd39-null monocyte/macrophages to nucleotides was impaired in vitro. This abnormality was associated with desensitization of nucleotide receptor P2Y-mediated signaling pathways. CONCLUSIONS: Our findings demonstrate a role for NTPDase1 and phosphohydrolysis of extracellular nucleotides in the regulation of the cellular infiltration and new vessel growth in a model of angiogenesis.

  • 49. Goodman, Shaun G.
    et al.
    Clare, Robert
    Pieper, Karen S.
    Mahaffey, Kenneth W.
    Harrington, Robert A.
    Nicolau, Jose C.
    Storey, Robert F.
    Cantor, Warren J.
    Angiolillo, Dominick J.
    Husted, Steen
    Cannon, Christopher P.
    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.
    Kilhamn, Jan
    Steg, Ph. Gabriel
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Response to Letter Regarding Article, "Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor: Insights From PLATO"2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 126, no 11, p. E171-E172Article in journal (Refereed)
  • 50. Goodman, Shaun G.
    et al.
    Clare, Robert
    Pieper, Karen S.
    Nicolau, Jose C.
    Storey, Robert F.
    Cantor, Warren J.
    Mahaffey, Kenneth W.
    Angiolillo, Dominick J.
    Husted, Steen
    Cannon, Christopher P.
    James, Stefan K
    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.
    Kilhamn, Jan
    Steg, P. Gabriel
    Harrington, Robert A.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor: Outcomes With Clopidogrel and Ticagrelor2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, no 8, p. 978-986Article in journal (Refereed)
    Abstract [en]

    Background-The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear. Methods and Results-We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The primary end point rates were higher for individuals on a PPI (n = 6539) compared with those not on a PPI (n = 12 060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.04 -1.38) and ticagrelor (11.0% versus 9.2%; HR, 1.24; 95% CI, 1.07-1.45) groups. Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, HR, 0.98; 95% CI, 0.79-1.23; ticagrelor, HR, 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR, 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI, 1.14-1.49). Conclusions-The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel. However, a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of cardiovascular events.

12345 1 - 50 of 211
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf