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  • 1. Akbaraly, Tasmine
    et al.
    Sexton, Claire
    Zsoldos, Eniko
    Mahmood, Abda
    Filippini, Nicola
    Kerleau, Clarisse
    Verdier, Jean-Michel
    Virtanen, Marianna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Public Health.
    Gabelle, Audrey
    Ebmeier, Klaus
    Kivimäki, Mika
    Association of Long-Term Diet Quality with Hippocampal Volume:: Longitudinal Cohort Study2018In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 131, no 11, p. 1372-1381Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    Diet quality is associated with brain aging outcomes. However, few studies have explored in humans the brain structures potentially affected by long-term diet quality. We examined whether cumulative average of the Alternative Healthy Eating Index 2010 (AHEI-2010) score during adult life (an 11-year exposure period) is associated with hippocampal volume.

    METHODS

    Analyses were based on data from 459 participants of the Whitehall II imaging sub-study (mean age [standard deviation] (SD) = 59.6 [5.3] years in 2002-2004, 19.2% women). Multimodal magnetic resonance imaging examination was performed at the end of follow-up (2015-2016). Structural images were acquired using a high-resolution 3-dimensional T1-weighted sequence and processed with Functional Magnetic Resonance Imaging of the Brain Software Library (FSL) tools. An automated model-based segmentation and registration tool was applied to extract hippocampal volumes.

    RESULTS

    Higher AHEI-2010 cumulative average score (reflecting long-term healthy diet quality) was associated with a larger total hippocampal volume. For each 1 SD (SD = 8.7 points) increment in AHEI-2010 score, an increase of 92.5 mm3 (standard error = 42.0 mm3) in total hippocampal volume was observed. This association was independent of sociodemographic factors, smoking habits, physical activity, cardiometabolic health factors, cognitive impairment, and depressive symptoms, and was more pronounced in the left hippocampus than in the right hippocampus. Of the AHEI-2010 components, no or light alcohol consumption was independently associated with larger hippocampal volume.

    CONCLUSIONS

    Higher long-term AHEI-2010 scores were associated with larger hippocampal volume. Accounting for the importance of hippocampal structures in several neuropsychiatric diseases, our findings reaffirm the need to consider adherence to healthy dietary recommendation in multi-interventional programs to promote healthy brain aging

  • 2. Armstrong, Paul W.
    et al.
    Westerhout, Cynthia M.
    Fu, Yuling
    Harrington, Robert A.
    Storey, Robert F.
    Katus, Hugo
    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.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Quantitative ST-depression in Acute Coronary Syndromes: the PLATO Electrocardiographic Substudy2013In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 126, no 8, p. 723-+Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We evaluated whether electrocardiogram (ECG) characteristics were aligned with clinical outcomes and the effect of ticagrelor within the diverse spectrum of non-ST-elevation acute coronary syndrome patients enrolled in the PLATelet inhibition and patient Outcomes (PLATO) trial. METHODS: There were 8884 PLATO patients who had baseline ECGs assessed by a core laboratory; of these, 4935 had an ECG at hospital discharge that also was assessed. Associations with study treatment on vascular death or myocardial infarction within 1 year were examined. RESULTS: At baseline, most patients had either no or <= 0.5 mm of ST-segment depression (57%); 26% had 1.0 mm, and 17% had more extensive depression (>1.0 mm). Across the baseline ST-segment depression strata, there was a consistent treatment benefit with ticagrelor versus clopidogrel on vascular death/myocardial infarction. The extent of residual ST-segment depression at discharge was similar in the treatment groups, and the treatment effect did not differ by the extent of discharge ST-segment depression. There was a progressive increase in vascular death/myocardial infarction with increasing extent of baseline ST-segment depression (1.0 mm [vs no/0.5 mm]: hazard ratio [HR] 1.22; 95% confidence interval [CI], 1.03-1.45; > 1.0 mm: HR 1.49; 95% CI, 1.24-1.78; P < .001) and at discharge (HR 1.28; 95% CI, 1.02-1.61; HR 2.13; 95% CI, 1.54-2.95; P <. 001). CONCLUSION: The treatment effect of ticagrelor among non-ST-segment-elevation acute coronary syndrome patients was consistently expressed across all baseline ST-segment depression strata. There was no indication of an anti-ischemic benefit of ticagrelor as reflected on the discharge ECG. Our data affirm the independent prognostic relationship of both baseline and hospital discharge ST-segment depression on outcomes within 1 year in non-ST-segment-elevation acute coronary syndrome patients. 

  • 3.
    Baron, Tomasz
    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.
    Hambraeus, Kristina
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden..
    Sundstrom, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Jernberg, Tomas
    Karolinska Inst, Karolinska Univ Hosp, Dept Cardiol, Dept Med, 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.
    Impact on Long-Term Mortality of Presence of Obstructive Coronary Artery Disease and Classification of Myocardial Infarction2016In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 129, no 4, p. 398-406Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In contrast to the associated-with-thromboembolic-event type 1 myocardial infarction, type 2 myocardial infarction is caused by acute imbalance between oxygen supply and demand of myocardium. Type 2 myocardial infarction may be present in patients with or without obstructive coronary artery disease, but knowledge about patient characteristics, treatments, and outcome in relation to coronary artery status is lacking. We aimed to compare background characteristics, triggering mechanisms, treatment, and long-term prognosis in a large real-life cohort of patients with type 1 and type 2 myocardial infarction with and without obstructive coronary artery disease.

    METHODS: All 41,817 consecutive patients with type 1 and type 2 myocardial infarction registered in the Swedish myocardial infarction registry (SWEDEHEART) who underwent coronary angiography between January 1, 2011 and December 31, 2013, with the last follow-up on December 31, 2014, were studied.

    RESULTS: In 92.8% of 40,501 patients classified as type 1 and in 52.5% of patients classified as type 2 myocardial infarction, presence of an obstructive coronary artery disease could be shown. Within the patients with obstructive coronary artery disease, those with type 2 myocardial infarction were older, and had more comorbidities and smaller necrosis as compared with type 1 myocardial infarction. In contrast, there was almost no difference in risk profile and extent of myocardial infarction between type 1 and type 2 myocardial infarction patients with nonobstructive coronary artery stenosis. The crude long-term mortality was higher in type 2 as compared with type 1 myocardial infarction with obstructive coronary artery disease (hazard ratio [HR] 1.72; 95% confidence interval [CI], 1.45-2.03), but was lower after adjustment (HR 0.76; 95% CI, 0.61-0.94). In myocardial infarction patients with nonobstructive coronary artery stenosis, the mortality risk was similar regardless of the clinical myocardial infarction type (crude HR 1.14; 95% CI, 0.84-1.55; adjusted HR 0.82; 95% CI, 0.52-1.29).

    CONCLUSIONS: The substantial differences in risk factors, treatment, and outcome in patients with type 1 and type 2 myocardial infarction with obstructive coronary artery disease supports the relevance of the division between type 1 and type 2 in this population. On the contrary, in patients with nonobstructive coronary artery stenosis, irrespective of the clinical type, a similar risk profile, extent of necrosis, and longterm prognosis were observed, indicating that distinction between type 1 and type 2 myocardial infarction in these patients seems to be inappropriate.

  • 4.
    Baron, Tomasz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hambraeus, Kristina
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Erlinge, David
    Lund Univ, Dept Cardiol, Skane Univ Hosp, Lund, Sweden..
    Jernberg, Tomas
    Karolinska Univ Hosp, Dept Cardiol, Karolinska Inst, Dept Med Huddinge, 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.
    Reply to: Prognosis in Patients with Different Types of Myocardial Infarction and Presence of Obstructive Coronary Artery Disease Reply2017In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 130, no 9, p. E417-E418Article in journal (Other academic)
  • 5.
    Eggers, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, Tomas
    Karolinska Univ Hosp, Karolinska Inst, Cardiol Sect, Dept Med, Huddinge, 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.
    Prognostic Importance of Sex-Specific Cardiac Troponin T 99(th) Percentiles in Suspected Acute Coronary Syndrome2016In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 129, no 8, article id 880.e1Article in journal (Refereed)
    Abstract [en]

    Objective

    Cardiac troponin levels differ between the sexes, with higher values commonly seen in men. The use of sex-specific troponin thresholds is, thus, subject of an ongoing debate. We assessed whether sex-specific cardiac troponin T (cTnT) 99th percentiles would improve risk prediction in patients admitted to Swedish coronary care units due to suspected acute coronary syndrome.

    Methods

    In this retrospective register-based study (48,250 patients), we investigated the prediction of all-cause mortality and the composite of cardiovascular death or nonfatal myocardial infarction within 1 year using the single 99th cTnT percentile (>14 ng/L) or sex-specific cTnT 99th percentiles (>16/9 ng/L).

    Results

    A total of 1078 men (3.0%) with cTnT 15-16 ng/L and 1854 women (8.4%) with cTnT 10-14 ng/L would have been reclassified regarding their cTnT status by the means of sex-specific 99th percentiles. The prevalence of cardiovascular risk factors and crude event rates increased across higher cTnT strata in both men and women. Multivariable-adjusted Cox models, however, did not demonstrate better risk prediction by sex-specific 99th percentiles. Assessing cTnT as a continuous variable demonstrated an increase in multivariable-adjusted risk starting at levels around 10-12 ng/L in both men and women.

    Conclusions

    We found no evidence supporting the use of sex-specific cTnT 99th percentiles in men and women admitted because of suspected acute coronary syndrome. This likely depends on sex-specific differences in disease mechanisms associated with small cTnT elevations. From a pragmatic perspective, a single cTnT cutoff slightly below 14 ng/L seems to be preferable as a threshold for medical decision-making.

  • 6.
    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.

  • 7.
    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.

  • 8.
    James, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Armstrong, Paul
    Califf, Robert
    Simoons, Maarten L.
    Venge, Per
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Troponin T levels and risk of 30-day outcomes in patients with the acute coronary syndrome: prospective verification in the GUSTO-IV trial2003In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 115, no 3, p. 178-184Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A third-generation troponin T assay with improved precision and a lower detection limit has been developed. However, the appropriate cutoff for identifying patients with the acute coronary syndrome who are at low risk of subsequent mortality has not been established.

    METHODS: A retrospective evaluation of data from the Fragmin and fast Revascularization during InStability in Coronary artery disease II (FRISC-II) trial suggested that a cutoff below 0.1 microg/L for troponin T levels might be more useful in risk stratification. A prospective validation of two cutoff levels (0.03 microg/L and 0.01 microg/L) was performed in 7115 patients with non-ST-elevation acute coronary syndrome from the Global Utilization of Strategies To open Occluded arteries IV (GUSTO-IV) trial.

    RESULTS: Patients with troponin T levels >0.1 microg/L had greater 30-day mortality (5.5% [201/3679]) than did those with levels <or=0.1 microg/L (2.2% [75/3436], P <0.001). A cutoff value of 0.03 microg/L provided better discrimination between high and low risk: 5.1% (234/4552) versus 1.6% (42/2563). However, a cutoff value at the lower limit of detection, 0.01 microg/L, provided the best discrimination: 5.0% (254/5123) versus 1.1% (22/1992) (P<0.001). This cutoff level had the highest negative predictive value; it also discriminated best for the combined endpoint of death and myocardial infarction.

    CONCLUSION: Using a cutoff of <or=0.01 microg/L for the third-generation troponin T assay, the detection level of the assay, is useful for identifying patients with the acute coronary syndrome who are at low risk of subsequent mortality.

  • 9.
    James, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Armstrong, Paul
    Califf, Robert
    Simoons, Maarten L.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Troponin T levels and risk of 30-day outcomes in patients with the acute coronary syndrome: prospective verification in the GUSTO-IV trial2003In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 115, no 3, p. 178-184Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A third-generation troponin T assay with improved precision and a lower detection limit has been developed. However, the appropriate cutoff for identifying patients with the acute coronary syndrome who are at low risk of subsequent mortality has not been established.

    METHODS: A retrospective evaluation of data from the Fragmin and fast Revascularization during InStability in Coronary artery disease II (FRISC-II) trial suggested that a cutoff below 0.1 microg/L for troponin T levels might be more useful in risk stratification. A prospective validation of two cutoff levels (0.03 microg/L and 0.01 microg/L) was performed in 7115 patients with non-ST-elevation acute coronary syndrome from the Global Utilization of Strategies To open Occluded arteries IV (GUSTO-IV) trial.

    RESULTS: Patients with troponin T levels >0.1 microg/L had greater 30-day mortality (5.5% [201/3679]) than did those with levels <or=0.1 microg/L (2.2% [75/3436], P <0.001). A cutoff value of 0.03 microg/L provided better discrimination between high and low risk: 5.1% (234/4552) versus 1.6% (42/2563). However, a cutoff value at the lower limit of detection, 0.01 microg/L, provided the best discrimination: 5.0% (254/5123) versus 1.1% (22/1992) (P<0.001). This cutoff level had the highest negative predictive value; it also discriminated best for the combined endpoint of death and myocardial infarction.

    CONCLUSION: Using a cutoff of <or=0.01 microg/L for the third-generation troponin T assay, the detection level of the assay, is useful for identifying patients with the acute coronary syndrome who are at low risk of subsequent mortality.

  • 10. Kholaif, Naji
    et al.
    Zheng, Yinggan
    Jagasia, Pushpa
    Himmelmann, Anders
    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.
    Steg, Philippe Gabriel
    Storey, Robert F.
    Westerhout, Cynthia M.
    Armstrong, Paul W.
    Baseline Q Waves and Time From Symptom Onset to ST-segment Elevation Myocardial Infarction: Insights From PLATO on the Influence of Sex2015In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 128, no 8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The prognostic value of time from symptom onset to reperfusion may be enhanced by the identification of Q waves on the presenting electrocardiogram (ECG) in patients with ST-segment elevation myocardial infarction (STEMI). We evaluated whether the relative prognostic utility of these 2 metrics was altered by sex. METHODS: Q waves in the distribution of the ST-segment elevation on the baseline ECG were evaluated by a blinded core laboratory in 2838 STEMI patients (2163 men and 675 women) from the PLATelet inhibition and patient Outcomes (PLATO) trial who underwent percutaneous coronary intervention (PCI) within 12 hours of symptom onset. RESULTS: Women were older (median 63 vs 57 years), more likely to be diabetic (24.1% vs 15.5%), hypertensive (69.2% vs 50.9%), and a higher Killip class > I (8.6% vs 5.9%), as compared with men. Whereas the Q waves frequency rose progressively over time to ECG in men, this relationship was attenuated in women (P = .057). Q waves on the baseline ECG were associated with a higher excess hazard of 1-year vascular death in men (hazard ratio [HR] 2.03; 95% confidence interval [CI], 1.13-3.72), and a similar trend existed in women (HR 1.97; 95% CI, 0.86-4.51). Women with baseline Q waves tended to have higher risk of 1-year vascular death than men as continuous time from symptom onset to PCI increased (P[interaction] = .182). CONCLUSIONS: These differences in the evolution of baseline Q waves and relationship between time from symptom onset and vascular death in women and men deserve recognition in future studies of STEMI.

  • 11.
    Koshizaka, Masaya
    et al.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.;Chiba Univ Hosp, Clin Res Ctr, Div Diabet Metab & Endocrinol, Chiba, Japan..
    Lopes, Renato D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Newby, L. Kristin
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Clare, Robert M.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Schulte, Phillip J.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Tricoci, Pierluigi
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Mahaffey, Kenneth W.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Ogawa, Hisao
    Natl Cerebral & Cardiovasc Ctr, Osaka, Japan..
    Moliterno, David J.
    Univ Kentucky, Gill Heart Inst, Lexington, KY 40506 USA.;Univ Kentucky, Div Cardiovasc Med, Lexington, KY 40506 USA..
    Giugliano, Robert P.
    Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Huber, Kurt
    Wilhelminen Hosp, Cardiol & Intens Care Med, Med Dept 3, Vienna, Austria.;Sigmund Freud Private Univ, Med Sch, Vienna, Austria..
    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.
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Alexander, John H.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Obesity, Diabetes, and Acute Coronary Syndrome: Differences Between Asians and Whites2017In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 130, no 10, p. 1170-1176Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Most diabetes and cardiovascular studies have been conducted in white patients, with data being extrapolated to other population groups.

    METHODS:

    For this analysis, patient-level data were extracted from 5 randomized clinical trials in patients with acute coronary syndrome; we compared obesity levels between Asian and white populations, stratified by diabetes status. By using an adjusted Cox proportional hazards model, hazard ratios (HRs) for cardiovascular outcomes after an acute coronary syndrome were determined.

    RESULTS:

    We identified 49,224 patient records from the 5 trials, with 3176 Asians and 46,048 whites. Whites with diabetes had higher body mass index values than those without diabetes (median 29.3 vs 27.2 kg/m(2); P <.0001), whereas Asians with diabetes and without diabetes had similar body mass index (24.7 vs 24.2 kg/m2). Asians with diabetes (HR, 1.63; 95% confidence interval [CI], 1.32-2.02), whites with diabetes (HR, 1.15; 95% CI, 1.06-1.25), and Asians without diabetes (HR, 1.36; 95% CI, 1.14-1.64) had higher rates of the composite of death, myocardial infarction, or stroke at 30 days than whites without diabetes. Asians with diabetes (HR, 1.84; 95% CI, 1.47-2.31), whites with diabetes (HR, 1.47; 95% CI, 1.33-1.62), and Asians without diabetes (HR, 1.38; 95% CI, 1.11-1.73) had higher rates of death at 1 year compared with whites without diabetes. There were no significant interactions between race and diabetes for ischemic outcomes.

    CONCLUSIONS:

    Although Asians with diabetes and acute coronary syndrome are less likely to be obese than their white counterparts, their risk for death or recurrent ischemic events was not lower.

  • 12. Lingman, Markus
    et al.
    Albertsson, Per
    Herlitz, Johan
    Bergfeldt, Lennart
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    The Impact of Hypertension and Diabetes on Outcome in Patients Undergoing Percutaneous Coronary Intervention2011In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 124, no 3, p. 265-275Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Information relating the outcome of percutaneous coronary intervention to diabetes mellitus or hypertension is limited. The study objective was to describe the outcome in patients undergoing percutaneous coronary intervention in relation to diabetes and hypertension. METHODS: Data were extracted from 5 national registers: the Swedish Coronary Angiography and Angioplasty Register (all percutaneous coronary interventions), the Prescribed Drug Registry (all prescribed pharmaceuticals purchased in Swedish pharmacies), the Swedish Hospital Discharge Register (data on myocardial infarction, revascularization, stroke, and congestive heart failure from in-hospital and specialist health care), and the National Population Register and Cause of Death Register (data on death). We included all "first percutaneous coronary interventions" between January 1, 2006, and December 31, 2008 (n = 44,268; followed an average of 1.9 [+/- 0.9] years). RESULTS: Mortality was 6.4% and highest in patients with diabetes plus hypertension. Hypertension per se did not increase mortality or the risk for repeat intervention, but carried a 10% increased risk for subsequent myocardial infarction, increasing to a 4-fold increase when combined with diabetes. Stroke occurred in 2%; the importance of hypertension was evident in nondiabetic patients, but even stronger in diabetic patients. Congestive heart failure caused hospital admission in 8%, with a negative influence from hypertension with and without diabetes. CONCLUSION: After percutaneous coronary intervention and with modern pharmacotherapy, diabetes had a negative effect on the outcome, especially when combined with hypertension. Hypertension per se was not associated with increased mortality but with an increased risk for myocardial infarction, stroke, and congestive heart failure, probably related to widespread coronary artery disease. Improved diabetes care might improve the prognosis.

  • 13. Lopes, Renato D.
    et al.
    Starr, Aijing
    Pieper, Carl F.
    Al-Khatib, Sana M.
    Newby, L. Kristin
    Mehta, Rajendra H.
    Van de Werf, Frans
    Mahaffey, Kenneth W.
    Armstrong, Paul W.
    Harrington, Robert A.
    White, Harvey D.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, Christopher B.
    Warfarin Use and Outcomes in Patients with Atrial Fibrillation Complicating Acute Coronary Syndromes2010In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 123, no 2, p. 134-140Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We examined warfarin use at discharge (according to Congestive heart failure, Hypertension, Age > 75 years, Diabetes, Prior Stroke/transient ischemic attack score and bleeding risk) and its association with 6-month death or myocardial infarction in patients with post-acute coronary syndrome atrial fibrillation. METHODS: Of the 23,208 patients enrolled in the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy, Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network A, and Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors trials, 4.0% (917 patients) had atrial fibrillation as an in-hospital complication and were discharged alive. Cox proportional hazards models were performed to assess 6-month outcomes after discharge. RESULTS: Overall, 13.5% of patients with an acute coronary syndrome complicated by atrial fibrillation received warfarin at discharge. Warfarin use among patients with atrial fibrillation had no relation with estimated stroke risk; similar rates were observed across Congestive heart failure, Hypertension, Age > 75 years, Diabetes, Prior Stroke/transient ischemic attack (CHADS(2)) scores (0, 13%; 1, 14%: >= 2, 13%) and across different bleeding risk categories (low risk, 11.9%: intermediate risk, 13.3%; high risk, 11.1%). Among patients with in-hospital atrial fibrillation, warfarin use at discharge was independently associated with a lower risk of death or myocardial infarction within 6 months of discharge (hazard ratio 0.39; 95% confidence interval, 0.15-0.98). CONCLUSION: Warfarin is associated with better 6-month outcomes among patients with atrial fibrillation complicating an acute coronary syndrome, but its use is not related to CHADS(2) score or bleeding risk.

  • 14. Melloni, Chiara
    et al.
    Dunning, Allison
    Granger, Christopher B
    Thomas, Laine
    Khouri, Michel G
    Garcia, David A
    Hylek, Elaine M
    Hanna, Michael
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gersh, Bernard J
    Douglas, Pamela S
    Alexander, John H
    Lopes, Renato D
    Efficacy and Safety of Apixaban Versus Warfarin in Patients with Atrial Fibrillation and a History of Cancer: Insights from the ARISTOTLE Trial.2017In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 130, no 12, p. 1440-1448.e1, article id S0002-9343(17)30713-1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cancer is associated with a prothrombotic state and increases the risk of thrombotic events in patients with atrial fibrillation. We described the clinical characteristics and outcomes and assessed the safety and efficacy of apixaban versus warfarin in patients with atrial fibrillation and cancer in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

    METHODS: The association between cancer and clinical outcomes was assessed using Cox regression models. At baseline, 1236 patients (6.8%) had a history of cancer; 12.7% had active cancer, and 87.3% had remote cancer.

    RESULTS: There were no significant associations between history of cancer and stroke/systemic embolism, major bleeding, or death. The effect of apixaban versus warfarin for the prevention of stroke/systemic embolism was consistent among patients with a history of cancer (event/100 patient-years = 1.4 vs 1.2; hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.53-2.26) and no cancer (1.3 vs 1.6; HR, 0.77; 95% CI, 0.64-0.93) (P interaction = .37). The safety and efficacy of apixaban versus warfarin were preserved among patients with and without active cancer. Apixaban was associated with a greater benefit for the composite of stroke/systemic embolism, myocardial infarction, and death in active cancer (HR, 0.30; 95% CI, 0.11-0.83) versus without cancer (HR, 0.86; 95% CI, 0.78-0.95), but not in remote cancer (HR, 1.46; 95% CI, 1.01-2.10) (interaction P = .0028).

    CONCLUSIONS: Cancer was not associated with a higher risk of stroke. The superior efficacy and safety of apixaban versus warfarin were consistent in patients with and without cancer. Our positive findings regarding apixaban use in patients with atrial fibrillation and cancer are exploratory and promising, but warrant further evaluation.

  • 15.
    Potpara, Tatjana S.
    et al.
    Univ Belgrade, Sch Med, Belgrade, Serbia.;Clin Ctr Serbia, Cardiol Clin, Belgrade, Serbia..
    Lip, Gregory Y. H.
    Univ Belgrade, Sch Med, Belgrade, Serbia.;Univ Birmingham, Inst Cardiovasc Sci, Birmingham, W Midlands, England.;Aalborg Univ, Aalborg Thrombosis Res Unit, Dept Clin Med, Aalborg, Denmark..
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Chiang, Chern-En
    Taipei Vet Gen Hosp, Gen Clin Res Ctr, Taipei, Taiwan.;Taipei Vet Gen Hosp, Div Cardiol, Taipei, Taiwan.;Natl Yang Ming Univ, Taipei, Taiwan..
    Camm, A. John
    St Georges Univ London, Cardiol Clin Acad Grp, London, England..
    Viewpoint: Stroke Prevention in Recent Guidelines for the Management of Patients with Atrial Fibrillation: An Appraisal2017In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 130, no 7, p. 773-779Article, review/survey (Refereed)
    Abstract [en]

    Formal guidelines play an important role in disseminating the best available evidence knowledge and are expected to provide simple and practical recommendations for the most optimal management of patients with various conditions. Such guidelines have important implications for many disease states, which thereby could be more professionally managed in everyday clinical practice by clinicians with divergent educational backgrounds, and also more easily implemented in wards or outpatient clinics, eliminating inequalities in health care management. In this brief Viewpoint we provide an appraisal on the recommendations pertinent to the prevention of atrial fibrillation-related stroke or systemic thromboembolism, as provided in recently published guidelines for the management of this arrhythmia.

  • 16. Rao, Meena P
    et al.
    Vinereanu, Dragos
    Wojdyla, Daniel M
    Alexander, John H
    Atar, Dan
    Hylek, Elaine M
    Hanna, Michael
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lopes, Renato D
    Gersh, Bernard J
    Granger, Christopher B
    Clinical Outcomes and History of Fall in Patients with Atrial Fibrillation Treated with Oral Anticoagulation: Insights From the ARISTOTLE Trial2018In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 131, no 3, p. 269-275.e2Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We assessed outcomes among anticoagulated patients with atrial fibrillation and a history of falling, and whether the benefits of apixaban vs warfarin are consistent in this population.

    METHODS: Of the 18,201 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study, 16,491 had information about history of falling-753 with history of falling and 15,738 without history of falling. The primary efficacy outcome was stroke or systemic embolism; the primary safety outcome was major bleeding.

    RESULTS: -VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or TIA or thromboembolism, Vascular disease, Age 65-74 years, Sex category female) and HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratio, Elderly, Drugs or alcohol) scores. Patients with a history of falling had higher rates of major bleeding (adjusted hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.05-1.84; P = .020), including intracranial bleeding (adjusted HR 1.87; 95% CI, 1.02-3.43; P = .044) and death (adjusted HR 1.70; 95% CI, 1.36-2.14; P < .0001), but similar rates of stroke or systemic embolism and hemorrhagic stroke. There was no evidence of a differential effect of apixaban compared with warfarin on any outcome, regardless of history of falling. Among those with a history of falling, subdural bleeding occurred in 5 of 367 patients treated with warfarin and 0 of 386 treated with apixaban.

    CONCLUSIONS: Patients with atrial fibrillation and a history of falling receiving anticoagulation have a higher risk of major bleeding, including intracranial, and death. The efficacy and safety of apixaban compared with warfarin were consistent, irrespective of history of falling.

  • 17.
    Steg, Philippe Gabriel
    et al.
    Univ Paris Diderot, Hop Bichat, AP HP, Paris, France.;INSERM, U1148, Lab Vasc Translat Sci, Paris, France..
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Himmelmann, Anders
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Pieper, Karen S.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Unreliable Observations from a Confounded Analysis of a Skewed Database2017In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 130, no 8, article id e355Article in journal (Refereed)
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