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  • 1. Alsén, Martin
    et al.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Eggers, Kai
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    »HEART score« – lösningen på säker handläggning av patienter med misstänkt akut kranskärlsjukdom på akutmottagningen?: ["HEART score"--the solution for secure management of patients with suspected acute coronary syndrome in the emergency department?]2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 27-28, p. 1297-Article in journal (Other academic)
  • 2.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Aldous, Sally
    Greenslade, Jaimi H.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Parsonage, William A.
    Pickering, John W.
    Than, Martin
    Cullen, Louise
    Two-hour diagnostic algorithms for early assessment of patients with acute chest pain - Implications of lowering the cardiac troponin I cut-off to the 97.5th percentile2015In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 445, p. 19-24Article in journal (Refereed)
    Abstract [en]

    Aims: Assessment of patients with suspected non-ST elevation myocardial infarction (NSTEMI) is based on cardiac troponin (cTn) levels with the 99th percentile as cut-off. However, cardiovascular risk starts already at lower troponin concentrations. We therefore, aimed to investigate the utility of 2-hour algorithms using the high-sensitivity cardiac troponin I (hs-cTnI) 97.5th percentile as cut-off which corresponds to the standard URL for most biomarkers. Methods: Hs-cTnI was measured at presentation and 2 h in 1624 chest pain patients. Diagnostic algorithms were developed applying hs-cTnI levels dichotomized at the 99th and 97.5th percentiles combined with hs-cTnI changes and/or ECG findings. Results: The prevalence of NSTEMI was 13.9%. The adjusted odds ratios for 1-year mortality were 2.7(95% CI 1.4-5.1) for the 99th percentile and 3.1 (95% CI 1.6-5.9) for the 97.5th percentile. The best-performing 99th percentile-based algorithms provided a positive predictive value (PPV) of 863% and a negative predictive value (NPV) of 993%. Using 97.5th percentile-based algorithms to define NSTEMI resulted in few reclassifications and yielded similar diagnostic estimates (PPV 85.4%, NPV 99.4%). Conclusion: The hs-cTnI 97.5th percentile integrated into 2-hour algorithms provided high diagnostic estimates and could, due to better prognostic properties serve as an alternative to the 99th percentile.

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

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

  • 4.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Dellborg, Mikael
    Johnston, Nina
    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.
    Swahn, Eva
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Myeloperoxidase is not useful for the early assessment of patients with chest pain2010In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 43, no 3, p. 240-245Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Myeloperoxidase (MPO) has been listed as a potentially useful risk marker in acute coronary syndrome. However, its clinical utility in patients with acute chest pain is not yet defined. DESIGN AND METHODS: MPO (Architect, Abbott Diagnostics) was measured in 120 healthy controls and 303 chest pain patients who had been admitted to the coronary care units of three Swedish hospitals. RESULTS: Chest pain patents had significantly higher median MPO levels compared to healthy controls (120.6 vs. 78. 9 pmol/L; p<0.001). However, MPO was not useful for the diagnosis of myocardial infarction (c-statistics 0.61 [95% CI 0.54-0.67]), and Cox regression analysis revealed no independent association between MPO and mortality (adjusted hazard ratio 1.3 [95% CI 0.8-2.0]) or the composite endpoint (adjusted hazard ratio 1.1 [95% CI 0.8-1.5]) after a median follow-up of 4.9 years. CONCLUSIONS: MPO provided no clinically relevant information in the present population of chest pain patients.

  • 5.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Cardiac troponin I levels in patients with non-ST-elevation acute coronary syndrome: the importance of gender2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, no 3, p. 317-324.e1Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 6.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cardiac troponin I levels in an elderly population from the community - The implications of sex2015In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 12, p. 751-756Article in journal (Refereed)
    Abstract [en]

    Objectives: The importance of sex on cardiac troponin levels is increasingly recognized. We investigated whether the entities associated with troponin leakage and the prognostic consequences thereof would differ between elderly men and women from the community. Design and methods: Cardiac troponin I (cTnI) levels were measured using a high-sensitivity assay (Abbott Laboratories) in 70-year old men (n = 502) and women (n = 502) from the PIVUS study. All study participants were followed up for 10 years regarding all-cause mortality and incident cardiovascular (CV) disease. Results: Median cTnI levels were 4.1 and 3.0 ng/L in men and women, respectively (p < 0.001). By multiple linear regression, the relative contribution of lower left-ventricular ejection fraction and ischemic ECG changes to cTnI levels was greater in men compared to women. For other clinical and echocardiographic variables, similar associations were found. cTnI independently predicted all-cause mortality in men (n = 93 [18.5%]; hazard ratio [HR] 1.38 [1.12-1.70]) and women (n = 62 [12.4%]; HR 1.59 [1.11-2.28]) but not incident CV disease in subjects being CV healthy at baseline (n = 163/857). The interaction terms of sex on the associations of cTnI with both outcomes were non-significant. Sex-specific cut-offs did not improve prognostication. Variations in the pattern of entities associated with cTnI leakage had no impact on event rates. Conclusions: We found some differences in the entities associated with higher cTnI levels in elderly community-dwelling men and women. However, this did not translate into differences in the associations of cTnI with adverse outcome.

  • 7.
    Henriksson, Catrin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hallberg, Theresa
    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.
    Johnston, Nina
    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.
    Quality of Life in Patients under Investigation for Unclear Chest Pain: Before and After Coronary Angiography2015In: Journal of Cardiovascular Diseases & Diagnosis, ISSN 2329-9517, Vol. 3, article id 230Article in journal (Refereed)
    Abstract [en]

    Background

    Patients with unclear chest pain experience more anxiety compared to those receiving a clear diagnosis, and they also report lower quality of life (QoL) than a general population. The aim was to investigate if there were differences in QoL before coronary angiography compared to six months later.

    Methods

    This was a quantitative study using the questionnaire EQ-5D. The study population consisted of patients (N=150) with unclear chest pain, referred for elective coronary angiography. They were asked to complete a questionnaire the day before coronary angiography and six months later.

    Results

    Significant improvements were seen regarding usual activities, pain/discomfort and total health status on the day before coronary angiography compared to at six months follow up.

    Conclusions

    Patients with unclear chest pain seem to estimate their total health status before coronary angiography worse than both the general population and myocardial infarction patients. Those with coronary artery disease CAD rated better total health status in comparison to those with a final diagnosis of no CAD. However, six months later significant improvements were seen.

  • 8.
    Humphries, K. H.
    et al.
    Univ British Columbia, Div Cardiol, Vancouver, BC, Canada.;BC Ctr Improved Cardiovasc Hlth, Vancouver, BC, Canada..
    Izadnegandar, M.
    BC Ctr Improved Cardiovasc Hlth, Vancouver, BC, Canada..
    Sedlak, T.
    Univ British Columbia, Div Cardiol, Vancouver, BC, Canada..
    Saw, J.
    Univ British Columbia, Div Cardiol, Vancouver, BC, Canada..
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Schenck-Gustafsson, K.
    Karolinska Univ Hosp, Dept Med, Cardiac Unit, Solna, Sweden.;Karolinska Univ Hosp, Ctr Gender Med, Solna, Sweden.;Karolinska Inst, Solna, Sweden..
    Shah, R. U.
    Univ Utah, Sch Med, Div Cardiovasc Med, Salt Lake City, UT USA..
    Regitz-Zagrosek, V.
    Charite Univ Med Berlin, Inst Gender Med GIM, Partner Site, Berlin, Germany.;Charite Univ Med Berlin, Ctr Cardiovasc Res CCR, Partner Site, Berlin, Germany.;DZHK, Partner Site, Berlin, Germany..
    Grewal, J.
    Univ British Columbia, Div Cardiol, Vancouver, BC, Canada..
    Vaccarino, V.
    Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.;Emory Univ, Sch Med, Dept Med, Atlanta, GA USA..
    Wei, J.
    Cedars Sinai Heart Inst, Barbra Streisand Womens Heart Ctr, Los Angeles, CA USA..
    Merz, C. N. Bairey
    Cedars Sinai Heart Inst, Barbra Streisand Womens Heart Ctr, Los Angeles, CA USA..
    Sex differences in cardiovascular disease: Impact on care and outcomes2017In: Frontiers in neuroendocrinology (Print), ISSN 0091-3022, E-ISSN 1095-6808, Vol. 46, p. 46-70Article, review/survey (Refereed)
  • 9.
    James, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Flodin, Mats
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The antibody configurations of cardiac troponin I assays may determine their clinical performance2006In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 52, no 5, p. 832-837Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous studies have shown superior clinical performance of the cardiac troponin I (cTnI) assay from Beckman-Coulter Diagnostics. This assay had a unique combination of monoclonal antibodies with 2 monoclonal antibodies directed against epitopes near the NH(2) terminus of the heart-specific region of troponin I. The approach has been adopted by the new cTnI assay from Abbott Diagnostics. The aim of our study was to investigate whether this approach affects the clinical performance of cTnI assays. METHODS: Cardiac troponin concentrations were measured in a random sample of patients with unstable coronary artery disease included in the GUSTO IV trial (n = 696) by the AccuTnI (Beckman-Coulter Diagnostics), Architect cTnI (Abbott Diagnostics), Immulite 2500 cTnI (Diagnostics Products Corporation), and Elecsys 2010 cTnT (Roche Diagnostics) assays and related to the 1-year mortality. The primary cutoff concentrations were based on the 99th percentile upper reference limits and an imprecision (CV) < or =10%. RESULTS: The sensitivities of the AccuTnI and Architect cTnI assays in identifying patients who died within 1 year were equal and were significantly higher (P <0.05) than those of the Immulite 2500 cTnI and the Elecsys cTnT assays. The concordance between the AccuTnI and Architect cTnI assays was 97%, but concordances between the Architect cTnI and the Elecsys cTnT assays were 89%-92% with more at-risk patients (P <0.01 to P <0.001) identified by the Architect cTnI assay. CONCLUSIONS: The Architect cTnI assay has clinical performance similar to that of the AccuTnI, probably as a result of the inclusion of a monoclonal antibody against troponin I epitope 41-49 in the assay

  • 10.
    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.

  • 11.
    Jernberg, Tomas
    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.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, 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.
    Johnston, Nina
    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.
    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, 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.
    Natriuretic peptides in unstable coronary artery disease2004In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 25, no 17, p. 1486-1493Article in journal (Other academic)
    Abstract [en]

    Patients with unstable coronary artery disease (CAD), i.e., unstable angina or non-ST-elevation myocardial infarction, vary widely in clinical presentation, prognosis and response to treatment. To select appropriate therapy, early risk stratification has become increasingly important. This review focuses on the emerging role of natriuretic peptides in the early assessment of patients with unstable CAD. We conclude that levels of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are strongly associated to mortality and the risk of future congestive heart failure, and carry important prognostic information independent from previously known risk factors in unstable CAD. There are some data indicating that these markers can also be helpful in the selection of appropriate therapy in these patients but further studies are needed. Before a routine use of BNP or NT-proBNP in unstable CAD can be recommended, the cost-effectiveness of adding these new markers to the currently routine markers and their impact on selection of treatment needs further evaluation.

  • 12.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Bergdahl, Ellinor
    Samnegard, Ann
    Kenttä, Linda
    Holm, Anna
    Petursson, Petur
    Bäck, Magnus
    [ST-elevation myocardial infarction and dual antiplatelet therapy: new guidelines].2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, article id E7UIArticle in journal (Refereed)
    Abstract [sv]

    This report summarizes some of the most important changes and new recommendations from the ESC ST-elevation myocardial infarction and double antiplatelet therapy guidelines for 2017, which are of interest for physicians managing patients with coronary artery disease.

  • 13.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bornefalk-Hermansson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Schenck-Gustafsson, Karin
    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.
    Goodman, Shaun G
    Yan, Andrew T
    Bierman, Arlene S
    Do clinical factors explain persistent sex disparities in the use of acute reperfusion therapy in STEMI in Sweden and Canada?2013In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 2, no 4, p. 350-358Article in journal (Refereed)
    Abstract [en]

    AIMS:

    This study examined clinical factors associated with sex differences in the use of acute reperfusion therapy (fibrinolysis or primary percutaneous coronary intervention) in ST-elevation myocardial infarction (STEMI) patients, and the interaction between sex and these factors in Sweden and Canada.

    METHODS:

    Patients with STEMI in Sweden (n=32,676 from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) were compared with similar patients in Canada (n=3375 from the Canadian Global Registry of Acute Coronary Events) for the period 2004-2008.

    RESULTS:

    Unadjusted vs. age-adjusted odds ratios (OR) for no reperfusion (women vs. men) were for Sweden 1.57 (95% CI 1.49-1.64) vs. 1.14 (95% CI 1.08-1.20), and for Canada 1.61 (95% CI 1.39-1.87) vs. OR 1.18 (95% CI 1.01-1.39). Sex differences persisted after multivariable adjustments (including prehospital delay, atypical symptoms, diabetes), factors for which no interaction with sex was found. Among women <60 years, adjusting for atypical symptoms in Canada and angiographic data in Sweden made the greatest contribution to explaining observed sex differences.

    CONCLUSIONS:

    In both countries, acute reperfusion therapy in STEMI was used less often in women than in men. Factors associated with these sex differences appear to differ between older and younger women. Targeted interventions are needed to optimize care for women with STEMI, as well as sex- and age-stratified reporting of quality indicators to assess their effectiveness.

  • 14.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Christersson, Christina
    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.
    Sex-Specific Research: A Key Component in Improving Prognosis After Transcatheter Aortic Valve Replacement2016In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 164, no 6, p. 442-443Article in journal (Other academic)
  • 15.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, Tomas
    Lagerqvist, Bo
    Siegbahn, Agneta
    Wallentin, Lars
    Improved identification of patients with coronary artery disease by the use of new lipid and lipoprotein biomarkers2006In: American Journal of Cardiology, Vol. 97, p. 640-5Article in journal (Refereed)
  • 16.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, Tomas
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Improved identification of patients with coronary artery disease by the use of new lipid and lipoprotein biomarkers2006In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 97, no 5, p. 640-5Article in journal (Refereed)
    Abstract [en]

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

  • 17.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Oxidized low-density lipoprotein as a predictor of outcome in patients with unstable coronary artery disease2006In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 113, no 2, p. 167-173Article in journal (Refereed)
    Abstract [en]

    Background: The prognostic value of circulating oxidized low-density lipoprotein (OxLDL) in patients with unstable coronary artery disease (CAD) is unknown.

    Methods: Plasma levels of OxLDL were measured in 433 patients with unstable CAD included in FRISC-II (Fragmin and fast Revascularisation in Instability in Coronary artery disease trial) and in 233 of these patients at follow-up 4-7 weeks later. Mortality and myocardial infarction (MI) at 2 years of follow-up was related to above (n 226) or below (n =207) the median level of OxLDL (76 U/L) at study entry.

    Results: After adjustment for other well-known predictors of risk, OxLDL levels > 76 U/L were associated with a higher risk for recurrent MI (Odds Ratio [95% CI]: 1.90 [1.05-3.39]). When patients were divided according to troponin T (TnT) status, the prognostic value of OxLDL was most evident in the TnT negative group with a risk of MI of 16.9% in patients with elevated OxLDL compared to 1.7% (p = 0.004) in those without. No association was found between levels of OxLDL and mortality. At follow-up levels of OxLDL were similar to levels during the acute phase unless patients were treated with statins in which levels were significantly lower.

    Conclusions: Elevated levels of OxLDL may identify patients with unstable CAD, at increased risk for future MI independent of other risk variables, particularly those without evidence of myocardial damage. OxLDL levels appear to be similar in patients during the unstable and stable phase of CAD unless statin therapy is initiated.

  • 18.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Early invasive treatment benefits patients with renal dysfunction in unstable coronary artery disease2006In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 152, no 6, p. 1052-1058Article in journal (Refereed)
    Abstract [en]

    Background: Few studies have investigated the effects of an early revascularization in relation to renal function in patients with unstable coronary artery disease (CAD). Methods: Patients (n = 2457) with unstable CAD randomized to a noninvasive or invasive treatment strategy in the Fast Revascularisation during InStability in Coronary artery disease (FRISC-II) trial were stratified according to tertiles of creatinine clearance (CrCl < 69 mL/min, CrCl 69-90 mL/min, CrCl > 90 mL/min) and followed for 2 years regarding death and/or myocardial infarction (MI). Results: In the noninvasive cohort, the rate of death or MI at 2 years was 22.4% at CrCl < 69 mL/min, 14.6% at CrCl 60-90 mL/min, and 11.6% at CrCl > 90 mL/min. In the invasive cohort, the rate of death or MI was reduced to 14.6% (P = .003) at CrCl < 69 mL/min and to 9.9% (P = .048) at CrCl 69 to 90 mL/min, but no significant reduction (11.2%) at CrCl > 90 mL/min. In a logistic regression analysis adjusting for other important covariables, CrCl < 69 mL/min remained independently associated with the risk of the combined end point in the noninvasively treated group (odds ratio, 1.96; 95% confidence interval, 1.12-3.42) but not in the invasively treated group (odds ratio, 1.09; 95% confidence interval, 0.56-2.14). When the interaction term for treatment strategy and CrCl group was included in the analysis, the interaction between treatment strategy and CrCl <90 mL/min was independently associated with the risk of future MI (P = .006). Conclusion: In unstable CAD, an early invasive treatment strategy reduces the long-term risk of future death and MI in patients with mildly to moderately reduced CrCl.

  • 19.
    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.

  • 20.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jönelid, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Schenck-Gustafsson, Karin
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Effect of Gender on Patients With ST-Elevation and Non-ST-Elevation Myocardial Infarction Without Obstructive Coronary Artery Disease2015In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 115, no 12, p. 1661-1666Article in journal (Refereed)
    Abstract [en]

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

  • 21.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sarno, Giovanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    Larsson, Bertil
    Bild- och funktionsmedicinskt centrum, Akademiska sjukhuset, Uppsala, Sweden.
    Tornvall, Per
    Varenhorst, Christoph
    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.
    Spontan kranskärls­dissektion kan orsaka akut koronart syndrom: ovanligt tillstånd som kräver genomtänkt handläggning och mer forskning2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, article id DRFWArticle in journal (Refereed)
    Abstract [en]

    Spontaneous coronary artery dissection (SCAD) is a non-traumatic and non-iatrogenic injury occurring in the vessel wall caused by either a primary intimal dissection or a primary hematoma in the medial layer. SCAD is more common among women than men and accounts for a small minority of acute coronary syndromes. The causes of SCAD are multifactorial. Peripartum SCAD is most common. Fibromuscular dysplasia has a strong association with SCAD. As spontaneous healing is common in SCAD and PCI is associated with complications an initial conservative approach should always be considered. Medical treatment is based on the underlying cause. Beta blockers are recommended to all patients. The prognosis varies; the highest mortality is reported among women suffering peripartum SCAD. Quality of life is often affected in SCAD patients and accompanied by a high rate of rehospitalizations. More research which focuses on the underlying causes, optimal treatment and rehabilitation is needed.

  • 22.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Schenck-Gustafsson, Karin
    Karolinska Univ Hosp, Stockholm, Sweden.
    Spontaneous coronary artery dissection: A need for raised awareness among healthcare professionals evaluating pregnant and post-partum women with chest pain2017In: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 104, p. 123-124Article in journal (Other academic)
  • 23.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Schenck-Gustafsson, Karin
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Are we using cardiovascular medications and coronary angiography appropriately in men and women with chest pain?2011In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 32, no 11, p. 1331-1336Article in journal (Refereed)
    Abstract [en]

    Aims The main purpose of the present study was to analyse the contemporary use of cardiovascular medications and diagnostic coronary angiography in men and women with suspected coronary artery disease (CAD). Furthermore, we examined the association of outcomes (death, myocardial infarction, repeat coronary angiography, procedural complications) with angiographic findings.

    Methods All patients with stable chest pain (n = 12 200) referred for a first-time elective diagnostic coronary angiography during 2006-08 and registered in the Swedish Coronary Angiography and Angioplasty Register (SCAAR) were included. Significant CAD was defined as ≥50% luminal narrowing in any epicardial coronary artery.

    Results In the youngest age group (≤59 years), more women than men (78.8 vs. 42.3%, P< 0.001) had normal/non-significant CAD, whereas more men had either left-main or three-vessel disease (18.2 vs. 4.2%, P < 0.001). Event rates were similarly low for men and women with normal/non-significant CAD, except for a higher procedural complication rate in women. Prior to angiography, fewer women than men with high-risk features were prescribed aspirin (83 vs. 86.1%, P = 0.001).

    Conclusion In women, normal/non-significant CAD was highly prevalent, especially among younger women, and associated cardiovascular event rates were low. In men, findings of advanced disease were more common than in women, even younger men. Fewer high-risk women than men were initially prescribed aspirin. The observed sex differences suggest a need for improved identification of women appropriate for investigation with coronary angiography, earlier diagnostics in men, and heightened attention in the evidence-based use of aspirin in risk patients, especially women.

  • 24.
    Jönelid, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Kragsterman, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ankle brachial index most important to identify polyvascular disease in patients with non-ST elevation or ST-elevation myocardial infarction2016In: European journal of internal medicine, ISSN 0953-6205, E-ISSN 1879-0828, Vol. 30, p. 55-60Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Atherosclerosis is a systemic disease. In patients with acute myocardial infarction (MI) the extent of polyvascular disease (PvD) is largely unknown. In this study we investigate the prevalence and clinical characteristics predictive of PvD in patients with non-ST-elevation (NSTEMI) and ST-elevation (STEMI) MI.

    METHOD: 375 patients with acute MI included in the REBUS (Relevance of Biomarkers for Future Risk of Thromboembolic Events in Unselected Post-myocardial Infarction Patients) study were examined. Atherosclerotic changes were assessed in three arterial beds by coronary angiography, carotid ultrasound and ankle brachial index (ABI). Results compared findings of atherosclerosis in three arterial beds to fewer than 3 beds. PvD was defined as atherosclerosis in all three arterial beds.

    RESULTS: A medical history of MI, peripheral artery disease (PAD) or stroke was reported at admission in 17.9%, 2.1% and 3.7% of the patients, respectively. After evaluation, abnormal ABI was found in 20.3% and carotid artery atherosclerosis in 54.9% of the patients. In the total population, PvD was found in 13.8% of patients with no significant differences observed between NSTEMI and STEMI patients. Age (p<0.001), diabetes (p=0.039), previous PAD (p=0.009) and female gender (p=0.016) were associated with PvD. ABI was the most important predictor of PvD with a positive predictive value of 68.4% (95% CI 57.7-79.2%) and specificity of 92.4% (95% CI 89.5-95.4%).

    CONCLUSIONS: PvD is underdiagnosed in patients suffering from MI, both NSTEMI and STEMI. ABI is a useful and simple measurement that appears predictive of widespread atherosclerosis in these patients.

  • 25.
    Jönelid, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kragsterman, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Low Walking Impairment Questionnaire score after a recent myocardial infarction identifies patients with polyvascular disease2019In: JRSM Cardiovascular Disease, ISSN 2048-0040, Vol. 8, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate whether the Walking Impairment Questionnaire score could identify patients with polyvascular disease in a population with recent myocardial infarction and their association with cardiovascular events during two-year follow-up.

    Design: A prospective observational study.

    Setting: Patients admitted to the acute coronary care unit, the Department of Cardiology, Uppsala University Hospital.

    Participants: Patients admitted with acute Non-STEMI- or STEMI-elevation myocardial infarction.

    Main outcome measures: The Walking Impairment Questionnaire, developed as a self-administered instrument to assess walking distance, speed, and stair climbing in patients with peripheral artery disease, predicts future cardiovascular events and mortality. Two hundred and sixty-three patients with recent myocardial infarction answered Walking Impairment Questionnaire. Polyvascular disease was defined as abnormal findings in the coronary- and carotid arteries and an abnormal ankle-brachial index. The calculated score for each of all three categories were divided into quartiles with the lowest score in first quartile.

    Results: The lowest (worst) quartile in all three Walking Impairment Questionnaire categories was associated with polyvascular disease, fully adjusted; distance, odds ratio (OR) 5.4 (95% confidence interval (CI) 1.8-16.1); speed, OR 7.4 (95% CI 1.5-36.5); stair climbing, OR 8.4 (95% CI 1.0-73.6). In stair climbing score, patients with the lowest (worst) score had a higher risk for the composite cardiovascular endpoint compared to the highest (best) score; hazard ratio 5.3 (95% CI 1.5-19.0). The adherence to medical treatment was high (between 81.7% and 99.2%).

    Conclusions: The Walking Impairment Questionnaire is a simple tool to identify myocardial infarction patients with more widespread atherosclerotic disease and although well treated medically, stair climbing predicts cardiovascular events.

  • 26. Kempf, Tibor
    et al.
    Horn-Wichmann, Rüdiger
    Brabant, Georg
    Peter, Timo
    Allhoff, Tim
    Klein, Gunnar
    Drexler, Helmut
    Johnston, Nina
    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.
    Wollert, Kai C.
    Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay2007In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 53, no 2, p. 284-291Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Growth-differentiation factor 15 (GDF15) is a member of the transforming growth factor beta (TGF-beta) cytokine superfamily. There has been increasing interest in using circulating GDF15 as a biomarker in patients, for example those with cardiovascular disease. METHODS: We developed an IRMA that uses a polyclonal, affinity chromatography-purified goat antihuman GDF15 IgG antibody, assessed the preanalytic characteristics of GDF15, and determined circulating GDF15 concentrations in 429 apparently healthy elderly individuals and 153 patients with chronic heart failure (CHF). RESULTS: The assay had a detection limit of 20 ng/L, an intraassay imprecision of < or =10.6%, and an interassay imprecision of < or =12.2%. Specificity was demonstrated with size-exclusion chromatography, parallel measurements with polyclonal and monoclonal anti-GDF15 antibody, and lack of cross-reactivity with TGF-beta. The assay was not appreciably influenced by the anticoagulant matrix or unrelated biological substances. GDF15 was stable at room temperature for 48 h and resistant to 4 freeze-thaw cycles. Apparently healthy, elderly individuals presented with a median GDF15 concentration of 762 ng/L (25th-75th percentiles, 600-959 ng/L). GDF15 concentrations were associated with age and with cystatin C and C-reactive protein concentrations. CHF patients had increased GDF15 concentrations that were closely related to disease severity. CONCLUSION: The IRMA can detect GDF15 in human serum and plasma with excellent sensitivity and specificity. The reference limits and confounding variables defined for apparently healthy elderly individuals and the favorable preanalytic characteristics of GDF15 are expected to facilitate future studies of GDF15 as a biomarker in various disease settings, including CHF.

  • 27.
    Kunadian, Vijay
    et al.
    Newcastle Univ, Inst Cellular Med, Fac Med Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.;Newcastle Tyne Hosp Natl Hlth Serv Fdn TrUst, Freeman Hosp, Ctr Cardiothorac, Newcastle Upon Tyne, Tyne & Wear, England..
    Qiu, Weiliang
    Harvard Med Sch, Brigham & Womens Hosp, Dept Medicine, Channing Div Network Med, Boston, MA USA..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sinclair, Hannah
    Newcastle Univ, Inst Cellular Med, Fac Med Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.;Newcastle Tyne Hosp Natl Hlth Serv Fdn TrUst, Freeman Hosp, Ctr Cardiothorac, Newcastle Upon Tyne, Tyne & Wear, England..
    Tan, Ying
    Newcastle Univ, Inst Cellular Med, Fac Med Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.;Newcastle Tyne Hosp Natl Hlth Serv Fdn TrUst, Freeman Hosp, Ctr Cardiothorac, Newcastle Upon Tyne, Tyne & Wear, England..
    Ludman, Peter
    Queen Elizabeth Hosp, Birmingham, W Midlands, England..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sarno, Giovanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gender Differences in Outcomes and Predictors of All-Cause Mortality After Percutaneous Coronary Intervention (Data from United Kingdom and Sweden)2017In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 119, no 2, p. 210-216Article in journal (Refereed)
    Abstract [en]

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

  • 28.
    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.

  • 29.
    Mälarstig, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Tenno, Taavo
    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.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Genetic variations in the tissue factor gene are associated with clinical outcome in acute coronary syndrome and expression levels in human monocytes2005In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 25, no 12, p. 2667-2672Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Tissue factor (TF) has, among other factors, a prominent role in acute coronary syndrome (ACS). Our goal was to investigate whether single nucleotide polymorphisms (SNP) in the TF gene (F3) are associated with plasma TF, risk, and outcome in patients with ACS. Moreover, we wanted to investigate the impact of associated TF SNPs on mRNA production in human monocytes.

    METHODS AND RESULTS:

    In 725 patients with ACS [Fragmin and Fast Revascularization during Instability in Coronary Artery Disease II (FRISC-II) study] and 376 controls, 13 SNPs were genotyped and plasma TF measured. Thereafter, the 5466 A>G and the -1812 C>T were genotyped among all of the FRISC-II participants (n=3143) and assessed concerning clinical outcome. Associated SNPs were genotyped in 92 healthy blood donors for comparison of TF activity and TF mRNA expression. None of the SNPs were associated with patient/control status. The 5466 A>G SNP was associated with cardiovascular death (odds ratio, 1.8; P=0.025). The CG haplotype by -1812 C>T and 5466 A>G was associated with a 3-fold increased risk of death (P<0.001). TF mRNA and basal TF activity was significantly lower among 5466 AG carriers, whereas the increase in monocyte TF activity on lipopolysaccharide stimulation was significantly stronger (P=0.04).

    CONCLUSIONS:

    The 5466 AG genotype is a novel predictor of cardiovascular death in ACS and may act through a high TF response.

  • 30.
    Oldgren, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Xa inhibition and coagulation activity: the influence of prolonged dalteparin treatment and gender in patients with acute coronary syndrome and healthy individuals2008In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 155, no 3, p. 493.e1-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We evaluated coagulation activity in relation to gender in patients with acute coronary syndromes and in healthy individuals of similar age, and related coagulation activity to levels of Xa inhibition during dalteparin treatment. METHODS: Serial blood samples were obtained from 555 (172 women) of 2267 patients in the Scandinavian FRISC II study, and a single sample in 457 (151 women) apparently healthy age- and sex-matched individuals. After randomization, all patients received dalteparin 120 IU/kg s.c. (maximum 10,000 IU) twice daily for 5 to 7 days inhospital and thereafter placebo (n = 285) or sex- and weight-adjusted doses of dalteparin (5000 or 7500 IU) twice daily (n = 270) for 3 months. RESULTS: Before randomization, 96% of the patients had open-label anticoagulation with unfractionated heparin or dalteparin. Therapeutic anti-Xa levels (> 0.5 IU/mL) were found in 74%, 55%, 58%, and 33% of the dalteparin-treated patients at randomization, 2 days, 4 to 7 weeks, and 3 months, respectively, and were significantly related to lower levels of coagulation activity, ie, factor VIIa, prothrombin fragment 1+2, and D-dimer, during prolonged treatment. Female patients had higher anti-Xa levels than men at randomization (median 0.69 vs 0.60 IU/mL, P = .01) and at 2 days (0.65 vs 0.59 IU/mL, P < .001). Female patients had also significantly higher levels of all 3 coagulation markers at randomization, 2 days, 4 to 7 weeks, and 3 and 6 months. Similarly, healthy women had higher prothrombin fragment 1+2 levels (median 1.19 vs 0.94 nmol/L) and D-dimer levels than men (26 vs 21 microg/L) (both P < .001). CONCLUSIONS: Despite weight-adjusted dosing, female patients reached higher anti-Xa levels, suggesting increased sensitivity to dalteparin treatment. Healthy women and female patients also had higher coagulation activity, which might increase the risk of thrombus formation. The large proportion of patients with subtherapeutic anti-Xa during prolonged dalteparin treatment may reflect poor compliance and could thus contribute to the gradual loss of clinical efficacy.

  • 31. Poon, Stephanie
    et al.
    Goodman, Shaun G
    Yan, Raymond T
    Bugiardini, Raffaele
    Bierman, Arlene S
    Eagle, Kim A
    Johnston, Nina
    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.
    Huynh, Thao
    Grondin, Francois R
    Schenck-Gustafsson, Karin
    Yan, Andrew T
    Bridging the gender gap: Insights from a contemporary analysis of sex-related differences in the treatment and outcomes of patients with acute coronary syndromes2012In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 163, no 1, p. 66-73Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The question of whether gender-related disparities still exist in the treatment and outcomes of patients presenting with acute coronary syndromes (ACS) remains controversial. Using data from 4 registries spanning a decade, we sought to determine whether sex-related differences have persisted over time and to examine the treating physician's rationale for adopting a conservative management strategy in women compared with men.

    METHODS:

    From 1999 to 2008, 14,196 Canadian patients with non-ST-segment elevation ACS were recruited into the Acute Coronary Syndrome I (ACSI), ACSII, Global Registry of Acute Coronary Events (GRACE/GRACE(2)), and Canadian Registry of Acute Coronary Events (CANRACE) prospective multicenter registries.

    RESULTS:

    Women in the study population were found to be significantly older than men and were more likely to have a history of heart failure, diabetes, or hypertension. Fewer women were treated with thienopyridines, heparin, and glycoprotein IIb/IIIa inhibitors compared with men in GRACE and CANRACE. Female gender was independently associated with a lower in-hospital use of coronary angiography (adjusted odds ratio 0.76, 95% CI 0.69-0.84, P < .001) and higher in-hospital mortality (adjusted odds ratio 1.26, 95% CI 1.02-1.56, P = .036), irrespective of age (P for interaction =.76). Underestimation of patient risk was the most common reason for not pursuing an invasive strategy in both men and women.

    CONCLUSIONS:

    Despite temporal increases in the use of invasive cardiac procedures, women with ACS are still more likely to be treated conservatively, which may be due to underestimation of patient risk. Furthermore, they have worse in-hospital outcomes. Greater awareness of this paradox may assist in bridging the gap between current guidelines and management practices.

  • 32. Schenck-Gustafsson, Karin
    et al.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Women with Nonobstructive Coronary Artery Disease Are Not Necessarily Healthy2015In: Journal of Women's Health, ISSN 1540-9996, E-ISSN 1931-843X, Vol. 24, no 5, p. 329-330Article in journal (Other academic)
  • 33.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bodegard, J.
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Jerstrom, S.
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Akesson, J.
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Brorsson, H.
    Statisticon AB, Uppsala, Sweden..
    Alfredsson, J.
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Fac Hlth Sci, Linkoping, Sweden..
    Albertsson, P.
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Karlsson, J. E.
    Ryhov Cty Hosp, Dept Internal Medicin, Jonkoping, Sweden..
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Dept Med Sci, Cardiol, Uppsala, Sweden..
    Effects of interactive patient support with a smartphone app on drug adherence and lifestyle changes in myocardial infarction patients2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 1 Supplement, p. 1202-1202Article in journal (Other academic)
  • 34.
    Varenhorst, Christoph
    et al.
    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.
    RE: Letter to the editor, Dr Cheng et al: "Smartphone apps and secondary prevention after myocardial infarction-How can long-term usage be improved?"2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 184, p. e2-e2Article in journal (Other academic)
  • 35.
    Venge, Per
    et al.
    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, Cardiology.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Clinical and analytical performance of the liaison cardiac troponin I assay in unstable coronary artery disease, and the impact of age on the definition of reference limits: A FRISC-II substudy2003In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 49, no 6 Pt 1, p. 880-886Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Measurements of cardiac troponins are currently used as the standard for the detection of myocardial injury. None of the current assays complies with the new requirements on assay imprecision as proposed by the European Society of Cardiology/American College of Cardiology. Our aim was to evaluate the clinical and analytical performance of the Liaison cardiac troponin I (cTnI) assay.

    METHODS:

    EDTA-plasma was used, and cardiac troponins were assayed with the first-generation AxSYM assay, the second-generation AccuTnI assay, the third-generation Elecsys assay, and the first-generation Liaison assay.

    RESULTS:

    In a 6-day imprecision study, the Liaison cTnI assay had mean CV < or =10% at 0.027 microg/L and < or =20% at 0.015 microg/L. The 99th percentile of the upper reference limit (URL) of a reference population was 0.041 microg/L (age range, 41-76 years). Individuals <60 years had a significantly (P = 0.001) lower 99th percentile, 0.022 microg/L. The FRISC-II study participants with cTnI > or =0.041 microg/L had a poorer outcome relating to death/acute myocardial infarction than those with cTnI <0.041 microg/L (P <0.001). Treatment with low-molecular-weight heparin (dalteparin) or an invasive strategy reduced cardiac events only in patients with concentrations >0.041 microg/L (P = 0.002 and 0.02, respectively). Comparison with the AccuTnI assay showed that a large cohort of the patients with poor prognosis was identified by the AccuTnI assay but not by the Liaison cTnI assay.

    CONCLUSION:

    The Liaison cTnI assay is a sensitive assay with a CV < or =10% at the 99th percentile URL. The ability to detect age-related differences among apparently healthy individuals is unique among today's commercial assays. The results indicate that different assays seem to identify different patient cohorts for cardiac risk in the lower range of cTnI concentrations.

  • 36.
    Venge, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Johnston, Nina
    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.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Normal plasma levels of cardiac troponin I measured by the high-sensitivity cardiac troponin I access prototype assay and the impact on the diagnosis of myocardial ischemia2009In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 54, no 13, p. 1165-1172Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study sought to evaluate the analytical and clinical performance of the novel hypersensitive cardiac troponin I (cTnI) prototype assay from Beckman Coulter (Fullerton, California). BACKGROUND: Studies on patients with acute coronary syndromes and on seemingly healthy subjects have shown that even very minor elevations of cardiac troponins are associated with an increased risk of death. However, the normal plasma levels of cardiac troponins are still not known. METHODS: cTnI plasma levels were measured in 542 healthy subjects, 319 men (age 59.9 +/- 11.8 years) and 213 women (age 59.8 +/- 13.1 years), and in 1,503 randomly selected patients of the GUSTO IV (Global Utilization of Strategies To open Occluded arteries IV) cohort with unstable angina and non-ST-segment elevation myocardial infarctions (MIs). RESULTS: The cTnI levels at 10% coefficient of variation and 20% coefficient of variation imprecision were 0.0033 and 0.0016 microg/l, respectively. The cTnI levels were measurable in >95% of the healthy subjects. The median level of healthy subjects <60 years of age was 0.0032 microg/l (range 0.0011 to 0.0079 microg/l) with the 99th percentile being 0.010 microg/l. No sex differences were observed. A receiver-operator characteristic curve analysis showed an optimal discrimination between healthy subjects and patients at 0.0064 microg/l with a sensitivity of 84.8% (95% confidence interval: 82.8% to 86.6%) and specificity of 89.7% (95% confidence interval: 86.8% to 92.2%). Outcomes as to death and/or MI were significantly different at this level (p < 0.01) in the GUSTO IV cohort. CONCLUSIONS: The novel high-sensitivity cTnI prototype assay from Beckman Coulter allows for the first time the measurement of cTnI levels in almost all healthy subjects. Our data indicate that the assay may be a powerful aid in the diagnosis and outcome prediction of patients with suspected myocardial ischemia and question any definition of myocardial infarction.

  • 37. Wollert, Kai C.
    et al.
    Kempf, Tibor
    Peter, Timo
    Olofsson, Sylvia
    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.
    Johnston, Nina
    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.
    Horn-Wichmann, Rüdiger
    Brabant, Georg
    Simoons, Maarten L.
    Armstrong, Paul W.
    Califf, Robert M.
    Drexler, Helmut
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome2007In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 115, no 8, p. 962-971Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Growth-differentiation factor-15 (GDF-15) is a member of the transforming growth factor-beta cytokine superfamily that is induced in the heart after ischemia-and-reperfusion injury. Circulating levels of GDF-15 may provide prognostic information in patients with non-ST-elevation acute coronary syndrome. METHODS AND RESULTS: Blood samples were obtained on admission from 2081 patients with acute chest pain and either ST-segment depression or troponin elevation who were included in the Global Utilization of Strategies to Open Occluded Arteries (GUSTO)-IV Non-ST-Elevation Acute Coronary Syndrome trial and from a matching cohort of 429 apparently healthy individuals. GDF-15 levels were determined by immunoradiometric assay. Approximately two thirds of patients presented with GDF-15 levels above the upper limit of normal in healthy controls (1200 ng/L); one third presented with levels >1800 ng/L. Increasing tertiles of GDF-15 were associated with an enhanced risk of death at 1 year (1.5%, 5.0%, and 14.1%; P<0.001). By multiple Cox regression analysis, only the levels of GDF-15 and N-terminal pro-B-type natriuretic peptide, together with age and a history of previous myocardial infarction, contributed independently to 1-year mortality risk. Receiver operating characteristic curve analyses further illustrated that GDF-15 is a strong marker of 1-year mortality risk (area under the curve, 0.757; best cutoff, 1808 ng/L). At this cutoff value, GDF-15 added significant prognostic information in patient subgroups defined by age; gender; time from symptom onset to admission; cardiovascular risk factors; previous cardiovascular disease; and the risk markers ST-segment depression, troponin T, N-terminal pro-B-type natriuretic peptide, C-reactive protein, and creatinine clearance. CONCLUSIONS: GDF-15 is a new biomarker of the risk for death in patients with non-ST-elevation acute coronary syndrome that provides prognostic information beyond that provided by established clinical and biochemical markers.

  • 38. Wu, Alan H B
    et al.
    Packer, Milton
    Smith, Andrew
    Bijou, Rachel
    Fink, Daniel
    Mair, Johannes
    Wallentin, Lars
    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.
    Feldcamp, Carolyn S
    Haverstick, Doris M
    Ahnadi, Charaf E
    Grant, Andrew
    Despres, Normand
    Bluestein, Barry
    Ghani, Farooq
    Analytical and clinical evaluation of the Bayer ADVIA Centaur automated B-type natriuretic peptide assay in patients with heart failure: a multisite study2004In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 50, no 5, p. 867-873Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    B-Type natriuretic peptide (BNP) is released from the left ventricle of the heart into the circulation in response to ventricular stretching and volume overload. Increased BNP concentrations are associated with heart failure (HF).

    METHODS:

    We evaluated the analytical and clinical performance of the Bayer ADVIA Centaur BNP assay. Studies included precision, analytical correlation (against the Shionogi ShionoRIA and Biosite Triage BNP assays), BNP results for blood collected in plastic tubes containing EDTA vs other collection tubes, high-dose hook effect, detection limits, and interferences. The clinical performance was tested on 2243 blood samples collected from 983 apparently healthy individuals, 538 patients with chronic disease but without HF (renal insufficiency, chronic obstructive pulmonary disease, diabetes, and hypertension), and 722 patients with HF (New York Heart Association classes I-IV).

    RESULTS:

    The ADVIA Centaur assay had total imprecision (CV) of 3.4%, 2.9%, and 2.4% at BNP concentrations of 48, 461, and 1768 ng/L, respectively. The Passing-Bablok correlations to the ShionoRIA and Triage were as follows: ADVIA Centaur = 1.11(ShionoRIA) - 1.19 ng/L (r = 0.98); ADVIA Centaur = 0.78(Triage) + 5.89 ng/L (r = 0.92), respectively. Of the different blood collection tubes, only EDTA plastic tubes (with and without the barrier gel) were acceptable. The lower detection limit was 0.5 ng/L, and there were no interferences from common analytes, other neuropeptides, or unusual antibodies. BNP exhibited different reference intervals according to age and gender. BNP concentrations increased progressively as the severity of HF increased.

    CONCLUSIONS:

    The ADVIA Centaur is the first commercially available BNP assay for use on an automated immunochemistry platform. This assay has good analytical and clinical performance characteristics for diagnosing HF.

  • 39.
    Zethelius, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Johnston, Nina
    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.
    Troponin I as a predictor of coronary heart disease and mortality in 70-year-old men: a community-based cohort study2006In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 113, no 8, p. 1071-1078Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cardiac troponin I (cTnI), a standard for detection of myocardial damage, has recently been reported to predict acute myocardial infarction or death in patients with unstable coronary heart disease (CHD). Cardiac TnI concentrations increase with age in subjects free from clinical signs of CHD, suggesting silent myocardial damage. We investigated the association between cTnI and future CHD and mortality in a community-based cohort of men.

    METHODS AND RESULTS: A community-based study was conducted from August 1991 to May 1995 among 1203 men in Uppsala, Sweden, aged 70 years at baseline with a follow-up of up to 10.4 years with the use of registry data (National Board of Health and Welfare, Sweden). CHD was defined with the use of data taken from the Cause of Death Registry or from first-time hospitalization for CHD as recorded in the Hospital Discharge Registry. Cardiac TnI concentrations were measured blinded for outcome, in frozen baseline plasma samples, with the use of the AccuTnI from Beckman Coulter, Inc. Hazard ratios (HRs) from Cox proportional hazards are presented with 95% confidence intervals (CIs) for a 1-SD increase. In men free from cardiovascular disease (CVD), cTnI predicted death (HR, 1.26; 95% CI, 1.08 to 1.46; P=0.003) or first CHD event (HR, 1.31; 95% CI, 1.11 to 1.54; P=0.001) after adjustment for conventional risk factors: total and HDL cholesterol, plasma glucose, body mass index, smoking, and systolic blood pressure.

    CONCLUSIONS: In this first longitudinal report, cTnI was shown to predict death and first CHD event in men free from CVD at baseline, indicating the importance of silent cardiac damage in the development of CHD and mortality.

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