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  • 1.
    Berglund, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Garmo, Hans
    Lindbäck, Johan
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Maximum likelihood estimation of correction for dilution bias in simple linear regression using replicates from subjects with extreme first measurements2008In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 27, no 22, p. 4397-4407Article in journal (Refereed)
    Abstract [en]

    The least-squares estimator of the slope in a simple linear regression model is biased towards zero when the predictor is measured with random error. A corrected slope may be estimated by adding data from a reliability study, which comprises a subset of subjects from the main study. The precision of this corrected slope depends on the design of the reliability study and estimator choice.Previous work has assumed that the reliability study constitutes a random sample from the main study. A more efficient design is to use subjects with extreme values on their first measurement. Previously, we published a variance formula for the corrected slope, when the correction factor is the slope in the regression of the second measurement on the first. In this paper we show that both designs improve by maximum likelihood estimation (MLE). The precision gain is explained by the inclusion of data from all subjects for estimation of the predictor's variance and by the use of the second measurement for estimation of the covariance between response and predictor. The gain of MLE enhances with stronger true relationship between response and predictor and with lower precision in the predictor measurements. We present a real data example on the relationship between fasting insulin, a surrogate market, and true insulin sensitivity measured by a gold-standard euglycaemic insulin clamp, and simulations, where the behavior of profile-likelihood-based confidence intervals is examined. MLE was shown to be a robust estimator for non-normal distributions and efficient for small sample situations.

  • 2.
    Berglund, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Garmo, Hans
    Regional Oncologic Center, University Hospital, Uppsala.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Correction for regression dilution bias using replicates from subjects with extreme first measurements2007In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 26, no 10, p. 2246-2257Article in journal (Refereed)
    Abstract [en]

    The least squares estimator of the slope in a simple linear regression model will be biased towards zero when the predictor is measured with random error, i.e. intra-individual variation or technical measurement error. A correction factor can be estimated from a reliability study where one replicate is available on a subset of subjects from the main study. Previous work in this field has assumed that the reliability study constitutes a random subsample from the main study.We propose that a more efficient design is to collect replicates for subjects with extreme values on their first measurement. A variance formula for this estimator of the correction factor is presented. The variance for the corrected estimated regression coefficient for the extreme selection technique is also derived and compared with random subsampling. Results show that variances for corrected regression coefficients can be markedly reduced with extreme selection. The variance gain can be estimated from the main study data. The results are illustrated using Monte Carlo simulations and an application on the relation between insulin sensitivity and fasting insulin using data from the population-based ULSAM study.In conclusion, an investigator faced with the planning of a reliability study may wish to consider an extreme selection design in order to improve precision at a given number of subjects or alternatively decrease the number of subjects at a given precision.

  • 3.
    Björklund, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stenestrand, Ulf
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Svensson, Leif
    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.
    Prehospital diagnosis and start of treatment reduces time delay and mortality in real-life patients with STEMI2005In: Journal of Electrocardiology, ISSN 0022-0736, E-ISSN 1532-8430, Vol. 38, no 4 Suppl, p. 186-Article in journal (Other academic)
  • 4.
    Björklund, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stenestrand, Ulf
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Svensson, Leif
    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.
    Pre-hospital thrombolysis delivered by paramedics is associated with reduced time delay and mortality in ambulance-transported real-life patients with ST-elevation myocardial infarction2006In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 27, no 10, p. 1146-1152Article in journal (Refereed)
    Abstract [en]

    AIMS: There are sparse data on the impact of pre-hospital thrombolysis (PHT) in real-life patients. We therefore evaluated treatment delays and outcome in a large cohort of ambulance-transported real-life patients with ST-elevation myocardial infarction (STEMI) according to PHT delivered by paramedics or in-hospital thrombolysis. METHODS AND RESULTS: Prospective cohort study used data from the Swedish Register of Cardiac intensive care on patients admitted to the coronary care units of 75 Swedish hospitals in 2001-2004. Ambulance-transported thrombolytic-treated patients younger than age 80 with a diagnosis of acute myocardial infarction were included. Patients with PHT (n=1690) were younger, had a lower prevalence of co-morbid conditions, fewer complications, and a higher ejection fraction (EF) than in-hospital-treated patients (n=3685). Median time from symptom onset to treatment was 113 min for PHT and 165 min for in-hospital thrombolysis. One-year mortality was 7.2 vs. 11.8% for PHT and in-hospital thrombolysis, respectively. In a multivariable analysis, after adjusting for baseline characteristics and rescue angioplasty, PHT was associated with lower 1-year mortality (odds ratio 0.71, 0.55-0.92, P=0.008). CONCLUSION: When compared with regular in-hospital thrombolysis, pre-hospital diagnosis and thrombolysis with trained paramedics in the ambulances are associated with reduced time to thrombolysis by almost 1 h and reduced adjusted 1-year mortality by 30% in real-life STEMI patients.

  • 5.
    Cato, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sylvén, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rubertsson, Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Risk factors of exclusive breastfeeding less than two months: identifying women in need of targeted breastfeeding supportArticle in journal (Other academic)
  • 6.
    Cato, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Sylvén, Sara M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Rubertsson, Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Risk factors for exclusive breastfeeding lasting less than two months-Identifying women in need of targeted breastfeeding support2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, article id e0179402Article in journal (Refereed)
    Abstract [en]

    Background: Breastfeeding rates in Sweden are declining, and it is important to identify women at risk for early cessation of exclusive breastfeeding.

    Objective: The aim of this study was to investigate factors associated with exclusive breastfeeding lasting less than two months postpartum.

    Methods: A population-based longitudinal study was conducted at Uppsala University Hospital, Sweden. Six hundred and seventy-nine women were included in this sub-study. Questionnaires were sent at five days, six weeks and six months postpartum, including questions on breastfeeding initiation and duration as well as several other background variables. The main outcome measure was exclusive breastfeeding lasting less than two months postpartum. Multivariable logistic regression analysis was used in order to calculate adjusted Odds Ratios (AOR) and 95% Confidence Intervals (95% CI).

    Results: Seventy-seven percent of the women reported exclusive breastfeeding at two months postpartum. The following variables in the multivariate regression analysis were independently associated with exclusive breastfeeding lasting less than two months postpartum: being a first time mother (AOR 2.15, 95% CI 1.32 +/- 3.49), reporting emotional distress during pregnancy (AOR 2.21, 95% CI 1.35 +/- 3.62) and giving birth by cesarean section (AOR 2.63, 95% CI 1.34 +/- 5.17).

    Conclusions: Factors associated with shorter exclusive breastfeeding duration were determined. Identification of women experiencing emotional distress during pregnancy, as well as scrutiny of caregiving routines on cesarean section need to be addressed, in order to give individual targeted breastfeeding support and promote longer breastfeeding duration.

  • 7.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Auner, U
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Enlund, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Post-operative atelectasis: a randomised trial investigating a ventilatory strategy and low oxygen fraction during recovery2014In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, no 6, p. 681-688Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy with a combination of 1) continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) and 2) a reduced end-expiratory oxygen concentration during recovery would reduce post-operative atelectasis.

    METHODS: Sixty patients were randomized into two groups. During anaesthesia induction, inspiratory oxygen fraction (FI O2 ) was 1.0, and depending on weight, CPAP 6, 7 or 8 cmH2 O was applied in both groups via facemask. During maintenance of anaesthesia, a laryngeal mask airway (LMA) was used, and PEEP was 6-8 cmH2 O in both groups. Before removal of the LMA, FI O2 was set to 0.3 in the intervention group and 1.0 in the control group. Atelectasis was studied by computed tomography (CT) approximately 14 min post-operatively.

    RESULTS: In one patient in the group given an FI O2 of 0.3 before removal of the LMA a CT scan could not be performed so the patient was excluded. The area of atelectasis was 5.5, 0-16.9 cm(2) (median and range), and 6.8, 0-27.5 cm(2) in the groups given FI O2 0.3 or FI O2 1.0 before removal of the LMA, a difference that was not statistically significant (P = 0.48). Post-hoc analysis showed dependence of atelectasis on smoking (despite all were clinically lung healthy) and American Society of Anesthesiologists class (P = 0.038 and 0.015, respectively).

    CONCLUSION: Inducing anaesthesia with CPAP/PEEP and FI O2 1.0 and deliberately reducing FI O2 during recovery before removal of the LMA did not reduce post-operative atelectasis compared with FI O2 1.0 before removal of the LMA.

  • 8.
    Edmark, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Auner, Udo
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Enlund, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Atelectasis after anaesthesia: a randomised trial of positive airway pressure and low oxygen2013Article in journal (Other academic)
    Abstract [en]

    Background:

    Atelectasis is common during and after general anaesthesia. We hypothesized that a ventilation strategy with a combination of 1) continuous positive airway pressure (CPAP) or positive end-expiratory pressure (PEEP) and 2) a reduced end-expiratory oxygen fraction (FETO2) before extubation would reduce postoperative atelectasis.

    Methods:

    Sixty patients were randomized into two groups. During anaesthesia induction, inspiratory oxygen fractions (FIO2) were 1.0, and depending on weight, CPAP 6–8 cm H2O was applied in both groups via face mask. During maintenance of anaesthesia, a laryngeal mask airway was used, and depending on weight, PEEP was 6–8 cm H2O in both groups. Before extubation, FIO2 was set to 0.3 in the intervention groups and 1.0 in the control group. Atelectasis was studied by computed tomography approximately 13 min postoperatively.

    Results:

    The area of atelectasis was 5.5, 0–16.9 cm2 (median and range), and 6.8, 0–27.5 cm2 in the groups given FIO2 0.3 or FIO2 1.0 before extubation, a difference that was not statistically significant.

    Conclusion:

    Inducing anaesthesia with CPAP/PEEP and FIO2 1.0 and deliberately reducing FIO2 before extubation did not reduce postoperative atelectasis compared with FIO2 1.0 before extubation.

  • 9.
    Farrokhnia, N
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Björk, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Lindbäck, J
    Terent, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Blood glucose in acute stroke, different therapeutic targets for diabetic and non-diabetic patients?2005In: Acta Neurol Scand, ISSN 0001-6314, Vol. 112, no 2, p. 81-7Article in journal (Other scientific)
  • 10.
    Farrokhnia, N
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Roos, MW
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Lindback, J
    Terent, Andreas
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Differences early mitogen-activated protein kinase activation in hyperglycemic ischmic brain injury in the rat.2005In: Eur J Clin Invest, Vol. 35, no 7, p. 457-463Article in journal (Refereed)
  • 11.
    Hallberg, Pär
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindbäck, Johan
    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.
    Stenestrand, Ulf
    Melhus, Håkan
    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.
    Digoxin and mortality in atrial fibrillation: a prospective cohort study2007In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 63, no 10, p. 959-971Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study showed that rhythm-control treatment of patients with atrial fibrillation (AF) offered no survival advantage over a rate-control strategy. In a subgroup analysis of that study, it was found that digoxin increased the death rate [relative risk (RR) = 1.42), but it was suggested that this may have been attributable to prescription of digoxin for patients at greater risk of death, such as those with congestive heart failure (CHF). No study has investigated a priori the effect of digoxin on mortality in patients with AF. This study aimed to address this question. METHODS: Using data from the Registry of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA), we studied the 1-year mortality among patients admitted to coronary care units with AF, CHF, or AF+CHF with or without digoxin (n = 60,764) during 1995-2003. Adjustment for differences in background characteristics and other medications and treatments was made by propensity scoring. RESULTS: Twenty percent of patients with AF without CHF in this cohort were discharged with digoxin. This group had a higher mortality rate than the corresponding group not given digoxin [adjusted RR 1.42 (95% CI 1.29-1.56)], whereas no such difference was seen among patients with CHF with or without AF, although these patients had a nearly three-times higher mortality. CONCLUSION: The results suggest that long-term therapy with digoxin is an independent risk factor for death in patients with AF without CHF.

  • 12. Hallmarker, Ulf
    et al.
    Michaëlsson, Karl
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindbäck, Johan
    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.
    Outcome After Myocardial Infarction In A Cohort Study Of Cross Country Skiers In Sweden2014In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 63, no 12, p. A1345-A1345Article in journal (Refereed)
  • 13.
    Hijazi, Ziad
    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, 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.
    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.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, Christopher B.
    Duke Univ, Med Ctr, Durham, NC USA..
    Alexander, John H.
    Duke Univ, Med Ctr, Durham, NC USA..
    Gersh, Bernard J.
    Mayo Clin, Coll Med, Rochester, MN USA..
    Hanna, Michael
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Harjola, Veli-Pekka
    Helsinki Univ Cent Hosp, Div Emergency Care, Dept Med, Helsinki, Finland..
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA USA..
    Lopes, Renato D.
    Duke Univ, Med Ctr, Durham, NC USA..
    Siegbahn, Agneta
    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.
    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.
    Repeated Measurements of Cardiac Biomarkers in Atrial Fibrillation and Validation of the ABC Stroke Score Over Time2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 6, article id e004851Article in journal (Refereed)
    Abstract [en]

    Background: Cardiac biomarkers are independent risk markers in atrial fibrillation, and the novel biomarker-based ABC stroke score (age, biomarkers, and clinical history of prior stroke) was recently shown to improve the prediction of stroke risk in patients with atrial fibrillation. Our aim was to investigate the short-term variability of the cardiac biomarkers and evaluate whether the ABC stroke risk score provides a stable short- term risk estimate.

    Methods and Results: According to the study protocol, samples were obtained at entry and also at 2 months in 4796 patients with atrial fibrillation followed for a median of 1.8 years in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Cardiac troponin I, cardiac troponin T, and N-terminal pro-B-type natriuretic peptide were measured with high-sensitivity immunoassays. Associations with outcomes were evaluated by Cox regression. C indices and calibration plots were used to evaluate the ABC stroke score at 2 months. The average changes in biomarker levels during 2 months were small ( median change cardiac troponin T +2.8%, troponin I +2.0%, and N-terminal pro-B-type natriuretic peptide +13.5%) and within-subject correlation was high ( all >= 0.82). Repeated measurement of cardiac biomarkers provided some incremental prognostic value for mortality but not for stroke when combined with clinical risk factors and baseline levels of the biomarkers. Based on 8702 person-years of follow-up and 96 stroke/systemic embolic events, the ABC stroke score at 2 months achieved a similar C index of 0.70 (95% CI, 0.65-0.76) as compared with 0.70 (95% CI, 0.65-0.75) at baseline. The ABC stroke score remained well calibrated using predefined risk classes.

    Conclusions: In patients with stable atrial fibrillation, the variability of the cardiac biomarkers and the biomarker- based ABC stroke score during 2 months are small. The prognostic information by the ABC stroke score remains consistent and well calibrated with similar good predictive performance if patients are retested after 2 months.

    Clinical Trial Registration --URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

  • 14.
    Hijazi, Ziad
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John H.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Hanna, Michael
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA USA..
    Lopes, Renato D.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    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.
    Stewart, Ralph A. H.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland 1, New Zealand..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland 1, New Zealand..
    Granger, Christopher B.
    Duke Med, 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.
    The ABC (age, biomarkers, clinical history) stroke risk score: a biomarker-based risk score for predicting stroke in atrial fibrillation2016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, no 20, p. 1582-1590Article in journal (Refereed)
    Abstract [en]

    Aims: Atrial fibrillation (AF) is associated with an increased risk of stroke, which is currently estimated by clinical characteristics. The cardiac biomarkers N-terminal fragment B-type natriuretic peptide (NT-proBNP) and cardiac troponin high-sensitivity (cTn-hs) are independently associated with risk of stroke in AF. Our objective was to develop and validate a new biomarker-based risk score to improve prognostication of stroke in patients with AF.

    Methods: and results A new risk score was developed and internally validated in 14 701 patients with AF and biomarkers levels determined at baseline, median follow-up of 1.9 years. Biomarkers and clinical variables significantly contributing to predicting stroke or systemic embolism were assessed by Cox-regression and each variable obtained a weight proportional to the model coefficients. External validation was performed in 1400 patients with AF, median follow-up of 3.4 years. The most important predictors were prior stroke/transient ischaemic attack, NT-proBNP, cTn-hs, and age, which were included in the ABC (Age, Biomarkers, Clinical history) stroke risk score. The ABC-stroke score was well calibrated and yielded higher c-indices than the widely used CHA2DS2-VASc score in both the derivation cohort (0.68 vs. 0.62, P < 0.001) and the external validation cohort (0.66 vs. 0.58, P < 0.001). Moreover, the ABC-stroke score consistently provided higher c-indices in several important subgroups.

    Conclusion: A novel biomarker-based risk score for predicting stroke in AF was successfully developed and internally validated in a large cohort of patients with AF and further externally validated in an independent AF cohort. The ABC-stroke score performed better than the presently used clinically based risk score and may provide improved decision support in AF.

  • 15.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, J. H.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hanna, M.
    Lopes, R. D.
    Oldgren, J.
    Granger, C. B.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    A new biomarker based risk score for predicting major bleeding in atrial fibrillation - the ABC (age, biomarkers, current disease) risk score2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 357-357Article in journal (Refereed)
  • 16.
    Hijazi, Ziad
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Östlund, Olof Petter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, J. H.
    Duke Univ, Med Ctr, Durham, NC 27706 USA..
    Granger, C. B.
    Duke Univ, Med Ctr, Durham, NC 27706 USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stewart, R. A. H.
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1, New Zealand..
    White, H. D.
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1, New Zealand..
    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.
    External validation of the biomarker-based ABC-stroke risk score for atrial fibrillation2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 710-711Article in journal (Other academic)
  • 17.
    Hijazi, Ziad
    et al.
    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, 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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Connolly, Stuart
    Eikelboom, John
    Ezekowitz, Michael
    Granger, Christopher
    Hylek, Elaine
    Lopes, Renato
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Yusuf, Salim
    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.
    External Validation Of The Biomarker-Based ABC-Bleeding Risk Score For Atrial Fibrillation2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 893-893Article in journal (Other academic)
  • 18.
    Hijazi, Ziad
    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.
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John H.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Connolly, Stuart J.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Eikelboom, John W.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Ezekowitz, Michael D.
    Thomas Jefferson Med Coll & Heart Ctr, Wynnewood, PA USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA USA..
    Lopes, Renato D.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Siegbahn, Agneta
    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.
    Yusuf, Salim
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Granger, Christopher B.
    Duke Med, 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.
    The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study2016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, no 10035, p. 2302-2311Article in journal (Refereed)
    Abstract [en]

    Background: The benefit of oral anticoagulation in atrial fibrillation is based on a balance between reduction in ischaemic stroke and increase in major bleeding. We aimed to develop and validate a new biomarker-based risk score to improve the prognostication of major bleeding in patients with atrial fibrillation.

    Methods: We developed and internally validated a new biomarker-based risk score for major bleeding in 14 537 patients with atrial fibrillation randomised to apixaban versus warfarin in the ARISTOTLE trial and externally validated it in 8468 patients with atrial fibrillation randomised to dabigatran versus warfarin in the RE-LY trial. Plasma samples for determination of candidate biomarker concentrations were obtained at randomisation. Major bleeding events were centrally adjudicated. The predictive values of biomarkers and clinical variables were assessed with Cox regression models. The most important variables were included in the score with weights proportional to the model coefficients. The ARISTOTLE and RE-LY trials are registered with ClinicalTrials.gov, numbers NCT00412984 and NCT00262600, respectively.

    Findings: The most important predictors for major bleeding were the concentrations of the biomarkers growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (cTnT-hs) and haemoglobin, age, and previous bleeding. The ABC-bleeding score (age, biomarkers [GDF-15, cTnT-hs, and haemoglobin], and clinical history [previous bleeding]) score yielded a higher c-index than the conventional HAS-BLED and the newer ORBIT scores for major bleeding in both the derivation cohort (0.68 [95% CI 0.66-0.70] vs 0.61 [0.59-0.63] vs 0.65 [0.62-0.67], respectively; ABC-bleeding vs HAS-BLED p< 0.0001 and ABC-bleeding vs ORBIT p= 0.0008). ABC-bleeding score also yielded a higher c-index score in the the external validation cohort (0.71 [95% CI 0.68-0.73] vs 0.62 [0.59-0.64] for HAS-BLED vs 0.68 [0.65-0.70] for ORBIT; ABC-bleeding vs HAS-BLED p< 0.0001 and ABC-bleeding vs ORBIT p= 0.0016). A modified ABC-bleeding score using alternative biomarkers (haematocrit, cTnI-hs, cystatin C, or creatinine clearance) also outperformed the HAS-BLED and ORBIT scores.

    Interpretation: The ABC-bleeding score, using age, history of bleeding, and three biomarkers (haemoglobin, cTn-hs, and GDF-15 or cystatin C/CKD-EPI) was internally and externally validated and calibrated in large cohorts of patients with atrial fibrillation receiving anticoagulation therapy. The ABC-bleeding score performed better than HAS-BLED and ORBIT scores and should be useful as decision support on anticoagulation treatment in patients with atrial fibrillation.

  • 19.
    Hijazi, Ziad
    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.
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John H.
    Duke Hlth, Duke Clin Res Inst, Durham, NC USA..
    Connolly, Stuart J.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Eikelboom, John W.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Ezekowitz, Michael D.
    Thomas Jefferson Med Coll, Wynnewood, PA USA.;Ctr Heart, Wynnewood, PA USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA USA..
    Lopes, Renato D.
    Duke Hlth, Duke Clin Res Inst, Durham, NC USA..
    Yusuf, Salim
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Granger, Christopher B.
    Duke Hlth, Duke Clin Res Inst, Durham, NC USA..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 6, p. 477-485Article in journal (Refereed)
    Abstract [en]

    Aims: In atrial fibrillation (AF), mortality remains high despite effective anticoagulation. A model predicting the risk of death in these patients is currently not available. We developed and validated a risk score for death in anticoagulated patients with AF including both clinical information and biomarkers.

    Methods and results: The new risk score was developed and internally validated in 14 611 patients with AF randomized to apixaban vs. warfarin for a median of 1.9 years. External validation was performed in 8548 patients with AF randomized to dabigatran vs. warfarin for 2.0 years. Biomarker samples were obtained at study entry. Variables significantly contributing to the prediction of all-cause mortality were assessed by Cox-regression. Each variable obtained a weight proportional to the model coefficients. There were 1047 all-cause deaths in the derivation and 594 in the validation cohort. The most important predictors of death were N-terminal pro B-type natriuretic peptide, troponin-T, growth differentiation factor-15, age, and heart failure, and these were included in the ABC (Age, Biomarkers, Clinical history)-death risk score. The score was well-calibrated and yielded higher c-indices than a model based on all clinical variables in both the derivation (0.74 vs. 0.68) and validation cohorts (0.74 vs. 0.67). The reduction in mortality with apixaban was most pronounced in patients with a high ABC-death score.

    Conclusion: A new biomarker-based score for predicting risk of death in anticoagulated AF patients was developed, internally and externally validated, and well-calibrated in two large cohorts. The ABC-death risk score performed well and may contribute to overall risk assessment in AF.

  • 20.
    Hijazi, Ziad
    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.
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. 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. psala, Sweden.;Uppsala Clin Res Ctr, Uppsala, Sweden..
    The ABC risk score for patients with atrial fibrillation Reply2016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, no 10055, p. 1980-1981Article in journal (Refereed)
  • 21.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Pol, Tymon
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John
    Granger, Christopher
    Lopes, Renato
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Novel Prognostic Biomarkers For Ischemic Stroke In Patients With Atrial Fibrillation Using Multimarker Screening: Insights From The Aristotle Trial2018In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 71, no 11, p. 506-506Article in journal (Other academic)
  • 22.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Mora Hosp, Dept Internal Med, S-79285 Mora, Sweden.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, S-79188 Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, S-17177 Stockholm, Sweden.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Wester, Per
    Umea Univ, Dept Publ Hlth & Clin Sci, S-90185 Umea, Sweden;Danderyd Hosp, Karolinska Inst, Dept Clin Sci, S-18288 Stockholm, Sweden.
    Hellberg, Dan
    Ctr Clin Res, S-79182 Falun, Sweden.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    Survival and incidence of cardiovascular diseases in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population2018In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 4, no 2, p. 91-97Article in journal (Refereed)
    Abstract [en]

    We studied the relationship between taking part in a long-distance ski race and incidence of cardiovascular diseases (CVDs) to address the hypothesis that lifestyle lowers the incidence. A cohort of 399 630 subjects in Sweden, half were skiers in the world's largest ski race, and half were non-skiers. Non-skiers were frequency matched for sex, age, and year of race. Individuals with severe diseases were excluded. The endpoints were death, myocardial infarction, or stroke. The subjects were followed up for a maximum of 21.8 years and median of 9.8 years. We identified 9399 death, myocardial infarction, or stroke events among non-skiers and 4784 among the Vasaloppet skiers. The adjusted hazard ratios (HRs) comparing skiers and non-skiers were 0.52 [95% confidence interval (CI) 0.49-0.54] for all-cause mortality, 0.56 (95% CI 0.52-0.60) for myocardial infarction and 0.63 (95% CI 0.58-0.67) for stroke and for all three outcomes 0.56 (95% CI 0.54-0.58). The results were consistent across subgroups: age, sex, family status, education, and race year. For skiers, a doubling of race time was associated with a higher age-adjusted risk of 19%, and male skiers had a doubled risk than female skiers, with a HR 2.06 (95% CI 1.89-2.41). The outcome analyses revealed no differences in risk of atrial fibrillation between skiers and non-skiers. This large cohort study provides additional support for the hypothesis that individuals with high level of physical activity representing a healthy lifestyle, as evident by their participation in a long-distance ski race, have a lower risk of CVD or death.

  • 23.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Medicinkliniken Mora Landstinget Dalarna.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Högskolan Dalarna, Falun.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Centrum för klinisk forskning, Dalarna, Falun.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Risk of recurrent ischaemic events after myocardial infarction in long-distance ski race participants2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 3, p. 282-290Article in journal (Refereed)
    Abstract [en]

    AIMS: To study whether a high level of physical activity prior to myocardial infarction (MI) also protects against recurrent MI (re-MI) or death.

    METHODS AND RESULTS: A longitudinal study of a primary cohort consisting of 204,038 skiers with a proved substantially high level of physical activity in the world's largest long-distance ski race, Vasaloppet, and 499,543 non-skiers selected from the Swedish population. Individuals with severe diseases at baseline were excluded. In the nationwide clinical register, Swedeheart, we identified 7092 individuals with a first MI incident between 1989 and 2010. Of these, 1039 (0.5%) were skiers and 6053 (1.2%) were non-skiers. One hundred and sixty-three (15.7%) skiers and 1352 (22.3%) non-skiers suffered a re-MI or died during follow-up (median 4.44 years), corresponding to an incidence rate of 38.9 (95% confidence interval (CI) 33.2-45.4)/1000 person-years and 55.6 (95% CI 52.7-58.7)/1000 person-years, respectively. Severity of MI in both groups was the same. For skiers compared to non-skiers the unadjusted hazard ratio (HR) for re-MI was 0.66 (95% CI 0.52-0.82). For death or re-MI, HR was 0.70 (95% CI 0.59-0.82) with consistent results in subgroups based on race year, age, gender, education level, marital status. After adjustment for also smoking, diabetes, hypertension and cardiovascular medication, HR was 0.80 (95% CI 0.67-0.97).

    CONCLUSIONS: This large cohort study supports the hypothesis that patients with MI and with prior physical activity and healthy lifestyle, as evidenced by their participation in a long-distance ski race, have a lower risk of subsequent re-MI or death.

  • 24.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Högskolan Dalarna Falun.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Centrum klinisk forskning Dalarna Falun.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wester, Per
    Medicin och folhälsa Umeå Universitet.
    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.
    Risk of Recurrent Stroke and Death After First Stroke in Long‐Distance Ski Race Participants2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 10, article id e002469Article in journal (Refereed)
    Abstract [en]

    Background Physical activity is of benefit for primary prevention of cardiovascular diseases, but it appears to increase the risk for atrial fibrillation. We aimed to study a cohort of patients following a first stroke in individuals with previous high physical activity, compare them to the general population with respect to recurrent stroke and death, and relate these to atrial fibrillation.

    Methods and Results From the participants of the Vasaloppet, the world's largest ski‐race, and matched individuals from the general population (n=708 604), we identified 5964 patients hospitalized with a first‐time stroke between 1994 and 2010. Individuals with severe diseases were excluded. One half percent of skiers and 1% of nonskiers were hospitalized due to stroke. The incidence rate was 8.3 per 100 person‐years among skiers and 11.1 among nonskiers. The hazard ratio (HR) for recurrent stroke or death between the 2 groups was 0.76 (95% CI 0.67 to 0.86). The result was consistent in subgroups. The HR for death was 0.66 (95% CI 0.56 to 0.78) and for recurrent stroke 0.82 (95% CI 0.70 to 0.96). After adjustment for smoking and socioeconomic factors, the HR for death was consistent at 0.70 (95% CI 0.56 to 0.87) while the HR for recurrent stroke was not statistically significant. Outcomes for skiers with atrial fibrillation tended to show a lower risk than for nonskiers.

    Conclusions This large cohort study supports the hypothesis that patients with a stroke and with prior regular physical activity have a lower risk of death, while their risk for recurrent stroke is similar to that of nonskiers. The skiers had a higher incidence of atrial fibrillation, but still no increased risk of recurring stroke.

  • 25.
    James, Stefan K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Tilly, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Armstrong, Paul
    Califf, Robert
    Simoons, Maarten L.
    Wallentin, Lars
    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.
    Troponin-T and N-terminal pro-B-type natriuretic peptide predict mortality benefit from coronary revascularization in acute coronary syndromes: a GUSTO-IV substudy2006In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 48, no 6, p. 1146-1154Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study was designed to evaluate biomarkers for selection of patients with non-ST-segment elevation acute coronary syndromes (ACS) that derive mortality benefit from revascularization. BACKGROUND: Biomarkers are essential for identification of patients at increased risk, which may be reduced by revascularization. METHODS: During the initial 30 days, 2,340 patients of 7,800 (30%) with non-ST-segment elevation ACS in the GUSTO (Global Utilization of Strategies To open Occluded arteries)-IV trial underwent coronary revascularization. The 1-year mortality was calculated in 30-day survivors stratified by status of revascularization and levels of biomarkers. A propensity score for receiving revascularization was constructed and included in a survival analysis that also included the time point of revascularization as a time-dependent covariate. RESULTS: Elevation of troponin-T or N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with a high mortality. In patients with either or both of these markers elevated, a lower mortality following revascularization was observed. In contrast, patients without elevation of these markers had low 1-year mortality without any reduction in mortality following revascularization. In fact, in patients with normal levels of both troponin-T and NT-proBNP, a significant increase in 1-year mortality after revascularization was observed. Elevation of C-reactive protein, interleukin-6, creatinine clearance, and ST-segment depression was also related to a higher mortality. However, independent of these markers, mortality was lower after revascularization. CONCLUSIONS: Markers of troponin-T and NT-proBNP not only assist in risk stratification of patients with non-ST-segment elevation ACS but also appear to identify patients who have a reduced mortality associated with early coronary revascularization.

  • 26.
    James, Stefan K
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    An acute inflammatory reaction induced by myocardial damage is superimposed on a chronic inflammation in unstable coronary artery disease2005In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 149, no 4, p. 619-626Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Inflammation plays an important role in unstable coronary artery disease (CAD). We assessed the kinetics of inflammatory markers from symptom onset in patients with unstable CAD and their relation to myocardial damage.

    METHODS:

    Serial measurements of inflammatory mediators were performed in consecutive patients with unstable CAD enrolled at selected sites in the FRISC II (n = 558) and the GUSTO IV (n = 404) trials. The time from symptom onset was calculated for every serum sample (total 4400 samples).

    RESULTS:

    Median levels of interleukin 6 and C-reactive protein reached their peaks at 36 to 42 hours and at 48 to 54 hours, respectively, from symptom onset and returned to early postsymptom levels within 6 weeks. The early increase occurred almost exclusively in patients with baseline troponin T elevation (>0.01 microg/L). In contrast, median levels of fibrinogen increased continuously up to 120 hours after symptom onset, independently of myocardial damage. At 6 months, fibrinogen levels were still higher than in the early phase after symptom onset. The median levels of interleukin 6, C-reactive protein, and fibrinogen were still higher at 6 months than in healthy controls matched for age and sex to a population with unstable CAD.

    CONCLUSIONS:

    An early acute inflammatory reaction induced by myocardial damage seems to be superimposed on a chronic inflammatory condition, both of which might influence long-term outcome in unstable CAD.

  • 27.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jernberg, Tomas
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Biochemical indicators of cardiac and renal function in a healthy elderly population2004In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 37, no 3, p. 210-216Article in journal (Refereed)
    Abstract [en]

    Objectives:

    To examine the distributions of NT-proBNP and cystatin C and their relation to age, gender, and other physiological factors in an apparently healthy elderly population.

    Method:

    NT-proBNP and cystatin C were analyzed in 407 and 408 healthy individuals, median age: 65 (range 40–76).

    Results:

    Increasing age, female gender and CRP were independently associated to higher NT-proBNP levels. Age, body mass index, and CRP level were independently associated to the cystatin C level. In women and men, ≤65 years, the 97.5th percentile value for NT-proBNP was 268 ng/l and 184 ng/l, in those older, 391 ng/l and 269 ng/l. For those ≤65 years the 97.5th percentile value for cystatin C was 1.12 mg/l, and for those older 1.21 mg/l.

    Conclusion:

    In a healthy elderly population, NT-proBNP is influenced by age and gender, whereas cystatin C is influenced by age but not by gender. Both markers seem to be associated to the CRP level.

  • 28.
    Kragsterman, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Pärsson, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bergqvist, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Outcomes of carotid endarterectomy in Sweden are improving: resluts from a population based registry2006In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 44, no 1, p. 79-85Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: In large randomized trials, carotid endarterectomy (CEA) for asymptomatic stenosis has shown a net benefit compared with best medical treatment. To justify an increased number of procedures for this indication, the perioperative risk of stroke or death must not exceed that of the trials. The aim of this study was to evaluate the outcome in routine clinical practice in Sweden in a population-based study. METHODS: The Swedish Vascular Registry (Swedvasc) covers all centers performing CEA. Data on all registered CEAs during 1994 to 2003 were analyzed both for the whole time period and for two 5-year periods to study alterations over time. Four validation procedures of the registry were performed. Medical records were reviewed for both a random sample and a target sample (a total of 12% of the CEAs for asymptomatic stenosis). Swedvasc data were cross-matched with the In-Patient-Registry (used for reimbursement) and the Population-registry (death). RESULTS: A total of 6182 CEAs were registered, 671 being for asymptomatic stenosis. In the validation process, no missed registration of major stroke or death was found. Patients with asymptomatic stenosis had, when the whole time-period was analyzed, a perioperative combined stroke or death rate of 2.1%. Outcome improved over time; the combined stroke or death rate decreased from 3.3% (11/330) from 1994 to 1998 to 0.9% (3/341) from 1999 to 2003 (P = .026). During the second time period, no patient with a perioperative major stroke or death was reported. CONCLUSIONS: This extensively validated national audit of CEA for patients with asymptomatic carotid artery stenosis showed results well comparable with those of the randomized trials. The results improved over time.

  • 29.
    Lagerqvist, Bo
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Stenestrand, Ulf
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Nilsson, Tage
    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.
    Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden2007In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 356, no 10, p. 1009-1019Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recent reports have indicated that there may be an increased risk of late stent thrombosis with the use of drug-eluting stents, as compared with bare-metal stents. METHODS: We evaluated 6033 patients treated with drug-eluting stents and 13,738 patients treated with bare-metal stents in 2003 and 2004, using data from the Swedish Coronary Angiography and Angioplasty Registry. The outcome analysis covering a period of up to 3 years was based on 1424 deaths and 2463 myocardial infarctions and was adjusted for differences in baseline characteristics. RESULTS: The two study groups did not differ significantly in the composite of death and myocardial infarction during 3 years of follow-up. At 6 months, there was a trend toward a lower unadjusted event rate in patients with drug-eluting stents than in those with bare-metal stents, with 13.4 fewer such events per 1000 patients. However, after 6 months, patients with drug-eluting stents had a significantly higher event rate, with 12.7 more events per 1000 patients per year (adjusted relative risk, 1.20; 95% confidence interval [CI], 1.05 to 1.37). At 3 years, mortality was significantly higher in patients with drug-eluting stents (adjusted relative risk, 1.18; 95% CI, 1.04 to 1.35), and from 6 months to 3 years, the adjusted relative risk for death in this group was 1.32 (95% CI, 1.11 to 1.57). CONCLUSIONS: Drug-eluting stents were associated with an increased rate of death, as compared with bare-metal stents. This trend appeared after 6 months, when the risk of death was 0.5 percentage point higher and a composite of death or myocardial infarction was 0.5 to 1.0 percentage point higher per year. The long-term safety of drug-eluting stents needs to be ascertained in large, randomized trials.

  • 30.
    Lindahl, Bertil
    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.
    Lindbäck, Johan
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Serial analyses of N-terminal pro-B-type natriuretic peptide in patients with non-ST-segment elevation acute coronary syndromes: a Fragmin and fast Revascularisation during In Stability in Coronary artery disease (FRISC)-II substudy2005In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 45, no 4, p. 533-541Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    The aim of this research was to describe N-terminal part of the pro-B-type natriuretic peptide (NT-proBNP) levels over time in non-ST-segment elevation acute coronary syndromes (NSTEACS), to elucidate factors associated with changes of NT-proBNP levels, and to examine association with long-term mortality.

    BACKGROUND:

    The NT-proBNP levels are associated with mortality. Long-term temporal changes of NT-proBNP levels and their relation to other factors have not been examined.

    METHODS:

    The NT-proBNP was analyzed at randomization and at 48 h, after 6 weeks, 3 and 6 months in NSTEACS patients enrolled in the Fragmin and fast Revascularisation during InStability in Coronary artery disease (FRISC)-II trial. The NT-proB-type natriuretic peptide was analyzed at least three time points in 1,216 patients.

    RESULTS:

    The median NT-proBNP level, which at randomization was 529 ng/l, decreased throughout the whole sampling period to 238 ng/l at six months. Elevated troponin T, C-reactive protein, and female gender were associated with higher reduction rates, and high age, diabetes, previous myocardial infarction, treatment with diuretics, and nitrates on admission with lower reduction rates. At each time point, the NT-proBNP level was predictive of the two-year mortality. However, the adjusted odds ratio increased for each time point.

    CONCLUSIONS:

    The initial rise of NT-proBNP in NSTEACS is mainly reversible. Factors associated with less reversibility are related to chronically impaired left ventricular function, and factors associated with greater reversibility are related to the acute myocardial damage. The NT-proBNP level measured during a chronic, relatively stable phase is a better predictor of mortality than during an acute unstable phase. The clinical setting and timing of measurement will be important to consider when using NT-proBNP for risk assessment.

  • 31.
    Lindbäck, Heidi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Inadequate adherence to Swedish guidelines for uncomplicated lower urinary tract infections among adults in general practice2017In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 125, no 9, p. 816-821Article in journal (Refereed)
    Abstract [en]

    In a primary care study of urinary tract infections (UTIs) performed 2008 in Uppsala County, Sweden, 43% of the patients were culture negative. In order to investigate the background to the observed overdiagnosis of UTI, study invitations were sent to the previously included patients. A total of 256 patients (88% women) approved to participate. Patient charts and recorded laboratory data were reviewed. Two or more of the cardinal symptoms were reported in 53% of the women and in 19% of the men. A dipstick test was performed in 93% of the consultations. The highest positive predicted values in women had a positive nitrite test (95%, 95% CI 87; 99) and dysuria in combination with urgency (81%, 95% CI 72; 88). Seventy-one percent of the women who fulfilled the symptom criteria received an antibiotic prescription directly, 87% of these had a positive culture. The drug of choice was pivmecillinam for women (51%) and quinolones (50%) for men. The treatment duration was too long for the women; 68% were treated for 7 days. In conclusion, the adherence to national guidelines/recommendations was inadequate. To reduce the selection of multiresistant bacteria, an improvement of the use of diagnostic criteria/tools and antibiotic drugs in primary care is necessary.

  • 32.
    Lindholm, Daniel
    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.
    Lindback, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Becker, R. C.
    Acad Med Ctr, Heart Lung & Vasc Inst, Div Cardiovasc Hlth & Dis, Cincinnati, OH USA..
    Himmelmann, A.
    AstraZeneca, Res & Dev, Molndal, Sweden..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Steg, P. G.
    INSERM, U1148, Paris, France. Univ Paris Diderot, Hop Bichat, AP HP, FIRE,NHLI Imperial Coll,INSERM,U1148, Paris, France..
    Katus, H. A.
    Univ Heidelberg Hosp, Med Klin, Heidelberg, Germany..
    Varenhorst, Christoph
    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.
    Biomarker-based prediction model for recurrent ischemic events in revascularised patients with acute coronary syndromes2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 10-11Article in journal (Other academic)
  • 33.
    Lindholm, Daniel
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Armstrong, Paul W.
    Budaj, Andrzej
    Cannon, Christopher P.
    Granger, Christopher B.
    Hagström, Emil
    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, 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.
    Koenig, Wolfgang
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stewart, Ralph A.H.
    Soffer, Joseph
    White, Harvey D.
    de Winter, Robbert J.
    Steg, Philippe Gabriel
    Siegbahn, Agneta
    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, Clinical Chemistry.
    Kleber, Marcus E.
    Dressel, Alexander
    Grammer, Tanja B.
    März, Winfried
    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.
    Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 70, no 7, p. 813-826Article in journal (Refereed)
    Abstract [en]

    Background Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD).Objectives This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD.Methods In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study.Results During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This “ABC-CHD” model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts.Conclusions This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903)

  • 34.
    Lindholm, Daniel
    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.
    Lindbäck, Johan
    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.
    Becker, Richard
    Cornel, Jan
    Himmelmann, Anders
    Giannitsis, Evangelos
    Harrington, Robert
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Husted, Steen
    Katus, Hugo
    Mahaffey, Kenneth
    Steg, Philippe Gabriel
    Storey, Robert
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Varenhorst, Christoph
    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.
    Prediction Of Major Bleeding In Revascularized Patients With Acute Coronary Syndromes: Development Of A Novel Biomarker-Based Clinical Prediction Model2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 493-493Article in journal (Other academic)
  • 35.
    Oldgren, Jonas
    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.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John
    Connolly, Stuart
    Eikelboom, John
    Ezekowitz, Michael
    Granger, Christopher
    Hylek, Elaine
    Lopes, Renato
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Yusuf, Salim
    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.
    External Validation Of The Biomarker-Based ABC-Stroke Risk Score For Atrial Fibrillation2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 879-879Article in journal (Other academic)
  • 36.
    Oldgren, Jonas
    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.
    Hijazi, Ziad
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John H
    Connolly, Stuart J
    Eikelboom, John W
    Ezekowitz, Michael D
    Granger, Christopher B
    Hylek, Elaine M
    Lopes, Renato D
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Yusuf, Salim
    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.
    Performance and Validation of a Novel Biomarker-Based Stroke Risk Score for Atrial Fibrillation2016In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 134, no 22, p. 1697-1707Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: -Atrial fibrillation (AF) is associated with increased but variable risk of stroke. Our aim was to validate the recently developed biomarker-based ABC-stroke risk score and compare its performance with the CHA2DS2VASc and ATRIA risk scores.

    METHODS: -ABC-stroke score includes Age, Biomarkers (NT-proBNP and high-sensitivity [hs] troponin [cTn]), and Clinical history (prior stroke). This validation was based on 8,356 patients, 16,137 person-years of follow-up, and 219 adjudicated stroke or systemic embolic (SE) events in anticoagulated patients with AF in the RE-LY study. Levels of NT-proBNP, hs-cTnT, and hs-cTnI were determined in plasma samples obtained at study entry.

    RESULTS: -The ABC-stroke score was well calibrated with 0.76 stroke/SE events per 100 person-years in the predefined low (<1%/year) risk group, 1.48 in the medium (1-2%/year) risk group, and 2.60 in the high (>2%/year) risk group for the ABC-stroke score with hs-cTnT. Hazard ratios for stroke/SE were 1.95 for medium versus low risk, and 3.44 for high versus low risk groups. ABC-stroke score achieved C indices of 0.65 with both hs-cTnT and hs-cTnI, as compared with 0.60 for CHA2DS2VASc (p=0.004 for hs-cTnT and p=0.022 hs-cTnI) and 0.61 for ATRIA scores (p=0.005 hs-cTnT and p=0.034 for hs-cTnI).

    CONCLUSIONS: -The biomarker-based ABC-stroke score was well calibrated and consistently performed better than both the CHA2DS2VASc and ATRIA stroke scores. The ABC score should be considered an improved decision support tool in the care of patients with AF.

  • 37.
    Pol, Tymon
    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.
    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.
    Westerbergh, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John H.
    Duke Hlth, Duke Clin Res Inst, Durham, NC USA..
    Alings, Marco
    Working Grp Cardiovasc Res Netherlands, Utrecht, Netherlands..
    Erol, Cetin
    Ankara Univ, Fac Med, Ankara, Turkey..
    Goto, Shinya
    Tokai Univ, Sch Med, Dept Med, Isehara, Kanagawa, Japan..
    Halvorsen, Sigrun
    Univ Oslo, Hosp Ulleval, Dept Cardiol, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Huber, Kurt
    Wilhelminenshop, Dept Med Cardiol & Intens Care Med 3, Vienna, Austria.;Sigmund Freud Univ, Med Sch, Vienna, Austria..
    Hanna, Michael
    Bristol Myers Squibb, Princeton, NJ USA..
    Lopes, Renato D.
    Duke Hlth, Duke Clin Res Inst, Durham, NC USA..
    Ruzyllo, Witold
    Inst Cardiol, Warsaw, Poland..
    Granger, Christopher B.
    Duke Hlth, Duke Clin Res Inst, Durham, NC USA..
    Hijazi, Ziad
    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.
    Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 3, article id e007444Article in journal (Refereed)
    Abstract [en]

    BackgroundDyslipidemia is a major risk factor for cardiovascular events. The prognostic importance of lipoproteins in patients with atrial fibrillation is not well understood. We aimed to explore the association between apolipoprotein A1 (ApoA1) and B (ApoB) and cardiovascular events in patients with atrial fibrillation receiving oral anticoagulation. Methods and ResultsUsing data from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, ApoA1 and ApoB plasma levels were measured at baseline in 14884 atrial fibrillation patients. Median length of follow-up was 1.9years. Relationships between continuous levels of ApoA1 and ApoB and clinical outcomes were evaluated using Cox models adjusted for cardiovascular risk factors, medication including statins, and cardiovascular biomarkers. A composite ischemic outcome (ischemic stroke, systemic embolism, myocardial infarction, and cardiovascular death) was used as the primary end point. Median (25th, 75th) ApoA1 and ApoB levels were 1.10 (0.93, 1.30) and 0.70g/L (0.55, 0.85), respectively. In adjusted analyses, higher levels of ApoA1 were independently associated with a lower risk of the composite ischemic outcome (hazard ratio, 0.81; P<0.0001). Similar results were observed for the individual components of the composite outcome. ApoB was not significantly associated with the composite ischemic outcome (P=0.8240). Neither apolipoprotein was significantly associated with major bleeding. There was no interaction between lipoproteins and randomized treatment for the primary outcome (both P values 0.2448). ConclusionsIn patients with atrial fibrillation on oral anticoagulation, higher levels of ApoA1 were independently associated with lower risk of ischemic cardiovascular outcomes. Investigating therapies targeting dyslipidemia may thus be useful to improve cardiovascular outcomes in patients with atrial fibrillation. Clinical Trial RegistrationURL: . Unique identifier: NCT00412984.

  • 38.
    Pol, Tymon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John
    Granger, Christopher
    Lopes, Renato
    Siegbahn, Agneta
    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.
    New Biomarkers Associated With Cardiovascular Death In Patients With Atrial Fibrillation Using Multimarker Screening: Insights From The Aristotle Trial2018In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 71, no 11, p. 330-330Article in journal (Other academic)
    Abstract [en]

    Background

    Atrial fibrillation (AF) is associated with significant mortality. Biomarkers have shown to add predictive value and could facilitate the understanding of key pathophysiologic mechanisms in AF. Using proximity extension assay (PEA), a new multiplex analytic technique enabling analysis of hundreds of plasma biomarkers, we explored the association between 255 cardiovascular and inflammatory biomarkers with cardiovascular death in patients with AF on oral anticoagulation.

    Methods

    From the ARISTOTLE trial of patients with AF, 517 cases of cardiovascular death and 4057 randomly selected controls were included in an unstratified case-control cohort study. Plasma obtained at randomization was analyzed with conventional immunoassays or the OLINK PEA- panels CVDII, CVDIII, and inflammation panel. Median follow-up time was 1.8 years. The association between biomarkers and cardiovascular death was evaluated using Random Forest and individual Cox-regression analyses adjusted for clinical characteristics, renal function, and cardiac biomarkers (NT-proBNP and cTnT-hs), with adjustment for multiple testing.

    Results

    Of the 255 studied biomarkers, NT-proBNP, cTnT-hs, interleukin-6 (IL-6), transferrin receptor protein 1 (TfR1) and fibroblast growth factor 23 (FGF-23) remained statistically significantly associated with cardiovascular death according to both the Random Forest and the adjusted Cox-regression analysis. In the adjusted Cox analysis, the hazard ratio (95% confidence intervals) per interquartile range was 1.58 (1.38 - 1.83) for NT-proBNP, 1.56 (1.40 -1.75) for cTnT-hs, 1.28 (1.14 - 1.44) for IL-6, 1.27 (1.14 - 1.41) for TfR1 and 1.18 (1.09 -1.28) for FGF-23.

    Conclusion

    Among a vast number of biomarkers, NT-proBNP, cTnT-hs, IL-6, TfR1 and FGF-23 had an independent association with cardiovascular death in patients with AF. The associations of TfR1 and FGF-23 with cardiovascular death in AF are novel and the role of iron regulation (TfR1), and phosphate metabolism (FGF-23), warrants further investigation.

  • 39. Stenestrand, Ulf
    et al.
    Lindbäck, Johan
    Wallentin, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Anticoagulation therapy in atrial fibrillation in combination with acute myocardial infarction influences long-term outcome: a prospective cohort study from the Register of Information and Knowledge About Swedish Heart Intensive Care Admissions (RIKS-HIA).2005In: Circulation, ISSN 1524-4539, Vol. 112, no 21, p. 3225-31Article in journal (Other scientific)
  • 40. Stenestrand, Ulf
    et al.
    Lindbäck, Johan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Hospital therapy traditions influence long-term survival in patients with acute myocardial infarction.2005In: Am Heart J, ISSN 1097-6744, Vol. 149, no 1, p. 82-90Article in journal (Refereed)
  • 41. Stenestrand, Ulf
    et al.
    Lindbäck, Johan
    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.
    Long-term outcome of primary percutaneous coronary intervention vs prehospital and in-hospital thrombolysis for patients with ST-elevation myocardial infarction2006In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 296, no 14, p. 1749-1756Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Whether the superior results of percutaneous coronary intervention (PCI) reported in clinical trials in which patients with ST-segment elevation myocardial infarction (STEMI) received reperfusion treatment can be replicated in daily practice has been questioned, especially whether it is superior to prehospital thrombolysis (PHT). OBJECTIVE: To evaluate the outcome of different reperfusion strategies in consecutive STEMI patients. DESIGN, SETTING, AND PATIENTS: A prospective observational cohort study of 26 205 consecutive STEMI patients in the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) who received reperfusion therapy within 15 hours of symptom onset. The registry includes more than 95% of all Swedish patients, of all ages, who were treated in a coronary intensive care unit between 1999 and 2004. INTERVENTIONS: Seven thousand eighty-four patients underwent primary PCI; 3078, PHT; and 16 043, in-hospital thrombolysis (IHT). MAIN OUTCOME MEASURES: Mortality, reinfarction, and readmissions as reported in the National Health Registries through December 31, 2005. RESULTS: After adjusting for younger age and less comorbidity, primary PCI was associated with lower mortality than IHT at 30 days (344 [4.9%] vs 1834 [11.4%]; hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.53-0.71) and at 1 year (541 [7.6%] vs 2555 [15.9%]; HR, 0.68; 95% CI, 0.60-0.76). Also primary PCI correlated with lower mortality than PHT at 30 days (344 [4.9%] vs 234 [7.6%]; HR, 0.70; 95% CI, 0.58-0.85) and 1 year (541 [7.6%] vs 317 [10.3%]; HR, 0.81; 95% CI, 0.69-0.94). Prehospital thrombolysis predicted a lower mortality than IHT at 30 days (HR, 0.87; 95% CI, 0.76-1.01) and at 1 year (HR, 0.84; CI 0.74-0.95). Beyond 2 hours' treatment delay, the observed mortality reductions with PHT tended to decrease while the benefits with primary PCI seemed to remain regardless of time delay. Primary PCI was also associated with shorter hospital stay and less reinfarction than either PHT or IHT. CONCLUSIONS: In unselected patients with STEMI, primary PCI, which compared favorably with IHT and PHT, was associated with reduced duration of hospital stay, readmission, reinfarction, and mortality.

  • 42.
    Stenestrand, Ulf
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Tabrizi, Fariborz
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Lindbäck, Johan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Englund, Anders
    Rosenqvist, Mårten
    Wallentin, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Comorbidity and myocardial dysfunction are the main explanations for the higher 1-year mortality in acute myocardial infarction with left bundle-branch block.2004In: Circulation, ISSN 1524-4539, Vol. 110, no 14, p. 1896-902Article in journal (Refereed)
  • 43.
    Tomasdottir, Maria
    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.
    Friberg, Leif
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Hijazi, Ziad
    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.
    Lindbäck, Johan
    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.
    Risk of ischemic stroke and utility of CHA2DS2-VASc score in women and men with atrial fibrillation2019In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 42, no 10, p. 1003-1009Article in journal (Refereed)
    Abstract [en]

    Background

    The magnitude of increased risk of stroke in women with atrial fibrillation (AF) remains uncertain.

    Hypothesis

    We investigated the risk of ischemic stroke and death in women and men with AF, and the risk associated with individual non‐sex CHA2DS2‐VASc risk factors.

    Methods

    Retrospective cohort study of 231 077 (48.1% women) nonselected patients with AF not receiving oral anticoagulation from 2006 to 2014. Data from cross‐linked national Swedish registers. The outcome was the first occurrence of ischemic stroke or death. Median age was 82 and 75 years in women and men, respectively. Mean follow‐up was 2.5 years.

    Results

    Hazard ratios, adjusted for non‐sex CHA2DS2‐VASc risk factors, for women vs men were 1.53, 95% CI: 1.49‐1.58 for ischemic stroke and 1.24, 95% CI: 1.22‐1.26 for death, respectively. When divided into age groups the differences in ischemic stroke rates between women and men were attenuated. In patients with only one non‐sex CHA2DS2‐VASc risk factor allotted 1 point, ischemic stroke rates per 100 person‐years were 1.22 in women (n = 9838) and 1.02 in men (n = 15 609), respectively, P < .006. In both women and men, age of 65 to 74 years was associated with higher ischemic stroke risk compared to other non‐sex CHA2DS2‐VASc risk factors allotted 1 point.

    Conclusions

    The risk of ischemic stroke was 1.5‐fold higher in women compared to men but this association appears to be the result of confounding by age. In the low risk end, the CHA2DS2‐VASc risk score underestimates the ischemic stroke risk conferred by age 65 to 74 years, while it overestimates the risk conferred by female sex.

  • 44.
    Tomasdottir, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Friberg, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Risk of stroke in women and men with atrial fibrillation and only one additional CHA2DS2-VASC risk factor2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 69, no 11 Suppl., p. 327-327Article in journal (Refereed)
  • 45.
    Wallentin, Lars C.
    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.
    Lindbäck, Johan
    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.
    Granger, C. B.
    Duke Clin Res Inst, Durham, NC USA..
    Koenig, W.
    Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany.;Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany..
    Stewart, R. A. H.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland 1, New Zealand..
    Tarka, E.
    GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, King Of Prussia, PA USA..
    De Winter, R. J.
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands..
    White, H. D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland 1, New Zealand..
    Siegbahn, Agneta
    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, Coagulation and inflammation science.
    Biomarker-based risk score for prediction of cardiovascular events in stable coronary heart disease - Experiences from the STABILITY biomarker substudy2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 1041-1042Article in journal (Other academic)
  • 46.
    Winell, Henric
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    A general score-independent test for order-restricted inference2018In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 37, no 21, p. 3078-3090Article in journal (Refereed)
    Abstract [en]

    In the analysis of ordered categorical data, the categories are often assigned a set of subjectively chosen order-restricted scores. To overcome the arbitrariness involved in the assignment of the scores, several score-independent tests have been proposed. However, these methods are limited to 2 x K contingency tables, where K is the number of ordered categories. We present an efficiency robust score-independent test that is applicable to more general situations. The test is embedded into a flexible framework for conditional inference and provides a natural generalization of many familiar tests involving ordered categorical data, such as the generalized Cochran-Mantel-Haenszel test for singly or doubly ordered contingency tables, the Page test for randomized block designs and the Tarone-Ware trend test for survival data. The proposed method is illustrated by several numerical examples.

1 - 46 of 46
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