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  • 201.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Defining acute myocardial infarction2015In: Heart and Metabolism, ISSN 1566-0338, no 67, p. 34-38Article in journal (Other academic)
    Abstract [en]

    The definition of myocardial infarction (MI) has evolved over the last decades, from rather simple criteriain the first World Health Organization documents, to a five-category classification in the 2007 and 2012universal definitions. In particular, the introduction of sensitive and cardiospecific biomarkers in clinicalpractice has had a clear impact in this regard, as well as a more differentiated perspective on thepathophysiology of myocardial injury, in particular in the setting of invasive coronary procedures. Theimplications of the revisions of the definition criteria of MI have been important as they have affected ourperception of MI as a disease state. In addition, they have contributed to an improved identification ofat-risk patients warranting customized treatment regimens. However, several aspects of the definitioncriteria of MI are still debated and will likely be subject to modifications in forthcoming updates of theuniversal definition.

  • 202.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Mental Stress and Cardiac Troponin2013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 62, no 18, p. 1702-1703Article in journal (Other academic)
  • 203.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Armstrong, Paul W.
    Califf, Robert M.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Simoons, Maarten L.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Clinical and prognostic implications of circulating pentraxin 3 levels in non ST-elevation acute coronary syndrome2013In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 46, no 16-17, p. 1655-1659Article in journal (Refereed)
    Abstract [en]

    Objectives: Pentraxin 3 (PTX3) is the prototype of the long pentraxin family. PTX3 is involved in inflammatory processes affecting the cardiovascular system, and PTX3 levels have been shown to be elevated and independently prognostic in ST-elevation myocardial infarction. Data on PTX3 levels in non-ST-elevation acute coronary syndrome (NSTE-ACS), in contrast, are limited. The aim of the present analysis was to investigate the implications of PTX3 levels in a fairly large sample of NSTE-ACS patients and in comparison to levels of C-reactive protein (CRP). Design and methods: We measured levels of PTX3 and CRP in both 82 healthy controls and 401 NSTE-ACS patients from the GUSTO IV study, and studied the associations of these biomarkers to clinical data and 1-year mortality. Results: NSTE-ACS patients had significantly higher median PTX3 levels compared to healthy controls (3.8 vs. 1.9 mu g/L; p < 0.001). PTX3 levels in patients with NSTE-ACS were independently related to female sex and cardiac troponin T levels, but not to age or cardiovascular risk factors. PTX3 levels were higher in patients who died within 1 year but did not emerge as an independent predictor of 1-year mortality (adjusted OR 1,2 [95% Cl 0.6-2.31). This was in contrast to CRP (adjusted OR 1.5 [95% Cl 1.1-2.3]). Neither PTX3 nor CRP yielded significant discriminative value regarding mortality prediction. Conclusions: PTX3 levels are elevated in NSTE-ACS. However, the prognostic information provided by PTX3 levels is limited and inferior compared to CRP. Our data, thus, do not support the measurement of PTX3 in patients with NSTE-ACS.

  • 204.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Baron, Tomasz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hambraeus, Kristina
    Department of Cardiology, Falun Hospital, Falun, Sweden.
    Jernberg, Tomas
    Department of Clinical Sciences, Cardiology, Danderyd Hospital, Karolinska Institute, Danderyd, Sweden.
    Nordenskjöld, Anna
    Faculty of Health, Department of Cardiology, Örebro University, Örebro, Sweden.
    Tornvall, Per
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Myocardial Infarction with Nonobstructive Coronary Arteries: The Importance of Achieving Secondary Prevention Targets2018In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 131, no 5, p. 524-531.e6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Approximately 5% to 10% of all patients with myocardial infarction have nonobstructive coronary arteries. Studies investigating the importance of follow-up and achievement of conventional secondary prevention targets in these patients are lacking.

    METHODS:

    In this analysis from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, we investigated 5830 patients with myocardial infarction with nonobstructive coronary arteries (group 1) and 54,637 patients with myocardial infarction with significant coronary artery disease (≥50% stenosis; group 2). Multivariable- and propensity score-adjusted statistics were used to assess the reduction in the 1-year risk of major adverse events associated with prespecified secondary preventive measures: participation in follow-up at 6 to 10 weeks after the hospitalization and achievement of secondary prevention targets (blood pressure and low-density lipoprotein cholesterol levels in the target ranges, nonsmoking, and participation in exercise training).

    RESULTS:

    Patients in group 1 were less often followed up compared with patients in group 2 and less often achieved any of the secondary prevention targets. Participation in the 6- to 10-week follow-up was associated with a 3% to 20% risk reduction in group 1, similar as for group 2 according to interaction analysis. The improvement in outcome in group 1 was mainly mediated by achieving target range low-density lipoprotein cholesterol levels (24%-32% risk reduction) and, to a smaller extent, by participation in exercise training (10%-23% risk reduction).

    CONCLUSIONS:

    Selected secondary preventive measures are associated with prognostic benefit in patients with myocardial infarction with nonobstructive coronary arteries, in particular achieving target range low-density lipoprotein cholesterol levels. Our results indicate that these patients should receive similar follow-up as myocardial infarction patients with significant coronary stenoses.

  • 205.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hjort, Marcus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Baron, Tomasz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, T.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Cardiol, Stockholm, Sweden.
    Nordenskjold, A. M.
    Orebro Univ, Dept Cardiol, Fac Hlth, Orebro, Sweden.
    Tornvall, P.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Morbidity and cause-specific mortality in first-time myocardial infarction with nonobstructive coronary arteries2019In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 285, no 4, p. 419-428Article in journal (Refereed)
    Abstract [en]

    Background

    Myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is receiving increasing interest as a prognostically adverse entity distinct from myocardial infarction with significant coronary artery disease (MI-CAD). However, data are still limited regarding long-term cardiovascular morbidity and cause-specific mortality in MINOCA.

    Methods

    This is a registry-based cohort study using data from patients admitted to Swedish coronary care units. We investigated various nonfatal outcomes (recurrent MI, hospitalization for heart failure or stroke) and fatal outcomes (cardiovascular, respiratory or cancer-related mortality) in 4069 patients without apparent acute cardiovascular disease, used as non-MI controls, 7266 patients with first-time MINOCA and 69267 patients with first-time MI-CAD.

    Results

    Almost all event rates (median follow-up 3.8years) increased in a stepwise fashion across the three cohorts [rates of major adverse events (MAE; composite of all-cause mortality, recurrent MI, hospitalization for heart failure or stroke): n=268 (6.6%), n=1563 (21.5%), n=17777 (25.7%), respectively]. Compared to non-MI controls, MINOCA patients had an adjusted hazard ratio (HR) of 2.12 (95% confidence interval 1.84-2.43) regarding MAE. MINOCA patients had a substantial risk of cardiovascular mortality and the highest numerical risks of respiratory and cancer-related mortality. Male sex, previous heart failure and chronic obstructive pulmonary disease had a stronger prognostic impact in MINOCA than in MI-CAD. Female MINOCA patients with atrial fibrillation were at particular risk.

    Conclusions

    Patients with first-time MINOCA have a considerable risk of adverse events. This stresses the need for a comprehensive search of the cause of MINOCA, thorough treatment of underlying disease triggers and close follow-up.

  • 206.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jaffe, Allan S
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    A novel approach to cardiac troponins to improve the diagnostic work-up in chest pain patients2012In: Critical Pathways in Cardiology, ISSN 1535-282X, E-ISSN 1535-2811, Vol. 11, no 4, p. 199-205Article in journal (Refereed)
    Abstract [en]

    In patients with acute chest pain, current guidelines recommend serial measurements of cardiac troponins at predefined and partly late time points. Consequently, diagnostic assessment in these patients tends to be lengthy and often results in unnecessary admissions. We, therefore, evaluated whether an approach integrating troponin results into the clinical context provided by the individual patient's presentation might facilitate the early diagnostic work-up. In 197 chest pain patients, cardiac troponin I (cTnI; Stratus CS) was measured serially within 12 hours after hospital admission. In patient cohorts with different chances of having myocardial infarction (MI) according to clinical data, electrocardiographic findings, and admission biomarker results, pretest probabilities for MI were calculated and compared with posttest probabilities derived from subsequent cTnI results after admission. Elevated cTnI levels at 1 to 2 hours after admission revealed ≥95.0% posttest probabilities for MI in cohorts with intermediate or high chances of having MI. The posttest probabilities for the absence of MI were 94.7% to 98.2% in cohorts with low or intermediate chances of having MI when cTnI was negative at 2 hours. Troponin testing considering the individual patient's pretest probability of MI seems, in conclusion, to provide clinically useful information already 1 to 2 hours after admission. Such an approach has the potential to identify both patient cohorts in whom early discharge or admittance for further evaluation would be appropriate. This could facilitate the early diagnostic work-up of chest pain patients, thereby improving patient flow and reducing overcrowding in healthcare facilities.

  • 207.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Prognostic implications of changes in cardiac troponin I levels in patients with non-ST elevation acute coronary syndrome2013In: Biomarkers, ISSN 1354-750X, E-ISSN 1366-5804, Vol. 18, no 8, p. 668-672Article in journal (Refereed)
    Abstract [en]

    Objective: Information is limited on the prognostic implications of cardiac troponin I (cTnI) changes during the first days of non-ST elevation acute coronary syndrome (NSTE-ACS). Methods: High-sensitivity cTnI levels were measured at study inclusion and after 48 h in 1615 conservatively managed NSTE-ACS patients from the Global Use of Strategies To Open Occluded Coronary Arteries (GUSTO) IV trial. Results: Patients with moderately increased cTnI levels and without a relevant decrease over time had a significantly raised mortality at 30 days and 1 year. No relevant associations between cTnI changes and recurrent myocardial infarction were seen. Conclusion: The cTnI change is predictive for subsequent mortality in selected conservatively managed NSTE-ACS patients.

  • 208.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, T.
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    High-sensitivity cardiac troponin T, left ventricular function, and outcome in non-ST elevation acute coronary syndrome2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 197, p. 70-76Article in journal (Refereed)
    Abstract [en]

    Background Cardiac troponin (cTn) levels reflect infarct size and depressed left ventricular ejection fraction (LVEF) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). However, there is very limited information on whether cTn measured with a high-sensitivity (hs) assay would provide incremental prognostic information to the LVEF in NSTE-ACS patients. Methods This was a registry-based study (SWEDEHEART registry) investigating 20,652 NSTE-ACS patients with available information on hs-cTnT (highest level recorded during the hospitalization) and the LVEF estimated using echocardiography. All patients had been followed for 1 year. Results Hs-cTnT levels independently predicted major cardiovascular events (MACE) in cohorts with normal, slightly depressed, moderately depressed, and severely depressed LVEF. The adjusted hazard ratios in these cohorts were 1.18 (95% CI 1.13-1.23), 1.12 (95% CI 1.06-1.18), 1.12 (95% CI 1.06-1.19), and 1.21 (95% CI 1.13-1.30), respectively. Hs-cTnT levels were particularly predictive for cardiovascular mortality and readmission for heart failure. Excluding patients with previous cardiac disease did not affect the overall interrelations of hs-cTnT and LVEF with MACE. Conclusions Hs-cTnT levels provide incremental prognostic value independent of the LVEF in patients with NSTE-ACS. Hs-cTnT is particularly predictive for MACE in patients with severely depressed LVEF but also in those with a normal LVEF. Accordingly, a normal LVEF should not be used as an argument not to target patients to thorough workup.

  • 209.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jernberg, Tomas
    Danderyd Hospital.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    REPLY: The Validity of "Without a Specific Diagnosis" in Patients With Chest Pain and Troponin Elevation2019In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 73, no 17, p. 2240-2241Article in journal (Other academic)
  • 210.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Unstable Angina in the Era of Cardiac Troponin Assays with Improved Sensitivity-A Clinical Dilemma2017In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 130, no 12, p. 1423-1430Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is an expectation that with the adoption of more sensitive cardiac troponin (cTn) assays, unstable angina would become a rarity. However, recent data from the SWEDEHEART registry demonstrated that 15% of patients admitted with non-ST-elevation acute coronary syndrome still were regarded as having unstable angina. We aimed to further investigate the clinical characteristics and outcome of these patients. METHODS: This was a retrospective, registry-based analysis (SWEDEHEART) including 3204 unstable patients, 18,194 non-ST-elevation myocardial infarction (NSTEMI) patients, and 977 controls without acute cardiovascular disease. All patients had available data on peak cTnT levels (more sensitive assay) and 1-year outcome. RESULTS: The annual proportions of patients with unstable angina (2009-2013) among those with non-STelevation acute coronary syndrome ranged from 9.4% to 15.3%. Only 1239 unstable angina patients (39.7%) had a peak cTnT level = 14 ng/L. Patients with unstable angina tended to be younger than those with NSTEMI but had higher prevalence of most cardiovascular risk factors and more advanced coronary artery disease. Compared with controls, the adjusted hazard ratios (95% confidence interval) regarding major cardiovascular events were 2.97 (1.30-6.78) and 5.44 (2.54-11.65) in unstable angina patients with peak cTnT = 14 ng/L and > 14 ng/L, respectively. CONCLUSION: The diagnosis of unstable angina is still commonly used, even in the era of more sensitive cTn assays. Minor cTnT elevation is common, which makes unstable angina difficult to distinguish from NSTEMI. Patients with unstable angina have a nonneglectable cardiovascular risk. We suggest that the clinical management of patients presenting with unstable symptoms should depend on their estimated cardiovascular risk rather than on strictly applied diagnostic criteria. (C) 2017 Elsevier Inc. All rights reserved.

  • 211.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    High-Sensitivity Cardiac Troponin T Levels Identify Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Who Benefit From Invasive Assessment2018In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, no 16, p. 1665-1667Article in journal (Other academic)
  • 212.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Ljung, Lina
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    High-Sensitivity Cardiac Troponin-Based Strategies for the Assessment of Chest Pain Patients: A Review of Validation and Clinical Implementation Studies2018In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 64, no 11, p. 1572-1585Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: The introduction of high-sensitivity cardiac troponin (hs-cTn) assays has improved the early assessment of chest pain patients. A number of hs-cTn-based algorithms and accelerated diagnostic protocols (ADPs) have been developed and tested subsequently. In this review, we summarize the data on the performance and clinical utility of these strategies. CONTENT: We reviewed studies investigating the diagnostic and prognostic performance of hs-cTn algorithms [level of detection (LoD) strategy, 0/1-h, 0/2-h, and 0/3-h algorithms) and of hs-cTn-based ADPs, together with the implications of these strategies when implemented as clinical routine. The LoD strategy, when combined with a nonischemic electrocardiogram, is best suited for safe rule-out of myocardial infarction and the identification of patients eligible for early discharge from the emergency department. The 0/1-h algorithms appear to identify most patients as being eligible for rule-out. The hs-cTn-based ADPs mainly focus on prognostic assessment, which is in contrast with the hs-cTn algorithms. They identify smaller proportions of rule-out patients, but there is increasing evidence from prospective studies on their successful clinical implementation. Such information is currently lacking for hs-cTn algorithms. CONCLUSIONS: There is a trade-off between safety and efficacy for different hs-cTn-based strategies. This trade-off should be considered for the intended strategy, along with its user-friendliness and evidence from clinical implementation studies. However, several gaps in knowledge remain. At present, we suggest the use of an ADP in conjunction with serial hs-cTn results to optimize the early assessment of chest pain patients. (C) 2018 American Association for Clinical Chemistry

  • 213.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Cardiac troponin I levels in patients with non-ST-elevation acute coronary syndrome: the importance of gender2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, no 3, p. 317-324.e1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Measurement of high-sensitivity cardiac troponin levels is increasingly used in non-ST-elevation acute coronary syndrome (NSTE-ACS). However, studies investigating the distribution and prognostic implications of high-sensitivity troponin levels in men and women separately are currently lacking.

    METHODS: Cardiac troponin I (cTnI) levels were determined using a high-sensitivity assay (Abbott Laboratories, Abbott Park, IL) in 1,677 male and 1,073 female NSTE-ACS patients participating in the GUSTO IV study. The prognostic associations of cTnI to outcome (30-day composite end point of recurrent myocardial infarction and 1-year mortality) were assessed in multivariable models, using cTnI both as a continuous variable and dichotomized at different sets of single and gender-specific 99th percentiles.

    RESULTS: Median cTnI levels were 947 and 175 ng/L in men and women, respectively (P < .001). The adjusted odds ratios for cTnI (ln) were similar in men and women. The adjusted odds ratios for cTnI above the tested 99th percentiles levels in contrast were twice as high in women compared with men. This was a consequence of differences in the cTnI distribution and risk gradients across cTnI levels, in particular due to lower event rates in women without cTnI elevation. Gender-specific cutoffs did not improve risk prediction.

    CONCLUSIONS: Despite overall lower levels, cTnI above the tested 99th percentiles exhibited stronger prognostic information in women with NSTE-ACS compared with men. This likely reflects differences in the pathophysiology and the clinical presentation in NSTE-ACS. Our data, thus, emphasize that women with symptoms of unstable coronary artery disease encompass a broader risk panorama than men.

  • 214.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kempf, T.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wollert, K. C.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Levels of GDF-15 increase over time in an elderly population and are a strong predictor of all-cause mortality2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 947-947Article in journal (Other academic)
  • 215.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kempf, Tibor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wollert, Kai C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Evaluation of Temporal Changes in Cardiovascular Biomarker Concentrations Improves Risk Prediction in an Elderly Population from the Community2016In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 62, no 3, p. 485-493Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There is increasing interest in measurements of cardiovascular (CV) biomarker concentrations for risk prediction in the general population. We investigated the prognostic utility of a panel of novel CV biomarkers and their changes over time.

    METHODS: We measured concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional proadrenomedullin, high-sensitivity cardiac troponin I, growth-differentiation factor-15 (GDF-15), soluble ST2 (sST2), and galectin-3 at baseline and 5 years later in 1016 elderly individuals participating in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Assessed outcomes included all-cause mortality and fatal and nonfatal CV events (in participants without CV disease at baseline) during 10 years of follow-up.

    RESULTS: GDF-15 exhibited the strongest association with all-cause mortality (n = 158) with a hazard ratio (HR) per 1-SD increase in standardized ln GDF-15 of 1.68 (95% CI, 1.44-1.96). NT-proBNP was the only biomarker to predict CV events (n = 163; HR 1.54 [95% CI, 1.30-1.84]). GDF-15 and NT-proBNP also improved metrics of discrimination and reclassification of the respective outcomes. Changes in GDF-15 concentrations between 70 and 75 years predicted all-cause mortality whereas changes in NT-proBNP predicted both outcomes. The other biomarkers and their temporal changes provided only moderate prognostic value apart from sST2 which had a neutral relationship with adverse events.

    CONCLUSIONS: Evaluation of temporal changes in GDF-15 and NT-proBNP concentrations improves risk prediction in an elderly population. These findings are of considerable interest given the emphasis on biomarkers as tools to identify and monitor at-risk individuals with preclinical and potentially modifiable stages of CV disease.

  • 216.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Factors Influencing the 99th Percentile of Cardiac Troponin I Evaluated in Community-Dwelling Individuals at 70 and 75 Years of Age2013In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 59, no 7, p. 1068-1073Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    We aimed to investigate the effects of sex, prevalent cardiovascular disease (CVD), and ageing on the 99th percentile of cardiac troponin I (cTnI).

    METHODS:

    cTnI was measured using a high-sensitivity assay (Abbott Diagnostics) in 814 community-dwelling individuals at both 70 and 75 years of age. We determined the cTnI 99th percentiles separately using nonparametric methods in the total sample, in men and women, and in individuals with and without CVD.

    RESULTS:

    The cTnI 99th percentile at baseline was 55.2 ng/L for the total cohort. Higher 99th percentiles were noted in men (69.3 ng/L) and individuals with CVD (74.5 ng/L). The cTnI 99th percentile in individuals free from CVD at baseline (n = 498) increased by 51% from 38.4 to 58.0 ng/L during the 5-year observation period. Relative increases ranging from 44% to 83% were noted across all subgroups. Male sex [odds ratio, 5.3 (95% CI, 1.5-18.3)], log-transformed N-terminal pro-B-type natriuretic peptide [odds ratio, 1.9 (95% CI, 1.2-3.0)], and left-ventricular mass index [odds ratio, 1.3 (95% CI, 1.1-1.5)] predicted increases in cTnI concentrations from below the 99th percentile (i.e., 38.4 ng/L) at baseline to concentrations above the 99th percentile at the age of 75 years.

    CONCLUSIONS:

    cTnI concentration and its 99th percentile threshold depend strongly on the characteristics of the population being assessed. Among elderly community dwellers, higher concentrations were seen in men and individuals with prevalent CVD. Ageing contributes to increasing concentrations, given the pronounced changes seen with increasing age across all subgroups. These findings should be taken into consideration when applying cTnI decision thresholds in clinical settings.

  • 217.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Carrero, Juan J.
    Karolinska Inst, Div Renal Med, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Evans, Marie
    Karolinska Inst, Div Renal Med, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Szummer, Karolina
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Jernberg, Tomas
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Cardiac Troponins and Their Prognostic Importance in Patients with Suspected Acute Coronary Syndrome and Renal Dysfunction2017In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 8, p. 1409-1417Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cardiac troponin (cTn) is important for risk assessment in patients with suspected acute coronary syndrome (ACS). cTn concentrations may, however, be affected by renal dysfunction, and the clinical importance of this interrelation is not well established. We investigated the association between cTnT and cTnI (measured with conventional assays and a more sensitive assay) with the estimated glomerular filtration rate (eGFR) and also assessed the ability of cTn to predict the 1-year all-cause mortality. METHODS: This retrospective registry-based study used data from 309454 admissions to Swedish coronary care units. cTn associations with eGFR and mortality were assessed using different regression models and by calculating multivariable-adjusted c-statistics. RESULTS: cTnT concentrations exhibited stronger associations with eGFR than cTnI concentrations (conventional cTnT assay: beta = -0.113; more sensitive cTnT assay: beta = -0.186; pooled conventional cTnI assays: beta = -0.098). Overall, cTnT provided greater prognostic accuracy than cTnI. This was most evident in non-ACS patients with normal or mildly reduced eGFR when using the more sensitive assay. Despite higher mortality rates, no consistent increases in the c-statistics of cTn were seen with severely reduced eGFR irrespective of the presence of ACS or non-ACS. CONCLUSIONS: cTnT concentrations exhibited stronger associations with reduced eGFR than cTnI concentrations in patients admitted because of suspected ACS. cTnT, particularly when measured using the more sensitive assay, also tended to be a stronger prognosticator. However, the relative significance of the obtained results must be considered in the context of the severity of renal dysfunction and whether ACS is present.

  • 218.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Predictors of 10-year changes in levels of N-terminal pro B-type natriuretic peptide and cardiac troponin I in the elderly2018In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 257, p. 300-305Article in journal (Refereed)
    Abstract [en]

    Background: Measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) might be useful for monitoring of cardiovascular disease in the elderly. However, it is not clear whether changes in these biomarkers are associated with changes in the cardiovascular risk profile and if this pattern could be modified by changes in lifestyle habits or medications.

    Methods: We measured levels of NT-proBNP and cTnI in community-dwelling subjects (PIVUS study) upon visits scheduled at age 70 (n = 1007), 75 (n = 825) and 80 (n = 602). The associations of these biomarkers with repeated measurements of clinical variables (risk factors, lifestyle habits, echocardiographic data and medications) were investigated using sex-adjusted linear mixed random effect models.

    Results: NT-proBNP and cTnI were positively associated with increasing age. NT-proBNP, but not cTnI, was affected by changes of renal function and the degree of obesity. NT-proBNP was more closely related than cTnI to changes in echocardiographic estimates of cardiac geometry and function. Biomarker levels and/or their changes were inversely associated with a physically more active lifestyle (both NT-proBNP and cTnI) and statin treatment at age 70 (only cTnI). Changes in smoking status or antihypertensive treatment had no effect on biomarker levels.

    Conclusions: Changes in NT-proBNP and cTnI levels are associated with different patterns of cardiovascular disease burden when using a longitudinal approach. However, levels of both biomarkers and their changes also reflect changes in the cardiovascular risk profile that might be modifiable. This is an important aspect for the use of any cardiovascular biomarker in an elderly population.

  • 219.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Mid-regional pro-atrial natriuretic peptide levels in the elderly: Clinical and prognostic implications, and comparison to B-type natriuretic peptides2013In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 419, p. 62-66Article in journal (Refereed)
    Abstract [en]

    Background: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is emerging as an indicator of cardiac abnormalities and adverse outcome in heart failure patients. However, there are only sparse data on its clinical value relative to the B-type natriuretic peptides in the general population. Methods: We measured levels of MR-proANP, B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in 999 community-dwelling subjects aged 70 years who were participating in the PIVUS study. Results: The MR-proANP and the B-type natriuretic peptides exhibited similar associations to previous or prevalent cardiovascular disease, and echocardiographic data. In subgroups with confounding conditions (female sex, obesity, renal dysfunction), MR-proANP did not exhibit stronger associations to echocardiographic data than the B-type natriuretic peptides. MR-proANP predicted cardiovascular mortality during 8 years of follow-up (adjusted hazard ratio 2.8 [95% confidence interval 1.3-6.1]) but not all-cause mortality (adjusted hazard ratio 1.6[95% confidence interval 1.0-2.5]). Overall, NT-proBNP provided the strongest predictive value regarding both outcomes. Conclusions: MR-proANP levels in an elderly community population are to a similar extent as the B-type natriuretic peptides related to manifestations of cardiovascular disease and echocardiographic data. MR-proANP also predicts long-term cardiovascular mortality but without being prognostically superior compared to the B-type natriuretic peptides.

  • 220.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Associations of mid-regional pro-adrenomedullin levels to cardiovascular and metabolic abnormalities, and mortality in an elderly population from the community2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, no 4, p. 3537-3542Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The mid-regional part of the prohormone of adrenomedullin (MR-proADM) is emerging as a novel risk indicator in patients with cardiac disease. We investigated MR-proADM levels and their changes over 5years in elderly community-dwellers, together with the underlying cardiovascular and metabolic conditions, and the prognostic implications of these measurements.

    METHODS AND RESULTS:

    MR-proADM was analyzed using a sandwich immunoassay (Thermo Fisher Scientific) in participants from the PIVUS study. Measurements were performed at 70 (n=1002) and 75years of age (n=795) together with various measurements of other markers of cardiovascular function. In cross-sectional analyses, MR-proADM was independently related to current smoking, renal dysfunction, obesity, lower left-ventricular ejection fraction, and higher levels of N-terminal pro-B-type natriuretic peptide and C-reactive protein. There were no independent associations to other cardiovascular risk factors or vascular pathologies. MR-proADM levels predicted all-cause mortality during 8.0years of follow-up independent of cardiovascular risk indicators (adjusted HR 5.1 [95% CI 2.8-9.5]; p<0.001) using results obtained at 70 and 75years as updated covariates. Baseline MR-proADM levels improved prognostic discrimination (IDI=0.018 [p=0.001]). Also the change in MR-proADM levels over time independently predicted all-cause mortality occurring after 75years (adjusted HR 13.4 [95% CI 3.5-50.5]; p<0.001).

    CONCLUSIONS:

    MR-proADM levels in the elderly integrate information on several relevant aspects in cardiovascular disease, namely cardiovascular risk factors including obesity, low-grade inflammation, renal dysfunction and left-ventricular abnormalities. Furthermore, MR-proADM and its changes over time predicted mortality, and might provide utility as an indicator of the overall cardiovascular risk burden.

  • 221.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Cardiac troponin I levels measured with a high-sensitive assay increase over time and are strong predictors of mortality in an elderly population2013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 61, no 18, p. 1906-1913Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Cardiac troponin levels are often detectable in community-dwellers when sensitive assays are applied. However, information on the course of troponin levels over time is limited.

    OBJECTIVES:

    We assessed changes in troponin levels, underlying conditions and the prognostic implications thereof in elderly subjects from the community.

    METHODS:

    Cardiac troponin I (cTnI) was measured using a novel high-sensitive assay from Abbott Laboratories in community-dwellers aged 70 years (PIVUS study). Measurements were performed at baseline (n=1004) and after 5 years (n=814). Total follow-up was 8.0 years.

    RESULTS:

    cTnI levels were detectable in 968 (96.4%) subjects at baseline, and independently predicted all-cause mortality (adjusted HR 1.44 [95% CI 1.18-1.77]) and cardiovascular mortality (adjusted HR 1.66 [95% CI 1.20-2.29]) when levels from baseline and 5-year follow-up were used as updated covariates. The integrated discrimination improvement of cTnI regarding all-cause mortality was 0.014 (p=0.04) and the category-free net reclassification improvement was 0.231 (p=0.02). Median cTnI levels increased by 45% between both measurements. The change in cTnI levels was significantly related to male sex (p=0.02), body mass index (p=0.01), HDL-cholesterol (p=0.005), N-terminal pro B-type natriuretic peptide (p=0.004) and the left-ventricular ejection fraction (p=0.04), and independently predicted all-cause mortality occurring after 5-year follow-up (adjusted HR 1.97 [1.14-3.40]; p=0.02).

    CONCLUSIONS:

    Using a novel high-sensitive assay, cTnI levels could be determined in nearly all elderly subjects. cTnI levels increased over time and were a strong marker of mortality risk. Our data suggest that cTnI might offer utility for clinical assessment of subjects in the general population.

  • 222.
    Ehret, Georg B.
    et al.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA.;Univ Hosp Geneva, Dept Med, Cardiol, Geneva, Switzerland..
    Ferreira, Teresa
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Schmidt, Ellen M.
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA..
    Johnson, Toby
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;GlaxoSmithKline, Stevenage, Herts, England..
    Thorleifsson, Gudmar
    deCODE Genet Amgen Inc, Reykjavik, Iceland..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge, England..
    Donnelly, Louise A.
    Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee, Scotland..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Petersen, Ann -Kristin
    Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany..
    Pihurl, Vasyl
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA..
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med, Cardiovasc Res Unit, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Ctr Mol Med, Stockholm, Sweden..
    Shungin, Dmitry
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Umea Univ, Dept Odontol, Umea, Sweden..
    Hughes, Maria F.
    Queens Univ Belfast, Ctr Excellence Publ Hlth, Belfast, Antrim, North Ireland..
    Meirelles, Osorio
    NIA, Genet Lab, Intramural Res Program, US Natl Inst Hlth, Baltimore, MD 21224 USA..
    Kaakinen, Marika
    Imperial Coll London, Sch Publ Hlth, Hammersmith Hosp, Dept Genom Common Dis, London, England..
    Bouatia-Naji, Nabila
    INSERM UMR 970, Paris Cardiovasc Res Ctr PARCC, Paris, France.;Univ Paris 05, Sorbonne Paris Cite, Paris, France..
    Kristiansson, Kati
    Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
    Shah, Sonia
    UCL, Dept Epidemiol & Publ Hlth, Genet Epidemiol Grp, London, England..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany..
    Guo, Xiuqing
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere, Finland..
    Fava, Cristiano
    Lund Univ, Dept Internal Med, Malmo, Sweden.;Univ Verona, Dept Med, Verona, Italy..
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Nolte, Ilja M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Salfati, Elias L.
    Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA..
    Rallidis, Loukianos S.
    Univ Athens, Sch Med, Attikon Hosp, Dept Cardiol 2, Athens, Greece..
    Theusch, Elizabeth
    Childrens Hosp Oakland Res Inst, Oakland, CA USA..
    Smith, Andrew J. P.
    UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England..
    Folkersen, Lasse
    Karolinska Inst, Dept Med, Cardiovasc Res Unit, Ctr Mol Med, Stockholm, Sweden..
    Witkowska, Kate
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, London, England..
    Pers, Tune H.
    Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.;Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Metab Sect, Genet,Fac Hlth & Med Sci, Copenhagen, Denmark.;Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark..
    Joehanes, Roby
    NHLBI, Framingham Heart Study, Framingham, MA USA..
    Kim, Stuart K.
    Stanford Univ, Med Ctr, Dept Dev Biol & Genet, Stanford, CA 94305 USA..
    Lataniotis, Lazaros
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Jansen, Rick
    Vrije Univ Amsterdam, Dept Psychiat, Med Ctr, Amsterdam, Netherlands..
    Johnson, Andrew D.
    NHLBI, Framingham Heart Study, Framingham, MA USA.;NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Bldg 10, Bethesda, MD 20892 USA..
    Warren, Helen
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, London, England..
    Kim, Young Jin
    Natl Inst Hlth, Ctr Genome Sci, Osong Hlth Technol Adm Complex, Chungcheongbuk Do, South Korea..
    Zhao, Wei
    Univ Penn, Dept Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA..
    Wu, Ying
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Tayo, Bamidele O.
    Loyola Univ, Chicago Stritch Sch Med, Dept Publ Hlth Sci, Maywood, IL 60153 USA..
    Bochud, Murielle
    CHU Vaudois, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland.;Univ Lausanne, Lausanne, Switzerland..
    Absher, Devin
    HudsonAlpha Inst Biotechnol, Huntsville, AL USA..
    Adair, Linda S.
    Univ N Carolina, Dept Nutr, Chapel Hill, NC USA..
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands..
    Arkingl, Dan E.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA..
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Baldassarre, Damian
    Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy.;IRCCS, Ctr Cardiol Monzino, Milan, Italy..
    Balkau, Beverley
    Univ Paris 11, Ctr Res Epidemiol & Populat Hlth, INSERM U1018, URMS 1018, Villejuif, France..
    Bandinelli, Stefania
    ASF, Geriatr Unit, Florence, Italy..
    Barnes, Michael R.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, London, England..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England.;Univ Cambridge, Inst Metab Sci, Addenbrookes Hosp, Metab Res Labs, Cambridge, England.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Inst Metab Sci, Cambridge, England..
    Bevan, Stephen
    Lincoln Univ, Joseph Banks Labs, Sch Life Sci, Lincoln, England..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA..
    Bjornsdottir, Gyda
    deCODE Genet Amgen Inc, Reykjavik, Iceland..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA..
    Bonnycastle, Lori L.
    NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Boomsma, Dorret I.
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands..
    Bornstein, Stefan R.
    Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, Dresden, Germany..
    Brown, Morris J.
    Queen Mary Univ London, Barts Heart Ctr, William Harvey Res Inst, London, England..
    Burnier, Michel
    CHU Vaudois, Nephrol, Lausanne, Switzerland.;Univ Lausanne, Lausanne, Switzerland..
    Cabrera, Claudia P.
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, London, England..
    Chambers, John C.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Chang, I-Shou
    Natl Inst Canc Res, Natl Hlth Res Inst, Zhunan Town, Taiwan..
    Cheng, Ching-Yu
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Duke NUS Grad Med Sch Singapore, Singapore, Singapore.;Natl Univ Singapore, Dept Ophthalmol, Singapore, Singapore.;Natl Univ Hlth Syst, Singapore, Singapore..
    Chines, Peter S.
    NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Chung, Ren-Hua
    Natl Hlth Res Inst, Div Biostat & Bioinformat, Inst Populat Hlth Sci, Zhunan Town, Taiwan..
    Collins, Francis S.
    NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Connell, John M.
    Univ Dundee, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Doring, Angela
    Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Dallongeville, Jean
    Univ Lille 2, INSERM UMR 1167, Inst Pasteur Lille, Lille, France..
    Danesh, John
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England..
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, Stockholm, Sweden..
    Delgado, Graciela
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany..
    Dominiczak, Anna F.
    Univ Glasgow, Inst Cardiovasc & Med Sci, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland..
    Doney, Alex S. F.
    Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee, Scotland..
    Drenos, Fotios
    UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England.;Univ Bristol, Sch Social & Community Med, Med Res Council Integrat Epidemiol Unit, Oakfield House, Bristol, Avon, England..
    Edkins, Sarah
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England..
    Eicher, John D.
    NHLBI, Framingham Heart Study, Framingham, MA USA.;NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Bldg 10, Bethesda, MD 20892 USA..
    Elosua, Roberto
    Inst Hosp Mar Invest Med IMIM, Cardiovasc Epidemiol & Genet, Barcelona, Spain..
    Enroth, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Erdmann, Jeanette
    Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany.;Deutsch Zentrum Herz Kreislauf Forsch DZHK, Partner Site Hamburg, Kiel, Germany..
    Eriksson, Per
    Karolinska Inst, Dept Med, Cardiovasc Res Unit, Ctr Mol Med, Stockholm, Sweden..
    Esko, Tonu
    Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Broad Inst MIT & Harvard, Cambridge, MA USA..
    Evangelou, Evangelos
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Ioannina, Greece..
    Evans, Alun
    Queens Univ Belfast, Ctr Excellence Publ Hlth, Belfast, Antrim, North Ireland..
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Farra, Martin
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England..
    Felixl, Janine F.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands..
    Ferrieres, Jean
    Toulouse Univ, Sch Med, Rangueil Univ Hosp, INSERM UMR 1027, Toulouse, France..
    Ferrucci, Luigi
    NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Forrester, Terrence
    Univ West Indies, Trop Metab Res Unit, Res Inst Trop Med, Kingston, Jamaica..
    Franceschinil, Nora
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Franco, Oscar H.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands..
    Franco-Cereceda, Anders
    Karolinska Inst, Dept Mol Med & Surg, Cardiothorac Surg Unit, Stockholm, Sweden..
    Fraser, Ross M.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.;Synpromics Ltd, Edinburgh, Midlothian, Scotland..
    Ganesh, Santhi K.
    Univ Michigan, Sch Med, Dept Cardiol, Ann Arbor, MI 48109 USA..
    Gao, He
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England..
    Gertow, Karl
    Karolinska Inst, Dept Med, Cardiovasc Res Unit, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Ctr Mol Med, Stockholm, Sweden..
    Gianfagna, Francesco
    Univ Insubria, Dept Clin & Expt Med, Epidemiol & Prevent Med EPIMED Res Ctr, Varese, Italy.;IRCCS, Ist Neurol Mediterraneo NEUROMED, Dept Epidemiol & Prevent, Pozzilli, Italy..
    Gigante, Bruna
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, Stockholm, Sweden..
    Giulianini, Franco
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Goe, Anuj
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England..
    Goodall, Alison H.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Goodarzi, Mark
    Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA..
    Gorski, Mathias
    Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, Regensburg, Germany.;Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany..
    Grassler, Jurgen
    Tech Univ Dresden, Dept Med 2, Div Pathobiochem, Dresden, Germany..
    Groves, Christopher J.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hallmans, Göran
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Hartikainen, Anna-Liisa
    Univ Oulu, Inst Clin Med Obstet & Gynaecol, Oulu, Finland.;Oulu Univ Hosp, Med Res Ctr, Oulu, Finland..
    Hassinen, Maija
    Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Havulinna, Aki S.
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Hayward, Caroline
    Western Gen Hosp, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Hercberg, Serge
    Univ Paris 13, UREN, INSERM U557, INRA U1125,Sorbonne Paris Cite, Bobigny, France..
    Herzig, Karl-Heinz
    Univ Oulu, Inst Biomed, Med Res Ctr Oulu, Oulu, Finland.;Oulu Univ Hosp, Oulu, Finland.;Univ Oulu, Bioctr Oulu, Oulu, Finland.;Poznan Univ Med Sci, Dept Gastroenterol & Metab, Poznan, Poland..
    Hicks, Andrew A.
    European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.;Univ Lubeck, Inst, Lubeck, Germany..
    Hingorani, Aroon D.
    UCL, Dept Epidemiol & Publ Hlth, Genet Epidemiol Grp, London, England..
    Hirschhorn, Joel N.
    Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.;Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Genet, Boston, MA USA..
    Hofmanl, Albert
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Holmen, Jostein
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway..
    Holmen, Oddgeir Lingaas
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway.;Univ Trondheim Hosp, St Olav Hosp, Trondheim, Norway..
    Hottenga, Jouke-Jan
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands..
    Howard, Phil
    UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England..
    Hsiung, Chao A.
    Natl Hlth Res Inst, Div Biostat & Bioinformat, Inst Populat Hlth Sci, Zhunan Town, Taiwan..
    Hunt, Steven C.
    Univ Utah, Sch Med, Cardiovasc Genet Div, Salt Lake City, UT USA.;Weill Cornell Med Coll Qatar, Dept Genet Med, Doha, Qatar..
    Ikram, M. Arfan
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Radiol, Rotterdam, Netherlands.;Erasmus MC, Univ Med Ctr Rotterdam, Dept Neurol, Rotterdam, Netherlands..
    Illig, Thomas
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.;Hannover Med Sch, Inst Human Genet, Hannover, Germany..
    Iribarren, Carlos
    Kaiser Permanente, Div Res, Oakland, CA USA..
    Jensen, Richard A.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.;Univ Tampere, Sch Med, Dept Clin Physiol, Tampere, Finland..
    Kahonen, Mika
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Kang, Hyun Min
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Kathiresan, Sekar
    Harvard Med Sch, Dept Med, Boston, MA USA.;Univ Penn, Dept Surg, Div Transplantat, Philadelphia, PA 19104 USA.;Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA..
    Keating, Brendan J.
    Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England.;Onassis Cardiac Surg Ctr, Dept Cardiol 1, Athens, Greece..
    Khaw, Kay-Tee
    Imperial Coll London, Hammersmith Hosp Campus, Natl Heart & Lung Inst, London, England..
    Kim, Yun Kyoung
    Natl Inst Hlth, Ctr Genome Sci, Osong Hlth Technol Adm Complex, Chungcheongbuk Do, South Korea..
    Kim, Eric
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA..
    Kivimaki, Mika
    UCL, Dept Epidemiol & Publ Hlth, Genet Epidemiol Grp, London, England..
    Klopp, Norman
    Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany..
    Kolovou, Genovefa
    Childrens Hosp Oakland, Res Inst, Dept Med, Oakland, CA 94609 USA..
    Komulainen, Pirjo
    Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Kooner, Jaspal S.
    Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England.;MRC Unit Lifelong Hlth & Ageing UCL, London, England..
    Kosova, Gulum
    Broad Inst MIT & Harvard, Cambridge, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA..
    Krauss, Ronald M.
    Univ Lausanne, Dept Med Genet, Lausanne, Switzerland..
    Kuh, Diana
    Swiss Inst Bioinformat, Lausanne, Switzerland..
    Kutalik, Zoltan
    Univ Eastern Finland, Dept Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland.;Univ Eastern Finland, Inst Biomed Physiol, Kuopio, Finland..
    Kuusisto, Johanna
    Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Kvaloy, Kirsti
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway..
    Lakka, Timo A.
    Kuopio Res Inst Exercise Med, Kuopio, Finland.;Off Populat Studies Fdn Inc, Cebu, Philippines.;Univ San Carlos, Dept Anthropol Sociol & Hist, Cebu, Philippines..
    Lee, Nanette R.
    Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrine & Metab, Taichung, Taiwan.;Natl Yang Ming Univ, Sch Med, Taipei, Taiwan..
    Lee, I-Te
    Taichung Vet Gen Hosp, Dept Med Res, Taichung, Taiwan.;NHLBI, Populat Sci Branch, US Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA..
    Lee, Wen-Jane
    Taichung Vet Gen Hosp, Cardiovasc Ctr, Taichung, Taiwan..
    Levy, Daniel
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Natl Yang Ming Univ, Inst Clin Med, Sch Med, Taipei, Taiwan..
    Li, Xiaohui
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA..
    Liang, Kae-Woei
    Boston Univ, Sch Med, Sect Computat Biomed, Dept Med, Boston, MA 02215 USA.;EGID, Lille, France..
    Lin, Honghuang
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Lille Pasteur Inst, CNRS UMR 8199, Lille, France..
    Lin, Li
    Univ Hosp Geneva, Dept Med, Cardiol, Geneva, Switzerland..
    Lindstrom, Jaana
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Lobbens, Stephane
    Univ Lille 2, Lille, France.;Univ Dresden, Med Fac Carl Gustav Carus, Ctr Evidence Based Healthcare, Dresden, Germany.;Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany..
    Mannisto, Satu
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Muller, Gabriele
    Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany..
    Muller-Nurasyid, Martina
    Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Cambridge, Neurol Unit, Biomed Campus, Cambridge, England.;Harokopio Univ, Dept Dietet Nutr, Athens, Greece..
    Mach, Francois
    Univ Hosp Geneva, Dept Med, Cardiol, Geneva, Switzerland..
    Markus, Hugh S.
    Univ Paris 13, Univ Paris 06, Sorbonne Univ, INSERM U1142,LIMICS,UMRS 1142, Paris, France..
    Marouli, Eirini
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    McKenzie, Colin A.
    Univ West Indies, Trop Metab Res Unit, Res Inst Trop Med, Kingston, Jamaica..
    Meneton, Pierre
    Univ Verona, Dept Life & Reprod Sci, Verona, Italy..
    Menni, Cristina
    Kuopio Univ Hosp, Dept Med, Kuopio, Finland..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Mijatovic, Vladan
    Oulu Univ Hosp, Unit Gen Practice, Oulu, Finland..
    Moilanen, Leena
    Univ Maryland, Sch Med, Dept Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA..
    Montasser, May E.
    Cittadella Univ Monseratto, IRGB, CNR, Cagliari, Italy..
    Morris, Andrew D.
    Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee, Scotland..
    Morrison, Alanna C.
    Tampere Univ Hosp, Ctr Heart, Dept Cardiol, Tampere, Finland..
    Mulas, Antonella
    Univ Tampere, Sch Med, Dept Cardiol, Tampere, Finland..
    Nagaraja, Ramaiah
    NIA, Genet Lab, Intramural Res Program, US Natl Inst Hlth, Baltimore, MD 21224 USA..
    Narisu, Narisu
    NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Nikus, Kjell
    NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA.;Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England..
    O'Donnell, Christopher J.
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA.;Childrens Hosp Boston, Genet & Program Genom, Boston, MA USA..
    O'Reilly, Paul F.
    Vrije Univ Amsterdam, Dept Psychiat, EMGO Inst, Med Ctr, Neurosci Campus, Amsterdam, Netherlands..
    Ong, Ken K.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge, England..
    Paccaud, Fred
    Childrens Hosp Oakland, Res Inst, Dept Med, Oakland, CA 94609 USA..
    Palmer, Cameron D.
    Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands..
    Parsa, Afshin
    Cittadella Univ Monseratto, IRGB, CNR, Cagliari, Italy..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Penninx, Brenda W.
    Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.;Imperial Coll London, Int Ctr Circulatory Hlth, London, England.;Gen Cent Hosp, Dept Neurol, Bolzano, Italy..
    Perola, Markus
    Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Peters, Annette
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Poulter, Neil
    Univ Lubeck, Dept Neurol, Lubeck, Germany..
    Pramstaller, Peter P.
    European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.;Univ Lubeck, Inst, Lubeck, Germany.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA..
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.;Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA.;Washington Univ, Sch Med, Div Biostat, St Louis, DC USA.;Ctr Noncommunicable Dis, Karachi, Pakistan..
    Quertermous, Thomas
    Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA..
    Rao, Dabeeru C.
    Umea Univ, Dept Biobank Res, Umea, Sweden..
    Rasheed, Asif
    Univ Med Greifswald, Inst Physiol, Greifswald, Germany..
    Rayner, N. William
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Renstrom, Frida
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Rettig, Rainer
    Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr Ontario, Ottawa, ON, Canada..
    Rice, Kenneth M.
    Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Roberts, Robert
    South Karelia Cent Hosp, Lappeenranta, Finland.;Deutsch Herzzentrum Munich, Munich, Germany..
    Rose, Lynda M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Rossouw, Jacques
    Childrens Hosp Boston, Genet & Program Genom, Boston, MA USA..
    Samani, Nilesh J.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Sanna, Serena
    Univ Tampere, Sch Med, Dept Cardiol, Tampere, Finland..
    Saramies, Jouko
    Tech Univ Munich, Munich, Germany..
    Schunkert, Heribert
    Deutsch Zentrum Herz Kreislauf Forsch DZHK, Munich, Germany.;Munich Heart Alliance, Munich, Germany.;Univ Oulu, Ctr Lifecourse Hlth Res, Oulu, Finland..
    Sebert, Sylvain
    Univ Oulu, Bioctr Oulu, Oulu, Finland.;Univ San Carlos, Dept Anthropol Sociol & Hist, Cebu, Philippines.;Natl Def Med Ctr, Coll Med, Taipei, Taiwan. Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore. Natl Univ Hlth Syst, Singapore, Singapore..
    Sheu, Wayne H-H
    Karolinska Univ Hosp Solna, Ctr Mol Med, Stockholm, Sweden.;Taichung Vet Gen Hosp, Dept Med Res, Taichung, Taiwan.;NHLBI, Populat Sci Branch, US Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA.;Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA..
    Shin, Young-Ah
    Natl Inst Hlth, Ctr Genome Sci, Osong Hlth Technol Adm Complex, Chungcheongbuk Do, South Korea..
    Sim, Xueling
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Univ Eastern Finland, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Smit, Johannes H.
    Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands..
    Smith, Albert V.
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Sosa, Maria X.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA..
    Spector, Tim D.
    Kuopio Univ Hosp, Dept Med, Kuopio, Finland..
    Stancakova, Alena
    Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin, Ireland..
    Stanton, Alice V.
    Univ Cambridge, Dept Haematol, Cambridge, England..
    Stirrups, Kathleen E.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Natl Univ Singapore, Dept Med, Singapore, Singapore.;Natl Univ Hlth Syst, Singapore, Singapore..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Swift, Amy J.
    NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Tai, E-Shyong
    Duke NUS Grad Med Sch Singapore, Singapore, Singapore.;Univ Eastern Finland, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland.;NIA, Intramural Res Program, Lab Cardiovasc Sci, US Natl Inst Hlth, Baltimore, MD 21224 USA..
    Tanaka, Toshiko
    NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA..
    Tarasov, Kirill V.
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Teumer, Alexander
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Thorsteinsdottir, Unnur
    deCODE Genet Amgen Inc, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Tobin, Martin D.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Tremoli, Elena
    Univ Milan, Dipartimento Sci Farmacol & Biomol, Milan, Italy.;IRCCS, Ctr Cardiol Monzino, Milan, Italy..
    Uitterlinden, Andre G.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.;Univ Eastern Finland, Dept Publ Hlth & Clin Nutr, Kuopio, Finland..
    Uusitupa, Matti
    Kuopio Univ Hosp, Res Unit, Kuopio, Finland.;Isfahan Univ Med Sci, Res Inst Primordial Prevent Noncommunicable Dis, Esfahan, Iran..
    Vaez, Ahmad
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.;Johns Hopkins Med Inst, Baltimore, MD 21205 USA..
    Vaidya, Dhananjay
    NGI Erasmus Med Ctr, Ctr Med Syst Biol CMSB 12, Rotterdam, Netherlands..
    van Duijn, Cornelia M.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands.;Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands..
    van Iperen, Erik P. A.
    ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;Boston Univ, Dept Med, Sect Prevent Med, Sch Med, Boston, MA USA..
    Vasan, Ramachandran S.
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med, Dept Med, Cardiol, Boston, MA 02215 USA.;Univ Penn, Perelman Sch Med, Dept Genet, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA..
    Verwoert, Germaine C.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands..
    Virtamo, Jarmo
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Vitart, Veronique
    Western Gen Hosp, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Voight, Benjamin F.
    Univ Lausanne Hosp, Dept Internal Med, Lausanne, Switzerland..
    Vollenweider, Peter
    Univ Strasbourg, EA3430, Dept Epidemiol & Publ Hlth, Strasbourg, France..
    Wagner, Aline
    Univ Michigan, Sch Med, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Wain, Louise V.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge, England..
    Watldns, Hugh
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England..
    Weder, Alan B.
    Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands..
    Westra, Harm Jan
    Univ West Indies, Res Inst Trop Med, Epidemiol Res Unit, Kingston, Jamaica..
    Wilks, Rainford
    Univ Tromso, Dept Community Med, Fac Hlth Sci, Tromso, Norway..
    Wilsgaard, Tom
    Univ Tromso, Fac Hlth Sci, Dept Clin Med, Tromso, Norway.;Univ Cambridge, MRC Canc Unit, Cambridge, England..
    Wilson, James F.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.;Western Gen Hosp, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Wong, Tien Y.
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Duke NUS Grad Med Sch Singapore, Singapore, Singapore.;Natl Univ Singapore, Dept Ophthalmol, Singapore, Singapore.;Natl Univ Hlth Syst, Singapore, Singapore..
    Yang, Tsun-Po
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Case Western Reserve Univ, Dept Epidemiol & Biostat, Sch Med, Cleveland, OH 44106 USA..
    Yao, Jie
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA..
    Yengo, Loic
    Univ Lille 2, Lille, France.;Univ Dresden, Med Fac Carl Gustav Carus, Ctr Evidence Based Healthcare, Dresden, Germany.;Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany..
    Zhang, Weihua
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge, England..
    Zhu, Xiaofeng
    Minist Hlth, Victoria, Seychelles..
    Bovet, Pascal
    CHU Vaudois, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland.;Univ Lausanne, Lausanne, Switzerland.;Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Cooper, Richard S.
    Loyola Univ, Chicago Stritch Sch Med, Dept Publ Hlth Sci, Maywood, IL 60153 USA..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Saleheen, Danish
    Univ Med Greifswald, Inst Physiol, Greifswald, Germany.;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England..
    Lee, Jong-Young
    Natl Inst Hlth, Ctr Genome Sci, Osong Hlth Technol Adm Complex, Chungcheongbuk Do, South Korea..
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    Gierman, Hinco J.
    Stanford Univ, Med Ctr, Dept Dev Biol & Genet, Stanford, CA 94305 USA.;Acad Med Ctr, Dept Vasc Med, Amsterdam, Netherlands..
    Willer, Cristen J.
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands..
    Franke, Lude
    Hovingh, G. Kees
    Taylor, Kent D.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA..
    Dedoussis, George
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Sever, Peter
    Univ Lubeck, Dept Neurol, Lubeck, Germany..
    Wong, Andrew
    Swiss Inst Bioinformat, Lausanne, Switzerland..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Assimes, Themistocles L.
    Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA..
    Njolstad, Inger
    Univ Tromso, Fac Hlth Sci, Dept Clin Med, Tromso, Norway.;Univ Cambridge, MRC Canc Unit, Cambridge, England..
    Schwarz, Peter E. H.
    Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, Dresden, Germany.;Univ Hosp, Paul Langerhans Inst Dresden, Helmholtz Ctr Munich, Dresden, Germany.;Tech Univ Dresden, Fac Med, Dresden, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge, England..
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Caulfield, Mark J.
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, London, England..
    Melander, E.
    Lund Univ, Dept Internal Med, Malmo, Sweden..
    Laakso, Markku
    Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Saltevo, Juha
    Cent Finland Hlth Care Dist, Dept Med, Jyvaskyla, Finland..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Kuopio, Finland.;Univ San Carlos, Dept Anthropol Sociol & Hist, Cebu, Philippines..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Helsinki, Finland.;Dasman Diabet Inst, Dasman, Kuwait.;King Abdulaziz Univ, Saudi Diabet Res Grp, Jeddah, Saudi Arabia.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere, Finland..
    Hveem, Kristian
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway..
    Palmas, Walter
    Columbia Univ, Dept Med, New York, NY USA..
    Marz, Winfried
    Synlab Acad, Synlab Serv, Mannheim, Germany.;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria..
    Kumar, Meena
    UCL, Dept Epidemiol & Publ Hlth, Genet Epidemiol Grp, London, England..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Chen, Yii-Der I.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA..
    Froguel, Philippe
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Lille 2, Lille, France.;Univ Dresden, Med Fac Carl Gustav Carus, Ctr Evidence Based Healthcare, Dresden, Germany.;Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany..
    Jarvelin, Marjo-Riitta
    Univ Oulu, Bioctr Oulu, Oulu, Finland.;Natl Def Med Ctr, Coll Med, Taipei, Taiwan. Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore. Natl Univ Hlth Syst, Singapore, Singapore.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.;Oulu Univ Hosp, Unit Primary Care, Oulu, Finland..
    Lakatta, Edward G.
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Kuulasmaa, Kari
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Franks, Paul W.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA..
    Hamsten, Anders
    Karolinska Inst, Dept Med, Cardiovasc Res Unit, Ctr Mol Med, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Ctr Mol Med, Stockholm, Sweden..
    Wichmann, H-Erich
    Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.;Harokopio Univ, Dept Dietet Nutr, Athens, Greece.;Tech Univ Munich, Inst Med Stat & Epidemiol, Munich, Germany..
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee, Scotland..
    Stefansson, Kari
    deCODE Genet Amgen Inc, Reykjavik, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Loos, Ruth J. F.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge, England.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth Dev Inst, New York, NY 10029 USA..
    Chalcravarti, Aravinda
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA..
    Deloukas, Panos
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Newton-Cheh, Christopher
    Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.;Broad Inst MIT & Harvard, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA..
    Munroe, Patricia B.
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, London, England..
    The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals2016In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, no 10, p. 1171-1184Article in journal (Refereed)
    Abstract [en]

    To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

  • 223.
    Eicher, John D.
    et al.
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Chami, Nathalie
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Kacprowski, Tim
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, D-17475 Greifswald, Germany.;Ernst Mortiz Arndt Univ Greifswald, D-17475 Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Nomura, Akihiro
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA 02115 USA.;Kanazawa Univ, Div Cardiovasc Med, Grad Sch Med Sci, Kanazawa, Ishikawa 9200942, Japan.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Chen, Ming-Huei
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA..
    Yanek, Lisa R.
    Johns Hopkins Univ, Div Gen Internal Med, Dept Med, Sch Med, Baltimore, MD 21205 USA..
    Tajuddin, Salman M.
    NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA..
    Schick, Ursula M.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Slater, Andrew J.
    GlaxoSmithKline, Genet, Target Sci, Res Triangle Pk, NC 27709 USA.;OmicSoft Corp, Cary, NC 27513 USA..
    Pankratz, Nathan
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55454 USA..
    Polfus, Linda
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Giri, Ayush
    Vanderbilt Univ, Inst Med & Publ Hlth, Div Epidemiol, Nashville, TN 37235 USA..
    Brody, Jennifer A.
    Univ Washington, Dept Med, Seattle, WA 98101 USA..
    Lange, Leslie A.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Manichaikul, Ani
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA 22908 USA..
    Hill, W. David
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Pazoki, Raha
    Erasmus MC, Dept Epidemiol, NL-3000 Rotterdam, Netherlands..
    Elliot, Paul
    Univ London Imperial Coll Sci Technol & Med, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, Sch Publ Hlth, London W2 1PG, England..
    Evangelou, Evangelos
    Univ London Imperial Coll Sci Technol & Med, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, Sch Publ Hlth, London W2 1PG, England.;Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Ioannina 45110, Greece..
    Tzoulaki, Ioanna
    Univ London Imperial Coll Sci Technol & Med, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, Sch Publ Hlth, London W2 1PG, England.;Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Ioannina 45110, Greece..
    Gao, He
    Univ London Imperial Coll Sci Technol & Med, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, Sch Publ Hlth, London W2 1PG, England..
    Vergnaud, Anne-Claire
    Univ London Imperial Coll Sci Technol & Med, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, Sch Publ Hlth, London W2 1PG, England..
    Mathias, Rasika A.
    Johns Hopkins Univ, Div Gen Internal Med, Dept Med, Sch Med, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Sch Med, Dept Med, Div Allergy, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Sch Med, Dept Med, Div Immunol, Baltimore, MD 21205 USA..
    Becker, Diane M.
    Johns Hopkins Univ, Div Gen Internal Med, Dept Med, Sch Med, Baltimore, MD 21205 USA..
    Becker, Lewis C.
    Johns Hopkins Univ, Div Gen Internal Med, Dept Med, Sch Med, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Div Cardiol, Dept Med, Sch Med, Baltimore, MD 21205 USA..
    Burt, Amber
    Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA..
    Crosslin, David R.
    Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98105 USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33514, Finland..
    Nikus, Kjell
    Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere 33521, Finland.;Univ Tampere, Sch Med, Tampere 33514, Finland..
    Hernesniemi, Jussi
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33514, Finland.;Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere 33521, Finland..
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.;Univ Tampere, Dept Clin Physiol, Tampere 33514, Finland..
    Raitoharju, Emma
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33514, Finland..
    Mononen, Nina
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33514, Finland..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33514, Finland..
    Cushman, Mary
    Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.;Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA..
    Zakai, Neil A.
    Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.;Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA..
    Nickerson, Deborah A.
    Univ Washington, Dept Genome Sci, Seattle, WA 98105 USA..
    Raffield, Laura M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Quarells, Rakale
    Morehouse Sch Med, Social Epidemiol Res Ctr, Cardiovasc Res Inst, Atlanta, GA 30310 USA..
    Willer, Cristen J.
    Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48108 USA.;Univ Michigan, Dept Computat Med & Bioinformat, Dept Human Genet, Ann Arbor, MI 48108 USA.;Univ Michigan, Dept Biostat, Ann Arbor, MI 48108 USA..
    Peloso, Gina M.
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02118 USA..
    Abecasis, Goncalo R.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48108 USA..
    Liu, Dajiang J.
    Penn State Univ Hosp, Dept Publ Hlth Sci, Coll Med, Hershey, PA 17033 USA..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, London E1 4NS, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia..
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Schunkert, Heribert
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80333 Munich, Germany.;Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80333 Munich, Germany..
    Erdmann, Jeanette
    Univ Lubeck, Inst Integrat & Expt Genom, D-23562 Lubeck, Germany.;DZHK German Res Ctr Cardiovasc Res, Partner Site Hamburg Lubeck Kiel, D-23562 Lubeck, Germany..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Richard, Melissa
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Tardif, Jean-Claude
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Rioux, John D.
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Dube, Marie-Pierre
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    de Denus, Simon
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Pharm, Montreal H3T 1J4, PQ, Canada..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Smith, Albert Vernon
    Icelandic Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Harris, Tamara B.
    NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Baltimore, MD 21224 USA..
    Launer, Lenore J.
    NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Baltimore, MD 21224 USA..
    Gudnason, Vilmundur
    Icelandic Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Edwards, Digna R. Velez
    Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Dept Obstet & Gynecol, Inst Med & Publ Hlth,Vanderbilt Genet Inst, Nashville, TN 37203 USA..
    Torstenson, Eric S.
    Vanderbilt Univ, Inst Med & Publ Hlth, Div Epidemiol, Nashville, TN 37235 USA..
    Liu, Yongmei
    Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC 27157 USA..
    Tracy, Russell P.
    Univ Vermont, Coll Med, Dept Pathol & Lab Med, Colchester, VT 05446 USA.;Univ Vermont, Coll Med, Dept Biochem, Colchester, VT 05446 USA..
    Rotter, Jerome I.
    Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA..
    Rich, Stephen S.
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA 22908 USA..
    Highland, Heather M.
    Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Univ Texas Sch Publ Hlth, Houston, TX 77030 USA.;Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Li, Jin
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Palo Alto, CA 94305 USA..
    Lange, Ethan
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA.;Univ N Carolina, Dept Biostat, Chapel Hill, NC 27514 USA..
    Wilson, James G.
    Univ Mississippi, Dept Physiol & Biophys, Med Ctr, Jackson, MS 39216 USA..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Hirschhorn, Joel
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Esko, Tonu
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Vacchi-Suzzi, Caterina
    SUNY Stony Brook, Dept Family Populat & Prevent Med, Stony Brook, NY 11794 USA..
    Nalls, Mike A.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 21224 USA..
    Zonderman, Alan B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA..
    Evans, Michele K.
    NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA..
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci Malmo, S-22100 Malmo, Sweden.;Skane Univ Hosp, S-22241 Malmo, Sweden..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci Malmo, S-22100 Malmo, Sweden.;Skane Univ Hosp, S-22241 Malmo, Sweden..
    Melander, Olle
    Lund Univ, Dept Clin Sci Malmo, S-22100 Malmo, Sweden.;Skane Univ Hosp, S-22241 Malmo, Sweden..
    O'Donoghue, Michelle L.
    Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA..
    Waterworth, Dawn M.
    GlaxoSmithKline, Target Sci, Genet, King Of Prussia, PA 19406 USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1142, New Zealand.;Univ Auckland, Auckland 1142, New Zealand..
    Floyd, James S.
    Univ Washington, Dept Med, Seattle, WA 98101 USA..
    Bartz, Traci M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Rice, Kenneth M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA.;Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA..
    Starr, J. M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Alzheimer Scotland Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Liewald, David C. M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Hayward, Caroline
    Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Greinacher, Andreas
    Univ Med Greifswald, Inst Immunol & Transfus Med, D-17475 Greifswald, Germany..
    Volker, Uwe
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, D-17475 Greifswald, Germany.;Ernst Mortiz Arndt Univ Greifswald, D-17475 Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany..
    Thiele, Thomas
    Univ Med Greifswald, Inst Immunol & Transfus Med, D-17475 Greifswald, Germany..
    Volzke, Henry
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.;Univ Med Greifswald, Inst Community Med, D-13347 Greifswald, Germany..
    van Rooij, Frank J. A.
    Erasmus MC, Dept Epidemiol, NL-3000 Rotterdam, Netherlands..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, NL-3000 Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;Netherlands Consortium Hlth Ageing, NL-3015 Rotterdam, Netherlands..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, NL-3000 Rotterdam, Netherlands..
    Dehghan, Abbas
    Erasmus MC, Dept Epidemiol, NL-3000 Rotterdam, Netherlands..
    Edwards, Todd L.
    Vanderbilt Univ, Inst Med & Publ Hlth, Div Epidemiol, Nashville, TN 37235 USA..
    Ganesh, Santhi K.
    Univ Michigan, Dept Internal & Human Genet, Ann Arbor, MI 48108 USA..
    Kathiresan, Sekar
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA 02115 USA..
    Faraday, Nauder
    Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Auer, Paul L.
    Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53205 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Reiner, Alex P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98105 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Lettre, Guillaume
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Johnson, Andrew D.
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals2016In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 99, no 1, p. 40-55Article in journal (Refereed)
    Abstract [en]

    Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common(ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV(PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.

  • 224. Eikelboom, John W.
    et al.
    Connolly, Stuart J.
    Hart, Robert G.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Reilly, Paul
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Yang, Sean
    Yusuf, Salim
    Balancing the Benefits and Risks of 2 Doses of Dabigatran Compared With Warfarin in Atrial Fibrillation2013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 62, no 10, p. 900-908Article in journal (Refereed)
    Abstract [en]

    Objectives This study sought to compare the net clinical benefit of dabigatran 110 mg bid and 150 mg bid with that of warfarin in patients with atrial fibrillation (AF). Background In patients with AF, dabigatran 110 mg bid and 150 mg bid are associated with similar rates of death. However, the higher dose reduces ischemic stroke and increases bleeding compared with the lower dose. Therefore, there is uncertainty about how to evaluate the overall benefit of the 2 doses. Methods In 18,113 AF patients in the RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy) trial, we used a previously developed method for integrating ischemic and bleeding events as "ischemic stroke equivalents" in order to compare a weighted benefit of 2 doses of dabigatran with each other, and with that of warfarin. Results Compared with warfarin, there was a significant decrease in ischemic stroke equivalents with both dabigatran doses: -0.92 per 100 patient years (95% confidence interval [CI]: -1.74 to -0.21, p = 0.02) with dabigatran 110 mg bid and -1.08 (95% CI: -1.86 to -0.34, p = 0.01) with dabigatran 150 mg bid. There was no significant difference in ischemic stroke equivalents between the 2 doses: -0.16 (95% CI: -0.80 to 0.43) comparing dabigatran 150 mg bid with 110 bid. When including death in the weighted benefit calculations, the results were similar. Conclusions On a group level both doses of dabigatran as compared with warfarin have similar benefits when considering a weighted estimate including both efficacy and safety. The similar overall benefits of the 2 doses of dabigatran versus warfarin support individualizing the dose based on patient characteristics and physician and patient preferences. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600)

  • 225. Elfstrom, P.
    et al.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ludvigsson, J. F.
    Systematic review with meta-analysis: associations between coeliac disease and type 1 diabetes2014In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 40, no 10, p. 1123-1132Article, review/survey (Refereed)
    Abstract [en]

    BackgroundIn the past decade, a number of population-based studies have examined the prevalence of coeliac disease in individuals with type 1 diabetes but prevalences have differed considerably. AimTo examine the prevalence of coeliac disease in individuals with type 1 diabetes. MethodsA systematic review of English-language articles published in PubMed Medline between 2000 and May 2014. Search terms included celiac disease' or coeliac disease' and diabetes mellitus'. Studies were selected with at least 100 individuals with type 1 diabetes being screened for coeliac disease where the coeliac diagnosis was later confirmed through small intestinal biopsy. Data synthesis used random-effects inverse variance-weighted models, and metaregression was used to examine heterogeneity in subgroups. ResultsA pooled analysis, based on 26,605 patients with type 1 diabetes, found a prevalence of biopsy-confirmed coeliac disease of 6.0% (95% CI=5.0-6.9%). Heterogeneity was large (I-2=93.2%). The prevalence was lower in adults with type 1 diabetes (2.7%), and in mixed populations with both children and adults with type 1 diabetes (4.7%) than in children (6.2%) with type 1 diabetes (P<0.001). Additional subgroup analyses could not explain the large variation in coeliac disease prevalence between studies. ConclusionMore than one in twenty patients with type 1 diabetes have biopsy-verified coeliac disease. This prevalence is high enough to motivate screening for coeliac disease among patients with type 1 diabetes.

  • 226.
    Elfwen, Ludvig
    et al.
    Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, Solna, Sweden.
    Lagedal, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jonsson, Martin
    Karolinska Inst, Ctr Resuscitat Sci, Dept Med, Solna, Sweden.
    Jensen, Ulf
    Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, Solna, Sweden.
    Ringh, Mattias
    Karolinska Inst, Ctr Resuscitat Sci, Dept Med, Solna, Sweden.
    Claesson, Andreas
    Karolinska Inst, Ctr Resuscitat Sci, Dept Med, Solna, Sweden.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Herlitz, Johan
    Univ Boras, Ctr Prehosp Res Western Sweden, Boras, Sweden;Univ Boras, Sch Hlth Sci, Boras, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nordberg, Per
    Karolinska Inst, Ctr Resuscitat Sci, Dept Med, Solna, Sweden.
    Coronary angiography in out-of-hospital cardiac arrest without ST elevation on ECG-Short- and long-term survival2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 200, p. 90-95Article in journal (Refereed)
    Abstract [en]

    Background: The potential benefit of early coronary angiography in out-of-hospital cardiac arrest (OHCA) patients without ST elevation on ECG is unclear. The aim of this study was to evaluate the association between early coronary angiography and survival in these patients.

    Methods: Nationwide observational study between 2008 and 2013. Included were patients admitted to hospital after witnessed OHCA, with shockable rhythm, age 18 to 80 years and unconscious. Patients with ST-elevation on ECG were excluded. Patients that underwent early CAG (within 24 hours) were compared with no early CAG (later during the hospital stay or not at all). Outcomes were survival at 30 days, 1 year, and 3 years. Multivariate analysis included pre-hospital factors, comorbidity and ECG-findings.

    Results: In total, 799 OHCA patients fulfilled the inclusion criteria, of which 275 (34%) received early CAG versus 524 (66%) with no early CAG. In the early CAG group, the proportion of patients with an occluded coronary artery was 27% and 70% had at least one significant coronary stenosis (defined as narrowing of coronary lumen diameter of >= 50%). The 30-day survival rate was 65% in early CAG group versus 52% with no early CAG (P < .001). The adjusted OR was 1.42 (95% CI 1.00-2.02). The one-year survival rate was 62% in the early CAG group versus 48% in the no early CAG group with the adjusted hazard ratio of 1.35 (95% CI 1.04-1.77).

    Conclusion: In this population of bystander-witnessed cases of out-of-hospital cardiac arrest with shockable rhythm and ECG without ST elevation, early coronary angiography may be associated with improved short and long term survival.

  • 227.
    Elfwen, Ludvig
    et al.
    Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Lagedal, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Nordberg, Per
    Karolinska Inst, Ctr Resuscitat Sci, Dept Med, Solna, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bohm, Felix
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Cardiol, Stockholm, Sweden.
    Lundgren, Peter
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden;Univ Boras, Prehospen Ctr Prehosp Res, Boras, Sweden.
    Rylander, Christian
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Anaesthesiol & Intens Care Med, Gothenburg, Sweden.
    van der Linden, Jan
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Hollenberg, Jacob
    Karolinska Inst, Ctr Resuscitat Sci, Dept Med, Solna, Sweden.
    Erlinge, David
    Lund Univ, Clin Sci, Dept Cardiol, Lund, Sweden.
    Cronberg, Tobias
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Div Neurol, Lund, Sweden.
    Jensen, Ulf
    Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Friberg, Hans
    Lund Univ, Skane Univ Hosp, Dept Anesthesiol & Intens Care Med, Lund, Sweden.
    Lilja, Gisela
    Lund Univ, Skane Univ Hosp, Dept Clin Sci, Div Neurol, Lund, Sweden.
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wallin, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Svensson, Leif
    Karolinska Inst, Ctr Resuscitat Sci, Dept Med, Solna, Sweden.
    Direct or subacute coronary angiography in out-of-hospital cardiac arrest (DISCO)-An initial pilot-study of a randomized clinical trial2019In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 139, p. 253-261Article in journal (Refereed)
    Abstract [en]

    Background: The clinical importance of immediate coronary angiography, with potentially subsequent percutaneous coronary intervention (PCI), in out-of-hospital cardiac arrest (OHCA) patients without ST-elevation on the ECG is unclear. In this study, we assessed feasibility and safety aspects of performing immediate coronary angiography in a pre-specified pilot phase of the 'DIrect or Subacute Coronary angiography in Out-of-hospital cardiac arrest' (DISCO) randomized controlled trial (ClinicalTrials.gov ID: NCT02309151). Methods: Resuscitated bystander witnessed OHCA patients > 18 years without ST-elevation on the ECG were randomized to immediate coronary angiography versus standard of care. Event times, procedure related adverse events and safety variables within 7 days were recorded. Results: In total, 79 patients were randomized to immediate angiography (n = 39) or standard of care (n = 40). No major differences in baseline characteristics between the groups were found. There were no differences in the proportion of bleedings and renal failure. Three patients randomized to immediate angiography and six patients randomized to standard care died within 24 h. The median time from EMS arrival to coronary angiography was 135 min in the immediate angiography group. In patients randomized to immediate angiography a culprit lesion was found in 14/38 (36.8%) and PCI was performed in all these patients. In 6/40 (15%) patients randomized to standard of care, coronary angiography was performed before the stipulated 3 days. Conclusion: In this out-of-hospital cardiac arrest population without ST-elevation, randomization to a strategy to perform immediate coronary angiography was feasible although the time window of 120 min from EMS arrival at the scene of the arrest to start of coronary angiography was not achieved. No significant safety issues were reported.

  • 228. Emilsson, L.
    et al.
    Carlsson, R.
    Holmqvist, M.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ludvigsson, J. F.
    The characterisation and risk factors of ischaemic heart disease in patients with coeliac disease2013In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 37, no 9, p. 905-914Article in journal (Refereed)
    Abstract [en]

    Background Studies have shown an increased risk of ischaemic heart disease (IHD) in patients with coeliac disease (CD), despite the patients' lack of traditional IHD risk factors. Aim To characterise IHD according to CD status. Methods Data on duodenal or jejunal biopsies were collected in 20062008 from all 28 pathology departments in Sweden and were used to define CD (equal to villous atrophy; Marsh stage 3). We used the Swedish cardiac care register SWEDEHEART to identify IHD and to obtain data on clinical status and risk factors at time of first myocardial infarction for this case-only comparison. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). CD patients were compared with general population reference individuals. Results We identified 1075 CD patients and 4142 reference individuals with subsequent IHD. CD patients with myocardial infarction had lower body mass index (P<0.001) and cholesterol values (P<0.001) and were less likely to be active smokers (OR=0.74; 95% CI=0.560.98) than reference individuals with myocardial infarction. CD patients had less extensive coronary artery disease at angiography (any stenosis: OR=0.80; 95% CI=0.660.97; three-vessel disease: OR=0.73; 95% CI=0.570.94); but there was no difference in the proportions of CD patients with positive biochemical markers of myocardial infarction (CD: 92.2% vs. reference individuals: 91.5%, P=0.766). Conclusion Despite evidence of an increased risk of IHD and higher cardiovascular mortality, patients with coeliac disease with IHD have a more favourable cardiac risk profile compared with IHD in reference individuals.

  • 229. Emilsson, L.
    et al.
    Carlsson, R.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ludvigsson, J. F.
    Letter: coeliac disease and ischaemic heart disease - a true additional risk factor? Authors' reply2013In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 37, no 11, p. 1118-1118Article in journal (Refereed)
  • 230.
    Emilsson, L.
    et al.
    Primary Care Res Unit, Varmlands Nysater, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Koster, M.
    Natl Board Hlth & Welf, Stockholm, Sweden..
    Lambe, M.
    Karolinska Inst, Stockholm, Sweden..
    Ludvigsson, J. F.
    Karolinska Inst, Stockholm, Sweden..
    Review of 103 Swedish Healthcare Quality Registers2015In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 44, p. 174-174Article in journal (Other academic)
  • 231. Emilsson, L.
    et al.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Koster, M.
    Lambe, M.
    Ludvigsson, J. F.
    Review of 103 Swedish Healthcare Quality Registries2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 1, p. 94-136Article in journal (Refereed)
    Abstract [en]

    Background and objectives: In the past two decades, an increasing number of nationwide, Swedish Healthcare Quality Registries (QRs) focusing on specific disorders have been initiated, mostly by physicians. Here, we describe the purpose, organization, variables, coverage and completeness of 103 Swedish QRs. Methods: From March to September 2013, we examined the 2012 applications of 103 QRs to the Swedish Association of Local Authorities and Regions (SALAR) and also studied the annual reports from the same QRs. After initial data abstraction, the coordinator of each QR was contacted at least twice between June and October 2013 and asked to confirm the accuracy of the data retrieved from the applications and reports. Results: About 60% of the QRs covered 80% of their target population (completeness). Data recorded in Swedish QRs include aspects of disease management (diagnosis, clinical characteristics, treatment and lead times). In addition, some QRs retrieve data on self-reported quality of life (EQ5D, SF-36 and disease-specific measures), lifestyle (smoking) and general health status (World Health Organization performance status, body mass index and blood pressure). ConclusionDetailed clinical data available in Swedish QRs complement information from government-administered registries and provide an important source not only for assessment and development of quality of care but also for research.

  • 232. Emilsson, Louise
    et al.
    Carlsson, Roland
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hambraeus, Kristina
    Ludvigsson, Jonas F.
    Follow-up of ischaemic heart disease in patients with coeliac disease2015In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 1, p. 83-90Article in journal (Refereed)
    Abstract [en]

    Patients with coeliac disease and myocardial infarction have a more favourable atherosclerotic risk factor profile than controls with myocardial infarction (MI). Therefore, MI prognosis and treatment may differ according to coeliac status. This paper reports on the study of Swedish MI patients with and without coeliac disease (equal to villous atrophy; Marsh histopathology stage 3) based on duodenal or jejunal biopsy data. We used the Swedish Quality Register (SWEDEHEART) to identify individuals with a record of MI from 2005 to 2008 and to obtain data on medication, coronary interventions, and clinical and laboratory parameters at 6-10 weeks and one year after first MI. One-year mortality and coronary interventions were assessed for 430 coeliac patients and 1988 controls. For other outcome variables, we compared 42 coeliac patients with MI and 201 general population controls with MI. Odds ratios (ORs) were calculated by logistic regression. The results showed that compared with controls with MI, coeliac individuals with MI had significantly higher one-year all-cause mortality (OR=1.43; 95% confidence interval (CI)=1.04-1.95) but less often underwent a percutaneous coronary intervention (OR=0.77; 95% CI=0.61-0.96). Coeliac patients were more often prescribed warfarin but less often aspirin and statins. The readmission rate due to cardiac events in coeliac patients was 15.2% vs. 12.6% in controls (p-value=0.69). Other clinical and laboratory parameters were similar. We conclude that the follow up of MI does not seem to differ between coeliac patients and controls, and is unlikely to explain the excess mortality from cardiovascular disease noted in Swedish patients with CD.

  • 233. Emilsson, Louise
    et al.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ludvigsson, Jonas F.
    Ischaemic heart disease in first-degree relatives to coeliac patients2014In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 44, no 4, p. 359-364Article in journal (Refereed)
    Abstract [en]

    ObjectiveCoeliac disease (CD) has been linked to an increased risk of ischaemic heart disease (IHD). We examined the risk of IHD in first-degree relatives and spouses to coeliac patients to ascertain the genetic contribution to IHD excess risk. Study design and settingCoeliac disease was defined as having a biopsy-verified villous atrophy (Marsh grade 3) in 1969-2008 (n=29096). Coeliac patients were matched to 144522 controls. Through Swedish registers, we identified all first-degree relatives and spouses to coeliac patients and their controls, in total 87622 unique coeliac relatives and 432655 unique control relatives. Our main outcome measure was IHD defined according to relevant international classification of disease codes in the Swedish Inpatient Registry or in the Cause of Death Registry. Hazard ratios (HR) and confidence intervals (CI) were estimated through Cox regression adjusted for sex, age-group and calendar year at study entry of the relative. ResultDuring a median follow-up of 10<bold>8</bold>years, 2880 coeliac relatives and 13817 control relatives experienced IHD. First-degree relatives of coeliac patients were at increased risk of IHD (HR=1<bold>05</bold>; 95% CI=1<bold>00</bold>-1<bold>09</bold>, P-value=0<bold>04</bold>), while spouses were at no increased risk (HR=0<bold>99</bold>; 95% CI=0<bold>87</bold>-1<bold>12</bold>). The excess risk of IHD in coeliac first-degree relatives aged 40-59years was 70/100000 person-years. ConclusionFirst-degree relatives to coeliac patients seem to be at an increased risk of IHD but the excess risk is so small that it has little clinical relevance.

  • 234.
    Eriksson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Axelsson, Tomas
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Connolly, Stuart
    Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Hamilton, ON, Canada..
    Eikelboom, John
    Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Hamilton, ON, Canada..
    Ezekowitz, Michael
    Thomas Jefferson Univ, Sidney Kimmel Med Collage, Philadelphia, PA 19107 USA..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Pare, Guillaume
    Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Hamilton, ON, Canada..
    Reilly, Paul
    Boehringer Ingelheim Pharma Inc, Ridgefield, CT USA..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Syvänen, Ann-Christine
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Wadelius, Claes
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Yusuf, Salim
    Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.;McMaster Univ, Hamilton, ON, Canada..
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genetic determinants of warfarin maintenance dose and time in therapeutic treatment range: a RE-LY genomics substudy2016In: Pharmacogenomics (London), ISSN 1462-2416, E-ISSN 1744-8042, Vol. 17, no 13, p. 1425-1439Article in journal (Refereed)
    Abstract [en]

    Aims: We investigated associations between genetic variation in candidate genes and on a genome-wide scale with warfarin maintenance dose, time in therapeutic range (TTR), and risk of major bleeding. Materials & methods: In total, 982 warfarin-treated patients from the RE-LY trial were studied. Results: After adjusting for SNPs in VKORC1 and CYP2C9, SNPs in DDHD1 (rs17126068) and NEDD4 (rs2288344) were associated with dose. Adding these SNPs and CYP4F2 (rs2108622) to a base model increased R-2 by 2.9%. An SNP in ASPH (rs4379440) was associated with TTR (-6.8% per minor allele). VKORC1 was associated with time less than INR 2.0. VKORC1 and CYP2C9 were associated with time more than INR 3.0, but not with major bleeding. Conclusions: We identified two novel genes associated with warfarin maintenance dose and one gene associated with TTR. These genes need to be replicated in an independent cohort.

  • 235. Erlinge, D.
    et al.
    Gurbel, P.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, T. L.
    Svensson, P.
    Brown, P. B.
    Zhou, C.
    Jakubowski, J. A.
    Ten Berg, J. M.
    Angiolillo, D. J.
    Prasugrel 5mg in the very elderly is non-inferior to prasugrel 10mg in non-elderly patients: the generations trial, a pharmacodynamic (PD) study in stable CAD patients2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 675-675Article in journal (Other academic)
  • 236.
    Erlinge, D.
    et al.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    Omerovic, E.
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Fröbert, O.
    Rebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Linder, R.
    Danderyd Hosp, Dept Cardiol, Danderyd, Sweden..
    Danielewicz, M.
    Karlstad Hosp, PCI Unit, Karlstad, Sweden..
    Hamid, M.
    Malarsjukhuset, Dept Cardiol, Eskilstuna, Sweden..
    Swahn, E.
    Linkoping Univ Hosp, Dept Cardiol, Linkoping, Sweden..
    Henareh, L.
    Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Wagner, H.
    Helsingborg Lasarett, Dept Cardiol, Helsingborg, Sweden..
    Hårdhammar, P.
    Halmstad Cty Hosp, Dept Cardiol, Halmstad, Sweden..
    Sjögren, I.
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden..
    Stewart, J.
    Skaraborgs Hosp, Dept Cardiol, Skovde, Sweden..
    Grimfjärd, P.
    Vastmanlands Sjukhus, Dept Internal Med, Vasteras, Sweden..
    Jensen, J.
    Karolinska Inst, Capio St Gorans Hosp, Dept Cardiol, Stockholm, Sweden..
    Aasa, M.
    Sodersjukhuset AB, Dept Cardiol, Stockholm, Sweden..
    Robertsson, L.
    Sodra Alvsborgs Sjukhus, Dept Cardiol, Boras, Sweden..
    Lindroos, P.
    Karolinska Inst, Capio St Gorans Hosp, Dept Cardiol, Stockholm, Sweden..
    Haupt, J.
    Sunderby Sjukhus, Dept Cardiol, Lulea, Sweden..
    Wikström, H.
    Kristianstad Hosp, Dept Cardiol, Kristianstad, Sweden..
    Ulvenstam, A.
    Ostersund Hosp, Dept Cardiol, Ostersund, Sweden..
    Bhiladvala, P.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    Lindvall, B.
    Sundsvall Hosp, Dept Cardiol, Sundsvall, Sweden..
    Lundin, A.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    Tödt, T.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    Ioanes, D.
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Råmunddal, T.
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Kellerth, T.
    Rebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Zagozdzon, L.
    Rebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Götberg, M.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    Andersson, J.
    Umea Univ, Dept Cardiol, Umea, Sweden..
    Angerås, O.
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Schersten, F.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    Eriksson, P.
    Umea Univ, Dept Cardiol, Umea, Sweden..
    Koul, S.
    Lund Univ, Dept Cardiol Clin Sci, Lund, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bivalirudin versus Heparin Monotherapy in Myocardial Infarction2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 12, p. 1132-1142Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y 12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y(12) inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. RESULTS A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P = 0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P = 0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P = 0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P = 0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P = 0.76). CONCLUSIONS Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others;

  • 237. Erlinge, D.
    et al.
    Ten Berg, J.
    Foley, D.
    Angiolillo, D. J.
    Wagner, H.
    Brown, P. B.
    Zhou, C.
    Luo, J.
    Jakubowski, J. A.
    Moser, B.
    Small, D. S.
    Bergmeijer, T.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Winters, K. J.
    Reduction in platelet reactivity with prasugrel 5 mg in low-body-weight patients is noninferior to prasugrel 10 mg in higher-body-weight patients2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 20, p. 2032-2040Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this study was to confirm prior modeling data suggesting that prasugrel 5 mg in low-body-weight (LBW) patients would be noninferior to prasugrel 10 mg in higher-body-weight (HBW) patients as assessed by maximal platelet aggregation (MPA). Background: Prasugrel 10 mg reduced ischemic events compared with clopidogrel 75 mg but increased bleeding, particularly in LBW patients. Methods: In this blinded, 3-period, crossover study in stable patients with coronary artery disease (CAD) taking aspirin, prasugrel 5 and 10 mg and clopidogrel 75 mg were administered to LBW (56.4 ± 3.7 kg; n = 34) and HBW patients (84.7 ± 14.9 kg; n = 38). Assays included light transmission aggregometry (LTA), VerifyNow P2Y12 (VN), and vasodilator-associated stimulated phosphoprotein (VASP) level measured predose and after each 12-day treatment. Results: Median MPA by LTA for prasugrel 5 mg in LBW patients was noninferior to the 75th percentile for prasugrel 10 mg in HBW patients (primary endpoint) and mean MPA was similar, but active metabolite exposure was lowered by 38%. Within LBW patients, prasugrel 5 mg lowered MPA more than clopidogrel (least squares mean difference [95% confidence interval]: -3.7% [-6.72%, -0.69%]) and resulted in lower rates of high on-treatment platelet reactivity (HPR). Within HBW patients, prasugrel 10 mg lowered MPA more than clopidogrel (-16.9% [-22.3%, -11.5%]). Similar results were observed by VN and VASP. Prasugrel 10 mg in LBW patients was associated with more mild to moderate bleeding (mainly bruising) compared with prasugrel 5 mg and clopidogrel. Conclusions: In aspirin-treated patients with CAD, prasugrel 5 mg in LBW patients reduced platelet reactivity to a similar extent as prasugrel 10 mg in HBW patients and resulted in greater platelet inhibition, lower HPR, and similar bleeding rates compared with clopidogrel. (Comparison of Prasugrel and Clopidogrel in Low Body Weight Versus Higher Body Weight With Coronary Artery Disease [FEATHER]; NCT01107925)

  • 238. Erlinge, David
    et al.
    Gotberg, Matthias
    Lang, Irene
    Holzer, Michael
    Noc, Marko
    Clemmensen, Peter
    Jensen, Ulf
    Metzler, Bernhard
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Botker, Hans Erik
    Omerovic, Elmir
    Engblom, Henrik
    Carlsson, Marcus
    Arheden, Hakan
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Harnek, Jan
    Olivecrona, Goran K.
    Rapid Endovascular Catheter Core Cooling Combined With Cold Saline as an Adjunct to Percutaneous Coronary Intervention for the Treatment of Acute Myocardial Infarction The CHILL-MI Trial: A Randomized Controlled Study of the Use of Central Venous Catheter Core Cooling Combined With Cold Saline as an Adjunct to Percutaneous Coronary Intervention for the Treatment of Acute Myocardial Infarction2014In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 63, no 18, p. 1857-1865Article in journal (Refereed)
    Abstract [en]

    Objectives The aim of this study was to confirm the cardioprotective effects of hypothermia using a combination of cold saline and endovascular cooling. Background Hypothermia has been reported to reduce infarct size (IS) in patients with ST-segment elevation myocardial infarctions. Methods In a multicenter study, 120 patients with ST-segment elevation myocardial infarctions (<6 h) scheduled to undergo percutaneous coronary intervention were randomized to hypothermia induced by the rapid infusion of 600 to 2,000 ml cold saline and endovascular cooling or standard of care. Hypothermia was initiated before percutaneous coronary intervention and continued for 1 h after reperfusion. The primary end point was IS as a percent of myocardium at risk (MaR), assessed by cardiac magnetic resonance imaging at 4 +/- 2 days. Results Mean times from symptom onset to randomization were 129 +/- 56 min in patients receiving hypothermia and 132 +/- 64 min in controls. Patients randomized to hypothermia achieved a core body temperature of 34.7 degrees C before reperfusion, with a 9-min longer door-to-balloon time. Median IS/MaR was not significantly reduced (hypothermia: 40.5% [interquartile range: 29.3% to 57.8%; control: 46.6% [interquartile range: 37.8% to 63.4%]; relative reduction 13%; p = 0.15). The incidence of heart failure was lower with hypothermia at 45 +/- 15 days (3% vs. 14%, p < 0.05), with no mortality. Exploratory analysis of early anterior infarctions (0 to 4 h) found a reduction in IS/MaR of 33% (p < 0.05) and an absolute reduction of IS/left ventricular volume of 6.2% (p = 0.15). Conclusions Hypothermia induced by cold saline and endovascular cooling was feasible and safe, and it rapidly reduced core temperature with minor reperfusion delay. The primary end point of IS/MaR was not significantly reduced. Lower incidence of heart failure and a possible effect in patients with early anterior ST-segment elevation myocardial infarctions need confirmation. (Efficacy of Endovascular Catheter Cooling Combined With Cold Saline for the Treatment of Acute Myocardial Infarction [CHILL-MI]; NCT01379261)

  • 239.
    Erlinge, David
    et al.
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden..
    Gotberg, Matthias
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden..
    Noc, Marko
    Ctr Intens Internal Med, Ljubljana, Slovenia..
    Lang, Irene
    Med Univ Vienna, Dept Cardiol, Vienna, Austria.;Med Univ Vienna, Dept Emergency Med, Vienna, Austria..
    Holzer, Michael
    Med Univ Vienna, Dept Cardiol, Vienna, Austria.;Med Univ Vienna, Dept Emergency Med, Vienna, Austria..
    Clemmensen, Peter
    Nykoebing F Hosp, Dept Cardiol, Nykoebing F, Denmark..
    Jensen, Ulf
    Karolinska Univ Hosp, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Metzler, Bernhard
    Univ Hosp Internal Med, Dept Cardiol, Innsbruck, Austria..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Botker, Hans Erik
    Aarhus Univ Hosp Skejby, Dept Cardiol, Aarhus, Denmark..
    Omerovic, Elmir
    Sahlgrenska Univ, Dept Cardiol, Gothenburg, Sweden..
    Koul, Sasha
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden..
    Engblom, Henrik
    Lund Univ, Dept Clin Psychol, S-22185 Lund, Sweden..
    Carlsson, Marcus
    Lund Univ, Dept Clin Psychol, S-22185 Lund, Sweden..
    Arheden, Hakan
    Lund Univ, Dept Clin Psychol, S-22185 Lund, Sweden..
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Klos, Bradley
    Philips Healthcare, San Diego, CA USA..
    Harnek, Jan
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden..
    Olivecrona, Goran K.
    Nykoebing F Hosp, Dept Cardiol, Nykoebing F, Denmark..
    Therapeutic Hypothermia for the Treatment of Acute Myocardial Infarction-Combined Analysis of the RAPID MI-ICE and the CHILL-MI Trials2015In: Therapeutic Hypothermia and Temperature Management, ISSN 2153-7658, E-ISSN 2153-7933, Vol. 5, no 2, p. 77-84Article in journal (Refereed)
    Abstract [en]

    In the randomized rapid intravascular cooling in myocardial infarction as adjunctive to percutaneous coronary intervention (RAPID MI-ICE) and rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction CHILL-MI studies, hypothermia was rapidly induced in conscious patients with ST-elevation myocardial infarction (STEMI) by a combination of cold saline and endovascular cooling. Twenty patients in RAPID MI-ICE and 120 in CHILL-MI with large STEMIs, scheduled for primary percutaneous coronary intervention (PCI) within <6 hours after symptom onset were randomized to hypothermia induced by rapid infusion of 600-2000mL cold saline combined with endovascular cooling or standard of care. Hypothermia was initiated before PCI and continued for 1-3 hours after reperfusion aiming at a target temperature of 33 degrees C. The primary endpoint was myocardial infarct size (IS) as a percentage of myocardium at risk (IS/MaR) assessed by cardiac magnetic resonance imaging at 4 +/- 2 days. Patients randomized to hypothermia treatment achieved a mean core body temperature of 34.7 degrees C before reperfusion. Although significance was not achieved in CHILL-MI, in the pooled analysis IS/MaR was reduced in the hypothermia group, relative reduction (RR) 15% (40.5, 28.0-57.6 vs. 46.6, 36.8-63.8, p=0.046, median, interquartile range [IQR]). IS/MaR was predominantly reduced in early anterior STEMI (0-4h) in the hypothermia group, RR=31% (40.5, 28.8-51.9 vs. 59.0, 45.0-67.8, p=0.01, median, IQR). There was no mortality in either group. The incidence of heart failure was reduced in the hypothermia group (2 vs. 11, p=0.009). Patients with large MaR (>30% of the left ventricle) exhibited significantly reduced IS/MaR in the hypothermia group (40.5, 27.0-57.6 vs. 55.1, 41.1-64.4, median, IQR; hypothermia n=42 vs. control n=37, p=0.03), while patients with MaR<30% did not show effect of hypothermia (35.8, 28.3-57.5 vs. 38.4, 27.4-59.7, median, IQR; hypothermia n=15 vs. control n=19, p=0.50). The prespecified pooled analysis of RAPID MI-ICE and CHILL-MI indicates a reduction of myocardial IS and reduction in heart failure by 1-3 hours with endovascular cooling in association with primary PCI of acute STEMI predominantly in patients with large area of myocardium at risk. (ClinicalTrials.gov id NCT00417638 and NCT01379261).

  • 240. Erlinge, David
    et al.
    Gurbel, Paul A.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Tomas L.
    Svensson, Peter
    Ten Berg, Jurrien M.
    Foley, David P.
    Wagner, Henrik
    Brown, Patricia B.
    Luo, Junxiang
    Zhou, Chunmei
    Moser, Brian A.
    Jakubowski, Joseph A.
    Small, David S.
    Winters, Kenneth J.
    Angiolillo, Dominick J.
    Prasugrel 5 mg in the Very Elderly Attenuates Platelet Inhibition But Maintains Noninferiority to Prasugrel 10 mg in Nonelderly Patients2013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 62, no 7, p. 577-583Article in journal (Refereed)
    Abstract [en]

    Objectives This study assessed pharmacodynamic (PD) response to the reduced prasugrel maintenance dose of 5 mg in very elderly (VE) patients (>= 75 years of age). Background In the TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction 38) study prasugrel 10 mg reduced ischemic events versus clopidogrel 75 mg, but increased bleeding in VE patients. Methods We examined PD and active metabolite pharmacokinetics (PKs) with prasugrel 5 and 10 mg and clopidogrel 75 mg in a 3-period (12 days each) blinded, crossover study in VE (n = 73; mean: 79 +/- 3 years of age) or (n 82) nonelderly (NE) (>= 45 to <65 years of age; mean: 56 +/- 5 years of age) stable coronary artery disease (CAD) patients receiving background aspirin. Assays included light transmission aggregometry (LTA), VerifyNow P2Y12 (VN-P2Y12), and vasodilator-associated stimulated phosphoprotein (VASP). The primary comparison was noninferiority of maximum platelet aggregation (MPA) comparing the median for prasugrel 5 mg in VE versus the 75th percentile for prasugrel 10 mg in NE, using a pre-specified 1-sided 97.5% confidence interval for the difference <15%. Results Prasugrel 5 mg in VE met the primary PD noninferiority criterion versus prasugrel 10 mg in NE. For prasugrel 5 mg, MPA was significantly lower (57 +/- 14%) than clopidogrel (63 +/- 14%; p < 0.001) in VE but higher than prasugrel 10 mg in NE (46 +/- 12%; p < 0.001). PD response by LTA, VN-P2Y12, and VASP during all treatments appeared similar between age cohorts. Prasugrel 5 mg resulted in fewer VE poor responders than clopidogrel. Rates of mild bleeding were higher with prasugrel 10 mg but similar for prasugrel 5 mg versus clopidogrel 75 mg. Conclusions In aspirin-treated stable CAD patients, prasugrel 5 mg in VE attenuated platelet inhibition while meeting pre-specified noninferiority criterion versus prasugrel 10 mg in NE, with significantly better PD response and fewer poor responders compared to clopidogrel 75 mg in VE. (Comparison of Prasugrel and Clopidogrel in Very Elderly and Non-Elderly Patients With Stable Coronary Artery Disease [GENERATIONS]; NCT01107912)

  • 241.
    Erlinge, David
    et al.
    Lund Univ, Lund, Sweden.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Correspondence: Bivalirudin versus Heparin Monotherapy in Myocardial Infarction2018In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 378, no 3, p. 300-300Article in journal (Refereed)
  • 242. Erlinge, David
    et al.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Duvvuru, Suman
    Jakubowski, Joseph A.
    Wagner, Henrik
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Tantry, Udaya S.
    Brown, Patricia B.
    Small, David
    Moser, Brian A.
    Sundseth, Scott S.
    Walker, Joseph R.
    Winters, Kenneth J.
    Gurbel, Paul A.
    Clopidogrel metaboliser status based on point-of-care CYP2C19 genetic testing in patients with coronary artery disease2014In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 111, no 5, p. 943-950Article in journal (Refereed)
    Abstract [en]

    We compared results obtained with the Nanosphere Verigene (R) System, a novel point-of-care (POC) genetic test capable of analysing 11, CYP2C19 variants within 3 hours, to an established, validated genotyping method (Affymetrix (TM) DMET+; reference assay) for identifying extensive and reduced metabolisers of clopidogrel. Based on genotyping, patients (N=82) with stable coronary artery disease on clopidogrel 75 mg daily were defined as extensive metabolisers (*1/*1, *1/*17,*17/*17), reduced metabolisers (*1/*2,*1/*8,*2/*2,*2/*3), or of indeterminate metaboliser status (*2/*17). Pharmacokinetic exposure to clopidogrel's active metabolite and pharmacodynamic measures with P2Y12 reaction units (PRU) (VerifyNow (R) P2Y12 assay), and VASP PRI (PRI) were also assessed. There was a 99.9% overall; concordance of marker-level data between the Nanosphere Verigene and DMET+ systems in identifying the CYP2C19 variants and 100% agreement in classifying the patients as extensive (n=59) or reduced metabolisers (n=15). Extensive metabolisers had significantly higher active metabolite exposure than reduced metabolisers (LS means 12.6 ng*h/ml vs 7.7 ng*h/ml; p<0.001). Extensive metabolisers also had lower PRU (LS means 158 vs 212; p=0.003) and VASP PRI (LS means 48% vs 63%, p=0.01) compared to reduced metabolisers. Rates of high on-treatment platelet reactivity were higher in reduced metabolisers compared to extensive metabolisers (VASP PRI >= 50%: 79% vs 47%; PRU >235: 33% vs 16%). The Nanosphere Verigene CBS system identified 11 CYP2C19 alleles in less than 3 hours with a high degree of accuracy when compared to a conventional method, and was further validated against pharmacokinetic and pharmacodynamic phenotypes.

  • 243.
    Erlinge, David
    et al.
    Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden..
    Koul, Sasha
    Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden..
    Eriksson, Peter
    Umea Univ, Dept Cardiol, Umea, Sweden..
    Schersten, Fredrik
    Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden..
    Omerovic, Elmir
    Sahlgrenska Univ, Dept Cardiol, Gothenburg, Sweden..
    Linder, Rikard
    Karolinska Univ, Dept Cardiol, Stockholm, Sweden..
    Ostlund, Olof Petter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Frobert, Ole
    Univ Orebro, Dept Cardiol, Fac Hlth, SE-70182 Orebro, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction-a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial)2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 175, p. 36-46Article in journal (Refereed)
    Abstract [en]

    Background The optimal anticoagulant for patients with acute coronary syndrome treated with percutaneous coronary intervention (PCI) has not been validated in current practice of radial approach and pretreatment with potent P2Y12 inhibitors. Several studies have indicated increased bleeding rate and, in some instances, even increased mortality by the routine use of heparin and glycoprotein IIb/IIIa inhibitors compared to bivalirudin. Direct comparison of bivalirudin versus heparin alone has yielded contradictory results depending on study designs. Methods/design The VALIDATE-SWEDEHEART trial is a multicenter, prospective, randomized, registry-based, controlled, and open-label clinical trial in patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing PCI pretreated with ticagrelor, prasugrel, or cangrelor. We hypothesize that bivalirudin is superior to heparin alone in reducing death, myocardial infarction, and major bleeding events at 180 days (primary end point). The trial will enroll 3,000 patients with STEMI and 3,000 patients with non-STEMI undergoing PCI. The trial will use a hybrid registry-based randomized clinical trial design where inclusion, randomization, and baseline data collection are performed using The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry. The primary composite end point (death, myocardial infarction, or major bleeding events at 180 days) will be identified through active screening after 7 and 180 days and adjudicated by a blinded central end point committee. Secondary end points and long-term outcomes will be recorded from national registries. Conclusion The VALIDATE-SWEDEHEART trial is founded on a nationwide clinical registry and uses a hybrid registry-based randomized clinical trial (RRCT) design methodology to evaluate efficacy and safety of bivalirudin as compared to heparin alone for acute coronary syndrome, in a large population receiving contemporary recommended therapies including predominantly radial invasive approach and pretreatment with potent P2Y12 inhibitors.

  • 244. Erlinge, David
    et al.
    Koul, Sasha
    Omerovic, Elmir
    Fröbert, Ole
    Linder, Rikard
    Danielewicz, Mikael
    Hamid, Mehmet
    Venetsanos, Dimitrios
    Henareh, Loghman
    Pettersson, Björn
    Wagner, Henrik
    Grimfjärd, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jensen, Jens
    Hofmann, Robin
    Ulvenstam, Anders
    Völz, Sebastian
    Petursson, Petur
    Östlund, Olof Petter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sarno, Giovanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wallentin, Lars
    Scherstén, Fredrik
    Eriksson, Peter
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bivalirudin versus heparin monotherapy in non-ST-segment elevation myocardial infarction.2018In: European heart journal. Acute cardiovascular care, ISSN 2048-8734, article id 2048872618805663Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The optimal anti-coagulation strategy for patients with non-ST-elevation myocardial infarction treated with percutaneous coronary intervention is unclear in contemporary clinical practice of radial access and potent P2Y12-inhibitors. The aim of this study was to investigate whether bivalirudin was superior to heparin monotherapy in patients with non-ST-elevation myocardial infarction without routine glycoprotein IIb/IIIa inhibitor use.

    METHODS: In a large pre-specified subgroup of the multicentre, prospective, randomised, registry-based, open-label clinical VALIDATE-SWEDEHEART trial we randomised patients with non-ST-elevation myocardial infarction undergoing percutaneous coronary intervention, treated with ticagrelor or prasugrel, to bivalirudin or heparin monotherapy with no planned use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. The primary endpoint was the rate of a composite of all-cause death, myocardial infarction or major bleeding within 180 days.

    RESULTS: A total of 3001 patients with non-ST-elevation myocardial infarction, were enrolled. The primary endpoint occurred in 12.1% (182 of 1503) and 12.5% (187 of 1498) of patients in the bivalirudin and heparin groups, respectively (hazard ratio of bivalirudin compared to heparin treatment 0.96, 95% confidence interval 0.78-1.18, p=0.69). The results were consistent in all major subgroups. All-cause death occurred in 2.0% versus 1.7% (hazard ratio 1.15, 0.68-1.94, p=0.61), myocardial infarction in 2.3% versus 2.5% (hazard ratio 0.91, 0.58-1.45, p=0.70), major bleeding in 8.9% versus 9.1% (hazard ratio 0.97, 0.77-1.24, p=0.82) and definite stent thrombosis in 0.3% versus 0.2% (hazard ratio 1.33, 0.30-5.93, p=0.82).

    CONCLUSION: Bivalirudin as compared to heparin during percutaneous coronary intervention for non-ST-elevation myocardial infarction did not reduce the composite of all-cause death, myocardial infarction or major bleeding in non-ST-elevation myocardial infarction patients receiving current recommended treatments with modern P2Y12-inhibitors and predominantly radial access.

  • 245. Ernst, Diana
    et al.
    Widera, Christian
    Baerlecken, Niklas T
    Schlumberger, Wolfgang
    Daehnrich, Cornelia
    Schmidt, Reinhold E
    Gabrysch, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Witte, Torsten
    Antibodies against MYC-Associated Zinc Finger Protein: An Independent Marker in Acute Coronary Syndrome?2017In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, article id 1595Article in journal (Refereed)
    Abstract [en]

    Introduction: Atherosclerosis is considered the pathophysiology underlying cardiovascular (CVD), cerebrovascular, and peripheral vascular diseases. Evidence supporting an autoimmune component is emerging, with imaging studies correlating MYC-associated zinc finger protein antibody (MAZ-Ab) optical density (OD) with plaque activity. This study compares MAZ-Ab OD on ELISA testing among patients presenting with acute coronary syndromes (ACSs) to healthy controls and investigates the association of MAZ-Ab to traditional CVD risk factors.

    Methods: Patients admitted with ACSs between August 2007 and July 2011 were included. Serum samples taken at presentation were retrospectively tested for MAZ-Ab and compared with serum from healthy volunteers with no CVD risk factors. Large-scale assessment of post-ACS prognostic relevance was performed using the established PLATO cohort.

    Results:  = 0.436).

    Conclusion: MAZ-Ab OD was higher or all ACS phenotypes compared with controls. Given current understanding of MAZ-Ab function, these findings support an autoimmune component to CVD independent of conventional risk factors and indeed the extent of end-organ damage.

  • 246.
    Escaned, Javier
    et al.
    Hosp Clin San Carlos, IDISSC, Madrid, Spain;Univ Complutense Madrid, Madrid, Spain.
    Ryan, Nicola
    Hosp Clin San Carlos, IDISSC, Madrid, Spain;Univ Complutense Madrid, Madrid, Spain.
    Mejia-Renteria, Hernan
    Hosp Clin San Carlos, IDISSC, Madrid, Spain;Univ Complutense Madrid, Madrid, Spain.
    Cook, Christopher M.
    Imperial Coll London, Hammersmith Hosp, London, England.
    Dehbi, Hakim-Moulay
    UCL, CRUK & UCL Canc Trials Ctr, London, England.
    Alegria-Barrero, Eduardo
    Hosp Univ Torrejon, Madrid, Spain;Univ Francisco de Vitoria, Madrid, Spain.
    Alghamdi, Ali
    King Abdulaziz Med City Cardiac Ctr, Riyadh, Saudi Arabia.
    Al-Lamee, Rasha
    Imperial Coll London, Hammersmith Hosp, London, England.
    Altman, John
    Colorado Heart & Vasc, Lakewood, CO USA.
    Ambrosia, Alphonse
    Baptista, Sergio B.
    Hosp Prof Doutor Fernando Fonseca, Amadora, Portugal.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bhindi, Ravinay
    Royal North Shore Hosp, Sydney, NSW, Australia.
    Birgander, Mats
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, Lund, Sweden.
    Bojara, Waldemar
    Kemperhof Koblenz, Gemeinschaftsklinikum Mittelrhein, Koblenz, Germany.
    Brugaletta, Salvatore
    Inst Invest Biomed August Pi & Sunyer, Hosp Clin, Cardiovasc Inst, Barcelona, Spain.
    Buller, Christopher
    St Michaels Hosp, Toronto, ON, Canada.
    Calais, Fredrik
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Silva, Pedro Canas
    Hosp Santa Maria, Lisbon, Portugal.
    Carlsson, Jorg
    Linnaeus Univ, Fac Hlth & Life Sci, Kalmar, Sweden;Kalmar Cty Hosp, Kalmar, Sweden.
    Christiansen, Evald H.
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
    Danielewicz, Mikael
    Karlstad Hosp, Dept Cardiol, Karlstad, Sweden.
    Di Mario, Carlo
    Univ Florence, Florence, Italy;Imperial Coll London, Royal Brompton Hosp, London, England.
    Doh, Joon-Hyung
    Inje Univ, Ilsan Paik Hosp, Daehwa Dong, South Korea.
    Erglis, Andrejs
    Pauls Stradins Clin Univ Hosp, Riga, Latvia.
    Erlinge, David
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, Lund, Sweden.
    Gerber, Robert T.
    Conquest Hosp, St Leonards On Sea, England.
    Going, Olaf
    Sana Klinikum Lichtenberg, Lichtenberg, Germany.
    Gudmundsdottir, Ingibjorg
    Reykjavik Univ Hosp, Dept Cardiol, Reykjavik, Iceland.
    Haerle, Tobias
    Carl von Ossietzky Univ Oldenburg, European Med Sch, Klinikum Oldenburg, Oldenburg, Germany.
    Hauer, Dario
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Cardiol, Linkoping, Sweden.
    Hellig, Farrel
    Sunninghill Hosp, Johannesburg, South Africa.
    Indolfi, Ciro
    Magna Graecia Univ Catanzaro, Catanzaro, Italy.
    Jakobsen, Lars
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
    Janssens, Luc
    Imelda Hosp, Bonheiden, Belgium.
    Jensen, Jens
    Sundsvall Hosp, Dept Med, Sundsvall, Sweden;Capio St Gorans Sjukhus, Unit Cardiol, Stockholm, Sweden;Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Jeremias, Allen
    SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA.
    Karegren, Amra
    Vastmanland Hosp Vasteras, Dept Internal Med, Vasteras, Sweden.
    Karlsson, Ann-Charlotte
    Halmstad Cty Hosp, Dept Cardiol, Halmstad, Sweden.
    Kharbanda, Rajesh K.
    Oxford Univ Hosp Fdn Trust, John Radcliffe Hosp, Oxford, England.
    Khashaba, Ahmed
    Ain Shams Univ, Cairo, Egypt.
    Kikuta, Yuetsu
    Fukuyama Cardiovasc Hosp, Fukuyama, Hiroshima, Japan.
    Krackhardt, Florian
    Univ Med, Charite Campus Virchow Klinikum, Berlin, Germany.
    Koo, Bon-Kwon
    Seoul Natl Univ Hosp, Seoul, South Korea.
    Koul, Sasha
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, Lund, Sweden.
    Laine, Mika
    Helsinki Univ Hosp, Helsinki, Finland.
    Lehman, Sam J.
    Flinders Univ S Australia, Adelaide, SA, Australia.
    Lindroos, Pontus
    St Goran Hosp, Dept Cardiol, Stockholm, Sweden.
    Malik, Iqbal S.
    Imperial Coll London, Hammersmith Hosp, London, England.
    Maeng, Michael
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
    Matsuo, Hitoshi
    Gifu Heart Ctr, Gifu, Japan.
    Meuwissen, Martijn
    Amphia Hosp, Breda, Netherlands.
    Nam, Chang-Wook
    Keimyung Univ, Dongsan Med Ctr, Daegu, South Korea.
    Niccoli, Giampaolo
    Univ Cattolica Sacro Cuore, Rome, Italy.
    Nijjer, Sukhjinder S.
    Imperial Coll London, Hammersmith Hosp, London, England.
    Olsson, Hans
    Karlstad Hosp, Dept Cardiol, Karlstad, Sweden.
    Olsson, Sven-Erik
    Helsingborg Hosp, Dept Cardiol, Helsingborg, Sweden;Helsingborg Hosp, Dept Radiol, Helsingborg, Sweden.
    Omerovic, Elmir
    Sahlgrenska Univ Gothenburg, Dept Cardiol, Gothenburg, Sweden.
    Panayi, Georgios
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Cardiol, Linkoping, Sweden.
    Petraco, Ricardo
    Imperial Coll London, Hammersmith Hosp, London, England.
    Piek, Jan J.
    Acad Med Ctr, AMC Heart Ctr, Amsterdam, Netherlands.
    Ribichini, Flavo
    Univ Hosp Verona, Verona, Italy.
    Samady, Habib
    Emory Univ, Atlanta, GA 30322 USA.
    Samuels, Bruce
    Cedars Sinai Heart Inst, Los Angeles, CA USA.
    Sandhall, Lennart
    Helsingborg Hosp, Dept Cardiol, Helsingborg, Sweden;Helsingborg Hosp, Dept Radiol, Helsingborg, Sweden.
    Sapontis, James
    MonashHeart, Melbourne, Vic, Australia;Monash Univ, Melbourne, Vic, Australia.
    Sen, Sayan
    Imperial Coll London, Hammersmith Hosp, London, England.
    Seto, Arnold H.
    Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA.
    Sezer, Murat
    Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey.
    Sharp, Andrew S. P.
    Univ Exeter, Exeter, Devon, England;Royal Devon & Exeter Hosp, Exeter, Devon, England.
    Shin, Eun-Seok
    Univ Ulsan, Coll Med, Ulsan Univ Hosp, Ulsan, South Korea.
    Singh, Jasvindar
    Washington Univ, Sch Med, St Louis, MO USA.
    Takashima, Hiroaki
    Aichi Med Univ Hosp, Nagakute, Aichi, Japan.
    Talwar, Suneel
    Royal Bournemouth Gen Hosp, Bournemouth, Dorset, England.
    Tanaka, Nobuhiro
    Tokyo Med Univ, Tokyo, Japan.
    Tang, Kare
    Anglia Ruskin Univ, Chelmsford, England;Essex Cardiothorac Ctr, Basildon, England.
    Van Belle, Eric
    Lille Univ Hosp, Inst Coeur Poumon, Lille, France;INSERM, Unite 1011, Lille, France.
    van Royen, Niels
    Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Vinhas, Hugo
    Hosp Garcia de Horta, Lisbon, Portugal.
    Vrints, Christiaan J.
    Antwerp Univ Hosp, Antwerp, Belgium.
    Walters, Darren
    Prince Charles Hosp, Brisbane, Qld, Australia.
    Yokoi, Hiroyoshi
    Fukuoka Sannou Hosp, Fukuoka, Japan.
    Frobert, Ole
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Patel, Manesh R.
    Duke Univ, Durham, NC USA.
    Serruys, Patrick
    Imperial Coll London, Dept Cardiol, London, England.
    Davies, Justin E.
    Imperial Coll London, Hammersmith Hosp, London, England.
    Gotberg, Matthias
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, Lund, Sweden.
    Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes2018In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, no 15, p. 1437-1449Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year.

  • 247.
    Essebag, Vidal
    et al.
    McGill Univ, Hlth Ctr, 1650 Cedar Ave,Room E5-200, Montreal, PQ H3G 1A4, Canada.;Hop Sacre Coeur, Montreal, PQ, Canada..
    Proietti, Riccardo
    Swansea Univ, Cardiol Dept, Morriston Hosp, Swansea SA6 6NL, W Glam, Wales.;Luigi Sacco Hosp, Cardiol Dept, Milan, Italy..
    Birnie, David H.
    Univ Ottawa Heart Inst, Ottawa, ON, Canada..
    Wang, Jia
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Douketis, James
    McMaster Univ, Dept Med, St Josephs Healthcare, Hamilton, ON, Canada..
    Coutu, Benoit
    Ctr Hosp Univ Montre, Montreal, PQ, Canada..
    Parkash, Ratika
    Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada..
    Lip, Gregory Y. H.
    Univ Birmingham, Inst Cardiovasc Sci, City Hosp, Birmingham, W Midlands, England..
    Hohnloser, Stefan H.
    Klinikum Johann Wolfgang Goethe Univ, Frankfurt, Germany..
    Moriarty, Andrew
    Craigavon Area Hosp, Portadown, Arm, North Ireland..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Connolly, Stuart J.
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Ezekowitz, Michael
    Thomas Jefferson Med Coll & Heart Ctr, Wynnewood, PA USA..
    Healey, Jeff S.
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Short-term dabigatran interruption before cardiac rhythm device implantation: multi-centre experience from the RE-LY trial2017In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 19, no 10, p. 1630-1636Article in journal (Refereed)
    Abstract [en]

    Aims: Cardiac implantable electronic device (CIED) surgery is commonly performed in patients with atrial fibrillation (AF). The current analysis was undertaken to compare peri-operative anticoagulation management, bleeding, and thrombotic events in AF patients treated with dabigatran vs. warfarin.

    Methods and results: This study included 611 patients treated with dabigatran vs. warfarin who underwent CIED surgery during the RE-LY trial. Among 201 warfarin-treated patients, warfarin was interrupted a median of 144 (inter-quartile range, IQR: 120-216) h, and 37 (18.4%) patients underwent heparin bridging. In dabigatran-treated patients (216 on 110 mg bid and 194 on 150 mg bid), the duration of dabigatran interruption was a median of 96 (IQR: 61-158) h. Pocket hematomas occurred in 9 (2.20%) patients on dabigatran and 8 (3.98%) patients on warfarin (P = 0.218). The occurrence of pocket hematomas was lower with dabigatran compared with warfarin with heparin bridging (RD: -8.62%, 95% CI: -24.15 to - 0.51%, P = 0.034) but not when compared with warfarin with no bridging (P = 0.880). Ischemic stroke occurred in 2 (0.3%) patients; one in the warfarin group (without bridging) and one in the dabigatran 150 mg bid group (P = 0.735).

    Conclusion: In patients treated with dabigatran undergoing CIED surgery, interruption of dabigatran is associated with similar or lower incidence of pocket hematoma, when compared with warfarin interruption without or with heparin bridging, respectively. Whether uninterrupted dabigatran can reduce pocket hematoma or ischemic stroke remains to be evaluated.

  • 248.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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 Dysfunction2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 14, p. 1687-1697Article in journal (Refereed)
    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.

  • 249.
    Ezekowitz, M. D.
    et al.
    Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA..
    Connolly, S. J.
    McMaster Univ, Hamilton, ON, Canada..
    Fraessdorf, M.
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Brueckmann, M.
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Kreuzer, J.
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Reilly, P.
    Boehringer Ingleheim Pharmaceut Inc, Ridgefield, CT USA..
    Yusuf, S.
    McMaster Univ, Hamilton, ON, Canada..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Clinical outcomes of atrial fibrillation patients receiving NSAIDs in the RE-LY trial2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 862-862Article in journal (Other academic)
  • 250.
    Ezekowitz, Michael D.
    et al.
    Thomas Jefferson Univ, Sidney Kimmel Med Coll, 1999 Sproul Rd, Philadelphia, PA 19107 USA.;Lankenau Med Ctr, Wynnewood, PA USA..
    Eikelboom, John
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.;Hamilton Hlth Sci, Hamilton, ON, Canada..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Reilly, Paul A.
    Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT USA..
    Brueckmann, Martina
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany.;Heidelberg Univ, Fac Med Mannheim, Mannheim, Germany..
    Kent, Anthony P.
    Thomas Jefferson Univ, Sidney Kimmel Med Coll, 1999 Sproul Rd, Philadelphia, PA 19107 USA..
    Pogue, Janice
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.;Hamilton Hlth Sci, Hamilton, ON, Canada..
    Spahr, Judith
    Lankenau Inst Med Res, Wynnewood, PA USA..
    Clemens, Andreas
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Noack, Herbert
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Diener, Hans-Christoph
    Univ Hosp Essen, Dept Neurol, Essen, Germany..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Yusuf, Salim
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.;Hamilton Hlth Sci, Hamilton, ON, Canada..
    Connolly, Stuart J.
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.;Hamilton Hlth Sci, Hamilton, ON, Canada..
    Long-term evaluation of dabigatran 150 vs. 110 mg twice a day in patients with non-valvular atrial fibrillation2016In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 18, no 7, p. 973-978Article in journal (Refereed)
    Abstract [en]

    Aims The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial allowed patients who completed the trial receiving their assigned dabigatran 150 mg (D150) or 110 mg (D110) twice a day to continue into the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial. This permitted assessment of outcomes over a median of 4.6 and a maximum of 6.7 years, respectively. Methods and results The analysed population included only those patients who completed RE-LY on dabigatran and continued into RELYABLE without interruption of assigned dabigatran. Cumulative risk was expressed as Kaplan-Meier plots. Outcomes were compared using Cox proportional hazard modelling. Stroke or systemic embolization rates were 1.25 and 1.54% per year (D150 and D110, respectively); hazard ratio (HR) 0.81 [95% confidence interval (CI): 0.68-0.96] (P = 0.02). Ischaemic stroke was 1.03 (D150) and 1.29%/year (D110); HR 0.79 (95% CI: 0.66-0.95) (P = 0.01). Haemorrhagic stroke rates were 0.11 (D150) and 0.13%/year (D110); HR 0.91 (95% CI: 0.51-1.62) (P = 0.75). Rates of major haemorrhage were 3.34 (D150) and 2.76%/year (D110); HR 1.22 (95% CI: 1.08-1.37) (P = 0.0008). Intracranial haemorrhage rates were 0.32 (D150) and 0.23%/year (D110); HR 1.37 (95% CI: 0.93-2.01) (P = 0.11). Mortality was 3.43 (D150) and 3.55%/year (D110); HR 0.97 (95% CI: 0.87-1.08) (P = 0.54). Conclusion Annualized rates of all outcomes were constant with better efficacy of D150, less major bleeding with D110, and low intracerebral haemorrhage rates for both doses. There were no additional safety concerns. This is the longest continuous randomized experience of a novel anticoagulant.

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