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  • 1. Brito, F. S. B. De Souza
    et al.
    Åkerblom, Axel A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Wojdyla, D. W.
    Steg, P. G. S.
    Wallentin, Lars W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    James, Stefan K. J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Katus, H. A. K.
    Himmelmann, A. H.
    Becker, R. C. B.
    Lopes, R. D. L.
    Efficacy and safety of ticagrelor in patients with acute coronary syndrome and heart failure: insights from the platelet inhibition and patient outcomes (PLATO) trial2014Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, s. 202-203Artikel i tidskrift (Refereegranskat)
  • 2.
    Evans, Marie
    et al.
    Karolinska Inst, Renal Med, CLINTEC, Stockholm, Sweden..
    Carrero, Juan-Jesus
    Karolinska Inst, Renal Med, CLINTEC, Stockholm, Sweden.;Karolinska Inst, Inst Mol Med, Stockholm, Sweden..
    Szummer, Karolina
    Karolinska Inst, Dept Med, Cardiol Sect, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Edfors, Robert
    Karolinska Inst, Dept Med, Cardiol Sect, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Spaak, Jonas
    Karolinska Inst, Dept Clin Sci, Danderyd Univ Hosp, Stockholm, Sweden..
    Jacobson, Stefan H.
    Karolinska Inst, Dept Clin Sci, Danderyd Univ Hosp, Stockholm, Sweden..
    Andell, Pontus
    Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden..
    Lindhagen, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Jernberg, Tomas
    Karolinska Inst, Dept Med, Cardiol Sect, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Myocardial Infarction Patients With Renal Dysfunction2016Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, nr 14, s. 1687-1697Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND There is no consensus whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) should be used for secondary prevention in all or in only high-risk patients after an acute myocardial infarction (AMI).

    OBJECTIVES This study sought to investigate whether ACEI/ARB treatment after AMI is associated with better outcomes across different risk profiles, including the entire spectrum of estimated glomerular filtration rates.

    METHODS This study evaluated discharge and continuous follow-up data on ACEI/ARB use among AMI survivors (2006 to 2009) included in a large Swedish registry. The association between ACEI/ARB treatment and outcomes (mortality, myocardial infarction, stroke, and acute kidney injury [AKI]) was studied using Cox proportional hazards models (intention-to-treat and as treated).

    RESULTS In total, 45,697 patients (71%) were treated with ACEI/ARB. The 3-year mortality was 19.8% (17.4% of ACEI/ARB users and 25.4% of nonusers). In adjusted analysis, significantly better survival was observed for patients treated with ACEI/ARB (3-year hazard ratio: 0.80; 95% confidence interval: 0.77 to 0.83). The survival benefit was consistent through all kidney function strata, including dialysis patients. Overall, those treated with ACEI/ARB also had lower 3-year risk for myocardial infarction (hazard ratio: 0.91; 95% confidence interval: 0.87 to 0.95), whereas treatment had no significant effect on stroke risk. The crude risk for AKI was in general low (2.5% and 2.0% for treated and nontreated, respectively) and similar across estimated glomerular filtration rate categories but was significantly higher with ACEI/ARB treatment. However, the composite outcome of AKI and mortality favored ACEI/ARB treatment.

    CONCLUSIONS Treatment with ACEI/ARB after AMI was associated with improved long-term survival, regardless of underlying renal function, and was accompanied by low rates of adverse renal events.

  • 3.
    Fokkema, Marieke L.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    James, Stefan K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Albertsson, Per
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden.
    Aasa, Mikael
    Soder Sjukhuset, Dept Cardiol, Stockholm, Sweden.
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Calais, Fredrik
    Univ Orebro, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Eriksson, Peter
    Umea Univ Hosp, Dept Cardiol, Umea, Sweden.
    Jensen, Jens
    Sundsvall Harnosand Cty Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden.
    Schersten, Fredrik
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden.
    de Smet, Bart J
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands; Meander Med Ctr, Dept Cardiol, Amersfoort, Netherlands.
    Sjögren, Iwar
    Falun Lasarett, Dept Cardiol, Falun, Sweden.
    Tornvall, Per
    arolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden.
    Lagerqvist, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Outcome after percutaneous coronary intervention for different indications: long-term results from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)2016Ingår i: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 12, nr 3, s. 303-311Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: The aim of this study was to evaluate clinical outcome for different indications for PCI in an unselected, nationwide PCI population at short- and long-term follow-up. Methods and results: We evaluated clinical outcome up to six years after PCI in all patients undergoing a PCI procedure for different indications in Sweden between 2006 and 2010. A total of 70,479 patients were treated for stable coronary artery disease (CAD) (21.0%), unstable angina (11.0%), non-ST-elevation myocardial infarction (NSTEMI) (36.6%) and ST-elevation myocardial infarction (STEMI) (31.4%). Mortality was higher in STEMI patients at one year after PCI (9.6%) compared to NSTEMI (4.7%), unstable angina (2.2%) and stable CAD (2.0%). At one year after PCI until the end of follow-up, the adjusted mortality risk (one to six years after PCI) and the risk of myocardial infarction were comparable between NSTEMI and STEMI patients and lower in patients with unstable angina and stable CAD. The adjusted risk of stent thrombosis and heart failure was highest in STEMI patients. Conclusions: The risk of short-term mortality, heart failure and stent thrombosis is highest for STEMI patients after PCI. Therapies to reduce stent thrombosis and heart failure appear to be most important in decreasing mortality in patients with STEMI or NSTEMI undergoing PCI.

  • 4.
    Fokkema, Marieke L
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    James, Stefan K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Albertsson, Per
    Akerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Calais, Fredrik
    Eriksson, Peter
    Jensen, Jens
    Nilsson, Tage
    de Smet, Bart J
    Sjögren, Iwar
    Thorvinger, Björn
    Lagerqvist, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Population Trends in Percutaneous Coronary Intervention: 20 Year Results from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry)2013Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 61, nr 12, s. 1222-1230Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES:

    The aim of this study was to describe the characteristics and outcome of all consecutive patients treated with PCI in an unselected nation-wide cohort over the last 2 decades.

    BACKGROUND:

    Over the last 20 years, treatment with percutaneous coronary intervention (PCI) has evolved dramatically but the change in patient characteristics has not been well described.

    METHODS:

    We included all patients undergoing a PCI procedure for the first time between January 1990 and December 2010 from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Patients were divided in different cohorts based on the year of the first PCI procedure.

    RESULTS:

    A total of 144,039 patients were included. The mean age increased from 60.1 (SD±9.9) years in 1990-1995 to 67.1 (±11.2) years in 2009-2010. The proportion of patients presenting with unstable coronary artery disease and STEMI increased from 27.4% and 6.2% to 47.7% and 32.5% respectively. Diabetes and multivessel disease were more often present in the later year cohorts. The 1-year mortality increased from 2.2% in 1990-1995 to 5.9% in 2009-2010, but after adjustment for age and indication a modest decrease was shown, mainly in STEMI patients.

    CONCLUSIONS:

    Characteristics of PCI patients have changed substantially over time reflecting the establishment of new evidence. The increasing age and proportion of patients undergoing PCI for acute coronary syndromes greatly influence outcome. The understanding of the changing patient characteristics is important for the translation of evidence to real-world clinical practice.

  • 5.
    Goel, Kashish
    et al.
    Mayo Clinic, Rochester, MN, USA.
    Baheti, Saurabh
    Mayo Clinic, Rochester, MN, USA.
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Goodman, Shaun
    Mayo Clinic, Rochester, MN, USA.
    Jenkins, Greg
    Mayo Clinic, Rochester, MN, USA.
    Bielinski, Suzette
    Mayo Clinic, Rochester, MN, USA.
    Roger, Veronique
    Mayo Clinic, Rochester, MN, USA.
    Rihal, Charanjit
    Mayo Clinic, Rochester, MN, USA.
    Pereira, Naveen
    Mayo Clinic, Rochester, MN, USA.
    Novel Cyp2C19 Genetic Variants associated with Stent Thrombosis: a Next Generation Sequencing Study2018Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 71, nr 11, s. 1205-1205Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background

    Commonly tested Loss-of-function (LOF) alleles in CYP2C19 are present in 30-40% of patients who experience stent thrombosis. The objective of this study was to identify novel genetic variants in CYP2C19 gene associated with stent thrombosis.

    Methods

    We included 70 patients with definite stent thrombosis while on clopidogrel who had stored DNA samples in our institutional (n=12) or PLATO trial (n=70) biorepository. Cases were matched 1:1 with controls for age, race, sex, diabetes, type of stent, and presentation. All controls were on clopidogrel and free of recurrent events. Clinical Pharmacogenetics (PGx) Implementation Consortium (CPIC) guidelines were used to determine the list of known PGx variants and dbSNP version 142 was used to assess novel variants. Whole exome sequencing was performed using the protocol for Agilent's SureSelect Human All Exon v5 + UTRs 75 MB kit and additional custom primers were designed to cover the entire CYP2C19 gene.

    Results

    Mean age was 63 ± 12 years, and 71% were male. We identified a total of 456 single nucleotide variants (SNV) in the CYP2C19 gene (cases: 376; controls: 288), of which 5 were synonymous, 6 non-synonymous, 46 indels and 449 intronic SNVs. There were 168 vs. 80 novel CYP2C19 variants and 10 vs. 5 indels in cases vs. controls, respectively. Four SNVs (3 missense and 1 synonymous) were present only in cases, whereas 3 SNVs (1 misssense, 1 synonymous and 1 intron) were unique to controls. There were no detectable differences in the frequency of LOF CYP2C19*2 allele (cases 34% vs. controls 31%) or other CPIC annotated PGx variants in cases and controls. After excluding the known PGx variants, there were 10 indels (all intronic) out of which 7 were novel in cases and were not present in controls.

    Conclusion

    We describe several novel genetic variants in the CYP2C19 gene in patients treated with clopidogrel after coronary stenting. We identified 168 novel SNVs and 10 novel indels in the CYP2C19 gene of patients with stent thrombosis. Four SNVs and 9 indels were unique to cases. Functional validation of these CYP2C19 genetic variants may provide important insights of CYP2C19 and the pathophysiology of stent thrombosis in clopidogrel treated patients.

  • 6.
    Hagström, Emil
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Johansson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Bertilsson, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Barratt, Bryan J.
    Becker, Richard C.
    Himmelmann, Anders
    James, Stefan K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Katus, Hugo A.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Steg, Philippe G.
    Storey, Robert F.
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Varenhorst, Christoph
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Are There Any Causal Relations Between Growth Differentiation Factor 15 and Outcomes in Patients With Acute Coronary Syndrome?: - A Report From the Plato Gwas Study2013Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, nr 22Artikel i tidskrift (Övrigt vetenskapligt)
  • 7.
    James, Stefan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Cannon, Christopher P.
    Emanuelsson, Håkan
    Husted, Steen
    Katus, Hugo
    Skene, Allan
    Steg, Philippe Gabriel
    Storey, Robert F.
    Harrington, Robert
    Becker, Richard
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial2009Ingår i: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 157, nr 4, s. 599-605Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Antiplatelet therapy is essential treatment for acute coronary syndromes (ACS). Current therapies, however, have important limitations affecting their clinical success. Ticagrelor, the first reversible oral P2Y(12) receptor antagonist, provides faster, greater, and more consistent adenosine diphosphate-receptor inhibition than clopidogrel. The phase III PLATelet inhibition and patient Outcomes (PLATO) trial is designed to test the hypothesis that ticagrelor compared with clopidogrel will result in a lower risk of recurrent thrombotic events in a broad patient population with ACS. METHODS: PLATO is an international, randomized, double-blind, event-driven trial involving >18,000 patients hospitalized for ST-elevation ACS with scheduled primary percutaneous coronary intervention or for non-ST-elevation ACS. After loading doses of ticagrelor 180 mg or clopidogrel 300 mg in a double-blind, double-dummy fashion (with provision for additional 300 mg clopidogrel at percutaneous coronary intervention), patients will receive ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 6 to 12 months on top of acetylsalicylic acid. The primary efficacy end point is time to first occurrence of death from vascular causes, myocardial infarction, or stroke. The primary safety variable is PLATO-defined major bleeding. An extensive substudy program will explore the pathophysiology of ACS, indicators of prognosis and response to treatment, mechanisms of effect and safety of the study medications, health economics, and quality of life. CONCLUSION: The PLATO study will provide a pivotal comparison of the efficacy and safety of ticagrelor with those of clopidogrel in ACS patients, together with extensive information on treatment outcomes in different subsets of ACS in a broad patient population.

  • 8. Koutouzis, Michael
    et al.
    Lagerqvist, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Oldgren, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Wahlin, Magnus
    Karlsson, Thomas
    Albertsson, Per
    Matejka, Goran
    Grip, Lars
    Long-Term Results Following Switch From Abciximab to Eptifibatide During Percutaneous Coronary Intervention2010Ingår i: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 33, nr 11, s. 686-692Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The usage of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors improves the outcome during high-risk percutaneous coronary interventions (PCI). The aim of this study was to evaluate the long-term effects after a planned switch from abciximab to eptifibatide during PCI. Hypothesis: A switch from the general use of abciximab to eptifibatide as a GP IIb/IIIa in connection with PCI would not have any negative effects on long-term clinical outcomes. Methods: To reduce costs, a general switch from abciximab to eptifibatide was instituted in 2004 in 2 university hospitals in Sweden. All patients treated 6 months before and 6 months after the switch were followed for 30 months. During the study period, 1038 patients underwent PCI and received a GP IIb/IIIa receptor inhibitor, 481 (46%) before the switch (Group A) and 557 (54%) after the switch (Group B). The 2 groups had similar baseline characteristics. The primary endpoint was the composite of death, myocardial infarction, stroke, or new coronary revascularization (percutaneous or surgical); secondary endpoints were the individual components of this composite. A separate analysis was performed on patients treated for ST-segment elevation myocardial infarction, non ST-segment elevation myocardial infarction/unstable angina, and diabetes, respectively. Data were collected from the Swedish Coronary Angiography and Angioplasty Registry. Results: There were no differences between the groups in the primary endpoint (29.7% in Group A vs 29.3% in Group B; P = 0.48) or in any of the secondary endpoints. Conclusions: A switch from the general usage of abciximab to eptifibatide as a GP IIb/IIIa receptor inhibitor in connection with PCI did not seem to have any negative effects on long-term clinical outcomes.

  • 9.
    Pagidipati, N.
    et al.
    Duke Clin Res Inst, Cardiol, Durham, NC USA..
    Hess, C. N.
    Univ Colorado, Aurora, CO USA..
    Clare, R. M.
    Duke Clin Res Inst, Cardiol, Durham, NC USA..
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Tricoci, P.
    Duke Clin Res Inst, Cardiol, Durham, NC USA..
    Wojdyla, D.
    Duke Clin Res Inst, Cardiol, Durham, NC USA..
    Keenan, R.
    Duke Univ, Med Ctr, Rheumatol, Durham, NC 27706 USA..
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Held, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Mahaffey, K.
    Stanford Univ, Med Ctr, Stanford, CA 94305 USA..
    Harrington, R.
    Stanford Univ, Med Ctr, Stanford, CA 94305 USA..
    Klein, A. B.
    AstraZeneca, Gaithersburg, MD USA..
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Roe, M. T.
    Duke Clin Res Inst, Cardiol, Durham, NC USA..
    Does a clinical history of gout influence the relationship of serum uric acid levels and cardiovascular outcomes among patients with acute coronary syndromes?2016Konferensbidrag (Refereegranskat)
  • 10.
    Pagidipati, Neha J.
    et al.
    Duke Univ Hlth Syst, Duke Clin Res Inst, Durham, NC USA..
    Hess, Connie N.
    Univ Colorado, Sch Med, Aurora, CO USA..
    Clare, Robert M.
    Duke Univ Hlth Syst, Duke Clin Res Inst, Durham, NC USA..
    Akerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Tricoci, Pierluigi
    Duke Univ Hlth Syst, Duke Clin Res Inst, Durham, NC USA..
    Wojdyla, Daniel
    Duke Univ Hlth Syst, Duke Clin Res Inst, Durham, NC USA..
    Keenan, Robert T.
    Duke Univ Hlth Syst, Durham, NC USA..
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Held, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Mahaffey, Kenneth W.
    Stanford Univ, Med Ctr, Stanford, CA 94305 USA..
    Klein, Alyssa B.
    AstraZeneca, Gaithersburg, MD USA..
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Roe, Matthew T.
    Duke Univ Hlth Syst, Duke Clin Res Inst, Durham, NC USA..
    An examination of the relationship between serum uric acid level, a clinical history of gout, and cardiovascular outcomes among patients with acute coronary syndrome2017Ingår i: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 187, s. 53-61Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Studies have suggested a relationship between higher baseline serum uric acid (sUA) levels and an elevated risk of subsequent ischemic cardiovascular outcomes among acute coronary syndrome (ACS) patients; this relationship may be modified by a clinical history of gout and has not been studied in large patient cohorts. We sought to understand the effect of sUA and gout on ACS outcomes. Methods Using PLATO and TRACER data on 27,959 ACS patients, we evaluated baseline sUA levels in relation to a composite of cardiovascular death, myocardial infarction (MI), or stroke. We assessed interaction terms to determine if a baseline clinical diagnosis of gout modified this putative relationship; 46% (n = 12,882) had sUA levels elevated >6.0 mg/dL. Results Patients with elevated levels were more often male with a history of prior MI, diabetes, and heart failure compared with those with sUA <6.0 mg/dL. The unadjusted risk of the composite endpoint increased with corresponding elevations in sUA levels (per 1 mg/dL increase) (HR = 1.23 [95% CI: 1.20-1.26]) above the statistical inflection point of 5.0 mg/dL. After adjustment, the association between sUA level and the composite outcome remained significant (HR = 1.07 [95% CI: 1.04-1.10]), and baseline gout did not modify this relationship. ' Conclusions In patients with ACS, increasing levels of sUA are associated with an elevated risk of cardiovascular events, regardless of a clinical diagnosis of gout. Further investigation is warranted to determine the mechanism behind this relationship and to delineate whether sUA is an appropriate therapeutic target to reduce cardiovascular risk.

  • 11.
    Parker, William A E
    et al.
    University of Sheffield, Immunity and Cardiovascular Disease, Department of Infection, Sheffield , United Kingdom.
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Becker, Richard C
    University of Cincinnati College of Medicine, Heart, Lung and Vascular Institute, Division of Cardiovascular Health and Disease, Cincinnati, OH, USA.
    Voora, Deepak
    Duke University Medical Center, Duke Clinical Research Institute, Durham, NC, USA.
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Himmelmann, Anders
    AstraZeneca Research and Development, Gothenburg, Sweden.
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Storey, Robert F
    University of Sheffield, Immunity and Cardiovascular Disease, Department of Infection, Sheffield , United Kingdom.
    Equilibrative nucleoside transporter 1 gene polymorphisms and clinical outcomes following acute coronary syndromes: findings from the PLATelet inhibition and patient Outcomes (PLATO) study2018Ingår i: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 30, nr 5, s. 579-588Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the PLATelet inhibition and patient Outcomes (PLATO) study, the P2Y12 inhibitors ticagrelor and clopidogrel were compared in the treatment of acute coronary syndromes (ACS). Ticagrelor was shown to reduce occurrence of the primary end point - a composite of death from vascular causes, myocardial infarction, or stroke - compared to clopidogrel. Ticagrelor's pleiotropic effects on reuptake of adenosine via inhibition of equilibrative nucleoside transporter 1 (ENT1) have been hypothesized to contribute to this. Several polymorphisms of ENT1 are known to exist. We explored the interaction between ENT1 polymorphisms and clinical outcomes in ACS patients participating in the PLATO genetic substudy. Using genotyping data obtained in a genome-wide association study, the gene region encoding ENT1 was assessed and 94 polymorphisms were identified. After quality control filtering, data from 9943 participants were included. Subjects were divided into discovery (phase 1, n = 3970) and replication (phase 2, n = 5973) cohorts. Cox-regression analysis of the relationship between variants and seven efficacy and safety outcomes was performed in discovery, replication, and combined cohorts. Treatment-marker interactions were also determined. Although 35 variants were found with associations to the investigated outcomes reaching p < 0.05 in the discovery cohort, only one of these was replicated in phase 2 of the analysis and also reached the predetermined level of statistical significance in the combined data, taking into account the number of tests performed: the rare polymorphism rs141034817, with a frequency of 0.2%, was significantly associated with bleeding. Thirty-three treatment-marker interactions were found with a significance level of p < 0.05 in phase 1, but none was replicated in phase 2. We found no significant interaction between ENT1 genotype and clinical outcomes in ACS patients treated with ticagrelor or clopidogrel, apart from the association between a rare polymorphism and bleeding that requires further study. If ticagrelor's pleiotropic effects on adenosine uptake are clinically relevant, these do not appear to be significantly affected by variation in the ENT1 gene.

  • 12.
    Patel, Riyaz S.
    et al.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
    Schmidt, Amand F.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;UMC, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
    Tragante, Vinicius
    UMC, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
    McCubrey, Raymond O.
    Intertermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA.
    Holmes, Michael, V
    Univ Oxford, Clin Trial Serv Unit, Nuffield Dept Populat Hlth, Oxford, England;Univ Oxford, Epidemiol Studies Unit, Nuffield Dept Populat Hlth, Oxford, England;Univ Oxford, Med Res Council Populat Hlth Res Unit, Oxford, England;Univ Oxford, Natl Inst Hlth Res, Oxford Biomed Res Ctr, Oxford, England.
    Howe, Laurence J.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England.
    Direk, Kenan
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England.
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Leander, Karin
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Virani, Salim S.
    Baylor Coll Med, Sect Cardiovasc Res, Michael & DeBakey Vet Affairs Med Ctr, Sect Cardiol, Houston, TX 77030 USA;Baylor Coll Med, Dept Med, Sect Cardiol, Houston, TX 77030 USA.
    Kaminski, Karol A.
    Med Univ Bialystok, Dept Populat Med & Civilizat Dis Prevent, Bialystok, Poland;Med Univ Bialystok, Dept Cardiol, Bialystok, Poland.
    Muehlschlegel, Jochen D.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England;Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA.
    Dube, Marie-Pierre
    Univ Montreal, Fac Med, Montreal, PQ, Canada.
    Allayee, Hooman
    USC, Dept Prevent Med, Los Angeles, CA USA;USC, Dept Biochem & Mol Med, Los Angeles, CA USA.
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Alver, Maris
    Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, Tartu, Estonia.
    Baranova, Ekaterina, V
    Univ Med Ctr, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
    Behlouli, Hassan
    McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada;German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Boeckx, Bram
    Katholieke Univ Leuven, Dept Human Genet, Lab Translat Genet, Leuven, Belgium;VIB, VIB Ctr Canc Biol, Lab Translat Genet, Ghent, Belgium.
    Braund, Peter S.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;Univ Leicester, Dept Hlth Sci, Leicester, Leics, England;Glenfield Hosp, NIHR, Leicester, Leics, England.
    Breitling, Lutz P.
    McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada;German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Delgado, Graciela
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany.
    Duarte, Nubia E.
    Univ Sao Paulo, Heart Inst, Sao Paulo, Brazil.
    Dufresne, Line
    McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Prevent & Genom Cardiol, Montreal, PQ, Canada.
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Foco, Luisa
    Univ Lubeck, Affiliated Inst, Eurac Res, Inst Biomed, Bolzano, Italy.
    Gijsberts, Crystel M.
    UMC, Lab Expt Cardiol, Utrecht, Netherlands.
    Gong, Yan
    Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA;Univ Florida, Ctr Pharmacogen, Gainesville, FL USA.
    Hartiala, Jaana
    USC, Dept Prevent Med, Los Angeles, CA USA;USC, Dept Biochem & Mol Med, Los Angeles, CA USA;USC, Keck Sch Med, Inst Genet Med, Los Angeles, CA USA.
    Heydarpour, Mahyar
    Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA.
    Hubacek, Jaroslav A.
    Inst Clin & Expt Med, Ctr Expt Med, Prague, Czech Republic.
    Kleber, Marcus
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany.
    Kofink, Daniel
    UMC, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
    Kuukasjarvi, Pekka
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr, Dept Cardiothorac Surg, Tampere, Finland.
    Lee, Vei-Vei
    Texas Heart Inst, Dept Biostat & Epidemiol, Houston, TX 77025 USA.
    Leiherer, Andreas
    VIVIT, Feldkirch, Austria;Private Univ Principal Liechtenstein, Triesen, Liechtenstein;Med Cent Labs, Feldkirch, Austria.
    Lenzini, Petra A.
    Washington Univ, Sch Med, Dept Genet, Stat Genom Div, St Louis, MO 63110 USA;Univ Sao Paulo, Hosp Univ, Ctr Pesquisa Clin, Sao Paulo, Brazil.
    Levin, Daniel
    Univ Dundee, Sch Med, Div Mol & Clin Med, Dundee, Scotland.
    Lyytikainen, Leo-Pekka
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr, Dept Clin Chem, Tampere, Finland;Fimlab Labs, Dept Clin Chem, Tampere, Finland.
    Martinelli, Nicola
    Univ Verona, Dept Med, Verona, Italy.
    Mons, Ute
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;Univ Leicester, Dept Hlth Sci, Leicester, Leics, England;Glenfield Hosp, NIHR, Leicester, Leics, England.
    Nikus, Kjell
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr, Dept Cardiol, Tampere, Finland;Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, Finland.
    Pilbrow, Anna P.
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Sch Med, Atlanta, GA 30322 USA.
    Ploski, Rafal
    Med Univ Warsaw, Dept Med Genet, Warsaw, Poland.
    Sun, Yan, V
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Sch Med, Atlanta, GA 30322 USA;Emory Univ, Sch Med, Dept Biomed Informat, Atlanta, GA 30322 USA.
    Tanck, Michael W. T.
    Univ Utrecht, Dept Internal Med, Sect Gerontol & Geriatr, Utrecht, Netherlands.
    Tang, W. H. Wilson
    Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA;Cleveland Clin, Dept Cardiovasc Med, Heart & Vasc Inst & Ctr Microbiome & Human Hlth, Cleveland, OH 44106 USA.
    Trompet, Stella
    Univ Utrecht, Dept Internal Med, Sect Gerontol & Geriatr, Utrecht, Netherlands;Univ Utrecht, Dept Cardiol, Utrecht, Netherlands.
    van der Laan, Sander W.
    Univ Med Ctr, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands;Univ Utrecht, Div Labs Pharm & Biomed Genet, Leiden Univ Med Ctr, Lab Clin Chem & Hematol, Utrecht, Netherlands.
    van Setten, Jessica
    ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
    Vilmundarson, Ragnar O.
    Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada;Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada.
    Anselmi, Chiara Viviani
    Humanitas Clin & Res Ctr, Dept Cardiovasc Med, Milan, Italy.
    Vlachopoulou, Efthymia
    Univ Helsinki, Transplantat Lab, Med, Helsinki, Finland.
    Boerwinkle, Eric
    Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
    Briguori, Carlo
    Clin Mediterranea, Naples, Italy.
    Carlquist, John F.
    Intertermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;Univ Utah, Dept Internal Med, Cardiol Div, Salt Lake City, UT 84112 USA.
    Carruthers, Kathryn F.
    Univ Edinburgh, Cardiovasc Sci, Edinburgh, Midlothian, Scotland.
    Casu, Gavino
    ATS Sardegna, ASL 3, Nuoro, Italy.
    Deanfield, John
    INESSS, Unite Evaluat Cardiovasc, Montreal, PQ, Canada.
    Deloukas, Panos
    Barts & London Med Sch, William Harvey Res Inst, London, England;Queen Mary Univ London, Ctr Genom Hlth, London, England.
    Dudbridge, Frank
    BHF Cardiovasc Res Ctr, Leicester, Leics, England.
    Fitzpatrick, Natalie
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England.
    Gigante, Bruna
    UMC, Dept Clin Chem & Hematol, Utrecht, Netherlands.
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Lokki, Marja-Liisa
    Univ Helsinki, Transplantat Lab, Med, Helsinki, Finland.
    Lotufo, Paulo A.
    Jagiellonian Univ, Med Coll, Dept Internal Med, Krakow, Poland.
    Marziliano, Nicola
    ATS Sardegna, ASL 3, Nuoro, Italy.
    Mordi, Ify R.
    Univ Dundee, Sch Med, Div Mol & Clin Med, Dundee, Scotland.
    Muhlestein, Joseph B.
    Univ Utah, Dept Internal Med, Cardiol Div, Salt Lake City, UT 84112 USA.
    Cheh, Chris Newton
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston & Program Med & Populat Genet, Brd Inst, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston & Program Med & Populat Genet, Brd Inst, Cambridge, MA USA.
    Pitha, Jan
    Inst Clin & Expt Med, Ctr Expt Med, Prague, Czech Republic.
    Saely, Christoph H.
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England;VIVIT, Feldkirch, Austria;Private Univ Principal Liechtenstein, Triesen, Liechtenstein.
    Samman-Tahhan, Ayman
    Emory Univ, Sch Med, Dept Med, Emory Clin Cardiovasc Res Inst, Atlanta, GA USA.
    Sandesara, Pratik B.
    Emory Univ, Sch Med, Dept Med, Emory Clin Cardiovasc Res Inst, Atlanta, GA USA.
    Teren, Andrej
    Heart Ctr Leipzig, Acad Teaching Hosp Feldkirch, Dept Med & Cardiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Timmis, Adam
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
    Van de Werf, Frans
    Katholieke Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium.
    Wauters, Els
    Katholieke Univ Leuven, Univ Hosp, Dept Resp Med, Resp Oncol Unit, Leuven, Belgium.
    Wilde, Arthur A. M.
    Princess Jawhara Brah Ctr Excellence Res Heredita, Jeddah, Saudi Arabia.
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Stott, David J.
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Algra, Ale
    Univ Med Ctr, Dept Neurol & Neurosurg, Brain Ctr Rudolf Magnus, Utrecht, Netherlands;Univ Med Ctr, Dept Neurol & Neurosurg, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
    Andreassi, Maria G.
    CNR, Inst Clin Physiol, Pisa, Italy.
    Ardissino, Diego
    Parma Univ Hosp, Cardiol Dept, Parma, OH USA.
    Arsenault, Benoit J.
    Inst Univ cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada;Univ Laval, Fac Med, Dept Med, Laval, PQ, Canada.
    Ballantyne, Christie M.
    Baylor Coll Med, Sect Cardiovasc Res, Michael & DeBakey Vet Affairs Med Ctr, Sect Cardiol, Houston, TX 77030 USA;Baylor Coll Med, Dept Med, Sect Cardiol, Houston, TX 77030 USA.
    Bergmeijer, Thomas O.
    St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands.
    Bezzina, Connie R.
    Univ Amsterdam, Clin Epidemiol & Biostat, AMC Heart Ctr, Amsterdam, Netherlands.
    Body, Simon C.
    Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA;Beth Israel Deaconess Med Ctr, Dept Anesthesia Pain & Crit Care, Boston, MA 02215 USA.
    Bogaty, Peter
    Inst Univ Cardiol & Pneumol Quebec, Dept Multidisciplinaire Cardiol, Serv Cardiol, Quebec City, PQ, Canada;INESSS, Unite Evaluat Cardiovasc, Montreal, PQ, Canada;Laval Univ, Inst Univ Cardiol & Pnemol Quebec, Quebec City, PQ, Canada.
    de Borst, Gert J.
    Univ Utrecht, Univ Med Ctr Utrecht, Dept Vasc Surg, Utrecht, Netherlands.
    Brenner, Hermann
    ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
    Burkhardt, Ralph
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Hosp Regensburg, Inst Clin Chem & Lab Med, Regensburg, Germany.
    Carpeggiani, Clara
    CNR, Inst Clin Physiol, Pisa, Italy.
    Condorelli, Gianluigi
    Humanitas Clin & Res Ctr, Dept Cardiovasc Med, Milan, Italy;Humanitas Univ, Dept Biomed Sci, Milan, Italy.
    Cooper-DeHoff, Rhonda M.
    Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA;Univ Florida, Ctr Pharmacogen, Gainesville, FL USA.
    Cresci, Sharon
    Washington Univ, Sch Med, Dept Genet, Stat Genom Div, St Louis, MO 63110 USA;Washington Univ, Sch Med, Dept Med, Cardiovasc Div, St Louis, MO 63110 USA.
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Doughty, Robert N.
    Univ Auckland, Heart Hlth Res Grp, Auckland, New Zealand.
    Drexel, Heinz
    VIVIT, Feldkirch, Austria;Private Univ Principal Liechtenstein, Triesen, Liechtenstein;Drexel Univ, Coll Med, Philadelphia, PA USA.
    Engert, James C.
    McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada;Royal Victoria Hosp, Dept Med, Div Cardiol, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Prevent & Genom Cardiol, Montreal, PQ, Canada.
    Fox, Keith A. A.
    Univ Edinburgh, Cardiol, Edinburgh, Midlothian, Scotland.
    Girelli, Domenico
    Univ Verona, Dept Med, Verona, Italy.
    Hagström, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Hazen, Stanley L.
    Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA;Cleveland Clin, Dept Cardiovasc Med, Heart & Vasc Inst, Cleveland, OH 44106 USA;Cleveland Clin, Dept Cardiovasc Med, Ctr Microbiome & Human Hlth, Cleveland, OH 44106 USA.
    Held, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Hemingway, Harry
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England.
    Hoefer, Imo E.
    UMC, Dept Clin Chem & Hematol, Utrecht, Netherlands.
    Hovingh, G. Kees
    Acad Med Ctr, Dept Vasc Med, Amsterdam, Netherlands.
    Johnson, Julie A.
    Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA;Univ Florida, Ctr Pharmacogen, Gainesville, FL USA;Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA.
    De Jong, Pim A.
    Univ Med Ctr, Dept Radiol, Utrecht, Netherlands.
    Jukema, J. Wouter
    Univ Utrecht, Dept Cardiol, Utrecht, Netherlands;Inter Univ, Cardiol Inst Netherlands, Utrecht, Netherlands.
    Kaczor, Marcin P.
    Jagiellonian Univ, Med Coll, Dept Internal Med, Krakow, Poland.
    Kahonen, Mika
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr, Dept Clin Physiol, Tampere, Finland;Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
    Kettner, Jiri
    Inst Clin & Expt Med, Cardiol Ctr, Prague, Czech Republic.
    Kiliszek, Marek
    Mil Inst Med, Dept Cardiol & Internal Dis, Warsaw, Poland.
    Klungel, Olaf H.
    Univ Med Ctr, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
    Lagerqvist, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Lambrechts, Diether
    Katholieke Univ Leuven, Dept Human Genet, Lab Translat Genet, Leuven, Belgium.
    Laurikka, Jari O.
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr, Dept Cardiothorac Surg, Tampere, Finland;Tampere Univ Hosp, Heart Ctr, Dept Cardiothorac Surg, Tampere, Finland.
    Lehtimaki, Terho
    Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr, Dept Clin Chem, Tampere, Finland;Fimlab Labs, Dept Clin Chem, Tampere, Finland.
    Lindholm, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Mahmoodi, Bakhtawar K.
    St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands.
    Maitland-van der Zee, Anke H.
    Univ Med Ctr, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands;Univ Amsterdam, Acad Med Ctr, Dept Resp Med, Clin & Expt Cardiol, Amsterdam, Netherlands.
    McPherson, Ruth
    Univ Ottawa Heart Inst, Ottawa, ON, Canada;Univ Ottawa, Dept Med, Ottawa, ON, Canada;Univ Ottawa, Dept Biochem, Ottawa, ON, Canada;Univ Ottawa, Dept Microbiol & Immunol, Ottawa, ON, Canada.
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden;Skane Univ Hosp, Dept Internal Med, Malmo, Sweden.
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia;Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, Tartu, Estonia.
    Pepinski, Witold
    Med Univ Bialystok, Dept Forens Med, Bialystok, Poland.
    Olivieri, Oliviero
    Univ Verona, Dept Med, Verona, Italy.
    Opolski, Grzegorz
    Med Univ Warsaw, Dept Cardiol, Warsaw, Poland.
    Palmer, Colin N.
    Ninewells Hosp & Med Sch, Div Mol & Clin Med, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Dundee, Scotland.
    Pasterkamp, Gerard
    UMC, Dept Clin Chem, Utrecht, Netherlands.
    Pepine, Carl J.
    Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA.
    Pereira, Alexandre C.
    Univ Sao Paulo, Heart Inst, Sao Paulo, Brazil.
    Note, Louise
    Humanitas Univ, Dept Biomed Sci, Milan, Italy.
    Quyyumi, Arshed A.
    Emory Univ, Sch Med, Dept Med, Emory Clin Cardiovasc Res Inst, Atlanta, GA USA.
    Richards, A. Mark
    Univ Otago, Christchurch Heart Inst, Dunedin, New Zealand;Natl Univ Singapore, Cardiovasc Res Inst, Singapore, Singapore.
    Sanak, Marek
    Jagiellonian Univ, Med Coll, Dept Internal Med, Krakow, Poland.
    Scholz, Markus
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Sinisalo, Juha
    Univ Helsinki, Helsinki Univ Hosp, Heart & Lung Ctr, Helsinki, Finland.
    Smith, J. Gustav
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden;Skane Univ Hosp, Malmo, Sweden;Wallenberg Ctr Mol Med, Malmo, Sweden;Lund Univ, Lund Univ Diabet Ctr, Lund, Sweden.
    Spertus, John A.
    St Lukes Mid Amer Heart Inst, Kansas City, MO USA;Univ Missouri, St Lukes Hlth Syst, Kansas City, MO 64110 USA.
    Stewart, Alexandre F. R.
    Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada;Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada.
    Szczeklik, Wojciech
    Jagiellonian Univ, Med Coll, Dept Internal Med, Krakow, Poland.
    Szpakowicz, Anna
    Med Univ Bialystok, Dept Cardiol, Bialystok, Poland.
    ten Berg, Jurrien M.
    Intertermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands.
    Thanassoulis, George
    Med Univ Bialystok, Dept Forens Med, Bialystok, Poland;Royal Victoria Hosp, Dept Med, Div Cardiol, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Prevent & Genom Cardiol, Montreal, PQ, Canada.
    Thieiy, Joachim
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Hosp, Clin Chem & Mol Diagnost, Inst Lab Med, Leipzig, Germany.
    van der Graaf, Yolanda
    Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
    Visseren, Frank L. J.
    McGill Univ Hlth Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Montreal, PQ, Canada.
    Waltenberger, Johannes
    Univ Munster, Dept Cardiovasc Med, Munster, Germany.
    Van der Harst, Pim
    Univ Groningen, Univ Med Ctr, Groningen, Netherlands.
    Tardif, Jean-Claude
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada;Univ Montreal, Fac Med, Montreal, PQ, Canada.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Lang, Chim C.
    Univ Dundee, Sch Med, Div Mol & Clin Med, Dundee, Scotland.
    Pare, Guillaume
    McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada;Populat Hlth Res Inst, Hamilton, ON, Canada.
    Brophy, James M.
    McGill Univ Hlth Ctr, Res Inst, Montreal, PQ, Canada.
    Anderson, Jeffrey L.
    Intertermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;Univ Utah, Dept Internal Med, Cardiol Div, Salt Lake City, UT 84112 USA.
    Maerz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany;Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany;Med Univ Graz, Clin Inst Med, Graz, Austria;Med Univ Graz, Chem Lab Diagnost, Graz, Austria.
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Cameron, Vicky A.
    Univ Otago, Christchurch Heart Inst, Dunedin, New Zealand.
    Horne, Benjamin D.
    UMC, Lab Expt Cardiol, Utrecht, Netherlands;Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA.
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England.
    Asselbergs, Folkert W.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England;UMC, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.
    Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events: A GENIUS-CHD Study of Individual Participant Data2019Ingår i: Circulation: Genomic and Precision Medicine, ISSN 2574-8300, Vol. 12, nr 4, artikel-id e002471Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.

    METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.

    RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).

    CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.

  • 13.
    Patel, Riyaz S.
    et al.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
    Tragante, Vinicius
    UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.
    Schmidt, Amand F.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.
    McCubrey, Raymond O.
    Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA.
    Holmes, Michael, V
    Univ Oxford, Nuffield Dept Populat Hlth, Med Res Council Populat Hlth Res Unit, Clin Trial Serv Unit, Oxford, England;Univ Oxford, Nuffield Dept Populat Hlth, Med Res Council Populat Hlth Res Unit, Epidemiol Studies Unit, Oxford, England;Oxford Univ Hosp, Natl Inst Hlth Res, Oxford Biomed Res Ctr, Oxford, England.
    Howe, Laurence J.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England.
    Direk, Kenan
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Leander, Karin
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Virani, Salim S.
    Michael E DeBakey VA Med Ctr, Sect Cardiol, Houston, TX USA;Baylor Coll Med, Sect Cardiovasc Res, Dept Med, Houston, TX 77030 USA.
    Kaminski, Karol A.
    Med Univ Bialystok, Dept Populat Med & Civilizat Dis Prevent, Bialystok, Poland;Med Univ Bialystok, Dept Cardiol, Bialystok, Poland.
    Muehlschlegel, Jochen D.
    Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Allayee, Hooman
    USC, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA;USC, Keck Sch Med, Dept Biochem, Los Angeles, CA USA;USC, Keck Sch Med, Dept Mol Med, Los Angeles, CA USA.
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Alver, Maris
    Univ Tartu, Estonian Genome Ctr, Dept Biotechnol, Inst Genom,Inst Mol & Cell Biol, Tartu, Estonia.
    Baranova, Ekaterina, V
    Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
    Behloui, Hassan
    McGill Univ, Hlth Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Montreal, PQ, Canada.
    Boeckx, Bram
    Katholieke Univ Leuven, Lab Translat Genet, Dept Human Genet, Leuven, Belgium;VIB Ctr Canc Biol, Lab Translat Genet, Leuven, Belgium.
    Braund, Peter S.
    Univ Leicester, Dept Cardiovasc Sci, BHF Cardiovasc Res Ctr, Leicester, Leics, England;Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    Breitling, Lutz P.
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Delgado, Gradela
    Heidelberg Univ, Dept Med 5, Med Fac Mannheim, Heidelberg, Germany.
    Duarte, Nubia E.
    Univ Sao Paulo, Heart Inst, Sao Paulo, Brazil.
    Dube, Marie-Pierre
    Montreal Heart Inst, Montreal, PQ, Canada;Univ Montreal, Fac Med, Montreal, PQ, Canada.
    Dufresne, Line
    McGill Univ, Hlth Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Prevent & Genom Cardiol, Montreal, PQ, Canada.
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Foco, Luisa
    Univ Lubeck, Inst Biomed, Eurac Res, Affiliated Inst, Bolzano, Italy.
    Scholz, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Gijsberts, Crystel M.
    UMC Utrecht, Lab Expt Cardiol, Utrecht, Netherlands.
    Glinge, Charlotte
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Heart Ctr, Amsterdam, Netherlands;Univ Amsterdam, Amsterdam UMC, Clin & Expt Cardiol, Amsterdam Cardiovasc Sci,AMC Heart Ctr, Amsterdam, Netherlands.
    Gong, Yan
    Univ Florida, Dept Pharmacotherapy & Translat Res, Ctr Pharmacogen, Gainesville, FL USA.
    Hartiala, Jaana
    USC, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA;USC, Keck Sch Med, Dept Biochem, Los Angeles, CA USA;USC, Keck Sch Med, Dept Mol Med, Los Angeles, CA USA;USC, Keck Sch Med, Inst Genet Med, Los Angeles, CA USA.
    Heydarpour, Mahyar
    Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Hubacek, Jaroslav A.
    Inst Clin & Expt Med, Ctr Expt Med, Prague, Czech Republic.
    Kleber, Marcus
    Heidelberg Univ, Dept Med 5, Med Fac Mannheim, Heidelberg, Germany.
    Kofink, Daniel
    Montreal Heart Inst, Montreal, PQ, Canada.
    Kotti, Salma
    URCEST CRCEST CRB HUEP UPMC, AP HP, Dept Clin Pharmacol, Platform Clin Res East Paris, Paris, France.
    Kuukasjarvi, Pekka
    Univ Tampere, Dept Cardiothorac Surg, Tampere, Finland.
    Lee, Vei-Vei
    Texas Heart Inst, Dept Biostat & Epidemiol, Houston, TX 77025 USA.
    Leiherer, Andreas
    VIVIT, Feldkirch, Austria;Private Univ Principal Liechtenstein, Triesen, Liechtenstein;Med Cent Labs, Feldkirch, Austria.
    Lenzini, Petra A.
    Washington Univ, Sch Med, Dept Genet, Stat Genom Div, St Louis, MO 63110 USA.
    Levin, Daniel
    Univ Dundee, Div Mol & Clin Med, Sch Med, Dundee, Scotland.
    Lyytikainen, Leo-Pekka
    Univ Tampere, Dept Clin Chem, Tampere, Finland;Fimlab Labs, Dept Clin Chem, Tampere, Finland.
    Martinelli, Nicola
    Univ Verona, Dept Med, Verona, Italy.
    Mons, Ute
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, BHF Cardiovasc Res Ctr, Leicester, Leics, England;Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    Nikus, Kjell
    Univ Tampere, Dept Cardiol, Tampere, Finland;Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, Finland.
    Pilbrow, Anna P.
    Univ Otago, Christchurch Heart Inst, Christchurch, New Zealand.
    Ploski, Rafal
    Med Univ Warsaw, Dept Med Genet, Warsaw, Poland.
    Sun, Yan, V
    Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA;Emory Univ, Sch Med, Dept Biomed Informat, Emory Clin Cardiovasc Res Inst, Atlanta, GA 30322 USA.
    Tanck, Michael W. T.
    Univ Amsterdam, Amsterdam UMC, Clin Epidemiol & Biostat, Amsterdam, Netherlands.
    Tang, W. H. Wilson
    Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA;Cleveland Clin, Dept Cardiovasc Med, Heart & Vasc Inst, Cleveland, OH 44106 USA;Cleveland Clin, Ctr Clin Genom, Cleveland, OH 44106 USA.
    Trompet, Stella
    Cleveland Clin, Sect Gerontol & Geriatr, Dept Internal Med, Cleveland, OH 44106 USA;Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    van der Laan, Sander W.
    Univ Utrecht, Div Labs Pharm & Biomed Genet, Lab Clin Chem & Hematol, UMC Utrecht, Utrecht, Netherlands.
    Van Setten, Jessica
    Univ Utrecht, Div Heart & Lungs, Dept Cardiol, UMC Utrecht, Utrecht, Netherlands.
    Vilmundarson, Ragnar O.
    Univ Ottawa, Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada;Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada.
    Anselmi, Chiara Viviani
    Humanitas Clin & Res Ctr, Dept Cardiovasc Med, Milan, Italy.
    Vlachopoulou, Efthymia
    Helsinki Univ Hosp, Transplantat Lab, Helsinki, Finland;Univ Helsinki, Helsinki, Finland.
    Al Ali, Lawien
    Univ Groningen, Univ Med Ctr, Groningen, Netherlands.
    Boerwinkle, Eric
    Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
    Briguori, Carlo
    Clin Mediterranea, Naples, Italy.
    Carlquist, John F.
    Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;Univ Utah, Cardiol Div, Dept Internal Med, Salt Lake City, UT USA.
    Carruthers, Kathryn F.
    Univ Edinburgh, Cardiovasc Sci, QMRI, Edinburgh, Midlothian, Scotland.
    Casu, Gavino
    Humanitas Clin & Res Ctr, Dept Cardiovasc Med, Milan, Italy;ASSL Nuoro Osped San Francesco, ATS Sardegna, Nuoro, Italy.
    Deanfield, John
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Med Sch, London, England;Queen Mary Univ London, Ctr Genom Hlth, London, England.
    Dudbridge, Frank
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Engstrom, Thomas
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Heart Ctr, Amsterdam, Netherlands;Lund Univ, Dept Cardiol, Lund, Sweden.
    Fitzpatrick, Natalie
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England.
    Fox, Kim
    Royal Brompton Hosp, Natl Heart & Lung Inst, Imperial Coll, London, England;Royal Brompton Hosp, Natl Heart & Lung Inst, Inst Cardiovasc Med & Sci, London, England.
    Gigante, Bruna
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Lokki, Marja-Liisa
    Helsinki Univ Hosp, Transplantat Lab, Helsinki, Finland;Univ Helsinki, Helsinki, Finland.
    Lotufo, Paulo A.
    Univ Sao Paulo, Hosp Univ, Ctr Pesquisa Clin, Sao Paulo, Brazil.
    Marziliano, Nicola
    ATS Sardegna, ASL Nuoro 3, Nuoro, Italy.
    Mordi, Ify R.
    Univ Dundee, Div Mol & Clin Med, Sch Med, Dundee, Scotland.
    Muhlestein, Joseph B.
    Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;Univ Utah, Cardiol Div, Dept Internal Med, Salt Lake City, UT USA.
    Newton-Cheh, Christopher
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
    Pitha, Jan
    Inst Clin & Expt Med, Ctr Expt Med, Prague, Czech Republic.
    Saely, Christoph H.
    VIVIT, Feldkirch, Austria;Private Univ Principal Liechtenstein, Triesen, Liechtenstein;Acad Teaching Hosp Feldkirch, Dept Med & Cardiol, Feldkirch, Austria.
    Samman-Tahhan, Ayman
    Emory Univ, Sch Med, Div Cardiol, Dept Med,Emory Clin Cardiovasc Res Inst, Atlanta, GA 30322 USA.
    Sandesara, Pratik B.
    Emory Univ, Sch Med, Div Cardiol, Dept Med,Emory Clin Cardiovasc Res Inst, Atlanta, GA 30322 USA.
    Teren, Andrej
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Heart Ctr Leipzig, Leipzig, Germany.
    Timmis, Adam
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
    Van de Werf, Frans
    Katholieke Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium.
    Wauters, Els
    Univ Hosp KU Leuven, Resp Oncol Unit, Dept Resp Med, Leuven, Belgium.
    Wilde, Arthur A. M.
    Univ Amsterdam, Amsterdam UMC, Clin & Expt Cardiol, Amsterdam Cardiovasc Sci,AMC Heart Ctr, Amsterdam, Netherlands;Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia.
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Stott, David J.
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Algra, Ale
    Univ Utrecht, Dept Neurol & Neurosurg, Brain Ctr Rudolf Magnus & Julius Ctr Hlth Sci & P, UMC Utrecht, Utrecht, Netherlands.
    Andreassi, Maria G.
    CNR, Inst Clin Physiol, Pisa, Italy.
    Ardissino, Diego
    Parma Univ Hosp, Cardiol Dept, Parma, Italy.
    Arsenault, Benoit J.
    Inst Univ Cardiol & Pneumol Quebec, Ctr Rech, Quebec City, PQ, Canada;Univ Laval, Dept Med, Fac Med, Laval, PQ, Canada.
    Ballantyne, Christie M.
    Baylor Coll Med, Sect Cardiovasc Res, Dept Med, Houston, TX 77030 USA.
    Bergmeijer, Thomas O.
    St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands.
    Bezzina, Connie R.
    Univ Amsterdam, Amsterdam UMC, Clin & Expt Cardiol, Amsterdam Cardiovasc Sci,AMC Heart Ctr, Amsterdam, Netherlands.
    Body, Simon C.
    Harvard Med Sch, Boston, MA 02115 USA;Beth Israel Deaconess Med Ctr, Boston, MA USA.
    Boersma, Eric H.
    Erasmus MC, Dept Cardiol, Thoraxctr, Rotterdam, Netherlands;Erasmus Med Ctr COEUR, Cardiovasc Res Sch, Rotterdam, Netherlands.
    Bogaty, Peter
    Laval Univ, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada.
    Bots, Michiel L.
    Univ Utrecht, Julius Ctr Hlth Sci & Primary Care, UMC Utrecht, Utrecht, Netherlands.
    Brenner, Hermann
    Heidelberg Univ, Network Aging Res, Heidelberg, Germany.
    Brugts, Jasper J.
    Erasmus MC, Dept Cardiol, Thoraxctr, Rotterdam, Netherlands.
    Burkhardt, Ralph
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Hosp Regensburg, Inst Clin Chem & Lab Med, Regensburg, Germany.
    Carpeggiani, Clara
    CNR, Inst Clin Physiol, Pisa, Italy.
    Condorelli, Gianluigi
    Humanitas Univ, Dept Biomed Sci, Milan, Italy.
    Cooper-DeHoff, Rhonda M.
    Univ Florida, Dept Pharmacotherapy & Translat Res, Ctr Pharmacogen, Gainesville, FL USA;Univ Florida, Div Cardiovasc Med, Coll Med, Gainesville, FL USA.
    Cresci, Sharon
    Washington Univ, Sch Med, Dept Genet, Stat Genom Div, St Louis, MO 63110 USA;Washington Univ, Dept Med, Cardiovasc Div, St Louis, MO 63110 USA.
    Danchin, Nicolas
    Univ Paris 05, Hop Europeen Georges Pompidou, AP HP, Dept Cardiol, Paris, France;Univ Paris 05, FACT, Paris, France;Univ Paris 05, Paris, France.
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Doughty, Robert N.
    Univ Auckland, Heart Hlth Res Grp, Auckland, New Zealand.
    Drexel, Heinz
    VIVIT, Feldkirch, Austria;Private Univ Principal Liechtenstein, Triesen, Liechtenstein;Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
    Engert, James C.
    McGill Univ, Res Inst, Hlth Ctr, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Prevent & Genom Cardiol, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Royal Victoria Hosp, Dept Med, Div Cardiol, Montreal, PQ, Canada.
    Fox, Keith A. A.
    Univ Edinburgh, Edinburgh, Midlothian, Scotland.
    Girelli, Domenico
    Univ Verona, Dept Med, Verona, Italy.
    Grobbee, Diederick E.
    Univ Utrecht, Julius Ctr Hlth Sci & Primary Care, UMC Utrecht, Utrecht, Netherlands.
    Hagström, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Hazen, Stanley L.
    Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA;Cleveland Clin, Dept Cardiovasc Med, Ctr Microbiome & Human Hlth, Heart & Vasc Inst, Cleveland, OH 44106 USA.
    Held, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Hemingway, Harry
    UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England.
    Hoefer, Imo E.
    UMC Utrecht, Dept Clin Chem & Hematol, Utrecht, Netherlands.
    Hovingh, G. Kees
    Acad Med Ctr, Dept Vasc Med, Amsterdam, Netherlands.
    Jabbari, Reza
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Heart Ctr, Amsterdam, Netherlands.
    Johnson, Julie A.
    Univ Florida, Dept Pharmacotherapy & Translat Res, Ctr Pharmacogen, Gainesville, FL USA;Univ Florida, Div Cardiovasc Med, Coll Med, Gainesville, FL USA.
    Jukema, J. Wouter
    Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands;LUMC, Einthoven Lab Expt Vasc Med, Leiden, Netherlands;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands.
    Kaczor, Marcin P.
    Jagiellonian Univ, Dept Internal Med, Med Coll, Krakow, Poland.
    Kahonen, Mika
    Univ Tampere, Dept Clin Physiol, Tampere, Finland;Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
    Kettner, Jiri
    Inst Clin & Expt Med, Cardiol Ctr, Prague, Czech Republic.
    Kiliszek, Marek
    Mil Inst Med, Dept Cardiol & Internal Dis, Warsaw, Poland.
    Klungel, Olaf H.
    Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
    Lagerqvist, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Lambrechts, Diether
    Katholieke Univ Leuven, Lab Translat Genet, Dept Human Genet, Leuven, Belgium;VIB Ctr Canc Biol, Lab Translat Genet, Leuven, Belgium.
    Laurikka, Jari O.
    Univ Tampere, Dept Cardiothorac Surg, Finnish Cardiovasc Res Ctr, Fac Med & Life Sci, Tampere, Finland;Tampere Univ Hosp, Dept Cardio Thorac Surg, Heart Ctr, Tampere, Finland.
    Lehtimaki, Terho
    Univ Tampere, Dept Clin Chem, Tampere, Finland;Fimlab Labs, Dept Clin Chem, Tampere, Finland.
    Lindholm, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Mahmoodi, B. K.
    St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands.
    Maitland-van der Zee, Anke H.
    Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands;Univ Amsterdam, Dept Resp Med, Acad Med Ctr, Amsterdam, Netherlands.
    McPherson, Ruth
    Univ Ottawa, Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada;Univ Ottawa, Dept Med, Ottawa, ON, Canada;Univ Ottawa, Dept Biochem, Ottawa, ON, Canada;Univ Ottawa, Dept Microbiol & Immunol, Ottawa, ON, Canada.
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden;Skane Univ Hosp, Dept Internal Med, Malmo, Sweden.
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Dept Biotechnol, Inst Genom,Inst Mol & Cell Biol, Tartu, Estonia.
    Niemcunowicz-Janica, Anna
    Med Univ Bialystok, Dept Forens Med, Bialystok, Poland.
    Olivieri, Oliviero
    Univ Verona, Dept Med, Verona, Italy.
    Opolski, Grzegorz
    Med Univ Warsaw, Chair 1, Warsaw, Poland;Med Univ Warsaw, Dept Cardiol, Warsaw, Poland.
    Palmer, Colin N.
    Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Div Mol & Clin Med, Dundee, Scotland.
    Pasterkamp, Gerard
    UMC Utrecht, Dept Clin Chem, Utrecht, Netherlands.
    Pepine, Carl J.
    Univ Florida, Div Cardiovasc Med, Coll Med, Gainesville, FL USA.
    Pereira, Alexandre C.
    Univ Sao Paulo, Heart Inst, Sao Paulo, Brazil.
    Pilote, Louise
    McGill Univ, Hlth Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Dept Med, Montreal, PQ, Canada.
    Quyyumi, Arshed A.
    Emory Univ, Sch Med, Div Cardiol, Dept Med,Emory Clin Cardiovasc Res Inst, Atlanta, GA 30322 USA.
    Richards, A. Mark
    Univ Otago, Christchurch Heart Inst, Christchurch, New Zealand;Natl Univ Singapore, Cardiovasc Res Inst, Singapore, Singapore.
    Sanak, Marek
    Jagiellonian Univ, Dept Internal Med, Med Coll, Krakow, Poland.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Simon, Tabassome
    Sorbonne Univ, Platform Clin Res East Paris URCEST CRCEST CRB HU, Dept Clin Pharmacol, AP HP,FACT, Paris, France;Paris Sorbonne Univ, UPMC Site St Antoine, Paris, France.
    Sinisalo, Juha
    Heart and Lung Centre (J.S.), Helsinki University Hospital and University of Helsinki, Finland.
    Smith, J. Gustav
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Lund Univ, Dept Cardiol Clin Sci, Skane Univ Hosp, Lund, Sweden;Lund Univ, Wallenberg Ctr Mol Med, Diabet Ctr, Lund, Sweden.
    Spertus, John A.
    Univ Missouri, St Lukes Mid Amer Heart Inst, Kansas City, MO 64110 USA;St Lukes Mid Amer Heart Insti, Kansas City, MO USA.
    Stender, Steen
    Copenhagen Univ Hosp, Dept Clin Biochem, Gentofte, Denmark.
    Stewart, Alexandre F. R.
    Univ Ottawa, Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada;Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada.
    Szczeklik, Wojciech
    Jagiellonian Univ, Dept Internal Med, Med Coll, Krakow, Poland.
    Szpakowicz, Anna
    Med Univ Bialystok, Dept Cardiol, Bialystok, Poland.
    Tardif, Jean-Claude
    Montreal Heart Inst, Montreal, PQ, Canada;Univ Montreal, Fac Med, Montreal, PQ, Canada.
    ten Berg, Jurrien M.
    St Antonius Hosp, Dept Cardiol, Nieuwegein, Netherlands.
    Tfelt-Hansen, Jacob
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Heart Ctr, Copenhagen, Denmark;Univ Copenhagen, Fac Med Sci, Dept Forens Med, Copenhagen, Denmark.
    Thanassoulis, George
    McGill Univ, Hlth Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Prevent & Genom Cardiol, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Royal Victoria Hosp, Dept Med, Div Cardiol, Montreal, PQ, Canada.
    Thiery, Joachim
    Univ Hosp, Inst Lab Med, Clin Chem & Mol Diagnost, Leipzig, Germany.
    Torp-Pedersen, Christian
    Aalborg Univ Hosp, Dept Hlth Sci & Technol, Unit Epidemiol & Biostat, Aalborg, Denmark.
    van der Graaf, Yolanda
    Univ Utrecht, Julius Ctr Hlth Sci & Primary Care, UMC Utrecht, Utrecht, Netherlands.
    Visseren, Frank L. J.
    Univ Utrecht, Dept Vasc Med, UMC Utrecht, Utrecht, Netherlands.
    Waltenberger, Johannes
    Univ Munster, Dept Cardiovasc Med, Munster, Germany.
    Weeke, Peter E.
    Herlev & Gentofte Hosp, Dept Cardiol, Hellerup, Denmark.
    Van der Harst, Pim
    Univ Groningen, Univ Med Ctr, Groningen, Netherlands.
    Lang, Chim C.
    Univ Dundee, Div Mol & Clin Med, Sch Med, Dundee, Scotland.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Cameron, Vicky A.
    Univ Otago, Christchurch Heart Inst, Christchurch, New Zealand.
    Anderson, Jeffrey L.
    Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;Univ Utah, Cardiol Div, Dept Internal Med, Salt Lake City, UT USA.
    Brophy, James M.
    McGill Univ, Hlth Ctr, Ctr Outcomes Res & Evaluat, Res Inst, Montreal, PQ, Canada;McGill Univ Hlth Ctr, Dept Med, Montreal, PQ, Canada.
    Pare, Guillaume
    McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada;Populat Hlth Res Inst, Hamilton, ON, Canada.
    Horne, Benjamin D.
    Intermt Med Ctr, Intermt Heart Inst, Salt Lake City, UT USA;Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA.
    Marz, Winfried
    Heidelberg Univ, Dept Med 5, Med Fac Mannheim, Heidelberg, Germany;Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, BHF Cardiovasc Res Ctr, Leicester, Leics, England;Glenfield Hosp, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    Hingorani, Aroon D.
    Institute of Cardiovascular Science, Faculty of Population Health Science, University College London, United Kingdom.
    Asselbergs, Folkert W.
    UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England;UCL, Inst Hlth Informat, Fac Populat Hlth Sci, London, England;UMC Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
    Subsequent Event Risk in Individuals With Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium2019Ingår i: Circulation: Genomic and Precision Medicine, ISSN 2574-8300, Vol. 12, nr 4, artikel-id e002470Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.

    METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.

    RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.

    CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.

  • 14.
    Siegbahn, Agneta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Johansson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Hagström, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Varenhorst, Christoph
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Bertilsson, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Barratt, Bryan J.
    Becker, Richard C.
    Himmelmann, Anders
    James, Stefan K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Katus, Hugo A.
    Steg, Philippe G.
    Storey, Robert F.
    Syvanen, Ann-Christine
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Evaluation of the Effect of Interleukin 18 Associated Genetic Polymorphisms on Risk of Cardiovascular Events in Patients With Acute Coronary Syndrome2013Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, nr 22Artikel i tidskrift (Övrigt vetenskapligt)
  • 15.
    Ueland, Thor
    et al.
    Univ Oslo, Res Inst Internal Med, Natl Hosp, Oslo, Norway;Univ Oslo, KG Jebsen Inflammatory Res Ctr, Oslo, Norway;Univ Tromso, KG Jebsen Thrombosis Res & Expertise Ctr, Tromso, Norway.
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ghukasyan, Tatevik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michelsen, Annika E.
    Univ Oslo, Res Inst Internal Med, Natl Hosp, Oslo, Norway.
    Aukrust, Pål
    Univ Oslo, Res Inst Internal Med, Natl Hosp, Oslo, Norway;Univ Oslo, KG Jebsen Inflammatory Res Ctr, Oslo, Norway;Univ Tromso, KG Jebsen Thrombosis Res & Expertise Ctr, Tromso, Norway;Oslo Univ Hosp, Rikshosp, Sect Clin Immunol & Infect Dis, Oslo, Norway.
    Becker, Richard C.
    Univ Cincinnati, Coll Med, Div Cardiovasc Hlth & Dis, Heart Lung & Vasc Inst, Cincinnati, OH USA.
    Bertilsson, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Himmelmann, Anders
    AstraZeneca Res & Dev, Gothenburg, Sweden.
    James, Stefan K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England.
    Kontny, Frederic
    Stavanger Univ Hosp, Dept Cardiol, Stavanger, Norway;Drammen Heart Ctr, Drammen, Norway.
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial2018Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, nr 2, artikel-id e007009Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 16.
    Ueland, Thor
    et al.
    Research Institute of Internal Medicine, National Hospital, University of Oslo, Norway ; K.G. Jebsen Inflammatory Research Center, University of Oslo, Norway ; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Norway .
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Ghukasyan, Tatevik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michelsen, Annika E
    From the Research Institute of Internal Medicine, National Hospital, University of Oslo, Norway .
    Becker, Richard C
    Division of Cardiovascular Health and Disease, Heart, Lung and Vascular Institute, University of Cincinnati College of Medicine, Ohio, USA.
    Bertilsson, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Himmelmann, Anders
    AstraZeneca Research and Development, Gothenburg, Sweden .
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Storey, Robert F
    Department of Infection, Immunity, and Cardiovascular Disease, University of Sheffield, United Kingdom .
    Kontny, Frederic
    Department of Cardiology, Stavanger University Hospital, Norway ; Drammen Heart Center, Norway .
    Aukrust, Pål
    Research Institute of Internal Medicine, National Hospital, University of Oslo, Norway ; K.G. Jebsen Inflammatory Research Center, University of Oslo, Norway ; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Norway ; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Norway .
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Admission Levels of DKK1 (Dickkopf-1) Are Associated With Future Cardiovascular Death in Patients With Acute Coronary Syndromes2019Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 39, nr 2, s. 294-302Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

  • 17.
    Varenhorst, Christoph
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Johansson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Barratt, Bryan J.
    Hagström, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Becker, Richard C.
    James, Stefan K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Katus, Hugo A.
    Husted, Steen
    Steg, Ph. Gabriel
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Voora, Deepak
    Teng, Renli
    Storey, Robert F.
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Effect of genetic variations on ticagrelor plasma levels and clinical outcomes2015Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, nr 29, s. 1901-1912Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims Ticagrelor, a direct-acting P2Y(12)-receptor antagonist, is rapidly absorbed and partly metabolized to the major metabolite AR-C124910XX (ARC). To identify single-nucleotide polymorphisms (SNPs) associated with pharmacokinetics of ticagrelor and clinical outcomes, we performed a genome-wide association study (GWAS) in patients treated with ticagrelor in the PLATO trial. Methods and results A two-stage design was used for the GWAS with discovery (discovery phase: n = 1812) and replication cohorts (replication phase: n = 1941). The steady-state area under the curve (AUCss) values, estimated by the population pharmacokinetic (PK) models, were log transformed and analysed on a genome-wide scale using linear regression. SNPs were analysed against clinical events using Cox-regression in 4990 patients. An SNP (rs113681054) in SLCO1B1 was associated with levels of ticagrelor (P = 1.1 x 10(-6)) and ARC (P = 4.6 x 10(-13)). This SNP is in linkage disequilibrium with a functional variant (rs4149056) that results in decreased OATP1B1 transporter activity. Ticagrelor levels were also associated with two independent SNPs (rs62471956, P = 7.7 x 10(-15) and rs56324128, P = 9.7 x 10(-12)) in the CYP3A4 region. Further, ARC levels were associated with rs61361928 (P = 3.0 x 10(-14)) in UGT2B7. At all loci, the effects were small. None of the identified SNPs that affected ticagrelor PK were associated with the primary composite outcome (cardiovascular death myocardial infarction, and stroke), non-CABG-related bleeds or investigator-reported dyspnoea. Conclusion In patients with ACS, ticagrelor pharmacokinetics is influenced by three genetic loci (SLCO1B1, UGT2B7, and CYP3A4). However, the modest genetic effects on ticagrelor plasma levels did not translate into any detectable effect on efficacy or safety during ticagrelor treatment.

  • 18.
    Varenhorst, Christoph
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Renlund, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Kunadian, V.
    Newcastle Univ, Fac Med Sci, Newcastle Upon Tyne, Tyne & Wear, England..
    James, Stefan K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Steg, P. G.
    Hop Bichat Claude Bernard, Dept Hosp Univ FIRE, Paris, France..
    Katus, H. A.
    Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany..
    Himmelmann, A.
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    Aylward, P.
    Flinders Univ S Australia, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.;Med Ctr, Adelaide, SA, Australia..
    Maurer, G.
    Med Univ Vienna, Vienna, Austria..
    Storey, R. F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England..
    Armstrong, P. W.
    Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada..
    Gibson, M.
    Harvard Med Sch, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA USA..
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Successful reperfusion is associated with lower levels of markers of myocardial damage and dysfunction in ST-elevation but not in non-ST-elevation myocardial infarction: insights from the PLATO trial2016Ingår i: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, s. 1282-1283Artikel i tidskrift (Refereegranskat)
  • 19.
    Voora, Deepak
    et al.
    Duke Clinical Research Institute, Durham, NC, USA.
    Ginsburg, GS
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Platelet RNA as a novel biomarker for the response to antiplatelet therapy2014Ingår i: Future Cardiology, ISSN 1479-6678, Vol. 10, nr 1, s. 9-12Artikel i tidskrift (Refereegranskat)
  • 20.
    Zewinger, Stephen
    et al.
    Saarland Univ Hosp, Dept Internal Med 4, Homburg, Germany..
    Kleber, Marcus E.
    Friedrich Schiller Univ, Inst Nutr, Jena, Germany..
    Tragante, Vinicius
    McCubrey, Raymond O.
    Univ Utah Sch Med, Intermountain Heart Inst, Intermountain Med Ctr, Salt Lake City, UT USA..
    Schmidt, Amand F.
    Direk, Kenan
    Laufs, Ulrich
    Saarland Univ Hosp, Dept Internal Med 3, Homburg, Germany..
    Werner, Christian
    Saarland Univ Hosp, Dept Internal Med 3, Homburg, Germany..
    Koenig, Wolfgang
    Univ Ulm Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany.;Tech Univ Munich, Deutsch Herzzentrum M nchen, Munich, Germany.;Partner site Munich Heart Alliance, German Ctr Cardiovasc Res DZHK, Munich, Germany..
    Rothenbacher, Dietrich
    German Canc Ctr DKFZ, Div Clin Epidemiol & Ageing Res, Heidelberg, Germany.;Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany.;German Ctr Cardiovasc Res DZHK eV, Kiel, Germany..
    Mons, Ute
    German Canc Ctr DKFZ, Div Clin Epidemiol & Ageing Res, Heidelberg, Germany..
    Breitling, Lutz P.
    German Canc Ctr DKFZ, Div Clin Epidemiol & Ageing Res, Heidelberg, Germany.;Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany..
    Brenner, Herrmann
    Heidelberg Univ, Dept Med, Network Ageing Res, Mannheim, Germany.;German Canc Ctr DKFZ, Div Clin Epidemiol & Ageing Res, Heidelberg, Germany..
    Jennings, Richard T.
    Saarland Univ Hosp, Dept Internal Med 4, Homburg, Germany.;Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany..
    Petrakis, Ioannis
    Saarland Univ Hosp, Dept Internal Med 4, Homburg, Germany..
    Triem, Sarah
    Saarland Univ Hosp, Dept Internal Med 4, Homburg, Germany..
    Klug, Mira
    Saarland Univ Hosp, Dept Internal Med 4, Homburg, Germany..
    Filips, Alexandra
    Saarland Univ Hosp, Dept Internal Med 4, Homburg, Germany.;UCL, Inst Cardiovasc Sci Facultyof Populat Hlth Sc, London, England..
    Blankenberg, Stefan
    Waldeyer, Christoph
    Sinning, Christoph
    Schnabel, Renate B.
    Lackner, Karl J.
    Univ Med Ctr Mainz, Inst Clin Chem & Lab Med, Mainz, Germany..
    Vlachopoulou, Efthymia
    Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki, Finland..
    Nygard, Ottar
    Univ Bergen, Dept Clin Sci, Bergen, Norway.;Haukeland Hosp, Dept Heart Dis, Bergen, Norway..
    Svingen, Gard Frodahl Tveitevag
    Univ Bergen, Dept Clin Sci, Bergen, Norway.;Haukeland Hosp, Dept Heart Dis, Bergen, Norway..
    Pedersen, Eva Ringdal
    Univ Bergen, Dept Clin Sci, Bergen, Norway.;Haukeland Hosp, Dept Heart Dis, Bergen, Norway..
    Tell, Grethe S.
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.;Helsinki Univ Hosp, Heart & Lung Ctr, Helsinki, Finland..
    Sinisalo, Juha
    Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria..
    Nieminen, Markku S.
    Natl Univ Singapore, Cardiovasc Res Inst, Singapore, Singapore..
    Laaksonen, Reijo
    Tampere Univ, Sch Med, Tampere, Finland.;Tampere Univ Hosp, Finnish Clin Biobank Tampere, Tampere, Finland..
    Trompet, Stella
    German Ctr Cardiovasc Res DZHK eV, Kiel, Germany.;Leiden Univ Med Ctr, Dept Geriat & Gerontol, Leiden, Netherlands.;Leiden Univ Med Ctr, Dept Cardiol, Leiden, Netherlands.;Leiden Univ Med Ctr, Einthoven Lab Expt Vasc Med, Leiden, Netherlands..
    Smit, Roelof A. J.
    Univ Utah Sch Med, Intermountain Heart Inst, Intermountain Med Ctr, Salt Lake City, UT USA.;Leiden Univ Med Ctr, Dept Geriat & Gerontol, Leiden, Netherlands.;Leiden Univ Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Sattar, Naveed
    Heidelberg Univ, Dept Med, Mannheim, Germany.;Helsinki Univ Hosp, Heart & Lung Ctr, Helsinki, Finland..
    Jukema, J. Wouter
    Helsinki Univ Hosp, Heart & Lung Ctr, Helsinki, Finland.;Leiden Univ Med Ctr, Einthoven Lab Expt Vasc Med, Leiden, Netherlands.;Leiden Univ Med Ctr, Einthoven Lab Expt Vasc Med, Leiden, Netherlands.;Inst Netherlands, Interunivers Cardiol, Utrecht, Netherlands..
    Groesdonk, Heinrich V.
    Saarland Univ Hosp, Dept Anesthesiol Intens Care Med & Pain Med, Homburg, Germany.;German Ctr Cardiovasc Res DZHK eV, Kiel, Germany.;Leiden Univ Med Ctr, Einthoven Lab Expt Vasc Med, Leiden, Netherlands.;Leiden Univ Med Ctr, Einthoven Lab Expt Vasc Med, Leiden, Netherlands.;Univ Otago, Christchurch Heart Inst, Christchurch, New Zealand..
    Delgado, Graciela
    Univ Utah Sch Med, Intermountain Heart Inst, Intermountain Med Ctr, Salt Lake City, UT USA.;Univ Glasgow, Inst Cardiovascular & Med Sci, Cardiovascular Res Ctr, BHF Glasgow, Glasgow, Lanark, Scotland.;Inst Netherlands, Interunivers Cardiol, Utrecht, Netherlands..
    Stojakovic, Tatjana
    Heidelberg Univ, Dept Med, Mannheim, Germany.;Leiden Univ Med Ctr, Einthoven Lab Expt Vasc Med, Leiden, Netherlands.;Univ Glasgow, Inst Cardiovascular & Med Sci, Cardiovascular Res Ctr, BHF Glasgow, Glasgow, Lanark, Scotland..
    Pilbrow, Anna P.
    Leiden Univ Med Ctr, Einthoven Lab Expt Vasc Med, Leiden, Netherlands..
    Cameron, Vicky A.
    Heart & Lungs Div, Dept Cardiol, Utrecht, Netherlands.;Helsinki Univ Hosp, Heart & Lung Ctr, Helsinki, Finland.;Univ Glasgow, Inst Cardiovascular & Med Sci, Cardiovascular Res Ctr, BHF Glasgow, Glasgow, Lanark, Scotland.;Univ Otago, Christchurch Heart Inst, Christchurch, New Zealand..
    Richards, A. Mark
    Univ Otago, Christchurch Heart Inst, Christchurch, New Zealand.;Natl Univ Singapore, Cardiovasc Res Inst, Singapore, Singapore..
    Doughty, Robert N.
    Univ Glasgow, Inst Cardiovascular & Med Sci, Cardiovascular Res Ctr, BHF Glasgow, Glasgow, Lanark, Scotland.;Univ Auckland, Hlth Res Grp, Auckland, New Zealand..
    Gong, Yan
    Heart & Lungs Div, Dept Cardiol, Utrecht, Netherlands.;Univ Utah Sch Med, Intermountain Heart Inst, Intermountain Med Ctr, Salt Lake City, UT USA.;Univ Glasgow, Inst Cardiovascular & Med Sci, Cardiovascular Res Ctr, BHF Glasgow, Glasgow, Lanark, Scotland..
    Cooper-DeHoff, Rhonda
    Johnson, Julie
    German Ctr Cardiovasc Res DZHK eV, Kiel, Germany.;Univ Otago, Christchurch Heart Inst, Christchurch, New Zealand..
    Scholz, Markus
    Univ Utah Sch Med, Intermountain Heart Inst, Intermountain Med Ctr, Salt Lake City, UT USA.;Natl Univ Singapore, Cardiovasc Res Inst, Singapore, Singapore.;Univ Leipzig, D-RES CTR C Leipzig, Germany..
    Beutner, Frank
    Univ Leipzig, Leipzig, Germany..
    Thiery, Joachim
    Univ Hosp, Leipzig, Germany..
    Smith, J. Gustav
    Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden.;Skane Univ Hoswpital, Lund, Sweden..
    Vilmundarson, Ragnar O.
    Univ Ottawa Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    McPherson, Ruth
    Univ Ottawa Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Stewart, Alexandre F. R.
    Natl Univ Singapore, Cardiovasc Res Inst, Singapore, Singapore.;Univ Florida, Dept Pharmacotherapy, Colleges Pharm, Gainesville, FL USA.;Univ Florida, Dept Pharmacotherapy, Translat Res & Ctr Pharmac, Gainesville, FL USA.;Univ Ottawa Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada.;Washington Univ, Sch Med, St Louis, MO USA..
    Cresci, Sharon
    Univ Ottawa Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada.;Washington Univ, Sch Med, Dept Med, St Louis, MO USA.;Washington Univ, Sch Med, Dept Genet, St Louis, MO USA..
    Lenzini, Petra A.
    Inst Med Informat, Stat & Epidemiol, Leipzig, Germany.;Univ Ottawa Heart Inst, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada.;Washington Univ, Sch Med, Stat Genom Div, Dept Genet, St Louis, MO USA..
    Spertus, John A.
    Inst Med Informat, Stat & Epidemiol, Leipzig, Germany.;St Lukes Mid Amer Heart Inst, Kansas City, MO USA.;Univ Missouri, Dept Biomed Hlth Informat, Kansas City, MO USA..
    Olivieri, Oliviero
    Heart & Lungs Div, Dept Cardiol, Utrecht, Netherlands.;Univ Verona, Dept Med, Verona, Italy..
    Girelli, Domenico
    Univ Florida, Dept Pharmacotherapy, Colleges Pharm, Gainesville, FL USA.;Univ Florida, Dept Pharmacotherapy, Translat Res & Ctr Pharmac, Gainesville, FL USA.;Univ Verona, Dept Med, Verona, Italy..
    Martinelli, Nicola I.
    Univ Verona, Dept Med, Verona, Italy..
    Leiherer, Andreas
    Univ Florida, Dept Pharmacotherapy, Colleges Pharm, Gainesville, FL USA.;Univ Florida, Dept Pharmacotherapy, Translat Res & Ctr Pharmac, Gainesville, FL USA.;Inst Med Informat, Stat & Epidemiol, Leipzig, Germany.;Vorarlberg Inst Vasc Invest & Treatment, Feldkirch, Austria.;Principal Liechtenstein, Private Univ, Triesen, Liechtenstein..
    Saely, Christoph H.
    Vorarlberg Inst Vasc Invest & Treatment, Feldkirch, Austria.;Principal Liechtenstein, Private Univ, Triesen, Liechtenstein..
    Drexel, Heinz
    Heart & Lungs Div, Dept Cardiol, Utrecht, Netherlands.;Univ Florida, Dept Pharmacotherapy, Colleges Pharm, Gainesville, FL USA.;Univ Florida, Dept Pharmacotherapy, Translat Res & Ctr Pharmac, Gainesville, FL USA.;Vorarlberg Inst Vasc Invest & Treatment, Feldkirch, Austria.;Principal Liechtenstein, Private Univ, Triesen, Liechtenstein.;Acad Teaching Hosp Feldkirch, Dept Med & Cardiol, Feldkirch, Austria.;Drexel Univ, Coll Med, Philadelphia, PA USA..
    Muendlein, Axel
    Vorarlberg Inst Vasc Invest & Treatment, Feldkirch, Austria..
    Braund, Peter S.
    Univ Florida, Dept Pharmacotherapy, Colleges Pharm, Gainesville, FL USA.;Univ Florida, Dept Pharmacotherapy, Translat Res & Ctr Pharmac, Gainesville, FL USA.;Univ Leicester, Glenfield Hosp, Dept Cardiovascular Sci, BHF Cardiovascular Res Ctr, Leicester, Leics, England..
    Nelson, Christopher P.
    Univ Leicester, Glenfield Hosp, Dept Cardiovascular Sci, BHF Cardiovascular Res Ctr, Leicester, Leics, England..
    Samani, Nilesh J.
    Heart & Lungs Div, Dept Cardiol, Utrecht, Netherlands.;Leicester NIHR Biomed Res Unit Cardiovasc Dis, Glenfield Hosp, Leicester, Leics, England.;Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden.;Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden..
    Kofink, Daniel
    Hoefer, Imo E.
    Pasterkamp, Gerard
    Quyyumi, Arshed A.
    Emory Univ, Emory Clin Cardiovascular Res Inst, Atlanta, GA USA.;Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden.;Uppsala Univ, Dept Med Sci, Clin Chem, Uppsala, Sweden..
    Ko, Yi-An
    Hartiala, Jaana A.
    Univ Southern Calif, Los Angeles, CA USA.;Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden..
    Allayee, Hooman
    Tang, W. H. Wilson
    Hazen, Stanley L.
    Heidelberg Univ, Dept Med, Mannheim, Germany..
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Held, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Hagström, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Siegbahn, A
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Karp, Igor
    Univ Western Ontario, Schulich Sch Med & Dent, Dept Epidemiol & Biostat, London, England..
    Labos, Christopher
    Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden.;McGill Univ, Dept Med, Montreal, PQ, Canada..
    Pilote, Louise
    McGill Univ, Dept Med, Montreal, PQ, Canada..
    Engert, James C.
    McGill Univ, Dept Med, Montreal, PQ, Canada..
    Brophy, James M.
    McGill Univ, Dept Med, Montreal, PQ, Canada.;Univ Laval, Dept Med, Laval, PQ, Canada..
    Thanassoulis, George
    McGill Univ, Dept Med, Montreal, PQ, Canada..
    Bogaty, Peter
    McGill Univ, Dept Med, Montreal, PQ, Canada..
    Szczeklik, Wojciech
    Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden.;Jagielonian Univ, Coll Med, Krakow, Poland..
    Kaczor, Marcin
    Jagielonian Univ, Coll Med, Krakow, Poland..
    Sanak, Marek
    Jagielonian Univ, Coll Med, Krakow, Poland..
    Virani, Salim S.
    Baylor Coll Med, Cardiol Sect, Michael DeBakey Vet Affairs Med Ctr, Houston, TX USA..
    Ballantyne, Christie M.
    Baylor Coll Med, Sect Cardiovasc, Dept Med, Houston, TX USA..
    Lee, Vei-Vei
    Texas Heart Inst, Dept Biostat 7, Houston, TX USA..
    Boerwinkle, Eric
    Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden.;Univ Texas Houston, Sch Publ Hlth, Houston, TX USA..
    Holmes, Michael V.
    Univ Oxford, Med Res Council Populat Hlth Res Unit, Oxford, England.;Univ Oxford, Natl Inst Hlth Res Oxford Biomed Res Ctr, Oxford, England..
    Horne, Benjamin D.
    Univ Oxford, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Epidemiol Studies Unit CTSU, Nuffield Dept Populat Hlth, Oxford, England..
    Hingorani, Aroon
    Asselbergs, Folkert W.
    Durrer Ctr Cardiogenet Res, ICIN, Utrecht, Netherlands..
    Patel, Riyaz S.
    Kraemer, Bernhard K.
    Scharnagl, Hubert
    Fliser, Danilo
    Maerz, Winfried
    Saarland Univ Hosp, Dept Internal Med 4, Homburg, Germany.;Synlab Acad, Synlab Holding, Mannheim, Germany..
    Speer, Thimoteus
    Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study2017Ingår i: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 5, nr 7, s. 534-543Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.

    Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts.

    Findings: The median follow-up was 9.9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1.44, 95% CI 1.14-1.83) and the presence of either LPA SNP (1.88, 1.40-2.53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0.95, 0.81-1.11 and either LPA SNP 1.10, 0.92-1.31) or cardiovascular mortality (0.99, 0.81-1.2 and 1.13, 0.90-1.40, respectively) or in the validation studies.

    Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.

  • 21.
    Åkerblom, Axel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Biomarkers of Renal Function in Acute Coronary Syndromes2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The thesis aimed to investigate cystatin C and creatinine-based estimates of glomerular filtration rate (eGFR), both at admission and during follow-up, on the combined endpoint of cardiovascular death and myocardial infarction in patients with acute coronary syndrome (ACS). We also evaluated two cystatin C assays and assessed genetic determinants of cystatin C concentrations.

    We used the PLATelet inhibition and Patient Outcomes study, where all types of ACS patients (n=18624) were randomized to ticagrelor or clopidogrel treatment. Multivariable Cox regression models, including clinical variables and biomarkers (troponin and NT-proBNP), and c-statistics were calculated.

    Cystatin C and the creatinine-based CKD-EPI equation exhibited similar significant prognostic impact on the combined endpoint, with Area Under Curves (AUC) 0.6923 and 0.6941, respectively. Follow-up samples of renal biomarkers did not improve risk prediction.

    Patients randomized to ticagrelor treatment were associated with a non-sustained larger increase in renal markers at discharge, but neither the change nor the difference between the randomized groups affected cardiovascular risk.

    Two different cystatin C assays exhibited good correlation 0.86 (95% confidence interval 0.85-0.86), however moderate level of agreement. Risk prediction with a combination of creatinine and cystatin C did not outperform the creatinine-based CKD-EPI equation, AUC: 0.6913 and 0.6924, respectively (n=13050).

    The genetic polymorphism rs6048952 independently affected the cystatin C concentration with mean levels of 0.85mg/L, 0.80mg/L and 0.73mg/L for the A/A, A/G, and G/G genotypes, respectively.

    The genetic polymorphism did not affect outcome overall, however in the non-ST-elevation ACS subgroup a signal that genetic polymorphism may be associated with cardiovascular death was observed (p=0.002).

    In conclusion: cystatin C or eGFR, irrespective of equation or assay, are important cardiovascular risk factors in ACS patients. Nonetheless, the incremental value of adding any renal variable, to a multivariable risk model, is small. Further research on the impact of cystatin C genetic polymorphism is warranted.

  • 22.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Duke Clin Res Inst, Durham, NC USA..
    Clare, Robert M.
    Duke Clin Res Inst, Durham, NC USA..
    Lokhnygina, Yuliya
    Duke Clin Res Inst, Durham, NC USA..
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Held, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Van de Werf, Frans
    Univ Leuven, Dept Cardiol, Leuven, Sweden..
    Moliterno, David J.
    Univ Kentucky, Gill Heart Inst, Lexington, KY USA.;Univ Kentucky, Div Cardiovasc Med, Lexington, KY USA..
    Patel, Uptal D.
    Duke Clin Res Inst, Durham, NC USA..
    Leonardi, Sergio
    Fdn IRCCS Policlin San Matteo, Pavia, Italy..
    Armstrong, Paul W.
    Univ Alberta, Div Cardiol, Edmonton, AB, Canada..
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand..
    Aylward, Philip E.
    Flinders Univ & Med Ctr, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia..
    Mahaffey, Kenneth W.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Tricoci, Pierluigi
    Duke Clin Res Inst, Durham, NC USA..
    Albuminuria and cardiovascular events in patients with acute coronary syndromes: Results from the TRACER trial2016Ingår i: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 178, s. 1-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Albuminuria is associated with cardiovascular (CV) outcomes. We evaluated albuminuria, alone and in combination with estimated glomerular filtration rate (eGFR), as a predictor of mortality and CV morbidity in 12,944 patients with non-ST-segment elevation acute coronary syndromes. Methods Baseline serum creatinine and urinary dipsticks were obtained, with albuminuria stratified into no/trace albuminuria, microalbuminuria (>= 30 but <300 mg/dL), or macroalbuminuria (>= 300 mg/dL). Kaplan-Meier rates and proportional Cox hazards models of CV death, overall mortality, CV death or myocardial infarction (MI), and bleeding were calculated. Incidence of acute kidney injury, identified by adverse event reporting and creatinine increase (absolute >= 0.3 mg/dL or relative >= 50%), was descriptively reported. Results Both dipstick albuminuria and creatinine values were available in 9473 patients (73.2%). More patients with macroalbuminuria, versus no/trace albuminuria, had diabetes (66% vs 27%) or hypertension (86% vs 68%). Rates for CV death and overall mortality per strata were 3.1% and 4.8% (no/trace albuminuria); 5.8% and 9.0% (microalbuminuria); and 7.7% and 12.6% (macroalbuminuria) at 2 years of follow-up. Corresponding rates for CV death or MI were 12.2%, 16.9%, and 23.5%, respectively. Observed acute kidney injury rates were 0.6%, 1.2%, and 2.9% (n = 79), respectively. Adjusted HRs for macroalbuminuria on CV mortality were 1.65 (95% CI 1.15-2.37), and after adjustment with eGFR, 1.37 (95% CI 0.93-2.01). Corresponding HRs for overall mortality were 1.82 (95% CI 1.37-2.42) and 1.47 (95% CI 1.08-1.98). Conclusions High-risk patients with non-ST-segment elevation acute coronary syndromes and albuminuria have increased morbidity and increased overall mortality independent of eGFR.

  • 23.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Becker, Richard C.
    Duke Clinical Research Institute, Durham, NC, USA.
    Budaj, Andrzej
    Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland.
    Himmelmann, Anders
    AstraZeneca Research and Development, Mölndal, Sweden.
    Husted, Steen
    Department of Cardiology, Århus University Hospital, Århus, Denmark.
    Storey, Robert F.
    Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
    Johansson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    James, Stefan K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Polymorphism of the cystatin C gene in patients with acute coronary syndromes: Results from the PLATelet Inhibition and Patient Outcomes (PLATO) Study2014Ingår i: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, nr 1, s. 96-102Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Purpose: Plasma cystatin C is independently associated with cardiovascular (CV) risk in non-ST-elevation acute coronary syndromes (NSTE-ACS). The effect of genetic variability on cystatin C concentrations and outcome is unclear.

    Methods: Plasma cystatin C concentrations were measured in blood, obtained within 24 hours of admission, in 16279 ACS patients from the PLATelet inhibition and patient Outcomes trial. 9978 patients were genome-wide genotyped with up to 2.5 million SNPs. The first occurrence of CV death or myocardial infarction (MI) within one year was evaluated by multivariable (clinical variables and biomarkers) Cox regression analysis and c-statistics both overall (all ACS) and in NSTE-ACS.

    Results: We observed SNPs association with cystatin C levels (up to p=7.82 x 10-16). The most significant SNP (rs6048952) was adjacent the CST3 gene with additive effect on cystatin C concentrations: 0.85mg/L, 0.80mg/L and 0.73mg/L for the A/A, A/G and G/G genotypes respectively. Multivariable c-statistics regarding the combined endpoint (CV death or MI) was 0.6619. Adding cystatin C concentrations or genetically adjusted cystatin C levels, exhibited c-statistics of 0.6705 and 0.6703, respectively.

    The overall hazard ratio for rs6048952 was 0.93 (95%CI 0.82-1.04) regarding the CV death or MI while 0.85 (95%CI 0.70-1.03) regarding CV death in all ACS patients. In the NSTE-ACS subgroup, the hazard ratio for rs6048952 was 0.72 (95%CI 0.54-0.95).

    Conclusions: Genetic polymorphism, independently of kidney function, affects cystatin C concentrations, but does not appear to influence ischemic outcome in an overall ACS population. However, genetic variation appears to affect cardiovascular mortality in moderate-to-high risk NSTE-ACS patients.

  • 24.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Helmersson, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Weitoft, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Seasonal variations of urate in a Swedish adult population2017Ingår i: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 36, nr 7, s. 1595-1598Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Seasonality in the incidence and prevalence of gout has previously been reported but the cause of this seasonality in gout is not explained. The aim of this study was to evaluate possible seasonal variations of urate in a large unselected Swedish adult population. We analyzed 170,915 urate test results from patients at a tertiary care hospital between 2000 and 2016. The results were divided according to sex and sampling month of the year. The median urate values were overall higher in males compared to females and both males and females had peak urate concentrations in the summer months (June-August). There is a seasonal pattern for urate concentrations in a large Swedish population similar to the previously reported seasonality for gout. This may be clinically important and could contribute to the circannual variation of gout. The seasonal pattern should be recognized when evaluating patient results both in clinical practice and in research studies.

  • 25.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Helmersson-Karlqvist, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Flodin, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Comparison between cystatin C and creatinine estimated GFR in cardiology patients2015Ingår i: Cardiorenal medicine, ISSN 1664-5502, Vol. 5, nr 4, s. 289-296Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Estimation of the glomerular filtration rate (GFR) is essential for identification, evaluation and risk prediction in patients with kidney disease. Estimated GFR (eGFR) is also needed for the correct dosing of drugs eliminated by the kidneys and to identify high-risk individuals in whom coronary angiography or other procedures may lead to kidney failure. Both cystatin C and creatinine are used for the determination of GFR, and we aimed to investigate if eGFR by the two methods differ in cardiology patients.

     Methods: We compared cystatin C and creatinine (CKD-EPI) eGFR calculated from the same request from a cardiology outpatient unit (n = 2,716), a cardiology ward (n = 980), a coronary care unit (n = 1,464), and an advanced coronary care unit (n = 518) in an observational, cross-sectional study. 

    Results: The median creatinine eGFR results are approximately 10 ml/min/1.73 m2 higher than the median cystatin C eGFR that is up to 90 ml/min/1.73 m2, irrespective of the level of care. Creatinine eGFR resulted in a less advanced eGFR category in the majority of patients with a cystatin C eGFR <60 ml/min/1.73 m2.

    Conclusions: Our study demonstrates a difference between creatinine and cystatin C eGFR in cardiology patients. It is important to be aware of which marker is used for the reported eGFR to minimize erroneous interpretations of the test results, as this could lead to under- or overmedication. Further studies are needed to determine the best method of estimating the GFR in cardiology units.

  • 26.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Bertilsson, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Himmelmann, Anders
    Huhn, Monika
    Pieper, Karen
    Husted, Steen
    Storey, Robert
    Becker, Richard
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Serum Uric Acid Is Associated With Cardiovascular Outcomes In Patients With Acute Coronary Syndromes: Results From The Platelet Inhibition And Patient Outcomes (Plato) Trial2016Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, nr 13, s. 556-556Artikel i tidskrift (Övrigt vetenskapligt)
  • 27.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    James, Stefan K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Koutouzis, Michail
    Lagerqvist, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Stenestrand, Ulf
    Svennblad, Bodil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Oldgren, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Eptifibatide Is Noninferior to Abciximab in Primary Percutaneous Coronary Intervention Results From the SCAAR (Swedish Coronary Angiography and Angioplasty Registry)2010Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 56, nr 6, s. 470-475Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives The aim of this study was to test the noninferiority of eptifibatide relative to abciximab in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Background Glycoprotein IIb/IIIa inhibitors are recommended by international guidelines in patients with acute coronary syndromes undergoing PCI. Abciximab is recommended with a higher level of evidence than eptifibatide in patients with STEMI. No large, prospective, randomized trial comparing abciximab and eptifibatide has been published. Methods All (n = 11,479) STEMI patients in Sweden who underwent primary PCI and received either eptifibatide or abciximab from 2004 to 2007 were derived from the SCAAR ( Swedish Coronary Angiography and Angioplasty Registry). The primary end point was death or myocardial infarction (MI) during 1-year follow-up, with adjustment for baseline differences with a multivariate logistic regression analysis including propensity score. The pre-specified noninferiority margin was set to 1.29. Results The combined end point occurred in 353 of 2,355 patients (15.0%) treated with eptifibatide and in 1,432 of 9,124 patients (15.7%) treated with abciximab. The unadjusted odds ratio ( OR) for eptifibatide versus abciximab was 0.95 (95% confidence interval [CI]: 0.84 to 1.08). Multivariate adjustment (n = 11,317) confirmed noninferiority, with an OR of 0.94 ( 95% CI: 0.82 to 1.09). The adjusted secondary end points of death and MI separately also showed noninferiority, with ORs of 0.99 ( 95% CI: 0.82 to 1.19) and 0.88 ( 95% CI: 0.73 to 1.05), respectively. Conclusions This large registry study suggests that eptifibatide is noninferior to abciximab in patients with STEMI undergoing primary PCI with respect to death or MI during 1 year, thereby supporting the use of either drug in clinical practice.

  • 28.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Oldgren, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Latva-Rasku, Aino
    Univ Turku, Turku PET Ctr, Turku, Finland;Turku Univ Hosp, Dept Endocrinol, Turku, Finland.
    Johansson, Lars
    Antaros Med AB, Gothenburg, Sweden.
    Lisovskaja, Vera
    AstraZeneca, Gothenburg, Sweden.
    Karlsson, Cecilia
    AstraZeneca, Gothenburg, Sweden.
    Oscarsson, Jan
    AstraZeneca, Gothenburg, Sweden.
    Nuutila, Pirjo
    Univ Turku, Turku PET Ctr, Turku, Finland;Turku Univ Hosp, Dept Endocrinol, Turku, Finland.
    Effects of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency, and myocardial contractile work in type 2 diabetes patients - a description of the DAPACARD study2019Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, nr 1, s. 59-64Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Diabetes increases the risk for cardiovascular (CV) events. It has recently been shown that the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors leads to a reduction in CV outcomes in patients with type 2 diabetes mellitus (T2DM), including mortality and heart failure hospitalization. The exact mechanisms of how SGLT2 inhibitors lead to this CV risk reduction remain incompletely understood. The study of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency and myocardial contractile work in type 2 diabetes patients (DAPACARD) (NCT03387683) explores the possible effects of dapagliflozin, an SGLT2 inhibitor, on cardiac work, metabolism, and biomarker levels.

    Methods: DAPACARD is an international, randomized, double-blind trial that aims to examine the effects of dapagliflozin versus matching placebo in 52 patients with T2DM that are on stable metformin therapy prior to and during the 6 weeks of treatment. The primary efficacy endpoint is change in global longitudinal strain of the left ventricle (GLSLV) measured with magnetic resonance imaging (MRI) between baseline (pre-treatment) and end of study (on-treatment). The secondary endpoint is the corresponding change in myocardial efficiency measured as external left ventricular work divided by total left ventricular work, which is estimated using [11C]-acetate clearance using positron emission tomography (PET).

    Conclusion: The DAPACARD study is an extensive investigation of cardiac function and metabolism, by advanced imaging with PET and MRI, as well as biomarkers, performed in order to further explore how the SGLT2 inhibitor dapagliflozin could influence cardiovascular outcomes in patients with T2DM.

  • 29.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Becker, Richard C.
    Duke Clinical Research Institute, Durham, NC, USA.
    Budaj, Andrzej
    Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland.
    Himmelmann, Anders
    AstraZeneca Research and Development, Mölndal, Sweden.
    Horrow, Jay
    AstraZeneca Research and Development, Wilmington, USA.
    Husted, Steen
    Department of Cardiology, Århus University Hospital, Århus, Denmark.
    Storey, Robert F.
    Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
    Åsenblad, Nils
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    James, Stefan K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Cystatin C- and Creatinine-based Estimates of Renal Function and Their Value for Risk Prediction in Patients with Acute Coronary Syndrome: Results from the PLATelet Inhibition and Patient Outcomes (PLATO) Study2013Ingår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 59, nr 9, s. 1369-1375Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The estimated glomerular filtration rate (eGFR) independently predicts cardiovascular (CV) death or myocardial infarction (MI), and can be estimated by creatinine and cystatin C concentrations. We evaluated two different cystatin C assays, alone or combined with creatinine, in patients with acute coronary syndromes.

    Methods: Plasma cystatin C, measured with assays from Gentian and Roche, and serum creatinine was analyzed in 16279 patients from the PLATelet inhibition and patient Outcomes trial. Pearson’s correlation and agreement (Bland–Altman) between methods was evaluated. Prognostic value in relation to CV death or MI during one year of follow up was evaluated by multivariable logistic regression analysis including clinical variables and biomarkers, c-statistics and relative Integrated Discrimination Improvement (IDI).

    Results: Median cystatin C concentrations (interquartile intervals) were 0.83 (0.68 - 1.01) mg/L (Gentian) and 0.94 (0.80 - 1.14) mg/L (Roche). Overall correlation was 0.86 (95% confidence interval 0.85-0.86). The level of agreement was ±0.39mg/L (±2 standard deviations) (n=16279).

    The area under curve (AUC) in the multivariable risk prediction model with cystatin C (Gentian, Roche) or Chronic Kidney Disease - Epidemiology (CKD-EPI) added was 0.6914, 0.6913 and 0.6932. Corresponding relative IDIs were 2.96%, 3.86% and 4.68%, respectively (n=13050). Addition of eGFR by the combined creatinine-cystatin C equation yielded AUC of 0.6923(Gentian) and 0.6924(Roche) with relative IDIs of 3.54% and 3.24% respectively.

    Conclusions: Despite differences in cystatin C concentrations, overall correlation between the Gentian and Roche assays was good while agreement was moderate.  The combined creatinine-cystatin C equation did not outperform risk prediction compared to CKD-EPI.

  • 30.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Becker, R. C.
    Budaj, A.
    Horrow, J.
    Husted, S.
    Katus, H.
    Claeys, M. J.
    Storey, R. F.
    Åsenblad, Nils
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    James, Stefan K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Outcome and causes of renal deterioration evaluated by serial cystatin C measurements in acute coronary syndrome patients: Results from the PLATelet inhibition and patient Outcomes (PLATO) study2012Ingår i: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 164, nr 5, s. 728-734Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: To investigate if ticagrelor treatment and other clinical characteristics were associated with increased cystatin C concentrations and if a deterioration in estimated renal function was associated with worse outcome in patients with acute coronary syndromes (ACS). Methods: Plasma cystatin C concentrations were determined within 24 hours of admission (baseline), at discharge, 1 month, and 6 months in the PLATO trial. The changes over time in relation to randomized treatment were analyzed by analysis of covariance. C-statistics and the relative Integrated Discrimination Improvement of the cystatin C concentrations regarding the primary outcome (cardiovascular death or myocardial infarction) was evaluated by multivariable analysis including background characteristics and biomarkers: N-terminal-pro-B-type natriuretic peptide and Troponin I. Results: Mean cystatin C concentrations in 2133 ticagrelor- and 2162 clopidogrel-treated patients were at baseline (0.86 mg/L and 0.86 mg/L), discharge (1.01 mg/L and 0.98 mg/L) (P <.0005), 1 month (1.00 mg/L and 0.98 mg/L) (P =.12), and 6 months (1.00 mg/L and 0.99 mg/L) (P =.17), respectively. Age, heart failure, and type of ACS were major determinants of the cystatin C concentration. c Statistics and the relative Integrated Discrimination Improvement of the primary outcome for the baseline cystatin C concentration were 0.687 and 5.2%, compared to 0.684 and 4.5% at discharge (n = 4034) and 0.693 and 5.1% at one month (n = 3096), respectively. Conclusions: Mean cystatin C concentrations increased in ACS patients, most importantly determined by age. The initial greater increase in ticagrelor-treated patients was not sustained over time. Risk prediction did not improve with serial measurements of renal markers.

  • 31.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Becker, R. C.
    Budaj, A.
    Katus, H.
    Claeys, M. J.
    Storey, R. F.
    Åsenblad, Nils Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    James, Stefan K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Serial cystatin C measurements and changes in glomerular filtration rate as predictors for death or myocardial infarction in ACS patients2012Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, nr Suppl 1, s. 135-135Artikel i tidskrift (Övrigt vetenskapligt)
  • 32.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Becker, Richard C
    Budaj, Andrzej
    Buck, Kristen
    Giannitsis, Evangelos
    Horrow, Jay
    Husted, Steen
    Katus, Hugo A
    Steg, Philippe Gabriel
    Storey, Robert F
    Åsenblad, Nils
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    James, Stefan K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Cystatin C and Estimated Glomerular Filtration Rate as Predictors for Adverse Outcome in Patients with ST-Elevation and Non-ST-Elevation Acute Coronary Syndromes: Results from the Platelet Inhibition and Patient Outcomes Study2012Ingår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 58, nr 1, s. 190-199Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    We evaluated the predictive ability of cystatin C and creatinine-based estimations of glomerular filtration rate (eGFR), including the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, in acute coronary syndrome (ACS) patients with (STE-ACS) or without (NSTE-ACS) ST elevation in a large contemporary ACS population.

    METHODS:

    Concentrations of cystatin C and creatinine, as well as eGFR at randomization, were measured in 16 401 patients in the Platelet Inhibition and Patient Outcomes (PLATO) study and evaluated as predictors of the composite end point of cardiovascular death or myocardial infarction within 1 year. Two Cox proportional hazards models were used, the first adjusting for clinical characteristics and the second for clinical characteristics plus the biomarkers N-terminal pro-B-type natriuretic peptide, troponin I, and C-reactive protein.

    RESULTS:

    The median cystatin C value was 0.83 mg/L. Increasing quartiles of cystatin C were strongly associated with poor outcome (6.9%, 7.1%, 9.5%, and 16.2%). The fully adjusted hazard ratios per SD of cystatin C in the NSTE-ACS and STE-ACS populations were 1.12 (95% CI 1.04-1.20) (n = 8053) and 1.06 (95% CI 0.97-1.17) (n = 5278), respectively. There was no significant relationship of cystatin C with type of ACS (STE or NSTE). c Statistics ranged from 0.6923 (cystatin C) to 0.6941 (CKD-EPI).

    CONCLUSIONS:

    Cystatin C concentration contributes independently in predicting the risk of cardiovascular death or myocardial infarction in NSTE-ACS, with no interaction by type of ACS. CKD-EPI exhibited the largest predictive value of all renal markers. Nevertheless, the additive predictive value of cystatin C or creatinine-based eGFR measures in the unselected ACS patient is small.

  • 33.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Koagulation och inflammationsvetenskap.
    Becker, Richard C.
    Budaj, Andrzej
    Himmelmann, Anders
    Husted, Steen
    Storey, Robert F.
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Johansson, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    James, Stefan K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Genetic Polymorphism and Relationship to Cystatin C Concentrations and Outcome - Results From the Platelet Inhibition and Patient Outcomes Study2013Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, nr 22Artikel i tidskrift (Övrigt vetenskapligt)
  • 34.
    Åkerblom, Axel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Wojdyla, Daniel M.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Wallentin, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Brito, Flavio de Souza
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Steg, Philippe Gabriel
    Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Paris, France;Paris Diderot Univ, Sorbonne Paris Cite, Paris, France;NHLI Imperial Coll, ICMS, Royal Brampton Hosp, London, England;FACT, FCRIN Network, INSERM U1148, Paris, France.
    Cannon, Christopher P.
    Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA.
    Katus, Hugo A.
    Univ Klinikum, Med Klin, Heidelberg, Germany.
    Himmelmann, Anders
    AstraZenca Res & Dev, Gothenburg, Sweden.
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England.
    Becker, Richard C.
    Acad Hlth Ctr, Div Cardiovasc Hlth & Dis, Heart Lung & Vasc Inst, Cincinnati, OH USA.
    Lopes, Renato D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Ticagrelor in patients with heart failure after acute coronary syndromes - Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial2019Ingår i: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 213, s. 57-65Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Heart failure (HF) following acute coronary syndromes (ACS) is associated with worse prognosis; however, the efficacy and safety of ticagrelor in patients with HF and if ticagrelor influences the risk of new-onset HF are unknown.

    Methods: We examined the efficacy and safety of ticagrelor compared to clopidogrel in patients with ACS in the randomized PLATelet inhibition and patient Outcomes (PLATO) trial subdivided by strata: (1) previous HF and/or clinical signs of HF on admission or (2) no HF on admission. The primary outcome was the combination of cardiovascular death, myocardial infarction, or stroke evaluated by multivariable Cox regression models. The safety outcome was major bleeding. New-onset HF was defined as an HF event after discharge in patients without previous HF.

    Results: Data were available in 18,556 patients, whom 2,862 (15.4%) patients had HF, including 1,584 (8.5%) patients with previous HF. Patients randomized to ticagrelor had lower risk of the composite end point regardless of HF status: hazard ratio (HR) 0.87 (95% CI: 0.73-1.03) in patients with HF and HR 0.84 (95% CI: 0.75-0.93) in patients with no HF (P = .76). Corresponding HR for major bleeding were HR 1.08 (95% CI: 0.87-1.34) and HR 1.03 (95% CI: 0.94-1.14) (P = .71). There was no difference in new-onset HF at 12 months between patients randomized to ticagrelor (4.1%, n = 278) or clopidogrel (4.0%, n = 276).

    Conclusions: In patients with ACS, ticagrelor is more efficacious in protecting against new ischemic events and mortality than clopidogrel irrespective of the presence of HF. There is no difference between ticagrelor or clopidogrel treatment in new-onset HF post-ACS.

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