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  • 1. Braunschweig, Frieder
    et al.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    von Bibra, Helene
    Olsson, Arne
    Rydén, Lars
    Långström, Bengt
    Linde, Cecilia
    Effects of biventricular pacing on myocardial blood flow and oxygen consumption using carbon-11 acetate positron emission tomography in patients with heart failure2003In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 92, no 1, p. 95-99Article in journal (Refereed)
  • 2. Cornel, Jan H.
    et al.
    Tricoci, Pierluigi
    Lokhnygina, Yuliya
    Moliterno, David J.
    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.
    Armstrong, Paul W.
    Aylward, Philip E.
    Clare, Robert M.
    Chen, Edmond
    Leonardi, Sergio
    de Werf, Frans Van
    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.
    Strony, John
    Mahaffey, Kenneth W.
    Harrington, Robert A.
    Glycoprotein IIb/IIIa Receptor Inhibitors in Combination With Vorapaxar, a Platelet Thrombin Receptor Antagonist, Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes (from the TRACER Trial)2015In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 115, no 10, p. 1325-1332Article in journal (Refereed)
    Abstract [en]

    We evaluated the interaction between protease-activated receptor-1 antagonist vorapaxar and concomitant glycoprotein (GP) IIb/IIIa receptor inhibitors in patients with non-ST-segment elevation acute coronary syndromes who underwent PCI. In Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome trial, 12,944 patients with non-ST-segment elevation acute coronary syndromes were randomized to vorapaxar or placebo. Administration of GP IIb/IIIa receptor inhibitors was allowed at the treating physician's discretion. We investigated whether use of GP IIb/IIIa receptor inhibitors modified vorapaxar's effect on non-coronary artery bypass grafting (CABG)-related bleeding at 7 days and ischemic events at 30 days. In total, 7,455 patients underwent PCI during index hospitalization. Of these, 2,023 patients (27.1%) received inhibitors and 5,432 (72.9%) did not. Vorapaxar was associated with a numerically higher rate of non-CABG-related moderate/severe Global Use of Strategies to Open Occluded Arteries (GUSTO) bleeding at 7 days compared with placebo in those who did (1.3% vs 1.0%) and did not (0.6% vs 0.4%) receive GP IIb/IIIa receptor inhibitors. Ischemic end point rates at 30 days were not significantly lower with vorapaxar versus placebo. Increased rates of non-CABG GUSTO moderate/severe bleeding were observed in patients who received GP IIb/IIIa receptor inhibitors versus those who did not (adjusted hazard ratio [HR] 1.77, 95% confidence interval [CI] 0.43 to 7.35 in placebo arm; adjusted HR 2.02, 95% CI 0.62 to 6.61 in vorapaxar arm) and in those who received vorapaxar versus placebo (adjusted HR 1.54, 95% CI 0.36 to 6.56 in the GP IIn/IIIa group; adjusted FIR 1.34, 95% CI 0.44 to 4.07 in the no-GP IIb/IIIa group). No interaction was found between vorapaxar and inhibitor use up to 7 days (P interaction = 0.89) nor at the end of the treatment (P interaction = 0.74); however, the event rate was low. Also, no interaction was observed for efficacy end points after PCI at 30 days or at the end of the treatment. In conclusion, GP IIb/IIIa receptor inhibitor use plus dual antiplatelet therapy in a population with non-ST-segment elevation myocardial infarction planned for PCI was frequent but did not interact with vorapaxar's efficacy or safety. Nonetheless, GP IIb/IIIa receptor inhibitors and vorapaxar were associated with increased bleeding risk, and their combined use may result in additive effects on bleeding rates.

  • 3.
    Damman, Peter
    et al.
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Holmvang, Lene
    Copenhagen Univ Hosp, Ctr Heart, Copenhagen, Denmark.
    Tijssen, Jan G P
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Clayton, Tim C
    London Sch Hyg & Trop Med, London WC1, England.
    Pocock, Stuart J
    London Sch Hyg & Trop Med, London WC1, England.
    Windhausen, Fons
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Hirsch, Alexander
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Fox, Keith A A
    Royal Infirm, Dept Med & Radiol Sci, Edinburgh, Midlothian, Scotland.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    de Winter, Robbert J
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Usefulness of the Admission Electrocardiogram to Predict Long-Term Outcomes After Non-ST-Elevation Acute Coronary Syndrome (from the FRISC II, ICTUS, and RITA-3 [FIR] Trials)2012In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 109, no 1, p. 6-12Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate the independent prognostic value of qualitative and quantitative admission electrocardiographic (ECG) analysis regarding long-term outcomes after non-ST-segment elevation acute coronary syndromes (NSTE-ACS). From the Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC II), Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS), and Randomized Intervention Trial of Unstable Angina 3 (RITA-3) patient-pooled database, 5,420 patients with NSTE-ACS with qualitative ECG data, of whom 2,901 had quantitative data, were included in this analysis. The main outcome was 5-year cardiovascular death or myocardial infarction. Hazard ratios (HRs) were calculated with Cox regression models, and adjustments were made for established outcome predictors. The additional discriminative value was assessed with the category-less net reclassification improvement and integrated discrimination improvement indexes. In the 5,420 patients, the presence of ST-segment depression (≥1 mm; adjusted HR 1.43, 95% confidence interval [CI] 1.25 to 1.63) and left bundle branch block (adjusted HR 1.64, 95% CI 1.18 to 2.28) were independently associated with long-term cardiovascular death or myocardial infarction. Risk increases were short and long term. On quantitative ECG analysis, cumulative ST-segment depression (≥5 mm; adjusted HR 1.34, 95% CI 1.05 to 1.70), the presence of left bundle branch block (adjusted HR 2.15, 95% CI 1.36 to 3.40) or ≥6 leads with inverse T waves (adjusted HR 1.22, 95% CI 0.97 to 1.55) was independently associated with long-term outcomes. No interaction was observed with treatment strategy. No improvements in net reclassification improvement and integrated discrimination improvement were observed after the addition of quantitative characteristics to a model including qualitative characteristics. In conclusion, in the FRISC II, ICTUS, and RITA-3 NSTE-ACS patient-pooled data set, admission ECG characteristics provided long-term prognostic value for cardiovascular death or myocardial infarction. Quantitative ECG characteristics provided no incremental discrimination compared to qualitative data.

  • 4.
    Damman, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Koul, Sasha
    Eriksson, Peter
    Erlinge, David
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Treatment Patterns and Outcomes in Patients Undergoing Percutaneous Coronary Intervention Treated With Prasugrel or Clopidogrel (from the Swedish Coronary Angiography and Angioplasty Registry [SCAAR])2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 113, no 1, p. 64-69Article in journal (Refereed)
    Abstract [en]

    Large real-world registry data are important for understanding the current use and outcomes of novel therapies. The aim of this study was to assess treatment patterns and outcomes in patients who underwent percutaneous coronary intervention (PCI) with prasugrel or clopidogrel. Consecutive patient data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for 2010 and 2011 were used. The study population consisted of all patients with acute coronary syndromes (ACS) and those without ACS who underwent PCI and were treated with prasugrel (with or without a clopidogrel loading dose) or solely with clopidogrel. Outcomes included were 30-day mortality and in-hospital bleeding. In 2010 and 2011, 23,994 patients were treated with clopidogrel during hospitalization for their first PCI during the study period, while 2,142 patients were treated with prasugrel. Prasugrel was mainly used in patients with ST-segment elevation myocardial infarction. Hemorrhagic risk factors such as older age, female gender, and previous stroke were more common in the clopidogrel-treated patients. However, Mehran bleeding risk scores were higher in prasugrel-treated patients. In the ACS group, lower mortality was observed in the prasugrel group compared with the clopidogrel group. Mortality was comparable in patients who underwent elective angiography and PCI. In-hospital bleeding was lower in prasugrel-treated patients. In conclusion, in this real world population of patients who underwent urgent or elective PCI, prasugrel was used mainly in patients with ACS, while it was avoided in patients with characteristics indicating increased bleeding risk. Mortality and bleeding rates were lower with prasugrel than clopidogrel, probably because of patient selection.

  • 5.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Will the universal definition of myocardial infarction criteria result in an overdiagnosis of myocardial infarction?2009In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 103, no 5, p. 588-591Article in journal (Refereed)
    Abstract [en]

    The Universal Definition of Myocardial Infarction (acute myocardial infarction [AMI]) requires detection of increasing or decreasing cardiac biomarkers (preferably cardiac troponin) with >or=1 value >99(th) percentile, together with either clinical symptoms, new ischemic electrocardiographic changes, or typical imaging findings indicative of myocardial necrosis as diagnostic criteria for AMI. However, a small cardiac troponin elevation together with ST-T segment abnormalities may also occur in clinically stable populations. Accordingly, 0.6% of elderly subjects from a community sample (PIVUS Study) and 6.7% of patients stabilized after an acute coronary syndrome (FRISC II Study) would have been labeled AMI following the Universal Definition of AMI when diagnostic classification had been based on a single cardiac troponin I result. In conclusion, our results emphasized the importance of a significant change in cardiac troponin to avoid misdiagnosis of AMI.

  • 6.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    B-type natriuretic peptides and their relation to cardiovascular structure and function in a population-based sample of subjects aged 70 years2009In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 103, no 7, p. 1032-1038Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate whether B-type natriuretic peptides (BNPs) could serve as screening markers for the detection of preclinical vascular disease in the community. BNP and N-terminal-pro-BNP were analyzed in 1,000 subjects aged 70 years participating in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study and were related to different measures of endothelial function and activation, arterial compliance, carotid atherosclerosis, and echocardiographic findings. The median levels were 42.0 ng/L for BNP and 110.7 ng/L for N-terminal-pro-BNP. On adjusted multivariate analysis, the 2 BNPs were related to increased left ventricular mass and impaired left ventricular systolic and diastolic function but not to any of the other assessed entities reflecting preclinical vascular disease. In conclusion, BNPs are strong markers of increased left ventricular mass and impaired cardiac performance but cannot be regarded as useful screening markers for the detection of preclinical states of vascular disease in elderly subjects.

  • 7.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Prognostic Usefulness of the Change in N-terminal pro B-type Natriuretic Peptide Levels to Predict Mortality in a Single Community Cohort Aged ≥70 Years2013In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 111, no 1, p. 131-136Article in journal (Refereed)
    Abstract [en]

    The levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) are closely related to cardiac abnormalities and adverse outcomes in the general population. However, little is known about the course of NT-proBNP levels over time, the underlying conditions, and the prognostic effect of changes. To investigate these issues, we measured the NT-proBNP levels (Elecsys 2010, Roche Diagnostics) in community-dwellers participating in the Prospective Investigation of the Vasculature in Uppsala Seniors study at 70 (n = 1,005) and 75 (n = 817) years of age. The total follow-up was 8.0 years. In subjects with available results from both examinations, the median NT-proBNP levels increased from 106 pg/ml (25th to 75th percentile 62 to 174) to 125 pg/ml (25th to 75th percentile 73-234; p <0.001). The change in NT-proBNP levels was positively and independently related to male gender, baseline information on ischemic electrocardiographic changes, renal dysfunction, impaired left ventricular ejection fraction, and intercurrent cardiovascular events (e.g., myocardial infarction, stroke, or coronary revascularization). The change in NT-proBNP levels independently predicted mortality after the measurements at 75 years of age (all-cause mortality, adjusted hazard ratio 2.4, 95% confidence interval 1.6 to 3.6; cardiovascular mortality, adjusted hazard ratio 2.3, 95% confidence interval 1.2 to 4.5). Compared to those without significant NT-proBNP changes (n = 606), subjects with increasing levels (n = 162) had markedly increased all-cause mortality (adjusted hazard ratio 4.3, 95% confidence interval 2.1 to 8.8). No subject with decreasing NT-proBNP levels (n = 49) died. In conclusion, repeat measurements of NT-proBNP might add useful information to the routine clinical assessment in subjects aged ≥70 years, because changes in their levels were associated with cardiovascular risk indicators and strongly predictive of mortality.

  • 8. Ezekowitz, Michael D.
    et al.
    Reilly, Paul A.
    Nehmiz, Gerhard
    Simmers, Timothy A.
    Nagarakanti, Rangadham
    Parcham-Azad, Kambiz
    Pedersen, K. Erik
    Lionetti, Dominick A.
    Stangier, Joachim
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study)2007In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 100, no 9, p. 1419-1426Article in journal (Refereed)
    Abstract [en]

    This is the first evaluation of dabigatran, an oral direct thrombin inhibitor, in patients with atrial fibrillation (AF). Patients (n = 502) were randomized to receive blinded doses of 50-, 150-, or 300-mg dabigatran twice daily alone or combined with 81- or 325-mg aspirin or open-label warfarin administered to achieve an international normalized ratio of 2 to 3 for 12 weeks. Dabigatran plasma concentrations, activated partial thromboplastin time, D-dimer, urinary 11-dehydrothromboxane B(2) (DTB2), and liver function were measured at baseline and at 1, 2, 4, 8, and 12 weeks. Clinical end points were assessed according to the treatment received at the time of the event. Overall, 92% of patients completed the study. Major hemorrhages were limited to the group treated with 300-mg dabigatran plus aspirin (4 of 64), and the incidence was significant versus 300-mg dabigatran alone (0 of 105, p <0.02). Total bleeding events were more frequent in the 300-mg (39 of 169, 23%) and 150-mg (30 of 169, 18%) dabigatran groups compared with the 50-mg groups (7 of 107, 7%; p = 0.0002 and p = 0.01, respectively). Thromboembolic events were limited to the 50-mg dabigatran dose groups (2 of 107, 2%). The mean trough d-dimer measurements were suppressed for the 2 highest doses of dabigatran and warfarin (international normalized ratio of 2 to 3). Aminotransferase levels >3 times the upper limit of normal were observed in 0.9% of the dabigatran recipients and in none of the warfarin recipients. Two dabigatran recipients had aminotransferase levels >5 times the upper limit of normal as a result of gallstones, which resolved. Trough activated partial thromboplastin time values were 1.2, 1.5, and 1.8 times the baseline level for the 50-, 150-, and 300-mg dabigatran groups, respectively. DTB2 concentrations after 12 weeks of 50-, 150-, and 300-mg dabigatran treatment were increased by 31%, 17%, and 23%, respectively, versus baseline (p = 0.02, p = 0.03, and p = 0.0004). In conclusion, major bleeding events were limited to patients treated with dabigatran 300 mg plus aspirin and thromboembolic episodes were limited to the 50-mg dabigatran groups. The 2 highest doses of dabigatran suppress D-dimer concentrations. Serious liver toxicity was not seen. The significance of the increase of DTB2 concentrations in dabigatran-treated patients needs resolution.

  • 9.
    Gaglia, Michael A., Jr.
    et al.
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Lipinski, Michael J.
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Lhermusier, Thibault
    Ctr Hosp Univ Toulouse, Div Cardiol, Toulouse, France..
    Steinvil, Arie
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Kiramijyan, Sarkis
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Pokharel, Shreejana
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Torguson, Rebecca
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Angiolillo, Dominick J.
    Univ Florida, Coll Med Jacksonville, Div Cardiol, Jacksonville, FL USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Storey, Robert F.
    Univ Sheffield, Div Cardiol, Sheffield, S Yorkshire, England..
    Waksman, Ron
    Medstar Heart & Vasc Inst, Div Cardiol, Washington, DC 20007 USA..
    Comparison of Platelet Reactivity in Black Versus White Patients With Acute Coronary Syndromes After Treatment With Ticagrelor2017In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 119, no 8, p. 1135-1140Article in journal (Refereed)
    Abstract [en]

    Ticagrelor, a potent platelet inhibitor, has primarily been studied in white patients. Platelet reactivity among black patients with acute coronary syndrome (ACS) on ticagrelor, however, is unknown. Our objective was to compare platelet reactivity in black versus white patients with ACS treated with ticagrelor. We conducted a prospective, pharmacodynamic study of 29 black patients with ACS treated with ticagrelor. Platelet reactivity was assessed at 1, 4, and 8 hours after a loading dose of ticagrelor 180 mg and at 30 days on a maintenance dose of ticagrelor 90 mg twice daily. Assays included light transmission aggregometry, VerifyNow P2Y12, and vasodilator-stimulated phosphoprotein. We provided comparison with a historical white cohort. Platelet reactivity among blacks with ACS on ticagrelor was similar to that in whites, except that blacks had lower values at 4 hours, 8 hours, and on maintenance therapy for light transmission aggregometry with 20 mu mol/L adenosine diphosphate. Among blacks, high-on-treatment platelet reactivity for all 3 assays was uncommon at 1 hour and nonexistent at 4 hours, 8 hours, and while on maintenance therapy. Blacks preloaded with clopidogrel (n = 17) had significantly lower results of VerifyNow (64 +/- 65 vs 198 +/- 86, p<0.001) and vasodilator-stimulated phosphoprotein (12.8 +/- 21.6 vs 58.9 +/- 19.9, p<0.001) at 1 hour compared with those with no clopidogrel prelOad. In conclusion, among patients with ACS receiving ticagrelor, levels of platelet reactivity in blacks are similar to that in whites. This suggests that the cardiovascular benefits of ticagrelor observed in the platelet inhibition and patient outcomes (PLATO) trial are likely to be observed in blacks and whites.

  • 10.
    Hambraeus, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Tydén, Patrik
    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.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Target-Attainment Rates of Low-Density Lipoprotein Cholesterol Using Lipid-Lowering Drugs One Year After Acute Myocardial Infarction in Sweden2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 113, no 1, p. 17-22Article in journal (Refereed)
    Abstract [en]

    The objective of this prospective cohort study was to describe real-life use of lipid-lowering drugs and low-density lipoprotein cholesterol (LDL-C) target-attainment rates 1 year after acute myocardial infarction (AMI). LDL-C was recorded at hospital admission for AMI and at follow-up at 2 and 12 months after AMI in 17,236 patients in the Swedish heart registry, SWEDEHEART, from 2004 through 2009. Lipid-lowering treatments were identified using the Swedish Prescribed Drug Register. More than 90% of patients received statins after ANT. Simvastatin <= 40 mg was used by 80% of patients at discharge and at 2 months and 68% at 1 year after AMI. Intensive statin therapy (LDL-C-lowering capacity >40%) was prescribed for 8.4%, 11.9%, and 12.2% at these time points, and combinations of statin/ezetimibe for 1.1%, 2.8%, and 5.0%, respectively. The LDL-C target of <2.5 mmol/L (97 mg/dl) was achieved in 74.5% of patients at 2 months and 72.3% at 12 months after AMI. Treatment was intensified for only 21.3% of patients with LDL-C above target at 2 months. In multivariate analysis, higher LDL-C levels at admission and at 2 months correlated to increased risk for under treatment at 12 months after AMI. In conclusion, statin treatment after AMI in Sweden has become standard, but titration to reach recommended LDL-C levels is still suboptimal. Strategies to further improve implementation of guidelines are needed.

  • 11. Henriksen, Egil
    et al.
    Landelius, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wesslén, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kangro, Toomas
    Jonason, Tommy
    Nyström-Rosander, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Niklasson, Urban
    Arnell, Henrik
    Rolf, Christer
    Hammarström, Eskil
    Lidell, Christer
    Ringqvist, Ivar
    Friman, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    An echocardiographic study comparing male Swedish elite orienteers with other elite endurance athletes1997In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 79, no 4, p. 521-524Article in journal (Refereed)
    Abstract [en]

    Between 1979 and 1992, there were 16 known cases of sudden unexpected cardiac death among young Swedish orienteers, whose autopsies showed myocarditis to be a common finding. Therefore, 96 elite orienteers and 47 controls underwent echocardiography, showing left ventricular wall motion abnormalities in 9% of the orienteers compared with 4% in the controls.

  • 12.
    James, Stefan K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Timmer, Jorik R.
    Ottervanger, Jan Paul
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Armstrong, Paul
    Califf, Robert
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Simoons, Maarten L.
    Usefulness of biomarkers for predicting long-term mortality in patients with diabetes mellitus and non-ST-elevation acute coronary syndromes (A GUSTO IV substudy)2006In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 97, no 2, p. 167-172Article in journal (Refereed)
    Abstract [en]

    The present study evaluated whether biomarkers of ischemia, inflammation, myocardial damage, and dysfunction are equally useful in patients who have diabetes mellitus (DM) for prediction of cardiac events in non-ST-elevation acute coronary syndrome (ACS). DM was present in 1,677 of 7,800 patients (21.5%) who had non-ST-elevation ACS and were included in the Fourth Global Utilization of Strategies To Open Occluded Arteries (GUSTO IV) trial. Creatinine, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin T, C-reactive protein, and interleukin-6 were analyzed in serum samples that were obtained at a median of 9.5 hours from symptom onset. One-year mortality rates were 13.5% among patients who had DM (n = 227) and 6.9% among those who did not (n = 418, p < 0.001). The median level of NT-pro-BNP was 2 times as high in patients who had DM, whereas troponin T levels did not differ by DM status. Mortality increased with ascending quartiles of NT-pro-BNP, with 1-year mortality rates of 3.9% (n = 11) in the bottom quartile and 29% (n = 103) in the top quartile. In multivariable analyses, factors that were predictive of 1-year mortality in patients who did not have DM were also significant for those who did. Presence of ST depression > 0.5 mm had the highest odds ratio of 2.3 (95% confidence interval 1.2 to 4.6). NT-pro-BNP levels > 669 ng/L (odds ratio 2.0, 95% confidence interval 1.1 to 3.6) and interleukin-6 levels > 10 ng/L (odds ratio 1.9, 95% confidence interval 1.2 to 3.0) were significant biomarker predictors. In conclusion, DM confers a high long-term mortality in non-ST-elevation ACS. Despite a larger proportion of ST depression and increased levels of NT-pro-BNP and interleukin-6 at admission, these factors provide independent prognostic information that may improve risk stratification and guidance of treatment.

  • 13.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, Tomas
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Improved identification of patients with coronary artery disease by the use of new lipid and lipoprotein biomarkers2006In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 97, no 5, p. 640-5Article in journal (Refereed)
    Abstract [en]

    Increasing attention is being directed toward new lipid and lipoprotein biomarkers as risk factors for coronary artery disease, although limited information is available on the diagnostic accuracy of these new biomarkers for the identification of patients with coronary artery disease. In the present study, levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, lipoprotein-associated phospholipase A2 (Lp-PLA2), and oxidized LDL/HDL cholesterol were determined in 431 apparently healthy men and women without clinical evidence of coronary artery disease who were matched for age and gender with 490 men and women with coronary artery disease who participated in the Second Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC-II) trial. Diagnostic accuracy was determined by receiver-operating characteristic curve analysis by measuring the area under the curve. The diagnostic accuracies of each lipid or lipoprotein biomarker (in descending order of area under the curve) were 0.867 for oxidized LDL/HDL cholesterol (95% confidence interval [CI] 0.844 to 0.890), 0.826 for oxidized LDL (95% CI 0.800 to 0.852), 0.775 for 1/HDL cholesterol (95% CI 0.745 to 0.805), 0.764 for total/HDL cholesterol (95% CI 0.733 to 0.795), 0.631 for triglycerides (95% CI 0.594 to 0.667), 0.597 for Lp-PLA2 (95% CI 0.558 to 0.615), 0.577 for LDL cholesterol (95% CI 0.539 to 0.615), and 0.520 for total cholesterol (95% CI 0.482 to 0.537). In conclusion, these findings indicate that the ratio of oxidized LDL to HDL cholesterol was a more potent biomarker for discriminating between subjects with and without coronary artery disease than traditionally measured lipids and lipoproteins and Lp-PLA2.

  • 14.
    Johnston, Nina
    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.
    Jönelid, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Schenck-Gustafsson, Karin
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Effect of Gender on Patients With ST-Elevation and Non-ST-Elevation Myocardial Infarction Without Obstructive Coronary Artery Disease2015In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 115, no 12, p. 1661-1666Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare the prognoses of patients with ST-segment elevation myocardial infarction (STEMI) and those with non-ST-segment elevation myocardial infarction (NSTEMI) without obstructive coronary artery disease (CAD) and the risk associated with gender for future cardiovascular events. The study population was selected from 95,849 patients who underwent coronary angiography for myocardial infarction from 2005 to 2010 and registered in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Outcome analyses, including all-cause death, myocardial infarction, congestive heart failure, stroke, and revascularization, were performed in 2,268 patients with STEMI and 10,904 with NSTEMI without obstructive CAD (<50% stenosis). Hazard ratios and 95% confidence intervals comparing women with men were calculated for events, adjusting for cardiovascular risk factors and age. Nonobstructive CAD was found in 7% of patients with STEMI (6% men, 10% women) and in 17% of those with NSTEMI (11% men, 28% women). During a median follow-up of 2.6 years, 8% of patients with STEMI and 5% of those with NSTEMI died. Gender-associated differences in risk were observed in patients with NSTEMI, with adjusted hazard ratios lower in women than men for mortality (hazard ratio 0.90, 95% confidence interval 0.50 to 0.73) and congestive heart failure (hazard ratio 0.61, 95% confidence interval 0.52 to 0.72). In the 2 groups, women underwent less revascularization. In conclusion, nonobstructive CAD was more common in patients with NSTEMI than those with STEMI, as well as in women compared with men. Long-term mortality in patients with nonobstructive CAD was higher after STEMI than NSTEMI. The gender differences in outcomes suggest gender differences in the underlying pathogenesis of myocardial infarction without obstructive CAD.

  • 15.
    Koltowski, Lukasz
    et al.
    1st Department of Cardiology, Medical University of Warsaw, Warsaw, Poland.
    Koltowska-Häggström, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Filipiak, Krzysztof Jerzy
    1st Department of Cardiology, Medical University of Warsaw, Poland.
    Kochman, Janusz
    1st Department of Cardiology, Medical University of Warsaw, Poland.
    Golicki, Dominik
    Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Poland.
    Pietrasik, Arkadiusz
    1st Department of Cardiology, Medical University of Warsaw, Poland.
    Huczek, Zenon
    1st Department of Cardiology, Medical University of Warsaw, Poland.
    Balsam, Pawel
    1st Department of Cardiology, Medical University of Warsaw, Poland.
    Scibisz, Anna
    1st Department of Cardiology, Medical University of Warsaw, Poland.
    Opolski, Grzegorz
    1st Department of Cardiology, Medical University of Warsaw, Poland.
    Quality of Life in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention-Radial Versus Femoral Access (from the OCEAN RACE Trial)2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 114, no 4, p. 516-521Article in journal (Refereed)
    Abstract [en]

    Numerous studies have compared transradial (TR) versus transfemoral (TF) access for percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction. These studies have focused on clinical efficacy and safety; yet little is known about the effect of the vessel access on the health-related quality of life (HRQoL). In the present study, patients were randomly assigned to TR (n = 52) or TF (n = 51) access groups. Generic (EQ-5D-3L) and cardiac-specific (Quality of Life Index and MacNew) tools were used to assess HRQoL before PCI and 2 hours and 4 days after PCI. Baseline HRQoL was comparable in both groups and improved after PCI. The mean +/- SD EQ-5D-3L health utility score 2 hours after PCI was 0.46 +/- 0.291 and was higher in the TR group (TR: 0.60 +/- 0.299 versus TF: 0.32 +/- 0.283, p <0.001). Patients in the TR group reported fewer problems with mobility (TR: 71.7% vs TF: 94.4%, p <0.01) and self-care (TR: 62.5% vs TF: 97.2%, p <0.001). At day 4, fewer patients reported problems with anxiety and/or depression in the TR group than in the TF group (TR: 42.9% vs TF: 75.0%, p <0.001); no differences between groups in other measures were observed (Quality of Life Index and MacNew). The N-terminal of the prohormone brain natriuretic peptide levels were inversely correlated with EQ-5D-3L visual analog scale (r = -0.348, p <0.05) and EQ-5D-3L health utility score (r = -0.322, p <0.05). There was a correlation between in-hospital mortality and 2 MacNew domains: physical (r = -0.329, p <0.05) and emotional (r = -0.374, p <0.01). In conclusion, radial access should be the preferred approach in patients with ST-segment elevation myocardial infarction undergoing PCI when considering HRQoL. Radial access is associated with fewer problems with mobility and self-care and better psychological outcome after PCI.

  • 16.
    Kunadian, Vijay
    et al.
    Newcastle Univ, Inst Cellular Med, Fac Med Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.;Newcastle Tyne Hosp Natl Hlth Serv Fdn TrUst, Freeman Hosp, Ctr Cardiothorac, Newcastle Upon Tyne, Tyne & Wear, England..
    Qiu, Weiliang
    Harvard Med Sch, Brigham & Womens Hosp, Dept Medicine, Channing Div Network Med, Boston, MA USA..
    Lagerqvist, Bo
    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.
    Johnston, Nina
    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.
    Sinclair, Hannah
    Newcastle Univ, Inst Cellular Med, Fac Med Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.;Newcastle Tyne Hosp Natl Hlth Serv Fdn TrUst, Freeman Hosp, Ctr Cardiothorac, Newcastle Upon Tyne, Tyne & Wear, England..
    Tan, Ying
    Newcastle Univ, Inst Cellular Med, Fac Med Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.;Newcastle Tyne Hosp Natl Hlth Serv Fdn TrUst, Freeman Hosp, Ctr Cardiothorac, Newcastle Upon Tyne, Tyne & Wear, England..
    Ludman, Peter
    Queen Elizabeth Hosp, Birmingham, W Midlands, England..
    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.
    Sarno, Giovanna
    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.
    Gender Differences in Outcomes and Predictors of All-Cause Mortality After Percutaneous Coronary Intervention (Data from United Kingdom and Sweden)2017In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 119, no 2, p. 210-216Article in journal (Refereed)
    Abstract [en]

    To determine gender differences and predictors of all-cause mortality (30 days and 1 year) after percutaneous coronary intervention (PCI) in patients with stable angina pectoris and acute coronary syndrome (non ST-elevation myocardial infarction/unstable angina pectoris and ST-elevation myocardial infarction) in the British Cardiovascular Intervention Society (BCIS) and Swedish Coronary Angiography and Angioplasty Registry (SCAAR) data sets, an analysis of prospectively collected data from 2007 to 2011 was performed. In total, 458,261 patients (BCIS: n = 368,492 [25.9% women]; Sweden: n = 89,769 [27.2% women]) who underwent PCI were included in this analysis. Using multiple regression analysis, in the BCIS registry, female gender was an independent predictor of all-cause mortality at 30 days (odds ratio [OR] 1.15, 95% CI 1.10 to 1.22, p <0.0001) and at 1 year (OR 1.08, 95% CI 1.04 to 1.12, p <0.0001) after PCI for all patients. Likewise, in the SCAAR registry, female gender was an independent predictor of all-cause mortality at 30 days (OR 1.15, 95% CI 1.05 to 1.26, p = 0.002) and 1 year (OR 1.09, 95% CI 1.03 to 1.17, p = 0.006) after PCI for all patients. In both data sets, there was no statistically significant interaction between age and gender for all-cause mortality at 30 days (BCIS, p = 0.59; SCAAR, p = 0.40) and at 1 year (BCIS, p = 0.11; SCAAR, p = 0.83). In conclusion, despite advances in care, women compared with men continue to experience higher all cause mortality after PCI for coronary artery disease. The patient's age at the time of PCI remains a strong predictive factor of mortality in this population. Strategies and further research are warranted to better address the management of coronary artery disease in women with possibly earlier diagnosis and more tailored treatments.

  • 17. Lipinski, Michael J.
    et al.
    Escarcega, Ricardo O.
    D'Ascenzo, Fabrizio
    Magalhaes, Marco A.
    Baker, Nevin C.
    Torguson, Rebecca
    Chen, Fang
    Epstein, Stephen E.
    Miro, Oscar
    Llorens, Pere
    Giannitsis, Evangelos
    Lotze, Ulrich
    Lefebvre, Sophie
    Sebbane, Mustapha
    Cristol, Jean-Paul
    Chenevier-Gobeaux, Camille
    Meune, Christophe
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Charpentier, Sandrine
    Twerenbold, Raphael
    Mueller, Christian
    Biondi-Zoccai, Giuseppe
    Waksman, Ron
    A Systematic Review and Collaborative Meta-Analysis to Determine the Incremental Value of Copeptin for Rapid Rule-Out of Acute Myocardial Infarction2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 113, no 9, p. 1581-1591Article in journal (Refereed)
    Abstract [en]

    Multiple studies have evaluated copeptin, a surrogate for arginine vasopressin, in the diagnosis of acute myocardial infarction (AMI) with mixed results. A systematic review and collaborative meta-analysis were performed for diagnosis of AMI and assessment of prognosis in patients presenting to the emergency department with chest pain. MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing copeptin in such patients. Study investigators were contacted, and many provided previously unpublished data. Random-effects methods were used to compare the data for copeptin, troponin, and their combination. There were a total of 9,244 patients from the 14 included studies. Mean age was 62 years; 64% were men; and 18.4% were ultimately diagnosed with AMI. Patients with AMI had a higher presentation copeptin level than those without AMI (22.8 vs 8.3 pmol/L, respectively, p <0.001). Although troponin had better diagnostic accuracy than copeptin for AMI, the combination of copeptin and troponin significantly improved the sensitivity (0.905 [0.888 to 0.921] vs 0.686 [0.661 to 0.710], respectively, p <0.001) and negative predictive value (0.97 [0.964 to 0.975] vs 0.93 [0.924 to 0.936], respectively, p <0.001) compared with troponin alone. Elevation in copeptin carried a similar risk of all-cause mortality to an elevation in troponin (odds ratio 5.84 vs 6.74, respectively, p = 0.67). In conclusion, copeptin not only identifies patients at risk of all-cause mortality, but its addition to troponin improved the sensitivity and negative likelihood ratio for diagnosis of AMI compared with troponin alone. Thus, copeptin may help identify patients who may be safely discharged early from the emergency department.

  • 18. Mahaffey, Kenneth W.
    et al.
    Huang, Zhen
    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.
    Storey, Robert F.
    Jennings, Lisa K.
    Tricoci, Pierluigi
    White, Harvey D.
    Armstrong, Paul W.
    Aylward, Philip E.
    Molitemo, David J.
    Van de Werf, Frans
    Chen, Edmond
    Leonardi, Sergio
    Rorick, Tyrus
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Strony, John
    Harrington, Robert A.
    Association of Aspirin Dose and Vorapaxar Safety and Efficacy in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome (from the TRACER Trial)2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 113, no 6, p. 936-944Article in journal (Refereed)
    Abstract [en]

    Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial compared vorapaxar and placebo in 12,944 high-risk patients with non ST-segment elevation acute coronary syndrome. We explored aspirin (ASA) use and its association with outcomes. Kaplan-Meier event rates were compared in groups defined by ASA dose (low, medium, and high). Landmark analyses with covariate adjustment were performed for 0 to 30, 31 to 180, and 181 to 365 days. Of 12,515 participants, 7,523, 1,049, and 3,943 participants were treated with low-, medium-, and high-dose ASA at baseline, respectively. Participants enrolled in North America versus elsewhere were more often treated with a high dose at baseline (66% vs 19%) and discharge (60% vs 3%). Unadjusted cardiovascular death, myocardial infarction, stroke, hospitalization for ischemia, or urgent revascularization event rates tended to be higher with higher baseline ASA (18.45% low, 19.13% medium, and 20.27% high; p for trend = 0.15573). Unadjusted and adjusted hazard ratios (95% confidence intervals) for effect of vorapaxar on cardiovascular (unadjusted p for interaction = 0.065; adjusted p for interaction = 0.140) and bleeding (unadjusted p for interaction = 0.915; adjusted p for interaction = 0.954) outcomes were similar across groups. Landmark analyses showed similar safety and efficacy outcomes with vorapaxar and placebo by ASA dose at each time point except for 0 to 30 days, when vorapaxar tended to be worse for efficacy (hazard ratio 1.13, 95% confidence interval 0.89 to 1.44, p for interaction = 0.0157). In conclusion, most TRACER participants were treated with low-dose ASA, although a high dose was common in North America. High-dose participants tended to have higher rates of ischemic and bleeding outcomes. Although formal statistical testing did not reveal heterogeneity in vorapaxar's effect across dose subgroups, consistent trends support use of low-dose ASA with other antiplatelet therapies.(c) 2014 Elsevier Inc. All rights reserved.

  • 19. Milonas, Christos
    et al.
    Jernberg, Tomas
    Lindbäck, Johan
    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.
    Agewall, Stefan
    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.
    Stenestrand, Ulf
    Effect of Angiotensin-Converting Enzyme Inhibition on One-Year Mortality and Frequency of Repeat Acute Myocardial Infarction in Patients With Acute Myocardial Infarction2010In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 105, no 9, p. 1229-1234Article in journal (Refereed)
    Abstract [en]

    Controversy exists regarding whether all patients with acute myocardial infarction (AM!) benefit from angiotensin-converting enzyme inhibitors (ACEIs). We examined the association between ACEI treatment and mortality in a large, unselected population of patients with AMI. The present study included 105,224 patients with AMI who were not treated with ACEIs on admission. A logistic regression analysis, including 33 variables, calculated a propensity score for each patient to estimate the probability of receiving ACEIs at discharge, given the background. The association between ACEI treatment at discharge and the 1-year outcome was evaluated in prespecified subgroups using the Cox regression analyses, adjusting for the propensity score and medications at discharge. A total of 38,395 patients (36.5%) received ACEIs at discharge. After adjustment, ACEI treatment was associated with a 24% reduction in mortality (relative risk 0.76, 95% confidence interval 0.73 to 0.80). The benefit was largest in patients with a history or present signs of heart failure. In patients without heart failure, a significant benefit of ACEI treatment was seen only in patients with renal dysfunction (relative risk 0.69, 95% confidence interval 0.54 to 0.88). In the whole group, the risk of AMI decreased by 7% (relative risk 0.93, 95% confidence interval 0.90 to 0.96), with a larger effect seen in patients with ST-segment elevation AMI or systolic left ventricular dysfunction. In conclusion, in unselected patients with AMI, ACEI treatment was associated with a reduction in 1-year mortality, mainly in patients with heart failure or renal dysfunction, and a small reduction in the risk of reinfarction, mainly in patients with ST-segment elevation AMI or systolic left ventricular dysfunction.

  • 20.
    Mohammad, Moman A.
    et al.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Koul, Sasha
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Smith, J. Gustav
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Noc, Marco
    Ctr Intens Internal Med, Ljubljana, Slovenia.
    Lang, Irene
    Med Univ Vienna, Dept Cardiol, Vienna, Austria.
    Holzer, Michael
    Med Univ Vienna, Dept Emergency Med, Vienna, Austria.
    Clemmensen, Peter
    Univ Heart Ctr, Dept Gen & Intervent Cardiol, Hamburg, Germany;Univ Southern Denmark, Nykoebing F Hosp, Div Cardiol, Dept Med, Odense, Denmark.
    Jensen, Ulf
    Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Engström, Thomas
    Univ Copenhagen, Rigshosp, Heart Ctr, Copenhagen, Denmark.
    Arheden, Håkan
    Lund Univ, Skane Univ Hosp, Dept Clin Physiol, Clin Sci, Lund, Sweden.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Metzler, Bernhard
    Dept Cardiol, Innsbruck, Austria.
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Predictive Value of High-Sensitivity Troponin T for Systolic Dysfunction and Infarct Size (Six Months) After ST-Elevation Myocardial Infarction2018In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 122, no 5, p. 735-743Article in journal (Refereed)
    Abstract [en]

    The association of markers of myocardial injury and dysfunction with infarct size (IS) and ejection fraction (EF) are well documented. However, limited data are available on the newer high-sensitivity troponin assays and comparison with morphologic and functional assessment with cardiac magnetic resonance imaging. We aimed to examine the associations of high-sensitivity cardiac Troponin-T (hs-cTnT), creatine kinase MB iso-enzyme (CKMB), and N-terminal pro B-type Natriuretic Peptide (NT-proBNP) to IS and EF at 6 months. Blood samples from 119 ST-segment elevation myocardial infarction patients from the Rapid Endovascular Catheter Core Cooling Combined With Cold Saline solution as an Adjunct to Percutaneous Coronary Intervention for the Treatment of Acute Myocardial Infarction trial were collected at baseline, 6, 24, and 48 hours after admission. Cardiac magnetic resonance was performed at 4 +/- 2 days and 6 months. The association of biomarker levels to IS and EF was tested with Pearson's correlation coefficients and linear regression models with bootstrap resampling. The correlation coefficient of biomarker to IS was (CKMB: r = 0.71); (NT-proBNP: r = 0.55); (hs-cTnT: r = 0.80); and for EF (CKMB: r = 0.57); (NT-proBNP: r = 0.48); and (peak hs-cTnT: r = 0.68). IS and EF at 4 +/- 2 days had the strongest correlations with IS and EF at 6 months respectively (IS: r = 0.84) and (EF: r = 0.74). Receiver operating characteristic of peak hs-cTnT for predicting EF <= 40% at 6 months was 0.87 compared with 0.75 for early IS. Early EF was a negative predictor of late EF <40%, 1-area under curve = 0.93. In conclusion, high-sensitivity Troponin T is a rapid, cheap, generally available tool for accurate prediction of systolic dysfunction in patients 6 months after first-time ST-segment elevation myocardial infarction.

  • 21.
    Nagarakanti, Rangadham
    et al.
    Electrophysiol Res Fdn, Warren, NJ USA.;Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Noack, Herbert
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Brueckmann, Martina
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany.;Heidelberg Univ, Fac Med Mannheim, Mannheim, Germany..
    Reilly, Paul
    Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT USA..
    Clemens, Andreas
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany.;Univ Med Ctr Mainz, Ctr Thrombosis & Hemostasis, Mainz, Germany..
    Connolly, Stuart J.
    McMaster Univ, Ottawa, ON, Canada..
    Yusuf, Salim
    McMaster Univ, Ottawa, ON, Canada..
    Ezekowitz, Michael D.
    Thomas Jefferson Univ, Sidney Kimmell Med Sch, Philadelphia, PA 19107 USA.;Lankenau Med Ctr, Wynnewood, PA USA..
    Comparison of Characteristics and Outcomes of Dabigatran Versus Warfarin in Hypertensive Patients With Atrial Fibrillation (from the RE-LY Trial)2015In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 116, no 8, p. 1204-1209Article in journal (Refereed)
    Abstract [en]

    Hypertension is frequent in patients with atrial fibrillation (AF) and is an independent risk factor for stroke. The Randomized Evaluation of Long Term Anticoagulant TherapY (RE-LY) trial found dabigatran 110 mg (D110) and 150 mg twice daily (D150) noninferior or superior to warfarin for stroke reduction in patients with AF, with either a reduction (D110) or similar rates (D150) of major bleeding. Baseline characteristics and outcomes were compared in patients with and without hypertension. The quality of blood pressure control was also assessed. In RE-LY, 14,283 patients (78.9%) had hypertension. The mean blood pressure at baseline was 132.6 +/- 17.6/77.7 +/- 10.6 and 124.8 +/- 16.7/74.6 +/- 10.0 mm Hg for patients with and without hypertension, respectively. More patients with hypertension were diabetic (25.6% vs 14.8%, p <0.001), women (38.6% vs 28.3%, p <0.001), and had greater CHADS(2) (2.3 vs 1.4, p <0.001) and CHA(2)DS(2)-VASc scores (3.8 vs 2.8, p <0.001). Mean blood pressure in all treatment arms in hypertensive patients was similar (130 +/- 18/76 +/- 11 mm Hg) during the trial. The efficacy and safety of D110 and D150 compared to warfarin were similar (p = nonsignificant) in hypertensive (stroke/systemic embolism rate of 1.47%, 1.20%, and 1.81% and major bleed rate of 2.89%, 3.70%, and 3.69% in the D110, D150, and W, respectively) and normotensive patients (stroke/systemic embolism rate of 1.79%, 0.78%, and 1.36% and major bleed rate of 2.84%, 2.37%, and 3.03% per year in the D110, D150, and W, respectively). Hypertensive patients had more major bleeds (3.39% vs. 2.76%; p = 0.007). Intracranial bleeds were similar (0.47% vs 0.31%; p = 0.12). In conclusion, patients with hypertension in RE-LY were more likely female, diabetic, with a greater CHADS(2) and CHA(2)DS(2)-VASc scores. Blood pressure control in RE-LY was excellent. The benefits of dabigatran over warfarin, including a substantial reduction of intracranial hemorrhage, were similar in both hypertensive and non-hypertensive patients.

  • 22. Ropers, Dieter
    et al.
    Ropers, Ulrike
    Marwan, Mohammed
    Schepis, Titiano
    Pflederer, Tobias
    Wechsel, Martin
    Klinghammer, Lutz
    Flachskampf, Frank A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Daniel, Werner G
    Achenbach, Stephan
    Comparison of dual-source computed tomography for the quantification of the aortic valve area in patients with aortic stenosis versus transthoracic echocardiography and invasive hemodynamic assessment2009In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 104, no 11, p. 1561-1567Article in journal (Refereed)
    Abstract [en]

    We compared the measurements of the aortic valve area (AVA) using dual-source computed tomography (DSCT) in patients with mid to severe aortic stenosis to measurements using transthoracic echocardiography (TTE) and invasive hemodynamic assessment. A total of 50 patients (mean age 73 ± 10 years) with suspected aortic stenosis were included. The computed tomographic data were acquired using DSCT with standardized scan parameters (2 × 64 × 0.6 mm collimation, 330-ms rotation, 120-kV tube voltage, 560 mA/rot tube current). After injection of 35 ml contrast agent (flow rate 5 ml/s), a targeted volume data set, ranging from the top of the leaflets to the infundibulum, was acquired. Ten cross-sectional data sets (slice thickness 1 mm, no overlap, increment 0.6 mm) were reconstructed during systole in 5% increments of the R-R interval. The AVA determined in systole by planimetry was compared to the calculated AVA values using the continuity equation on TTE and the Gorlin formula on catheterization. DSCT allowed the planimetry of the AVA in all patients. The mean AVA using DSCT was 1.16 ± 0.47 cm2 compared to a mean AVA of 1.04 ± 0.45 cm2 using TTE and 1.06 ± 0.45 cm2 using catheterization, with a significant correlation between DSCT/TTE (r = 0.93, p <0.001) and DSCT/cardiac catheterization (r = 0.97, p <0.001). However, DSCT demonstrated a slight, but significant, overestimation of the AVA compared to TTE (+0.12 ± 0.17 cm) and catheterization (+0.10 ± 0.12 cm2). In conclusion, DSCT permits one to assess the AVA with a high-image quality and diagnostic accuracy compared to TTE and invasive determination.

  • 23.
    Sarno, Giovanna
    et al.
    Department of Interventional Cardiology, Erasmus MC, Rotterdam, Netherlands.
    Räber, Lorenz
    Onuma, Yoshinobu
    Garg, Scot
    Brugaletta, Salvatore
    van Domburg, Ron T
    Pilgrim, Thomas
    Pfäffli, Nico
    Wenaweser, Peter
    Windecker, Stephan
    Serruys, Patrick
    Impact of body mass index on the five-year outcome of patients having percutaneous coronary interventions with drug-eluting stents2011In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 108, no 2, p. 195-201Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to assess the impact of body mass index (BMI) on clinical outcome of patients treated by percutaneous coronary intervention (PCI) using drug-eluting stents. Patients were stratified according to BMI as normal (<25 kg/m2), overweight (25 to 30 kg/m2), or obese (>30 kg/m2). At 5-year follow-up all-cause death, myocardial infarction, clinically justified target vessel revascularization (TVR), and definite stent thrombosis were assessed. A complete dataset was available in 7,427 patients, of which 45%, 22%, and 33% were classified according to BMI as overweight, obese, and normal, respectively. Mean age of patients was significantly older in those with a normal BMI (p <0.05). Incidence of diabetes mellitus, hypertension, and dyslipidemia increased as BMI increased (p <0.05). Significantly higher rates of TVR (15.3% vs 12.8%, p = 0.02) and early stent thrombosis (1.5% vs 0.9%, p = 0.04) were observed in the obese compared to the normal BMI group. No significant difference among the 3 BMI groups was observed for the composite of death/myocardial infarction/TVR or for definite stent thrombosis at 5 years, whereas the normal BMI group was at higher risk for all-cause death at 5 years (obese vs normal BMI, hazard ratio 0.74, confidence interval 0.53 to 0.99, p = 0.05; overweight vs normal BMI, hazard ratio 0.73, confidence interval 0.59 to 0.94, p = 0.01) in the multivariate Cox proportional hazard model. Age resulted in a linearly dependent covariate with BMI in the all-cause 5-year mortality multivariate model (p = 0.001). In conclusion, the “obesity paradox” observed in 5-year all-cause mortality could be explained by the higher rate of elderly patients in the normal BMI group and the existence of colinearity between BMI and age. However, obese patients had a higher rate of TVR and early stent thrombosis and a higher rate of other risk factors such as diabetes mellitus, hypertension, and hypercholesterolemia.

  • 24. Storey, Robert F
    et al.
    Becker, Richard C
    Harrington, Robert A
    Husted, Steen
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Cools, Frank
    Steg, Philippe Gabriel
    Khurmi, Nardev S
    Emanuelsson, Hakan
    Lim, Soo Teik
    Cannon, Christopher P
    Katus, Hugo A
    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.
    Pulmonary function in patients with acute coronary syndrome treated with ticagrelor or clopidogrel (from the Platelet Inhibition and Patient Outcomes [PLATO] pulmonary function substudy)2011In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 108, no 11, p. 1542-1546Article in journal (Refereed)
    Abstract [en]

    The Platelet Inhibition and Patient Outcomes (PLATO) trial showed that ticagrelor reduced the risk for cardiovascular events in patients with acute coronary syndromes compared to clopidogrel but was associated with increased incidence of dyspnea. This substudy assessed whether ticagrelor affects pulmonary function in patients with acute coronary syndromes: 199 patients enrolled in the PLATO trial and receiving randomized treatment with ticagrelor 90 mg twice daily (n = 101) or clopidogrel 75 mg/day (n = 98) took part in the pulmonary function substudy. Patients with advanced lung disease, congestive heart failure, or coronary artery bypass graft surgery after the index event were excluded. Pulse oximetry (blood oxygen saturation), spirometry (forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow between 25% and 75% of forced vital capacity before and 20 minutes after inhalation of a β(2) agonist), lung volumes (total lung capacity, functional residual capacity, residual volume), and diffusion capacity were performed after patients received study medication for 30 to 40 days. Tests were then repeated <10 days before and approximately 30 days after the discontinuation of study medication. After a mean treatment duration of 31 days, there were no differences between the groups for any of the pulmonary function parameters. At the end of treatment (mean 211 days) and after the discontinuation of study medication (mean 32 days after the last dose), there was also no evidence of a change in pulmonary function in either group. For example, forced expiratory volume in 1 second values before β(2) agonist inhalation in the ticagrelor and clopidogrel groups were 2.81 ± 0.73 and 2.70 ± 0.84 L, respectively, at the first visit and did not change significantly at subsequent visits. In conclusion, no effect of ticagrelor on pulmonary function was seen in this cohort of patients with acute coronary syndromes compared to clopidogrel.

  • 25. Timmer, Stefan A J
    et al.
    Germans, Tjeerd
    Götte, Marco J W
    Rüssel, Iris K
    Lubberink, Mark
    Department of Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam, The Netherlands.
    Ten Berg, Jurrien M
    Ten Cate, Folkert J
    Lammertsma, Adriaan A
    Knaapen, Paul
    van Rossum, Albert C
    Relation of coronary microvascular dysfunction in hypertrophic cardiomyopathy to contractile dysfunction independent from myocardial injury2011In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 107, no 10, p. 1522-1528Article in journal (Refereed)
    Abstract [en]

    We studied the spatial relations among hyperemic myocardial blood flow (hMBF), contractile function, and morphologic tissue alterations in 19 patients with hypertrophic cardiomyopathy (HC). All patients were studied with oxygen-15 water positron emission tomography during rest and adenosine administration to assess myocardial perfusion. Cardiovascular magnetic resonance was performed to derive delayed contrast-enhanced images and to calculate contractile function (Ecc) with tissue tagging. Eleven healthy subjects underwent similar positron emission tomographic and cardiovascular magnetic resonance scanning protocols and served as a control group. In the HC group, hMBF averaged 2.46 ± 0.91 ml/min/g and mean Ecc was −14.7 ± 3.4%, which were decreased compared to the control group (3.97 ± 1.48 ml/min/g and −17.7 ± 3.2%, respectively, p <0.001 for the 2 comparisons). Delayed contrast enhancement (DCE) was present only in patients with HC, averaging 6.2 ± 10.3% of left ventricular mass. In the HC group, Ecc and DCE in the septum (−13.7 ± 3.6% and 10.2 ± 13.6%) significantly differed from the lateral wall (−16.0 ± 2.8% and 2.4 ± 5.9%, p <0.001 for the 2 comparisons). In general, hMBF and Ecc were decreased in segments displaying DCE compared to nonenhanced segments (p <0.001 for the comparisons). In the HC group, univariate analysis revealed relations of hMBF to Ecc (r = −0.45, p <0.001) and DCE (r = −0.31, p <0.001). Multivariate analysis revealed that Ecc was independently related to hMBF (beta −0.37, p <0.001) and DCE (beta 0.28, p <0.001). In conclusion, in HC hMBF is impaired and related to contractile function independent from presence of DCE. When present, DCE reflected a progressed disease state as characterized by an increased perfusion deficit and contractile dysfunction.

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

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

  • 27. Verdecchia, Paolo
    et al.
    Reboldi, Gianpaolo
    Di Pasquale, Giuseppe
    Mazzotta, Giovanni
    Ambrosio, Giuseppe
    Yang, Sean
    Pogue, Janice
    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.
    Connolly, Stuart J.
    Yusuf, Salim
    Prognostic Usefulness of Left Ventricular Hypertrophy by Electrocardiography in Patients With Atrial Fibrillation (from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study)2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 113, no 4, p. 669-675Article in journal (Refereed)
    Abstract [en]

    It is unknown whether left ventricular hypertrophy (LVH) diagnosis by electrocardiography improves risk stratification in patients with atrial fibrillation (AF). We investigated the prognostic impact of LVH diagnosis by electrocardiography in a large sample of anticoagulated patients with AF included in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Study. We defined electrographic LVH (ECG-LVH) by strain pattern or Cornell voltage (R wave in aVL plus S wave in V-3) >2.0 mV (women) or >2.4 mV (men). LVH prevalence was 22.7%. During a median follow-up of 2.0 years, 303 patients developed a stroke, 778 died (497 from cardiovascular causes), and 140 developed a myocardial infarction. LVH was associated with a greater risk of stroke (1.99% vs 1.32% per year, hazard ratio [BR] 1.51, 95% confidence interval [CI] 1.18 to 1.93, p <0.001), cardiovascular death (4.52% vs 1.80% per year, HR 2.56, 95% CI 2.14 to 3.06, p <0.0001), all-cause death (6.03% vs 3.11% per year, HR 1.95, 95% CI 1.68 to 2.26, p <0.0001), and myocardial infarction (1.11% vs 0.55% per year, HR 2.07, 95% CI 1.47 to 2.92, p <0.0001). In multivariate analysis, the prognostic value of LVH was additive to CHA(2)DS(2)-VASc score and other covariates. The category-free net reclassification index and integrated discrimination improvement increased significantly after adding LVH to multivariate models. In conclusion, our study demonstrates for the first time that ECG-LVH, a simple and easily accessible prognostic indicator, improves risk stratification in anticoagulated patients with AF.

  • 28.
    Wilhelm, Matthias
    et al.
    Bern University, Deptm.of Cardiology, Switzerland.
    Brem, Matthias
    Erlangen University, Deptm. of Orthopedic Surgery, Germany.
    Rost, Christian
    Erlangen University, Deptm. of Cardiology, Germany.
    Klinghammer, Lutz
    Erlangen University, Deptm. of Cardiology, Germany.
    Hennig, Friedrich
    Erlangen University, Deptm. of Orthopedic Surgery, Germany.
    Daniel, Werner G.
    Erlangen University, Deptm. of Cardiology, Germany.
    Flachskampf, Frank
    Erlangen University, Deptm. of Cardiology, Germany.
    Early Repolarization, Left Ventricular Diastolic Function, and Left Atrial Size in Professional Soccer Players2010In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 106, no 4, p. 569-574Article in journal (Refereed)
    Abstract [en]

    Recent data have suggested a relation among long-term endurance sport practice, left atrial remodeling, and atrial fibrillation. We investigated the influence of an increased vagal tone, represented by the early repolarization (ER) pattern, on diastolic function and left atrial size in professional soccer players. Fifty-four consecutive athletes underwent electrocardiography, echocardiography, and exercise testing as part of their preparticipation screening. Athletes were divided into 2 groups according to presence or absence of an ER pattern, defined as a ST-segment elevation at the J-point (STE) ≥0.1 mm in 2 leads. For linear comparisons average STE was calculated. Mean age was 24 ± 4 years. Twenty-five athletes (46%) showed an ER pattern. Athletes with an ER pattern had a significant lower heart rate (54 ± 9 vs 62 ± 11 beats/min, p = 0.024), an increased E/e′ ratio (6.1 ± 1.2 vs 5.1 ± 1.0, p = 0.002), and larger volumes of the left atrium (25.6 ± 7.3 vs 21.8 ± 5.0 ml/m2, p = 0.031) compared to athletes without an ER pattern. There were no significant differences concerning maximum workload, left ventricular dimensions, and systolic function. Univariate regression analysis revealed significant correlations among age, STE, and left atrial volume. In a stepwise multivariate regression analysis age, STE and e′ contributed independently to left atrial size (r = 0.659, p <0.001). In conclusion, athletes with an ER pattern had an increased E/e′ ratio, reflecting a higher left atrial filling pressure, contributing to left atrial remodeling over time.

  • 29.
    Wändell, Per
    et al.
    Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Holzmann, Martin J.
    Karolinska Univ Hosp, Funct Area Emergency Med, Stockholm, Sweden.;Solna Karolinska Inst, Dept Internal Med, Stockholm, Sweden..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med & Primary Care, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.;Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Sundquist, Jan
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden.;Icahn Sch Med Mt Sinai, Dept Family Med & Community Hlth, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA..
    Sundquist, Kristina
    Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden.;Icahn Sch Med Mt Sinai, Dept Family Med & Community Hlth, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA..
    Comparison of Mortality and Nonfatal Cardiovascular Events in Adults With Atrial Fibrillation With Versus Without Levothyroxine Treatment2017In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 120, no 11, p. 1974-1979Article in journal (Refereed)
    Abstract [en]

    Levothyroxine has been suggested to be cardiotoxic, but previous studies on the risk of cardiovascular events associated with levothyroxine treatment have been inconclusive. We aimed to study the association between levothyroxine treatment and all-cause mortality as well as cardiovascular events. Study population included all adults (n = 12,283) >= 45 years diagnosed with atrial fibrillation (AF) at 75 primary care centers in Sweden in 2001 to 2007, with (n = 1,189; 283 men and 906 women) or without (n = 11,094) levothyroxine treatment. Outcome was defined as all-cause mortality and cardiovascular events, that is, myocardial infarction, ischemic stroke, and congestive heart failure until December 31, 2010. During a mean 5.8 years (standard deviation 2.4 years) of follow-up, a total of 3,954 patients died (32.2%), among whom 92 men (32.5%) and 266 women (29.4%) were treated with levothyroxine. In fully adjusted Cox regression models (age, co-morbidity, socioeconomic factors, and warfarin treatment), a significant association between levothyroxine treatment and lower mortality was found among women (hazard ratio 0.78, 95% confidence interval 0.68 to 0.91), but not among men (hazard ratio 0.87, 95% confidence interval 0.69 to 1.10). In the secondary analysis, levothyroxine treatment was not associated with the risk of myocardial infarction, ischemic stroke, or congestive heart failure (p > 0.05). In conclusion, in a large representative cohort, we found that levothyroxine treatment decreased the mortality risk in women with AF, which suggests that such treatment could be of benefit in this setting.

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