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  • 1.
    Aboyans, Victor
    et al.
    Dupuytren University Hospital.
    Criqui, Michael
    University of California, USA.
    Abraham, Pierre
    University Hospital of Angers, France.
    Allison, Matthew
    University of California, USA.
    Creager, Mark
    Brigham and Women’s Hospital, USA.
    Diehm, Curt
    Karlsbad Clinic/University of Heidelberg, Germany.
    Fowkes, Gerry
    University of Edinburgh, UK.
    Hiatt, William
    University of Colorado, USA.
    Jönsson, Björn
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Lacroix, Philippe
    Limoges University, France.
    Marin, Benoit
    Limoges Teaching Hospital, France.
    McDermott, Mary
    Northwestern University,USA.
    Norgren, Lars
    University Hospital, Örebro, Sweden.
    Pande, Reena
    Brigham and Women’s Hospital, USA.
    Preux, Pierre-Marie
    University of Limoges, France.
    Stoffers, H.E.
    Maastricht University, Netherlands.
    Treat-Jacobsson, Diane
    University of Minnesota, USA.
    Measurement and interpretation of the ankle-brachial index: a scientific statement from the Ammerican Heart Association2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539Article in journal (Refereed)
  • 2.
    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.

  • 3. 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.

  • 4.
    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.

  • 5.
    Alfredsson, Joakim
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Duke Clin Research Institute, NC 27705 USA.
    Stebbins, Amanda
    Duke Clin Research Institute, NC 27705 USA.
    Brennan, J. Matthew
    Duke University, NC USA.
    Matsouaka, Roland
    Duke University, NC USA.
    Afilalo, Jonathan
    McGill University, Canada.
    Peterson, Eric D.
    Duke Clin Research Institute, NC 27705 USA; Duke University, NC USA.
    Vemulapalli, Sreekanth
    Duke University, NC USA.
    Rumsfeld, John S.
    University of Colorado, CO USA.
    Shahian, David
    Massachusetts Gen Hospital, MA 02114 USA.
    Mack, Michael J.
    Baylor Scott and White Heatlh, TX USA.
    Alexander, Karen P.
    Duke Clin Research Institute, NC 27705 USA; Duke University, NC USA.
    Gait Speed Predicts 30-Day Mortality After Transcatheter Aortic Valve Replacement Results From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry2016In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 133, no 14, p. 1351-1359Article in journal (Refereed)
    Abstract [en]

    Background Surgical risk scores do not include frailty assessments (eg, gait speed), which are of particular importance for patients with severe aortic stenosis considering transcatheter aortic valve replacement. Methods and Results We assessed the association of 5-m gait speed with outcomes in a cohort of 8039 patients who underwent transcatheter aortic valve replacement (November 2011-June 2014) and were included in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. We evaluated the association between continuous and categorical gait speed and 30-day all-cause mortality before and after adjustment for Society of Thoracic Surgeons-predicted risk of mortality score and key variables. Secondary outcomes included in-hospital mortality, bleeding, acute kidney injury, and stroke. The overall median gait speed was 0.63 m/s (25th-75th percentile, 0.47-0.79 m/s), with the slowest walkers (&lt;0.5 m/s) constituting 28%, slow walkers (0.5-0.83 m/s) making up 48%, and normal walkers (&gt;0.83 m/s) constituting 24% of the population. Thirty-day all-cause mortality rates were 8.4%, 6.6%, and 5.4% for the slowest, slow, and normal walkers, respectively (P&lt;0.001). Each 0.2-m/s decrease in gait speed corresponded to an 11% increase in 30-day mortality (adjusted odds ratio, 1.11; 95% confidence interval, 1.01-1.22). The slowest walkers had 35% higher 30-day mortality than normal walkers (adjusted odds ratio, 1.35; 95% confidence interval, 1.01-1.80), significantly longer hospital stays, and a lower probability of being discharged to home. Conclusions Gait speed is independently associated with 30-day mortality after transcatheter aortic valve replacement. Identification of frail patients with the slowest gait speeds facilitates preprocedural evaluation and anticipation of a higher level of postprocedural care. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01737528.

  • 6.
    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)
  • 7.
    Altimiras, Jordi
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Zoology . Linköping University, The Institute of Technology.
    Milberg, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Ecology .
    Letter regarding article by Kahn et al. "Predictive adaptive responses to maternal high-fat diet prevent endothelial dysfunction but not hypertension in adult rat offspring" (Adaption is not predictive)2005In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 111, p. 166-166Article in journal (Other academic)
  • 8. 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.

  • 9.
    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.

  • 10.
    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.

  • 11.
    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.

  • 12.
    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)
  • 13. 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)
  • 14. 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.

  • 15.
    Artiach, Gonzalo
    et al.
    Karolinska Institute, Sweden.
    Carracedo, Miguel
    Karolinska Institute, Sweden.
    Plunde, Oscar
    Karolinska Institute, Sweden.
    Wheelock, Craig E
    Karolinska Institute, Sweden.
    Thul, Silke
    Karolinska Institute, Sweden.
    Sjövall, Peter
    RISE Research Institutes of Sweden, Materials and Production, Chemistry, Biomaterials and Textiles.
    Franco-Cereceda, Anders
    Karolinska Institute, Sweden.
    Laguna-Fernandez, Andres
    Karolinska Institute, Sweden.
    Arnardottir, Hildur
    Karolinska Institute, Sweden.
    Bäck, Magnus
    Karolinska Institute, Sweden.
    Omega-3 Polyunsaturated Fatty Acids Decrease Aortic Valve Disease through the Resolvin E1 and ChemR23 Axis.2020In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 142, p. 776-789Article in journal (Refereed)
    Abstract [en]

    Background: Aortic valve stenosis (AVS), which is the most common valvular heart disease, causes a progressive narrowing of the aortic valve as a consequence of thickening and calcification of the aortic valve leaflets. The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) in cardiovascular prevention have been recently demonstrated in a large randomized controlled trial. In addition, n-3 PUFA serve as the substrate for the synthesis of specialized pro-resolving mediators (SPMs), which are known by their potent beneficial anti-inflammatory, pro-resolving and tissue-modifying properties in cardiovascular disease. However, the effects of n-3 PUFA and SPMs on AVS have not yet been determined. The aim of this study was to identify the role of n-3 PUFA-derived SPMs in relation to the development of AVS. Methods: Lipidomic and transcriptomic analyses were performed in human tricuspid aortic valves. Apoe-/- mice and wire injury in C57BL/6J mice were used as models for mechanistic studies. Results: We found that n-3 PUFA incorporation into human stenotic aortic valves was higher in non-calcified regions compared with calcified regions. LC-MS-MS based lipid mediator lipidomics identified that the n-3 PUFA-derived SPM resolvin E1 (RvE1) was dysregulated in calcified regions and acted as a calcification inhibitor. Apoe-/- mice expressing the Caenorhabditis elegans Fat-1 transgene (Fat-1tgxApoe-/-), which enables the endogenous synthesis of n-3 PUFA, increased valvular n-3 PUFA content, exhibited reduced valve calcification, lower aortic valve leaflet area, increased M2 macrophage polarization and improved echocardiographic parameters. Finally, abrogation of the RvE1 receptor ChemR23 enhanced disease progression, and the beneficial effects of Fat-1tg were abolished in the absence of ChemR23. Conclusions: n-3 PUFA-derived RvE1 and its receptor ChemR23 emerge as a key axis in the inhibition of AVS progression, and may represent a novel potential therapeutic opportunity to be evaluated in patients with AVS.

  • 16. 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)
  • 17.
    Ballantyne, Christie M.
    et al.
    Baylor Coll Med, Dept Med, Houston, TX 77030 USA Linkoping Univ Hosp, Dept Internal Med, S-58185 Linkoping, Sweden Merck Res Labs, Rahway, NJ USA Aker Hosp, Med Clin, Oslo, Norway Natl Hosp Norway, Dept Med, Oslo, Norway.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Cook, Thomas J.
    Baylor Coll Med, Dept Med, Houston, TX 77030 USA Linköping Univ Hosp, Dept Internal Med, S-58185 Linkoping, Sweden Merck Res Labs, Rahway, NJ USA Aker Hosp, Med Clin, Oslo, Norway Natl Hosp Norway, Dept Med, Oslo, Norway.
    Mercuri, Michele F.
    Baylor Coll Med, Dept Med, Houston, TX 77030 USA Linkoping Univ Hosp, Dept Internal Med, S-58185 Linkoping, Sweden Merck Res Labs, Rahway, NJ USA Aker Hosp, Med Clin, Oslo, Norway Natl Hosp Norway, Dept Med, Oslo, Norway.
    Pedersen, Terje R.
    Baylor Coll Med, Dept Med, Houston, TX 77030 USA Linkoping Univ Hosp, Dept Internal Med, S-58185 Linkoping, Sweden Merck Res Labs, Rahway, NJ USA Aker Hosp, Med Clin, Oslo, Norway Natl Hosp Norway, Dept Med, Oslo, Norway.
    Kjekshus, John
    Baylor Coll Med, Dept Med, Houston, TX 77030 USA Linkoping Univ Hosp, Dept Internal Med, S-58185 Linkoping, Sweden Merck Res Labs, Rahway, NJ USA Aker Hosp, Med Clin, Oslo, Norway Natl Hosp Norway, Dept Med, Oslo, Norway.
    Low high-density lipoprotein cholesterol and response to simvastatin therapy in Scandinavian Simvastatin Survival Study (4S) - Response2002In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 106, no 2, p. E8-E8article id e8Article in journal (Other academic)
  • 18. Ballantyne, CM
    et al.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Cook, TJ
    Mercuri, MF
    Pedersen, TR
    Kjekshus, J
    Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S2001In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 104, no 25, p. 3046-3051Article in journal (Refereed)
    Abstract [en]

    Background - Patients with low HDL cholesterol (HDL-C) and elevated triglyceride had an increased risk for coronary heart disease (CHD) events and received the greatest benefit with fibrate therapy in substudy analyses of the Helsinki Heart Study and the Bezafibrate Infarction Prevention Study. Methods and Results - In this post hoc analysis of the Scandinavian Simvastatin Survival Study, which enrolled patients with elevated LDL cholesterol (LDL-C) and CHD, subgroups defined by HDL-C and triglyceride quartiles were compared to examine the influence of HDL-C and triglyceride on CHD events and response to therapy. Patients in the lowest HDL-C (<1.00 mmol/L [39 mg/dL]) and highest triglyceride (>1.80 mmol/L [159 mg/dL]) quartiles (lipid triad, n=458) had increased proportions of other features of the metabolic syndrome (increased body mass index, hypertension, diabetes), men, prior myocardial infarction, prior revascularization, and ▀-blocker use than patients in the highest HDL-C (>1.34 mmol/L [52 mg/dL]) and lowest triglyceride (<1.11 mmol/L [98 mg/dL]) quartiles (isolated LDL-C elevation, n=545). The major coronary event rate was highest in lipid triad patients on placebo (35.9%), and this subgroup had the greatest event reduction (relative risk 0.48, 95% CI 0.33 to 0.69), a significant treatment-by-subgroup interaction (P=0.03) indicated a greater treatment effect in the lipid triad subgroup than the isolated LDL-C elevation subgroup. Conclusions - Patients with elevated LDL-C, low HDL-C, and elevated triglycerides were more likely than patients with isolated LDL-C elevation to have other characteristics of the metabolic syndrome, had increased risk for CHD events on placebo, and received greater benefit with simvastatin therapy.

  • 19.
    Ban, Yifang
    et al.
    KTH, School of Architecture and the Built Environment (ABE), Urban Planning and Environment, Geodesy and Geoinformatics.
    Fredman, David
    Jonsson, Martin
    Svensson, Leif
    Multi-Criteria Evaluations for Improved Placement of Defibrillators: Preliminary Results2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22, p. 78-Article in journal (Other academic)
  • 20. 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.

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  • 21.
    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.

  • 22. Belonje, Anne M S
    et al.
    Voors, Adriaan A
    van der Meer, Peter
    van Gilst, Wiek H
    Jaarsma, Tiny
    van Veldhuisen, Dirk J
    Endogenous erythropoietin and outcome in heart failure.2010In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 121, no 2, p. 245-51Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Endogenous erythropoietin is increased in patients with heart failure (HF). Previous small-scale data suggest that these erythropoietin levels are related to prognosis. This study aims to analyze the clinical and prognostic value of erythropoietin levels in relation to hemoglobin in a large cohort of HF patients. METHODS AND RESULTS: In patients hospitalized for HF, endogenous erythropoietin levels were measured at discharge and after 6 months. In anemic patients, the relation between erythropoietin and hemoglobin levels was determined by calculating the observed/predicted ratio of erythropoietin levels. We studied data from 605 patients with HF. Mean age was 71+/-11 years; 62% were male; and mean left ventricular ejection fraction was 0.33+/-0.14. Median erythropoietin levels were 9.6 U/L at baseline and 10.5 U/L at 6 months. Higher erythropoietin levels at baseline were independently related to an increased mortality at 18 months (hazard ratio, 2.06; 95% confidence interval, 1.40 to 3.04; P<0.01). In addition, persistently elevated erythropoietin levels (higher than median at baseline and at 6 months) were related to an increased mortality risk (hazard ratio, 2.24; 95% confidence interval, 1.02 to 4.90; P=0.044). The observed/predicted ratio was determined in a subset of anemic patients, 79% of whom had erythropoietin levels lower than expected and 9% had levels higher than expected on the basis of their hemoglobin. Multivariate Cox regression analysis revealed that a higher observed/predicted ratio was related to an increased mortality risk (hazard ratio, 3.52; 95% confidence interval, 1.53 to 8.12; P=0.003). CONCLUSIONS: Erythropoietin levels predict mortality in HF patients, and persistently elevated levels have an independent prognostic value. In anemic HF patients, the majority had a low observed/predicted ratio. However, a higher observed/predicted ratio may be related to an independent increased mortality risk.

  • 23.
    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.

  • 24.
    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.

  • 25.
    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.

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  • 26.
    Bergström, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Andersson, B
    Edner, M
    Dept Cardiol, Linkoping, Sweden Gothenburg Univ, S-41124 Gothenburg, Sweden Linkoping Univ, S-58183 Linkoping, Sweden Danderyd Hosp, Stockholm, Sweden.
    Nylander, E
    Persson, H
    Dept Cardiol, Linkoping, Sweden Gothenburg Univ, S-41124 Gothenburg, Sweden Linkoping Univ, S-58183 Linkoping, Sweden Danderyd Hosp, Stockholm, Sweden.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Carvedilol improves diastolic function in patients with diastolic heart failure.2001In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 104, no 17, p. 3388-Conference paper (Other academic)
  • 27.
    Bergström, Göran
    et al.
    Department of Molecular and Clinical Medicine (G. Bergström, E.B., O.A., B.F., O.H., A.R.), University of Gothenburg, Sweden.;Departments of Clinical Physiology (G. Bergström, O.H.), Region Västra Götaland, Gothenburg, Sweden..
    Persson, Margaretha
    Department of Clinical Sciences (M.P., G. Berglund, G.E., M. Magnusson), Lund University, Malmö, Sweden.;Departments of Internal Medicine (M.P.), Skåne University Hospital, Malmö, Sweden..
    Adiels, Martin
    Sahlgrenska Academy, and School of Public Health and Community Medicine, Institute of Medicine (M.A., C.B.), University of Gothenburg, Sweden..
    Björnson, Elias
    Department of Molecular and Clinical Medicine (G. Bergström, E.B., O.A., B.F., O.H., A.R.), University of Gothenburg, Sweden..
    Bonander, Carl
    Sahlgrenska Academy, and School of Public Health and Community Medicine, Institute of Medicine (M.A., C.B.), University of Gothenburg, Sweden..
    Ahlström, Håkan
    Section of Radiology, Department of Surgical Sciences (H.A., O.D.), Uppsala University, Sweden..
    Alfredsson, Joakim
    Departments of Cardiology (J.A., E.S.), Linköping University, Sweden.;Health, Medicine and Caring Sciences (J.A., E.S., J.E.E., F.H.N., C.J.Ö., A.P.), Linköping University, Sweden..
    Angerås, Oskar
    Department of Molecular and Clinical Medicine (G. Bergström, E.B., O.A., B.F., O.H., A.R.), University of Gothenburg, Sweden.;Cardiology (O.A.), Region Västra Götaland, Gothenburg, Sweden..
    Berglund, Göran
    Department of Clinical Sciences (M.P., G. Berglund, G.E., M. Magnusson), Lund University, Malmö, Sweden..
    Blomberg, Anders
    Department of Public Health and Clinical Medicine, Medicine and Heart Centre (A.B., J.L., A. Sandström, A. Själander, S.S.), Umeå University, Sweden..
    Brandberg, John
    Department of Radiology, Institute of Clinical Sciences (J.B., E.F., A.F.), University of Gothenburg, Sweden.;Radiology (J.B., E.F., A.F.), Region Västra Götaland, Gothenburg, Sweden..
    Börjesson, Mats
    Institute of Medicine (M.B.), University of Gothenburg, Sweden.;Center for Health and Performance (M.B.), University of Gothenburg, Sweden.;Sahlgrenska University Hospital (M.B., B.F., A.R., K.T.), Region Västra Götaland, Gothenburg, Sweden..
    Cederlund, Kerstin
    Department of Clinical Science, Intervention and Technology (K.C.), Karolinska Institutet, Stockholm, Sweden..
    de Faire, Ulf
    Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine (U.d.F.), Karolinska Institutet, Stockholm, Sweden..
    Duvernoy, Olov
    Section of Radiology, Department of Surgical Sciences (H.A., O.D.), Uppsala University, Sweden..
    Ekblom, Örjan
    Swedish School of Sport and Health Sciences, GIH, Department of Physical Activity and Health.
    Engström, Gunnar
    Department of Clinical Sciences (M.P., G. Berglund, G.E., M. Magnusson), Lund University, Malmö, Sweden..
    Engvall, Jan E.
    Health, Medicine and Caring Sciences (J.A., E.S., J.E.E., F.H.N., C.J.Ö., A.P.), Linköping University, Sweden.;Clinical Physiology (J.E.E.), Linköping University, Sweden.;CMIV, Centre of Medical Image Science and Visualization (J.E.E., A.P., C.J.Ö.), Linköping University, Sweden..
    Fagman, Erika
    Department of Radiology, Institute of Clinical Sciences (J.B., E.F., A.F.), University of Gothenburg, Sweden.;Radiology (J.B., E.F., A.F.), Region Västra Götaland, Gothenburg, Sweden..
    Eriksson, Mats
    Department of Endocrinology, Metabolism &amp; Diabetes and Clinical Research Center, Karolinska University Hospital Huddinge, Stockholm, Sweden (M.E.)..
    Erlinge, David
    Department of Clinical Sciences Lund, Cardiology, Lund University and Skåne University Hospital, Lund, Sweden (D.E., M.A.M.)..
    Fagerberg, Björn
    Department of Molecular and Clinical Medicine (G. Bergström, E.B., O.A., B.F., O.H., A.R.), University of Gothenburg, Sweden.;Sahlgrenska University Hospital (M.B., B.F., A.R., K.T.), Region Västra Götaland, Gothenburg, Sweden..
    Flinck, Agneta
    Department of Radiology, Institute of Clinical Sciences (J.B., E.F., A.F.), University of Gothenburg, Sweden.;Radiology (J.B., E.F., A.F.), Region Västra Götaland, Gothenburg, Sweden..
    Gonçalves, Isabel
    Department of Clinical Sciences Malmö (I.G.), Lund University and Skåne University Hospital, Lund, Sweden..
    Hagström, Emil
    Cardiology (E.H.), Uppsala University, Sweden.;Department of Medical Sciences, and Uppsala Clinical Research Center (E.H.), Uppsala University, Sweden..
    Hjelmgren, Ola
    Department of Molecular and Clinical Medicine (G. Bergström, E.B., O.A., B.F., O.H., A.R.), University of Gothenburg, Sweden.;Departments of Clinical Physiology (G. Bergström, O.H.), Region Västra Götaland, Gothenburg, Sweden..
    Lind, Lars
    Clinical Epidemiology (L.L., J.S.), Uppsala University, Sweden..
    Lindberg, Eva
    Respiratory, Allergy and Sleep Research (E.L.), Uppsala University, Sweden..
    Lindqvist, Per
    Department of Surgical and Perioperative Sciences (P.L.), Umeå University, Sweden..
    Ljungberg, Johan
    Department of Public Health and Clinical Medicine, Medicine and Heart Centre (A.B., J.L., A. Sandström, A. Själander, S.S.), Umeå University, Sweden..
    Magnusson, Martin
    Department of Clinical Sciences (M.P., G. Berglund, G.E., M. Magnusson), Lund University, Malmö, Sweden.;Cardiology (M. Magnusson), Skåne University Hospital, Malmö, Sweden.;Wallenberg Center for Molecular Medicine, Lund University, Sweden (M. Magnusson).;North-West University, Hypertension in Africa Research Team (HART), Potchefstroom, South Africa (M. Magnusson)..
    Mannila, Maria
    Heart and Vascular Theme, Department of Cardiology, and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden (M. Mannila)..
    Markstad, Hanna
    Experimental Cardiovascular Research, Clinical Research Center, Clinical Sciences Malmö (H.M.), Lund University, Malmö, Sweden.;Center for Medical Imaging and Physiology (H.M.), Lund University and Skåne University Hospital, Lund, Sweden..
    Mohammad, Moman A.
    Department of Clinical Sciences Lund, Cardiology, Lund University and Skåne University Hospital, Lund, Sweden (D.E., M.A.M.)..
    Nystrom, Fredrik H.
    Health, Medicine and Caring Sciences (J.A., E.S., J.E.E., F.H.N., C.J.Ö., A.P.), Linköping University, Sweden..
    Ostenfeld, Ellen
    Department of Clinical Sciences Lund, Clinical Physiology (E.O.), Lund University and Skåne University Hospital, Lund, Sweden..
    Persson, Anders
    Health, Medicine and Caring Sciences (J.A., E.S., J.E.E., F.H.N., C.J.Ö., A.P.), Linköping University, Sweden.;Radiology (A.P.), Linköping University, Sweden.;CMIV, Centre of Medical Image Science and Visualization (J.E.E., A.P., C.J.Ö.), Linköping University, Sweden..
    Rosengren, Annika
    Department of Molecular and Clinical Medicine (G. Bergström, E.B., O.A., B.F., O.H., A.R.), University of Gothenburg, Sweden.;Sahlgrenska University Hospital (M.B., B.F., A.R., K.T.), Region Västra Götaland, Gothenburg, Sweden..
    Sandström, Anette
    Department of Public Health and Clinical Medicine, Medicine and Heart Centre (A.B., J.L., A. Sandström, A. Själander, S.S.), Umeå University, Sweden..
    Själander, Anders
    Department of Public Health and Clinical Medicine, Medicine and Heart Centre (A.B., J.L., A. Sandström, A. Själander, S.S.), Umeå University, Sweden..
    Sköld, Magnus C.
    Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine (M.C.S.), Karolinska Institutet, Stockholm, Sweden.;Department of Respiratory Medicine and Allergy, Karolinska University Hospital Solna, Stockholm, Sweden (M.C.S.)..
    Sundström, Johan
    Clinical Epidemiology (L.L., J.S.), Uppsala University, Sweden.;The George Institute for Global Health, University of New South Wales, Sydney, Australia (J.S.)..
    Swahn, Eva
    Departments of Cardiology (J.A., E.S.), Linköping University, Sweden.;Health, Medicine and Caring Sciences (J.A., E.S., J.E.E., F.H.N., C.J.Ö., A.P.), Linköping University, Sweden..
    Söderberg, Stefan
    Department of Public Health and Clinical Medicine, Medicine and Heart Centre (A.B., J.L., A. Sandström, A. Själander, S.S.), Umeå University, Sweden..
    Torén, Kjell
    Occupational and Environmental Medicine/School of Public Health and Community Medicine (K.T.), University of Gothenburg, Sweden.;Sahlgrenska University Hospital (M.B., B.F., A.R., K.T.), Region Västra Götaland, Gothenburg, Sweden..
    Östgren, Carl Johan
    Health, Medicine and Caring Sciences (J.A., E.S., J.E.E., F.H.N., C.J.Ö., A.P.), Linköping University, Sweden.;CMIV, Centre of Medical Image Science and Visualization (J.E.E., A.P., C.J.Ö.), Linköping University, Sweden..
    Jernberg, Tomas
    Department of Clinical Sciences, Danderyd University Hospital (T.J.), Karolinska Institutet, 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.

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  • 28. Bergström, Göran
    et al.
    Persson, Margaretha
    Adiels, Martin
    Björnson, Elias
    Bonander, Carl
    Ahlström, Håkan
    Alfredsson, Joakim
    Angerås, Oskar
    Berglund, Göran
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Brandberg, John
    Börjesson, Mats
    Cederlund, Kerstin
    de Faire, Ulf
    Duvernoy, Olov
    Ekblom, Örjan
    Engström, Gunnar
    Engvall, Jan E.
    Fagman, Erika
    Eriksson, Mats
    Erlinge, David
    Fagerberg, Björn
    Flinck, Agneta
    Gonçalves, Isabel
    Hagström, Emil
    Hjelmgren, Ola
    Lind, Lars
    Lindberg, Eva
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Ljungberg, Johan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Magnusson, Martin
    Mannila, Maria
    Markstad, Hanna
    Mohammad, Moman A.
    Nystrom, Fredrik H.
    Ostenfeld, Ellen
    Persson, Anders
    Rosengren, Annika
    Sandström, Anette
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Själander, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Sköld, Magnus C.
    Sundström, Johan
    Swahn, Eva
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Torén, Kjell
    Östgren, Carl Johan
    Jernberg, Tomas
    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.

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  • 29.
    Bergström, Göran
    et al.
    Sahlgrens Acad, Sweden; Reg Västra Götaland, Sweden.
    Persson, Margaretha
    Lund Univ, Sweden; Skåne Univ Hosp, Sweden.
    Adiels, Martin
    Univ Gothenburg, Sweden.
    Björnson, Elias
    Sahlgrens Acad, Sweden.
    Bonander, Carl
    Univ Gothenburg, Sweden.
    Ahlström, Håkan
    Uppsala Univ, Sweden.
    Alfredsson, Joakim
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Region Östergötland, Heart Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Angerås, Oskar
    Sahlgrens Acad, Sweden; Reg Västra Götaland, Sweden.
    Berglund, Göran
    Lund Univ, Sweden.
    Blomberg, Anders
    Umeå Univ, Sweden.
    Brandberg, John
    Sahlgrens Acad, Sweden; Reg Västra Götaland, Sweden.
    Börjesson, Mats
    Sahlgrens Acad, Sweden; Univ Gothenburg, Sweden.
    Cederlund, Kerstin
    Karolinska Inst, Sweden.
    de Faire, Ulf
    Karolinska Inst, Sweden.
    Duvernoy, Olov
    Uppsala Univ, Sweden.
    Ekblom, Örjan
    Swedish Sch Sport & Hlth Sci GIH, Sweden.
    Engström, Gunnar
    Lund Univ, Sweden.
    Engvall, Jan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Fagman, Erika
    Sahlgrens Acad, Sweden; Reg Vastra Gotaland, Sweden.
    Eriksson, Mats
    Karolinska Univ Hosp Huddinge, Sweden; Karolinska Univ Hosp Huddinge, Sweden.
    Erlinge, David
    Lund Univ, Sweden; Skåne Univ Hosp, Sweden.
    Fagerberg, Björn
    Sahlgrens Acad, Sweden; Sahlgrens Univ Hosp, Sweden.
    Flinck, Agneta
    Sahlgrens Acad, Sweden; Reg Västra Götaland, Sweden.
    Goncalves, Isabel
    Lund Univ, Sweden.
    Hagström, Emil
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Hjelmgren, Ola
    Sahlgrens Acad, Sweden; Reg Västra Götaland, Sweden.
    Lind, Lars
    Uppsala Univ, Sweden.
    Lindberg, Eva
    Uppsala Univ, Sweden.
    Lindqvist, Per
    Umea Univ, Sweden.
    Ljungberg, Johan
    Umeå Univ, Sweden.
    Magnusson, Martin
    Lund Univ, Sweden; Skåne Univ Hosp, Sweden; Lund Univ, Sweden; North West Univ, South Africa.
    Mannila, Maria
    Karolinska Univ Hosp, Sweden.
    Markstad, Hanna
    Lund Univ, Sweden; Lund Univ, Sweden.
    Mohammad, Moman A.
    Lund Univ, Sweden; Skåne Univ Hosp, Sweden.
    Nyström, Fredrik H
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.
    Ostenfeld, Ellen
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Persson, Anders
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Rosengren, Annika
    Sahlgrens Acad, Sweden; Sahlgrens Univ Hosp, Sweden.
    Sandström, Anette
    Umeå Univ, Sweden.
    Själander, Anders
    Umea Univ, Sweden; Umea Univ, Sweden.
    Sköld, Magnus C.
    Karolinska Inst, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Sundström, Johan
    Uppsala Univ, Sweden; Univ New South Wales, Australia.
    Swahn, Eva
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Cardiology in Linköping.
    Söderberg, Stefan
    Umeå Univ, Sweden.
    Torén, Kjell
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ekholmen. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jernberg, Tomas
    Danderyd Hosp, 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 &gt;= 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 (&gt;= 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 &gt;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.

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    fulltext
  • 30.
    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.

  • 31.
    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.

  • 32.
    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.

  • 33. Bohm, K
    et al.
    Rosenqvist, M
    Herlitz, Johan
    [external].
    Hollenberg, J
    Svensson, L
    Survival is similar after standard treatment and chest compression only in out-of-hospital bystander cardiopulmonary resuscitation.2007In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 116, no 25, p. 2908-2912Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We sought to compare the 1-month survival rates among patients after out-of-hospital cardiac arrest who had been given bystander cardiopulmonary resuscitation (CPR) in relation to whether they had received standard CPR with chest compression plus mouth-to-mouth ventilation or chest compression only. METHODS AND RESULTS: All patients with out-of-hospital cardiac arrest who received bystander CPR and who were reported to the Swedish Cardiac Arrest Register between 1990 and 2005 were included. Crew-witnessed cases were excluded. Among 11,275 patients, 73% (n=8209) received standard CPR, and 10% (n=1145) received chest compression only. There was no significant difference in 1-month survival between patients who received standard CPR (1-month survival=7.2%) and those who received chest compression only (1-month survival=6.7%). CONCLUSIONS: Among patients with out-of-hospital cardiac arrest who received bystander CPR, there was no significant difference in 1-month survival between a standard CPR program with chest compression plus mouth-to-mouth ventilation and a simplified version of CPR with chest compression only.

  • 34.
    Bolger, Ann F
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Eidenvall, Lars
    Ask, Per
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Loyd, Dan
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Wranne, Bengt
    Linköping University, Department of Medicine and Care, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    THE MULTIPLE DETERMINANTS OF CONTINUOUS WAVE SIGNAL INTENSITY1992In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 86, no 4, SArticle in journal (Refereed)
  • 35. 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.

  • 36.
    Bothe, Wolfgang
    et al.
    Stanford University School of Medicine, USA.
    Kuhl, Elllen
    Stanford University School of Medicine, USA.
    Kvitting, John-Peder Escobar
    Stanford University School of Medicine, USA.
    Rausch, Manuel K.
    Stanford University School of Medicine, USA.
    Göktepe, Serdar
    Stanford University School of Medicine, USA.
    Swanson, Julia C.
    Stanford University School of Medicine, USA.
    Farahmandnia, Saideh
    Stanford University School of Medicine, USA.
    Ingels, Neil B.
    Research Institute, Palo Alto Medical Foundation, USA.
    Miller, D. Craig
    Stanford University School of Medicine, USA.
    Rigid, complete annuloplasty rings increase anterior mitral leaflet strain in normal beating ovine heart2011In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 124, p. S81-S96Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Annuloplasty ring or band implantation during surgical mitral valve repair perturbs mitral annular dimensions, dynamics, and shape, which have been associated with changes in anterior mitral leaflet (AML) strain patterns and suboptimal long-term repair durability. We hypothesized that rigid rings with nonphysiological three-dimensional shapes, but not saddle-shaped rigid rings or flexible bands, increase AML strains.

    METHODS AND RESULTS:

    Sheep had 23 radiopaque markers inserted: 7 along the anterior mitral annulus and 16 equally spaced on the AML. True-sized Cosgrove-Edwards flexible, partial band (n=12), rigid, complete St Jude Medical rigid saddle-shaped (n=12), Carpentier-Edwards Physio (n=12), Edwards IMR ETlogix (n=11), and Edwards GeoForm (n=12) annuloplasty rings were implanted in a releasable fashion. Under acute open-chest conditions, 4-dimensional marker coordinates were obtained using biplane videofluoroscopy along with hemodynamic parameters with the ring inserted and after release. Marker coordinates were triangulated, and the largest maximum principal AML strains were determined during isovolumetric relaxation. No relevant changes in hemodynamics occurred. Compared with the respective control state, strains increased significantly with rigid saddle-shaped annuloplasty ring, Carpentier-Edwards Physio, Edwards IMR ETlogix, and Edwards GeoForm (0.14 ± 0.05 versus 0.16 ± 0.05, P=0.024, 0.15 ± 0.03 versus 0.18 ± 0.04, P=0.020, 0.11 ± 0.05 versus 0.14 ± 0.05, P=0.042, and 0.13 ± 0.05 versus 0.16 ± 0.05, P=0.009), but not with Cosgrove-Edwards band (0.15 ± 0.05 versus 0.15 ± 0.04, P=0.973).

    CONCLUSIONS:

    Regardless of three-dimensional shape, rigid, complete annuloplasty rings, but not a flexible, partial band, increased AML strains in the normal beating ovine heart. Clinical studies are needed to determine whether annuloplasty rings affect AML strains in patients, and, if so, whether ring-induced perturbations in leaflet strain states are linked to repair failure.

  • 37. Brodszki, J
    et al.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Marsal, K
    Ley, D
    Impaired vascular growth in late adolescence after intrauterine growth restriction2005In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 111, no 20, p. 2623-2628Article in journal (Refereed)
    Abstract [en]

    Background - Abnormal blood flow in a fetus small for gestational age indicates true fetal intrauterine growth restriction (IUGR). We tested the hypothesis that IUGR with abnormal fetal blood flow is associated with long-term abnormal vascular morphology and function in adolescence. Methods and Results - In a prospective study, vascular mechanical properties of the common carotid artery (CCA), abdominal aorta , and popliteal artery (PA) were assessed by echo-tracking sonography in 21 adolescents with IUGR and abnormal fetal aortic blood flow and in 23 adolescents with normal fetal growth and normal fetal aortic blood flow. Endothelium-dependent and -independent vasodilatation of the brachial artery was measured by high-resolution ultrasound. After adjustment for body surface area and sex, the IUGR group had significantly smaller end-diastolic vessel diameters than the referents in the abdominal aorta and PA (mean difference, 1.7 mm [95% CI, 0.62 to 2.74] and 0.6 mm [95% CI, 0.25 to 1.02], respectively) (P=0.003 and P=0.002, respectively), with a similar trend in the CCA (P=0.09). A higher resting heart rate was observed in the IUGR group (P=0.01). No differences were found in stiffness or in endothelium-dependent and -independent vasodilatation between the 2 groups. Conclusions - IUGR caused by placental insufficiency appears to be associated with impaired vascular growth persisting into young adulthood in both men and women. The smaller aortic dimensions and the higher resting heart rate seen in adolescents with previous IUGR may be of importance for future cardiovascular health. © 2005 American Heart Association, Inc.

  • 38.
    Brunstrom, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lindholm, Lars H.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Perspective from Sweden on the global impact of the 2017 american college of cardiology/american heart association hypertension guidelines: a "sprint" beyond evidence in the United States2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 137, no 9, p. 886-888Article in journal (Other academic)
  • 39. 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)
  • 40.
    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.

  • 41.
    Carlhäll, Carljohan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Physiology . Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Nguyen, Tom C.
    Itoh, Akinobu
    Ennis, Daniel B.
    Bothe, Wolfgang
    Liang, David
    Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Ingels, Neil B.
    Palo Alto Med Fdn, Res Inst, Palo Alto, CA 94301 USA.
    Miller, D. Craig
    Stanford Univ, Sch Med, Falk Cardiovasc Res Ctr, Dept Cardiothorac Surg, Stanford, CA 94305 USA.
    Alterations in transmural myocardial strain - An early marker of left ventricular dysfunction in mitral regurgitation?2008In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 118, no 14, p. S256-S262Article in journal (Refereed)
    Abstract [en]

    Background-In asymptomatic patients with severe isolated mitral regurgitation (MR), identifying the onset of early left ventricular (LV) dysfunction can guide the timing of surgical intervention. We hypothesized that changes in LV transmural myocardial strain represent an early marker of LV dysfunction in an ovine chronic MR model. Methods and Results-Sheep were randomized to control (CTRL, n = 8) or experimental (EXP, n = 12) groups. In EXP, a 3.5-or 4.8-mm hole was created in the posterior mitral leaflet to generate "pure" MR. Transmural beadsets were inserted into the lateral and anterior LV wall to radiographically measure 3-dimensional transmural strains during systole and diastolic filling, at 1 and 12 weeks postoperatively. MR grade was higher in EXP than CTRL at 1 and 12 weeks (3.0 [2-4] versus 0.5 [0-2], 3.0 [1-4] versus 0.5 [0-1], respectively, both P < 0.001). At 12 weeks, LV mass index was greater in EXP than CTRL (201 +/- 18 versus 173 +/- 17 g/m(2), P < 0.01). LVEDVI increased in EXP from 1 to 12 weeks (P = 0.015). Between the 1 and 12 week values, the change in BNP (-4.5 +/- 4.4 versus-3.0 +/- 3.6 pmol/L), PRSW (9 +/- 13 versus 23 +/- 18 mm Hg), tau (-3 +/- 11 versus-4 +/- 7 ms), and systolic strains was similar between EXP and CTRL. The changes in longitudinal diastolic filling strains between 1 and 12 weeks, however, were greater in EXP versus CTRL in the subendocardium (lateral:-0.08 +/- 0.05 versus 0.02 +/- 0.14, anterior:-0.10 +/- 0.05 versus-0.02 +/- 0.07, both P < 0.01). Conclusions-Twelve weeks of ovine "pure" MR caused LV remodeling with early changes in LV function detected by alterations in transmural myocardial strain, but not by changes in BNP, PRSW, or tau.

  • 42.
    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.

  • 43.
    Chan, Nathan
    et al.
    NIHR Leicester Biomed Res Ctr, England; NIHR Leicester Biomed Res Ctr, England.
    Premawardhana, Diluka
    NIHR Leicester Biomed Res Ctr, England; NIHR Leicester Biomed Res Ctr, England.
    Al-Hussaini, Abtehale
    NIHR Leicester Biomed Res Ctr, England; NIHR Leicester Biomed Res Ctr, England.
    Wood, Alice
    NIHR Leicester Biomed Res Ctr, England; NIHR Leicester Biomed Res Ctr, England.
    Bountziouka, Vasiliki
    NIHR Leicester Biomed Res Ctr, England; NIHR Leicester Biomed Res Ctr, England.
    Kotecha, Deevia
    NIHR Leicester Biomed Res Ctr, England; NIHR Leicester Biomed Res Ctr, England.
    Swahn, Eva
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Cardiology in Linköping.
    Palmefors, Henning
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Cardiology in Linköping.
    Pagonis, Christos
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Cardiology in Linköping.
    Sederholm Lawesson, Sofia
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Cardiology in Linköping.
    Kadziela, Jacek
    Natl Inst Cardiol, Poland.
    Garcia-Guimaraes, Marcos
    Hosp Univ La Princesa, Spain; Hosp Mar, Spain.
    Alfonso, Fernando
    Hosp Univ La Princesa, Spain.
    Escaned, Javier
    Univ Complutense, Spain.
    Macaya, Fernando
    Univ Complutense, Spain.
    Santas, Melisa
    Hosp Univ Lucus Augusti, Spain.
    Cerrato, Enrico
    San Luigi Gonzaga Univ Hosp, Italy; Rivoli Infermi Hosp, Italy.
    Maas, Angela H. E. M.
    Radboud Univ Nijmegen Med Ctr, Netherlands.
    Hlinomaz, Ota
    St Annes Univ Hosp, Czech Republic; Masaryk Univ, Czech Republic.
    Bogale, Nigussie
    Haukeland Hosp, Norway.
    Cortese, Bernardo
    Clin Polispecialist San Carlo, Italy; Fdn Ric & Innovaz Cardiovasc, Italy.
    Cheng, Mavis
    NIHR Leicester Biomed Res Ctr, England; St George Hosp, England.
    Bolger, Aidan
    NIHR Leicester Biomed Res Ctr, England; NIHR Leicester Biomed Res Ctr, England.
    Hussain, Shazia T.
    NIHR Leicester Biomed Res Ctr, England; NIHR Leicester Biomed Res Ctr, England.
    Samani, Nilesh J.
    NIHR Leicester Biomed Res Ctr, England; NIHR Leicester Biomed Res Ctr, England.
    Knight, Marian
    Univ Oxford, England.
    Cauldwell, Matthew
    NIHR Leicester Biomed Res Ctr, England; NIHR Leicester Biomed Res Ctr, England; St George Hosp, England.
    Adlam, David
    NIHR Leicester Biomed Res Ctr, England; NIHR Leicester Biomed Res Ctr, England.
    Pregnancy and Spontaneous Coronary Artery Dissection: Lessons From Survivors and Nonsurvivors2022In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 146, no 1, p. 69-72Article in journal (Other academic)
    Abstract [en]

    n/a

    Download full text (pdf)
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  • 44. 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)
  • 45. 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. 

  • 46.
    Connolly-Andersen, Anne-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Hammargren, Edvin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Whitaker, Heather
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Holmgren, Lars
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Klingstrom, Jonas
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Increased Risk of Acute Myocardial Infarction and Stroke During Hemorrhagic Fever With Renal Syndrome A Self-Controlled Case Series Study2014In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 129, no 12, p. 1295-1302Article in journal (Refereed)
    Abstract [en]

    Background We recently observed that cardiovascular causes of death are common in patients with hemorrhagic fever with renal syndrome (HFRS), which is caused by hantaviruses. However, it is not known whether HFRS is a risk factor for the acute cardiovascular events of acute myocardial infarction (AMI) and stroke. Methods and Results Personal identification numbers from the Swedish HFRS patient database (1997-2012; n=6643) were cross-linked with the National Patient Register from 1987 to 2011. Using the self-controlled case series method, we calculated the incidence rate ratio of AMI/stroke in the 21 days after HFRS against 2 different control periods either excluding (analysis 1) or including (analysis 2) fatal AMI/stroke events. The incidence rate ratios for analyses 1 and 2 for all AMI events were 5.53 (95% confidence interval [CI], 2.6-11.8) and 6.02 (95% CI, 2.95-12.3) and for first AMI events were 3.53 (95% CI, 1.25-9.96) and 4.64 (95% CI, 1.83-11.77). The incidence rate ratios for analyses 1 and 2 for all stroke events were 12.93 (95% CI, 5.62-29.74) and 15.16 (95% CI, 7.21-31.87) and for first stroke events were 14.54 (95% CI, 5.87-36.04) and 17.09 (95% CI, 7.49-38.96). The majority of stroke events occurred in the first week after HFRS. Seasonal effects were not observed, and apart from 1 study, neither sex nor age interacted with the associations observed in this study. Conclusions There is a significantly increased risk for AMI and stroke in the immediate time period after HFRS. Therefore, HFRS patients should be carefully monitored during the acute phase of disease to ensure early recognition of symptoms of impending AMI or stroke.

  • 47.
    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.

  • 48. 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.

  • 49. 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)
  • 50.
    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.

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