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  • 1.
    Aimo, Alberto
    et al.
    Scuola Super Sant Anna, Pisa, Italy.
    Januzzi, James L
    Massachusetts Gen Hosp, Boston, MA, USA; Harvard Clin Res Inst, Boston, MA USA.
    Vergaro, Giuseppe
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Ripoli, Andrea
    Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Latini, Roberto
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Masson, Serge
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Magnoli, Michela
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Anand, Inder S
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN, USA; VA Med Ctr, Dept Cardiol, Minneapolis, MN USA.
    Cohn, Jay N
    Univ Minnesota, Div Cardiovasc Med, Minneapolis, MN, USA.
    Tavazzi, Luigi
    ES Hlth Sci Fdn, GVM Hosp Care & Res, Cotignola, Italy.
    Tognoni, Gianni
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
    Gravning, Jørgen
    Oslo Univ Hosp, Dept Cardiol, Ulleval, Norway; Univ Oslo, Ctr Heart Failure Res, Oslo, Norway.
    Ueland, Thor
    Oslo Univ Hosp, Rikshosp, Internal Med Res Inst, Oslo, Norway; Univ Oslo, Fac Med, Oslo, Norway; Univ Tromso, Jebsen Thrombosis Res & Expertise Ctr, Tromso, Norway.
    Nymo, Ståle H
    Oslo Univ Hosp, Rikshosp, Internal Med Res Inst, Oslo, Norway.
    Brunner-La Rocca, Hans-Peter
    Maastricht Univ, Med Ctr, Dept Cardiol, Maastricht, Netherlands.
    Bayes-Genis, Antoni
    Hosp Badalona Germans Trias & Pujol, Badalona, Barcelona, Spain.
    Lupón, Josep
    Hosp Badalona Germans Trias & Pujol, Badalona, Barcelona, Spain.
    de Boer, Rudolf A
    Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
    Yoshihisa, Akiomi
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Takeishi, Yasuchika
    Fukushima Med Univ, Dept Cardiovasc Med, Fukushima, Japan.
    Egstrup, Michael
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
    Gustafsson, Ida
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
    Gaggin, Hanna K
    Massachusetts Gen Hosp, Boston, MA, USA; Harvard Clin Res Inst, Boston, MA, USA.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Huber, Kurt
    Wilhelminenspital Stadt Wien, Fac Internal Med, Vienna, Austria; Sigmund Freud Univ, Med Sch, Vienna, Austria.
    Tentzeris, Ioannis
    Wilhelminenspital Stadt Wien, Fac Internal Med, Vienna, Austria; Sigmund Freud Univ, Med Sch, Vienna, Austria.
    Tang, Wai H.W.
    Cleveland Clin, Inst Heart & Vasc, Cleveland, OH, USA.
    Grodin, Justin
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX USA.
    Passino, Claudio
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Emdin, Michele
    Scuola Super Sant Anna, Pisa, Italy; Fdn Toscana Gabriele Monasterio, Pisa, Italy.
    Prognostic Value of High-Sensitivity Troponin T in Chronic Heart Failure: An Individual Patient Data Meta-Analysis2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 137, no 3, p. 286-297Article in journal (Refereed)
    Abstract [en]

    Background: Most patients with chronic heart failure have detectable troponin concentrations when evaluated by high-sensitivity assays. The prognostic relevance of this finding has not been clearly established so far. We aimed to assess high-sensitivity troponin assay for risk stratification in chronic heart failure through a meta-analysis approach.

    Methods: Medline, EMBASE, Cochrane Library, and Scopus were searched in April 2017 by 2 independent authors. The terms were “troponin” AND “heart failure” OR “cardiac failure” OR “cardiac dysfunction” OR “cardiac insufficiency” OR “left ventricular dysfunction.” Inclusion criteria were English language, clinical stability, use of a high-sensitivity troponin assay, follow-up studies, and availability of individual patient data after request to authors. Data retrieved from articles and provided by authors were used in agreement with the PRISMA statement. The end points were all-cause death, cardiovascular death, and hospitalization for cardiovascular cause.

    Results: Ten studies were included, reporting data on 11 cohorts and 9289 patients (age 66±12 years, 77% men, 60% ischemic heart failure, 85% with left ventricular ejection fraction <40%). High-sensitivity troponin T data were available for all patients, whereas only 209 patients also had high-sensitivity troponin I assayed. When added to a prognostic model including established risk markers (sex, age, ischemic versus nonischemic etiology, left ventricular ejection fraction, estimated glomerular filtration rate, and N-terminal fraction of pro-B-type natriuretic peptide), high-sensitivity troponin T remained independently associated with all-cause mortality (hazard ratio, 1.48; 95% confidence interval, 1.41–1.55), cardiovascular mortality (hazard ratio, 1.40; 95% confidence interval, 1.33–1.48), and cardiovascular hospitalization (hazard ratio, 1.42; 95% confidence interval, 1.36–1.49), over a median 2.4-year follow-up (all P<0.001). High-sensitivity troponin T significantly improved risk prediction when added to a prognostic model including the variables above. It also displayed an independent prognostic value for all outcomes in almost all population subgroups. The area under the curve–derived 18 ng/L cutoff yielded independent prognostic value for the 3 end points in both men and women, patients with either ischemic or nonischemic etiology, and across categories of renal dysfunction.

    Conclusions: In chronic heart failure, high-sensitivity troponin T is a strong and independent predictor of all-cause and cardiovascular mortality, and of hospitalization for cardiovascular causes, as well. This biomarker then represents an additional tool for prognostic stratification.

  • 2. 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)
  • 3.
    Eggers, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Dellborg, Mikael
    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.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Risk prediction in chest pain patients by biochemical markers including estimates of renal function2008In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 128, no 2, p. 207-213Article in journal (Refereed)
    Abstract [en]

    Background: Early risk stratification of patients with chest pain may be improved by combining cardiac Troponin I (cTnI) results and ECG findings with markers of left-ventricular dysfunction, inflammation or renal function. Methods: Serial measurements of cTnI were prospectively performed in 452 chest pain patients with a non-diagnostic ECG for AMI and admitted to the coronary care unit. NT-pro BNP, CRP, cystatin C and creatinine-clearance were retrospectively analyzed in admission samples. The prognostic value of these markers alone and in different combinations together with ECG findings was evaluated by multivariate logistic regression models. Results: During follow-up, 14 deaths and 21 myocardial (re)-infarctions occurred. Independent predictors for the combined endpoint of death or (re)-infarction were peak cTnI ≥0.1 μg/L within 24 h (OR 3.9; 95% confidence interval [CI]1.5-10.4), cystatin C ≥1.28 mg/L (OR 5.6; 95% CI 1.9-16.3) and NT-pro BNP ≥550 ng/L (OR 2.7; 95% CI 1.0-7.3). At 2 h from admission, a combination of cTnI ≥0.1 μg/L, an abnormal ECG and NT-pro BNP or cystatin C as a third variable resulted in a similar stratification of patients to different risk groups. Conclusion: cTnI, NT-pro BNP and cystatin C are strong risk predictors in patients with chest pain. For pragmatic reasons, a combination of cTnI ≥0.1 μg/L, ECG findings and a marker of renal function, preferably cystatin C, appears to be most appropriate for early risk stratification of these patients.

  • 4.
    Eggers, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ellenius, Johan
    Dellborg, Mikael
    Groth, Torgny
    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
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Artificial neural network algorithms for early diagnosis of acute myocardial infarction and prediction of infarct size in chest pain patients2007In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 114, no 3, p. 366-374Article in journal (Refereed)
    Abstract [en]

    Background: To prospectively validate artificial neural network (ANN)-algorithms for early diagnosis of myocardial infarction (AMI) and prediction of 'major infarct' size in patients with chest pain and without ECG changes diagnostic for AMI. Methods: Results of early and frequent Stratus CS measurements of troponin I (TnI) and myoglobin in 310 patients were used to validate four prespecified ANN-algorithms with use of cross-validation techniques. Two separate biochemical criteria for diagnosis of AMI were applied: TnI ≥ 0.1 μg/L within 24 h ('TnI 0.1 AMI') and TnI ≥ 0.4 μg/L within 24 h ('TnI 0.4 AMI'). To be considered clinically useful, the ANN-indications of AMI had to achieve a predefined positive predictive value (PPV) ≥ 78% and a negative predictive value (NPV) ≥ 94% at 2 h after admission. 'Major infarct' size was defined by peak levels of CK-MB within 24 h. Results: For the best performing ANN-algorithms, the PPV and NPV for the indication of 'TnI 0.1 AMI' were 87% (p = 0.009) and 99% (p = 0.0001) at 2 h, respectively. For the indication of 'TnI 0.4 AMI', the PPV and NPV were 90% (p = 0.006) and 99% (p = 0.0004), respectively. Another ANN-algorithm predicted 'major AMI' at 2 h with a sensitivity of 96% and a specificity of 78%. Corresponding PPV and NPV were 73% and 97%, respectively. Conclusions: Specially designed ANN-algorithms allow diagnosis of AMI within 2 h of monitoring. These algorithms also allow early prediction of 'major AMI' size and could thus, be used as a valuable instrument for rapid assessment of chest pain patients.

  • 5.
    Eggers, Kai
    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.
    Hammarsten, Ola
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bedömning av patienter med bröstsmärta:: Kan vi nöja oss med mätning av troponin enbart vid ankomst?2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 25-26, p. 1132-1133Article in journal (Other (popular science, discussion, etc.))
  • 6.
    Eggers, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lagerqvist, Bo
    Venge, Per
    Wallentin, Lars
    Lindahl, Bertil
    Pathophysiologic mechanisms and prognostic value of persistent cardiac troponin I elevation in stabilized patients after an episode of acute coronary syndrome.2008In: American Heart Journal, Vol. 156, p. 588-94Article in journal (Refereed)
  • 7.
    Eggers, Kai
    et al.
    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.
    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.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Persistent cardiac troponin I elevation in stabilized patients after an episode of acute coronary syndrome predicts long-term mortality2007In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 116, no 17, p. 1907-1914Article in journal (Refereed)
    Abstract [en]

    BACKGROUND - In patients with non-ST-elevation acute coronary syndrome, any troponin elevation is associated with an increased risk for cardiovascular events. However, the prevalence and prognostic importance of persistent troponin elevation in stabilized patients after an episode of non-ST-elevation acute coronary syndrome are unknown and were therefore assessed in this study. METHODS AND RESULTS - Cardiac troponin I (cTnI) was measured in 1092 stabilized patients at 6 weeks and 3 and 6 months after enrollment in the FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC-II) trial. cTnI was analyzed with the Access AccuTnI assay with the application of different prognostic cutoffs. Outcomes were assessed through 5 years. Elevated cTnI levels >0.01 μg/L were found in 48% of the study patients at 6 weeks, in 36% at 6 months, and in 26% at all 3 measurements. cTnI elevation was associated with increased age and other cardiovascular high-risk features. The lowest tested cTnI cutoff (0.01 μg/L) was prognostically most useful and was independently predictive of mortality (hazard ratio, 2.1 [95% confidence interval, 1.3 to 3.3]; P=0.001) on multivariable analysis adjusted for cardiovascular risk factors and randomization to an invasive versus noninvasive treatment strategy, whereas it was related to myocardial infarction only on univariate analysis. CONCLUSIONS - Persistent minor cTnI elevation can be detected frequently in patients stabilized after an episode of non-ST-elevation acute coronary syndrome with the use of a sensitive assay. Elevated cTnI levels >0.01 μg/L predict mortality during long-term follow-up. Our results emphasize the importance of further troponin testing in non-ST-elevation acute coronary syndrome patients after hospital discharge.

  • 8.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Defining acute myocardial infarction2015In: Heart and Metabolism, ISSN 1566-0338, no 67, p. 34-38Article in journal (Other academic)
    Abstract [en]

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

  • 9.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Mental Stress and Cardiac Troponin2013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 62, no 18, p. 1702-1703Article in journal (Other academic)
  • 10.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Serial Measurement of Biomarkers after Acute Coronary Syndrome: Which One to Choose?2017In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 7, p. 1181-1183Article in journal (Other academic)
  • 11.
    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.

  • 12.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Al-Shakarchi, Jinan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    High-sensitive cardiac troponin T and its relations to cardiovascular risk factors, morbidity, and mortality in elderly men2013In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 166, no 3, p. 541-+Article in journal (Refereed)
    Abstract [en]

    Background Cardiac troponin is emerging as risk indicator in community-dwelling populations. In this study, we investigated the associations of cardiac troponin T (cTnT) to cardiovascular (CV) disease and outcome in elderly men. Methods Cardiac troponin T was measured using a high-sensitive assay in 940 men aged 71 years participating in the Uppsala Longitudinal Study of Adult Men. We assessed both the cross-sectional associations of cTnT to CV risk factors and morbidities including cancer and the longitudinal associations to outcomes over 10 years of follow-up. Results Cardiac troponin T levels were measurable in 872 subjects (92.8%). In the cross-sectional analyses, cTnT was associated to CV risk factors (diabetes, smoking, and obesity), renal dysfunction, CV disease including atrial fibrillation and coronary artery disease, and biomarkers of inflammation and left ventricular dysfunction. In the longitudinal analyses, cTnT independently predicted total mortality and CV events including stroke. The standardized adjusted hazard ratio regarding the composite CV end point was 1.5 (95% CI 1.3-1.8), P < .001, for men with prevalent CV disease and 1.2 (95% CI 1.0-1.4), P = .02, for men without. Cardiac troponin T improved discrimination metrics for all outcomes in the total population. This was mainly driven by the prognostic value of cTnT in subjects with prevalent CV disease. Conclusions In community-dwelling men, cTnT levels are associated to CV risk factors and morbidities and predict both fatal and nonfatal CV events. The relations to outcome are mainly seen in men with prevalent CV disease indicating that the prognostic value of cTnT in subjects free from CV disease is limited.

  • 13.
    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.

  • 14.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Armstrong, Paul W.
    Califf, Robert M.
    Simoons, Maarten L.
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    ST2 and mortality in non-ST-segment elevation acute coronary syndrome2010In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 159, no 5, p. 788-794Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: ST2 is a member of the interleukin-1 receptor family that is up-regulated in conditions associated with increased myocardial strain. ST2 has been shown to be independently predictive of adverse outcome in heart failure and ST-segment elevation myocardial infarction, but its prognostic value in non-ST-elevation acute coronary syndrome (NSTE-ACS) has not been established. METHODS: We measured ST2 at randomization and after 24, 48, and 72 hours in 403 NSTE-ACS patients from the GUSTO IV study, and studied its kinetics and its associations to clinical baseline factors and 1-year mortality. RESULTS: Median ST2 levels decreased from 28.4 U/mL at randomization to 21.8 U/mL at 72 hours (P < .001). Peak levels were noted 6 to 17 hours after symptom onset. Randomization ST2 levels were independently associated to N-terminal pro-B-type natriuretic peptide but otherwise exhibited only weak relations to cardiovascular risk factors and comorbidities, and biomarkers of myocardial necrosis or inflammation. ST2 was related to 1-year mortality independently of clinical risk indicators (odds ratio 2.3 [95% CI 1.1-4.6], P = .03) but lost its predictive value after additional adjustment for prognostic biomarkers, in particular N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: ST2 levels are elevated early in NSTE-ACS and predict 1-year mortality. Our data indicate that ST2 represents an interesting novel pathophysiologic pathway in the setting of ischemia-related myocardial dysfunction. However, future prospective evaluations in larger populations are needed before the clinical utility of ST2 can be determined.

  • 15.
    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.

  • 16.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Baron, Tomasz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hambraeus, Kristina
    Department of Cardiology, Falun Hospital, Falun, Sweden.
    Jernberg, Tomas
    Department of Clinical Sciences, Cardiology, Danderyd Hospital, Karolinska Institute, Danderyd, Sweden.
    Nordenskjöld, Anna
    Faculty of Health, Department of Cardiology, Örebro University, Örebro, Sweden.
    Tornvall, Per
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Myocardial Infarction with Nonobstructive Coronary Arteries: The Importance of Achieving Secondary Prevention Targets2018In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 131, no 5, p. 524-531.e6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

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

    METHODS:

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

    RESULTS:

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

    CONCLUSIONS:

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

  • 17.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jaffe, Allan S.
    Lind, Lars
    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, Clinical Chemistry.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Value of cardiac troponin I cutoff concentrations below the 99th percentile for clinical decision-making2009In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 55, no 1, p. 85-92Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The aim of this study was to evaluate factors influencing the 99th percentile for cardiac troponin I (cTnI) when this cutoff value is established on a highly sensitive assay, and to compare the value of this cutoff to that of lower cutoffs in the prognostic assessment of patients with coronary artery disease. METHODS: We used the recently refined Access AccuTnI assay (Beckman-Coulter) to assess the distribution of cTnI results in a community population of elderly individuals [PIVUS (Prospective Study of the Vasculature in Uppsala Seniors) study; n = 1005]. The utility of predefined cTnI cutoffs for risk stratification was then evaluated in 952 patients from the FRISC II (FRagmin and Fast Revascularization during InStability in Coronary artery disease) study at 6 months after these patients had suffered acute coronary syndrome. RESULTS: Selection of assay results from a subcohort of PIVUS participants without cardiovascular disease resulted in a decrease of the 99th percentile from 0.044 microg/L to 0.028 microg/L. Men had higher rates of cTnI elevation with respect to the tested thresholds. Whereas the 99th percentile cutoff was not found to be a useful prognostic indicator for 5-year mortality, both the 90th percentile (hazard ratio 3.1; 95% CI 1.9-5.1) and the 75th percentile (hazard ratio 2.8; 95% CI 1.7-4.7) provided useful prognostic information. Sex-specific cutoffs did not improve risk prediction. CONCLUSIONS: The 99th percentile of cTnI depends highly on the characteristics of the reference population from which it is determined. This dependence on the reference population may affect the appropriateness of clinical conclusions based on this threshold. However, cTnI cutoffs below the 99th percentile seem to provide better prognostic discrimination in stabilized acute coronary syndrome patients and therefore may be preferable for risk stratification.

  • 18.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jaffe, Allan S
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    A novel approach to cardiac troponins to improve the diagnostic work-up in chest pain patients2012In: Critical Pathways in Cardiology, ISSN 1535-282X, E-ISSN 1535-2811, Vol. 11, no 4, p. 199-205Article in journal (Refereed)
    Abstract [en]

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

  • 19.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jaffe, Allan S.
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Clinical implications of the change of cardiac troponin I levels in patients with acute chest pain - An evaluation with respect to the Universal Definition of Myocardial Infarction2011In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 412, no 1-2, p. 91-97Article in journal (Refereed)
    Abstract [en]

    Background: The Universal Definition of Myocardial Infarction incorporates elevated cardiac troponin levels (>99th percentile) together with a significant rise/fall of troponins as biochemical criterion. We sought to evaluate the clinical implications of the relative change of cardiac troponin I (cTnI) levels with respect to the Universal Definition in patients with acute chest pain. Methods: cTnI (Stratus CS) was measured serially in 454 patients within 24 h from admission. Acute myocardial infarction (AMI) was defined using the criteria adapted to the ESC/ACC consensus document, or corresponding to the Universal Definition together with prespecified cTnI changes of >= 20%, >= 50% and >= 100%. Follow-up was completed after 5.8 years. Results: A peak cTnI level above the 99th percentile together with a cTnI change of >= 20% was found in 160 patients of whom 25 did not have AMI according to the ESC/ACC criteria. These 160 patients had a significantly raised mortality (HR 2.5[95% CI 1.7-3.8]). Higher cTnI deltas were not associated with higher mortalities but identified smaller patient cohorts at risk. Conclusions: The Universal Definition of AMI together with a >= 20% cTnI change appears to improve the discrimination of acute from chronic causes of cTnI release, and allows a reliable identification of patients at risk.

  • 20.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Prognostic implications of changes in cardiac troponin I levels in patients with non-ST elevation acute coronary syndrome2013In: Biomarkers, ISSN 1354-750X, E-ISSN 1366-5804, Vol. 18, no 8, p. 668-672Article in journal (Refereed)
    Abstract [en]

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

  • 21.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, T.
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    High-sensitivity cardiac troponin T, left ventricular function, and outcome in non-ST elevation acute coronary syndrome2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 197, p. 70-76Article in journal (Refereed)
    Abstract [en]

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

  • 22.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Unstable Angina in the Era of Cardiac Troponin Assays with Improved Sensitivity-A Clinical Dilemma2017In: American Journal of Medicine, ISSN 0002-9343, E-ISSN 1555-7162, Vol. 130, no 12, p. 1423-1430Article in journal (Refereed)
    Abstract [en]

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

  • 23.
    Eggers, Kai M.
    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, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    High-Sensitivity Cardiac Troponin T Levels Identify Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Who Benefit From Invasive Assessment2018In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, no 16, p. 1665-1667Article in journal (Other academic)
  • 24.
    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.

  • 25.
    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.

  • 26.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kempf, Tibor
    Allhoff, Tim
    Lindahl, Bertil
    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.
    Wallentin, Lars
    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.
    Wollert, Kai C.
    Growth-differentiation factor-15 for early risk stratification in patients with acute chest pain2008In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 29, no 19, p. 2327-2335Article in journal (Refereed)
    Abstract [en]

    AIMS: Growth-differentiation factor-15 (GDF-15) has emerged as a biomarker of increased mortality and recurrent myocardial infarction (MI) in patients diagnosed with non-ST-elevation acute coronary syndrome. We explored the usefulness of GDF-15 for early risk stratification in 479 unselected patients with acute chest pain. METHODS AND RESULTS: Sixty-nine per cent of the patients presented with GDF-15 levels above the previously defined upper reference limit (1200 ng/L). The risks of the composite endpoint of death or (recurrent) MI after 6 months were 1.3, 5.1, and 12.6% in patients with normal (<1200 ng/L), moderately elevated (1200-1800 ng/L), or markedly elevated (>1800 ng/L) levels of GDF-15 on admission, respectively (P < 0.001). By multivariable analysis that included clinical characteristics, ECG findings, peak cardiac troponin I levels within 2 h (cTnI(0-2 h)), N-terminal pro-B-type natriuretic peptide, C-reactive protein, and cystatin C, GDF-15 remained an independent predictor of the composite endpoint. The ability of the ECG combined with peak cTnI(0-2 h) to predict the composite endpoint was markedly improved by addition of GDF-15 (c-statistic, 0.74 vs. 0.83; P < 0.001). CONCLUSION: GDF-15 improves risk stratification in unselected patients with acute chest pain and provides prognostic information beyond clinical characteristics, the ECG, and cTnI.

  • 27.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kempf, Tibor
    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.
    Lindahl, Bertil
    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.
    Olofsson, Sylvia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jantzen, Franziska
    Peter, Timo
    Allhoff, Tim
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wollert, Kai C.
    Wallentin, Lars
    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.
    Growth-differentiation factor-15 for long-term risk prediction in patients stabilized after an episode of non-ST-segment-elevation acute coronary syndrome2010In: Circulation: Cardiovascular Genetics, ISSN 1942-3268, Vol. 3, no 1, p. 88-96Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Growth-differentiation factor-15 (GDF-15) has emerged as a prognostic biomarker in patients with non-ST-segment-elevation acute coronary syndrome. This study assessed the time course and the long-term prognostic relevance of GDF-15 levels measured repetitively in patients with non-ST-segment-elevation acute coronary syndrome during 6 months after the acute event. METHODS AND RESULTS: GDF-15 and other biomarkers were measured at randomization, after 6 weeks, and after 3 and 6 months in 950 patients with non-ST-segment-elevation acute coronary syndrome included in the FRagmin and Fast Revascularization during InStability in Coronary artery disease II study. Study end points were death, recurrent myocardial infarction, and their composite during 5-year follow-up. Median GDF-15 levels decreased slightly from 1357 ng/L at randomization to 1302 ng/L at 6 months (P<0.001). GDF-15 was consistently related to cardiovascular risk factors and biochemical markers of hemodynamic stress, renal dysfunction, and inflammation. Moreover, GDF-15 was independently related to the 5-year risk of the composite end point when measured at both 3 months (adjusted hazard ratio, 1.8 [1.0 to 3.0]) and 6 months (adjusted hazard ratio, 2.3 [1.3 to 4.1]). Serial measurements of GDF-15 at randomization and 6 months helped to identify patient cohorts at different levels of risk, with patients with persistently elevated GDF-15 levels >1800 ng/L having the highest rate of the composite end point. CONCLUSIONS: GDF-15 is independently related to adverse events in non-ST-segment-elevation acute coronary syndrome both in the acute setting and for at least 6 months after clinical stabilization. Therefore, continued research on GDF-15 should be focused on the usefulness of GDF-15 for support of clinical management in acute and chronic ischemic heart disease.

  • 28.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kempf, Tibor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wollert, Kai C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Evaluation of Temporal Changes in Cardiovascular Biomarker Concentrations Improves Risk Prediction in an Elderly Population from the Community2016In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 62, no 3, p. 485-493Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 29.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kempf, Tibor
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    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.
    Wollert, Kai C
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Relations of growth-differentiation factor-15 to biomarkers reflecting vascular pathologies in a population-based sample of elderly subjects2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 1, p. 45-51Article in journal (Refereed)
    Abstract [en]

    Background.

    Growth-differentiation factor-15 (GDF-15) has recently emerged as a risk predictor in patients with cardiac diseases. GDF-15 is commonly related to cardiovascular risk factors, inflammatory activity and cardiac abnormalities. However, it is not clear whether it might be an indicator of vascular pathologies as well.

    Methods.

    Circulating levels of GDF-15 were measured in 1004 elderly community dwellers participating in the PIVUS study. The relations of GDF-15 to biomarkers of endothelial activation (E-selectin, P-selectin, ICAM-1, VCAM-1), extracellular matrix degradation (MMP-9, TIMP-1), coagulatory activity (D-dimer, von Willebrand factor, prothrombin fragment 1 + 2, factor VIIa), and fibrinolytic activity (PAI-1 activity, tPA-antigen) were assessed by multiple linear regressions.

    Results.

    The median GDF-15 level was 1135 ng/L. By linear correlation analysis, GDF-15 exhibited a moderate relation to von Willebrand factor (r = 0.30), and weak, albeit significant relations (r = 0.13-0.29) to E-selectin, P-selectin, ICAM-1, VCAM-1, MMP-9, TIMP-1, D-dimer, PAI-1 activity and tPA-antigen. The relations to the assessed biomarkers of endothelial activation, TIMP-1, D-dimer and von Willebrand factor remained significant applying multiple linear regression models adjusted for clinical covariates and echocardiographic data. There were no significant relations between GDF-15 and biomarkers solely reflecting coagulatory activity.

    Conclusions.

    In the elderly, GDF-15 reflects endothelial activation and vascular inflammation and thus, multiple pathways involved in the development and progression of atherosclerosis.

  • 30.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kempf, Tibor
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wollert, Kai C.
    Lindahl, Bertil
    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.
    Improving long-term risk prediction in patients with acute chest pain: The Global Registry of Acute Coronary Events (GRACE) risk score is enhanced by selected nonnecrosis biomarkers2010In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 160, no 1, p. 88-94Article in journal (Refereed)
    Abstract [en]

    Background The Global Registry of Acute Coronary Events (GRACE) risk score is widely recommended for risk assessment in patients with acute coronary syndrome. However, there is limited knowledge regarding the utility of this score for long-term risk prediction in unselected patients with acute chest pain and whether it might be improved by the integration of nonnecrosis biomarkers. Methods We calculated the GRACE risk score in 453 chest pain patients and assessed its value for risk assessment together with the additive prognostic information obtained from N-terminal pro-B-type natriuretic peptide, C-reactive protein, growth differentiation factor-15 (GDF-15), and cystatin C. Results After a median follow-up of 5.8 years, 92 patients (20.7%) had died. The GRACE risk score was significantly higher in patients who died (median 146 vs 93, P < .001) and provided a c-statistic regarding mortality of 0.78. A significant increase of the c-statistic was achieved only after addition of GDF-15 (c-statistic 0.81, P = .003) and, to a minor extent, after addition of cystatin C (c-statistic 0.81, P = .035). Assessment of the integrated discriminative improvement yielded similar results. N-terminal pro-B-type natriuretic peptide had only limited incremental prognostic value, and C-reactive protein was not predictive for outcome. Conclusion The GRACE risk score allows for the prediction of mortality in chest pain patients even after almost 6 years of follow-up. However, its predictive value could be further enhanced by the addition of selected nonnecrosis biomarkers, in particular GDF-15 or cystatin C. (Am Heart J 2010; 160: 88-94.)

  • 31.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kempf, Tibor
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wollert, Kai C
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Change in Growth Differentiation Factor 15 Concentrations Over Time Independently Predicts Mortality in Community-Dwelling Elderly Individuals2013In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 59, no 7, p. 1091-1098Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Growth differentiation factor 15 (GDF-15) is emerging as a powerful risk indicator in both cardiovascular disease patients and community-dwelling individuals. We investigated GDF-15 concentrations and their changes over 5 years in elderly individuals from the community, together with the underlying conditions and prognostic implications of these measurements.

    METHODS:

    We analyzed GDF-15 concentrations using a sandwich immunoassay in participants from the PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study. Measurements were performed at both 70 (n = 1004) and 75 (n = 813) years of age. Median follow-up was 8.0 years.

    RESULTS:

    Over time, GDF-15 concentrations increased by 11.0% (P < 0.001). These changes were related to male sex, hypertension, diabetes, heart failure, renal function, and concentrations of N-terminal pro–B-type natriuretic peptide (NT-proBNP). Significant relationships also emerged between changes in GDF-15 and NT-proBNP, C-reactive protein, and renal function between ages 70 and 75. The R2 value of this model was 0.20. GDF-15 concentrations independently predicted all-cause mortality [hazard ratio 4.0 (95% CI 2.7–6.0)] with results obtained at ages 70 and 75 as updated covariates. Baseline GDF-15 concentrations improved prognostic discrimination and reclassification [c-statistic 0.06 (P = 0.006); integrated discrimination improvement = 0.030 (P = 0.004); category-free net reclassification improvement = 0.281 (P = 0.006)]. Change in GDF-15 concentrations over time independently predicted even all-cause mortality occurring after age 75 [hazard ratio 3.6 (95% CI 2.2–6.0)].

    CONCLUSIONS:

    GDF-15 concentrations and their changes over time are powerful predictors of mortality in elderly community-dwelling individuals. GDF-15 concentrations increase with aging, and these changes are explained only partially by cardiovascular risk factors, indicators of neurohumoral activation and inflammation, and renal function. Thus GDF-15 reflects both cardiovascular and other biological processes closely related to longevity.

  • 32.
    Eggers, Kai M.
    et al.
    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.
    Oldgren, Jonas
    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, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pathophysiologic mechanisms of persistent cardiac troponin I elevation in stabilized patients after an episode of acute coronary syndrome2008In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 156, no 3, p. 588-594Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recently, a high prevalence of small persistent cardiac troponin I (cTnI) elevations has been reported in patients who had been stabilized after a recent episode of acute coronary syndrome (ACS). We now have studied the associations of persistently elevated cTnI levels to cardiac performance, inflammation, coagulation, coronary status, and treatment strategy in these patients. METHODS AND RESULTS: Cardiac troponin I was determined at 6 weeks, 3 months, and 6 months after randomization in 898 stabilized ACS patients from the FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC) II trial and using the high-sensitive Access AccuTnI assay (Beckman Coulter, Fullerton, CA). All patients were followed up for at least 5 years. Persistent cTnI elevation >0.01 microg/L at the 3 measurement instances was detected in 233 patients (26%). N-terminal pro-brain natriuretic peptide (NT-proBNP) at 6 months (OR 2.5, 95% CI 2.0-3.1), male sex (OR 2.2, 95% CI 1.4-3.7), and randomization to an early invasive strategy (OR 1.8, 95% CI 1.2-2.7) independently predicted persistently elevated cTnI levels. Persistently cTnI-positive patients in the invasive cohort had significantly lower NT-proBNP levels compared to noninvasively treated patients, indicating that the mechanisms causing cTnI elevation in this group may be prognostically less harmful. No independent associations were found for markers of inflammation or coagulation. CONCLUSION: Persistent cTnI elevation occurs frequently late after an ACS. The NT-proBNP level at 6 months was the strongest predictor for elevated cTnI levels that thus appear to be predominantly related to impaired left ventricular function.

  • 33.
    Eggers, Kai M.
    et al.
    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.
    Venge, Per
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Prognostic value of biomarkers during and after non-ST-segment elevation acute coronary syndrome2009In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 54, no 4, p. 357-364Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The aim of this study was to assess risk prediction by different biomarkers in patients with an ongoing non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and after clinical stabilization. BACKGROUND: Different biomarkers reflect different aspects of the pathobiology in NSTE-ACS. However, there is little information regarding their relative prognostic value during the time course of disease. METHODS: The N-terminal pro-brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP), cardiac troponin I (cTnI), and the estimated glomerular filtration rate (eGFR) were measured at randomization and after 6 weeks and 6 months in 877 NSTE-ACS patients included in the FRISC (FRagmin and fast revascularization during InStability in Coronary artery disease) II trial. The biomarkers' prognostic value during 5-year follow-up was evaluated by Cox regression models, calculation of the c-statistics, and estimation of the net reclassification improvement (NRI). RESULTS: Among the biomarkers measured at randomization, NT-proBNP was the strongest predictor for mortality (adjusted hazard ratio [HR]: 1.7; 95% confidence interval [CI]: 1.3 to 2.1; p < 0.001). Even during follow-up, NT-proBNP demonstrated the strongest association to the composite end point of death/myocardial infarction (adjusted HR at 6 weeks: 1.5; 95% CI: 1.3 to 1.7; p < 0.001; adjusted HR at 6 months: 1.4; 95% CI: 1.2 to 1.7; p = 0.001). Even CRP was independently predictive at 6 months for the composite end point (adjusted HR: 1.3; 95% CI: 1.1 to 1.5; p = 0.003). Only 6-week results of NT-proBNP provided significant incremental prognostic value to established risk indicators regarding the composite end point (c-statistics 0.69 [p = 0.03]; NRI 0.11 [p = 0.03]). CONCLUSIONS: The NT-proBNP is an independent risk predictor in patients with ongoing NSTE-ACS and after clinical stabilization. The CRP exhibits increasing predictive value at later measurements. However, only NT-proBNP provided incremental prognostic value and might therefore be considered as a complement for early follow-up controls after NSTE-ACS.

  • 34.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Ebeling Barbier, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    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.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Prevalence and pathophysiological mechanisms of elevated cardiac troponin 1 levels in a population-based sample of elderly subjects2008In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 29, no 18, p. 2252-2258Article in journal (Refereed)
    Abstract [en]

    AIMS: To evaluate the prevalence of cardiac troponin I (cTnI) elevation in an elderly community population and the association of cTnI levels with cardiovascular risk factors, vascular inflammation, atherosclerosis, cardiac performance, and areas indicative of infarcted myocardium identified by cardiac magnetic resonance imaging. METHODS AND RESULTS: cTnI elevation defined as cTnI levels >0.01 microg/L (Access AccuTnI, Beckman Coulter) was found in 21.8% of the study participants (n = 1005). cTnI > 0.01 microg/L was associated with cardiovascular high-risk features, the burden of atherosclerosis in the carotid arteries, left-ventricular mass, and impaired left-ventricular systolic function. No associations were found between cTnI and inflammatory activity, diastolic dysfunction, or myocardial scars. Male gender (OR 1.6; 95% CI 1.1-2.4), ischaemic ECG changes (OR 1.7; 95% CI 1.1-2.7), and NT-pro-brain natriuretic peptide levels (OR 1.4; 95% CI 1.1-1.7) independently predicted cTnI > 0.01 microg/L. cTnI > 0.01 microg/L correlated also to an increased cardiovascular risk according to the Framingham risk score. CONCLUSION: cTnI > 0.01 microg/L is relatively common in elderly subjects and is associated with cardiovascular high-risk features and impaired cardiac performance. Cardiac troponin determined by a highly sensitive assay might thus serve as an instrument for the identification of subjects at high cardiovascular risk in general populations.

  • 35.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Factors Influencing the 99th Percentile of Cardiac Troponin I Evaluated in Community-Dwelling Individuals at 70 and 75 Years of Age2013In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 59, no 7, p. 1068-1073Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

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

    METHODS:

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

    RESULTS:

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

    CONCLUSIONS:

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

  • 36.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    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.
    Will the universal definition of myocardial infarction criteria result in an overdiagnosis of myocardial infarction?2009In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 103, no 5, p. 588-591Article in journal (Refereed)
    Abstract [en]

    The Universal Definition of Myocardial Infarction (acute myocardial infarction [AMI]) requires detection of increasing or decreasing cardiac biomarkers (preferably cardiac troponin) with >or=1 value >99(th) percentile, together with either clinical symptoms, new ischemic electrocardiographic changes, or typical imaging findings indicative of myocardial necrosis as diagnostic criteria for AMI. However, a small cardiac troponin elevation together with ST-T segment abnormalities may also occur in clinically stable populations. Accordingly, 0.6% of elderly subjects from a community sample (PIVUS Study) and 6.7% of patients stabilized after an acute coronary syndrome (FRISC II Study) would have been labeled AMI following the Universal Definition of AMI when diagnostic classification had been based on a single cardiac troponin I result. In conclusion, our results emphasized the importance of a significant change in cardiac troponin to avoid misdiagnosis of AMI.

  • 37.
    Eggers, Kai M.
    et al.
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Application of Cardiac Troponin in Cardiovascular Diseases Other Than Acute Coronary Syndrome2017In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 1, p. 223-235Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Increased cardiac troponin concentrations in acute coronary syndrome (ACS) identify patients with ongoing cardiomyocyte necrosis who are at increased risk. However, with the use of more precise assays, cardiac troponin increases are commonly noted in other cardiovascular conditions as well. This has generated interest in the use of cardiac troponin for prognostic assessment and clinical management of these patients. In this review, we have summarized the data from studies investigating the implications of cardiac troponin concentrations in various acute and chronic conditions beyond ACS,, i.e., heart failure, myocarditis, Takotsubo cardiomyopathy, aortic dissection, supraventricular arrhythmias, valve disease, pulmonary arterial hypertension, stroke, and in the perioperative setting. CONTENT: Cardiac troponin concentrations are often detectable and frankly increased in non-ACS conditions, in particular when measured with high-sensitivity (hs) assays. With the exception of myocarditis and Takotsubo cardiomyopathy, cardiac troponin concentrations carry strong prognostic information, mainly with respect to mortality, or incipient and/or worsening heart failure. Studies investigating the prognostic benefit associated with cardiac troponin guided treatments however, are almost lacking and the potential role of cardiac troponin in the management of non-ACS conditions is not defined. SUMMARY: Increased cardiac troponin indicates increased risk for adverse outcome in patients with various cardiovascular conditions beyond ACS. Routine measurement of cardiac troponin concentrations can however, not be generally recommended unless there is a suspicion of ACS. Nonetheless, any finding of an increased cardiac troponin concentration in a patient without ACS should at least prompt the search for possible underlying conditions and these should be managed meticulously according to current guidelines to improve outcome.

  • 38.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    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.
    Prognostic Biomarkers in Acute Coronary Syndromes: Risk Stratification Beyond Cardiac Troponins2017In: Current Cardiology Reports, ISSN 1523-3782, E-ISSN 1534-3170, Vol. 19, no 4, article id 29Article, review/survey (Refereed)
    Abstract [en]

    Purpose of Review Cardiac troponin (cTn) plays an essential role for assessment of outcome in acute coronary syndrome (ACS). However, the prognostic value of cTn is not absolute. In this mini-review, we summarize the evidence on the utility of established biomarkers of left-ventricular dysfunction, hemodynamic stress, inflammation, and renal dysfunction for risk prediction beyond cTn in ACS. Recent Findings Only few biomarkers consistently demonstrate additive prognostic value to cTn levels. The B-type natriuretic peptides (NPs) and growth-differentiation factor-15 (GDF-15) are most promising in this regard. However, there are uncertainties regarding the role of these biomarkers for guidance of treatment decisions, and their prognostic increment to cTn levels measured with high-sensitivity assays is largely unknown. Summary The NPs and GDF-15 provide the strongest prognostic increment to cTn levels in ACS. However, the role of these biomarkers for clinical decision-making in contemporary settings has still to be defined.

  • 39.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Carrero, Juan J.
    Karolinska Inst, Div Renal Med, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Evans, Marie
    Karolinska Inst, Div Renal Med, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Szummer, Karolina
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Jernberg, Tomas
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Cardiac Troponins and Their Prognostic Importance in Patients with Suspected Acute Coronary Syndrome and Renal Dysfunction2017In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 8, p. 1409-1417Article in journal (Refereed)
    Abstract [en]

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

  • 40.
    Eggers, Kai M.
    et al.
    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, Clinical Chemistry.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    B-type natriuretic peptides and their relation to cardiovascular structure and function in a population-based sample of subjects aged 70 years2009In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 103, no 7, p. 1032-1038Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate whether B-type natriuretic peptides (BNPs) could serve as screening markers for the detection of preclinical vascular disease in the community. BNP and N-terminal-pro-BNP were analyzed in 1,000 subjects aged 70 years participating in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study and were related to different measures of endothelial function and activation, arterial compliance, carotid atherosclerosis, and echocardiographic findings. The median levels were 42.0 ng/L for BNP and 110.7 ng/L for N-terminal-pro-BNP. On adjusted multivariate analysis, the 2 BNPs were related to increased left ventricular mass and impaired left ventricular systolic and diastolic function but not to any of the other assessed entities reflecting preclinical vascular disease. In conclusion, BNPs are strong markers of increased left ventricular mass and impaired cardiac performance but cannot be regarded as useful screening markers for the detection of preclinical states of vascular disease in elderly subjects.

  • 41.
    Eggers, Kai M.
    et al.
    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.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Predictors of 10-year changes in levels of N-terminal pro B-type natriuretic peptide and cardiac troponin I in the elderly2018In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 257, p. 300-305Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 42.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Nygren, Magnus
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jernberg, Tomas
    Wikström, Bernt Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    High-sensitive troponin T and I are related to invasive hemodynamic data and mortality in patients with left-ventricular dysfunction and precapillary pulmonary hypertension2011In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 412, no 17-18, p. 1582-1588Article in journal (Refereed)
    Abstract [en]

    Background: High-sensitive (hs) cardiac troponin assays are clinically useful in various cardiac conditions. We aimed to extend current evidence by assessing the relations of hs-cardiac troponin T (hs-cTnT) and I (hs-cTnI) to invasive hemodynamic data and outcome in stable patients with left-ventricular (LV) dysfunction or precapillary pulmonary hypertension (PAH). Methods: Hs-cTnT (Roche Diagnostics) and hs-cTnI (Beckman-Coulter) were measured in 103 stable patients with LV-dysfunction and 56 patients with precapillary PAH referred for right-heart catheterization. Results: Up to 47.6% of patients with LV-dysfunction, and up to 37.5% of patients with precapillary PAH had hs-troponin levels above the respective 99th percentiles. In patients with LV-dysfunction, both hs-troponins exhibited significant associations to hemodynamics, NT-proBNP and mortality (hs-cTnT: age/sex-adjusted HR 2.0 [95% CI 1.3-3.1]: hs-cTnI: age/sex-adjusted HR 1.9 [1.2-2.8]). Both hs-troponins demonstrated weaker associations to hemodynamics in patients with precapillary PAH but correlated significantly to NT-proBNP. Mortality was only predicted by hs-cTnI (age/sex-adjusted HR 3.0 [1.5-6.1]). Conclusions: Hs-troponins are related to indices of impaired myocardial performance in patients with LV-dysfunction and precapillary PAH. Both hs-troponins were also predictive for mortality in patients with LV-dysfunction. In precapillary PAH, only hs-cTnI was independently prognostic which might depend on the superior analytical performance of this assay.

  • 43.
    Eggers, Kai M.
    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.
    Nordenskjöld, Anna
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Risk prediction in patients with chest pain: early assessment by the combination of troponin I results and electrocardiographic findings2005In: Coronary Artery Disease, ISSN 0954-6928, E-ISSN 1473-5830, Vol. 16, no 3, p. 181-9Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the prognostic value of point of care troponin I (TnI) results in combination with findings from the admission electrocardiogram (ECG) in patients with chest pain. METHODS: Rapid measurements of TnI were performed in 191 consecutive patients with chest pain and a non-diagnostic ECG for myocardial infarction. RESULTS: Within 6 h from admission, maximum TnI elevations of > or = 0.07 microg/l and > or = 0.1 microg/l were noted in 59 and 39% of all patients, respectively. TnI elevations in the range of 0.07-0.09 microg/l were found in many patients with diagnoses other than acute coronary syndrome. By 6-month follow-up, cardiac death had occurred in 7.1 and 11% of patients with maximum TnI > or = 0.07 microg/l and > or = 0.1 microg/l, respectively and myocardial reinfarction was documented in 12 and 15%, respectively. ST-segment depression on the admission ECG was present in 16% of all patients and was the electrocardiographic abnormality with the highest risk (cardiac death 7.7%, myocardial reinfarction 15%). The combination of TnI > or = 0.1 microg/l and ST-segment depression or an abnormal admission ECG in general allowed the identification of patients at low, intermediate and high cardiac risk, 3 h after admission. CONCLUSION: A threshold of TnI > or = 0.1 microg/l corresponding to the 10% coefficient of variation is prognostically most suitable for prediction of cardiac events in patients with chest pain. The combination of TnI results and findings from the admission ECG improves prognostic assessment and allows early and reliable risk stratification in this patient population.

  • 44.
    Eggers, Kai M.
    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.
    Nordensköld, Anna
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Combining different biochemical markers of myocardial ischemia does not improve risk stratification in chest pain patients compared to troponin I alone2005In: Coronary Artery Disease, ISSN 0954-6928, E-ISSN 1473-5830, Vol. 16, no 5, p. 315-9Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Early evaluation of patients with chest pain is important not only for the detection of acute myocardial infarction (AMI) but also for identification of patients at high risk for future cardiac events. A multimarker strategy applying results of early measurements of different biochemical markers of cardiac necrosis in combination may improve risk prediction in chest pain patients. METHODS: Rapid measurements of troponin I (TnI), creatine kinase MB and myoglobin were performed in 191 consecutive patients with chest pain and a non-diagnostic electrocardiogram for AMI. The prognostic value of these markers and different multimarker strategies was evaluated and compared. RESULTS: Ten (5.2%) patients died during follow-up, which for eight (4.2%) patients was due to cardiac causes. Myocardial reinfarctions occurred in 17 (6.8%) patients. TnI was most predictive for cardiac mortality (TnI>or=0.1 microg/l, 10.7% event rate compared with TnI<0.1 microg/l, 0%, P<0.001) and myocardial reinfarction (14.9% compared with 1.7%, P<0.001). The other markers and multimarker strategies had a lower capacity for predicting adverse events apart from myoglobin and the combination of TnI or myoglobin regarding the endpoint of total mortality. CONCLUSION: The combinations of different markers were prognostically non-superior compared to TnI, which thus, should be preferred as a biochemical marker for risk stratification in patients with chest pain.

  • 45.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Utility of B-type natriuretic peptides and cardiac troponins for population screening regarding cardiac abnormalities2012In: Pathology (Sydney), ISSN 0031-3025, E-ISSN 1465-3931, Vol. 44, no 2, p. 129-138Article in journal (Refereed)
    Abstract [en]

    AIMS:

    The increasing importance of cardiac disease has generated an interest in improved screening strategies regarding preclinical cardiac abnormalities and employing measurement of circulating biomarkers. This review focuses on the utility of the B-type natriuretic peptides (NP) and the cardiac troponins (cTns) for this purpose.

    RESULTS:

    Both the NPs and the cTns are closely related to cardiac structural and functional abnormalities that may progress to symptomatic heart disease, e.g., left ventricular (LV) hypertrophy, LV systolic and diastolic dysfunction. Both biomarkers provide incremental information to each other. However, biomarker results may be confounded by several non-cardiac conditions, and decision thresholds and recommendations on further clinical work-up are as yet not specified. Furthermore, cost issues will probably preclude widespread biomarker screening in general populations.

    CONCLUSIONS:

    Measurement of the NPs or cTns is an attractive option for screening for cardiac abnormalities. This may be particularly effective in patients at higher risk for developing overt heart disease. Nevertheless, appropriate diagnostic and therapeutic responses to biomarker results need to be defined before routine screening can be recommended in the community setting.

  • 46.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Mid-regional pro-atrial natriuretic peptide levels in the elderly: Clinical and prognostic implications, and comparison to B-type natriuretic peptides2013In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 419, p. 62-66Article in journal (Refereed)
    Abstract [en]

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

  • 47.
    Eggers, Kai M
    et al.
    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.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Prognostic Usefulness of the Change in N-terminal pro B-type Natriuretic Peptide Levels to Predict Mortality in a Single Community Cohort Aged ≥70 Years2013In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 111, no 1, p. 131-136Article in journal (Refereed)
    Abstract [en]

    The levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) are closely related to cardiac abnormalities and adverse outcomes in the general population. However, little is known about the course of NT-proBNP levels over time, the underlying conditions, and the prognostic effect of changes. To investigate these issues, we measured the NT-proBNP levels (Elecsys 2010, Roche Diagnostics) in community-dwellers participating in the Prospective Investigation of the Vasculature in Uppsala Seniors study at 70 (n = 1,005) and 75 (n = 817) years of age. The total follow-up was 8.0 years. In subjects with available results from both examinations, the median NT-proBNP levels increased from 106 pg/ml (25th to 75th percentile 62 to 174) to 125 pg/ml (25th to 75th percentile 73-234; p <0.001). The change in NT-proBNP levels was positively and independently related to male gender, baseline information on ischemic electrocardiographic changes, renal dysfunction, impaired left ventricular ejection fraction, and intercurrent cardiovascular events (e.g., myocardial infarction, stroke, or coronary revascularization). The change in NT-proBNP levels independently predicted mortality after the measurements at 75 years of age (all-cause mortality, adjusted hazard ratio 2.4, 95% confidence interval 1.6 to 3.6; cardiovascular mortality, adjusted hazard ratio 2.3, 95% confidence interval 1.2 to 4.5). Compared to those without significant NT-proBNP changes (n = 606), subjects with increasing levels (n = 162) had markedly increased all-cause mortality (adjusted hazard ratio 4.3, 95% confidence interval 2.1 to 8.8). No subject with decreasing NT-proBNP levels (n = 49) died. In conclusion, repeat measurements of NT-proBNP might add useful information to the routine clinical assessment in subjects aged ≥70 years, because changes in their levels were associated with cardiovascular risk indicators and strongly predictive of mortality.

  • 48.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lindahl, Bertil
    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.
    High-sensitive cardiac troponin T outperforms novel diagnostic biomarkers in patients with acute chest pain2012In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 413, no 13-14, p. 1135-1140Article in journal (Refereed)
    Abstract [en]

    Background: Measurement of high-sensitive cardiac troponin (hs-cTn) has facilitated the early diagnostic assessment of chest pain patients. However, the information obtained from hs-cTnT levels might be improved when combined with results of other biomarkers of myocardial injury.

    Methods: We measured admission levels of hs-cTnT (Roche Diagnostics), heart-type fatty-acid binding protein (H-FABP; Randox Laboratories) and copeptin using a novel ultra-sensitive (us) assay (Thermo Fisher Scientific) in 360 chest pain patients with a non-diagnostic ECG. Non-STEMI was defined according to the Universal Definition using cardiac troponin I (Stratus CS; Siemens Healthcare Diagnostics) as biochemical gold standard.

    Results: Non-STEMI was diagnosed in 128 (36%) patients. Hs-cTnT had a greater diagnostic accuracy regarding non-STEMI (C-statistics 0.84) compared to H-FABP (C-statistics 0.80; p = 0.04) and us-copeptin C-statistics(0.62; p < 0.001). Compared to hs-cTnT alone, no increase in the C-statistics was noted for the combination of hs-cTnT with H-FABP (0.85; p = 0.43) or with us-copeptin (0.84; p = 0.88). Due to suboptimal sensitivities and/or specificities, neither H-FABP nor us-copeptin dichotomized at commonly applied diagnostic thresholds added information to hs-cTnT that would have facilitated early diagnostic assessment.

    Conclusions: Hs-cTnT provides an excellent early diagnostic accuracy regarding non-STEMI already on admission. Neither H-FABP nor us-copeptin perform better or provide diagnostic increment to hs-cTnT levels.

  • 49.
    Eggers, Kai M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Associations of mid-regional pro-adrenomedullin levels to cardiovascular and metabolic abnormalities, and mortality in an elderly population from the community2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, no 4, p. 3537-3542Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

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

    METHODS AND RESULTS:

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

    CONCLUSIONS:

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

  • 50.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Cardiac troponin I levels measured with a high-sensitive assay increase over time and are strong predictors of mortality in an elderly population2013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 61, no 18, p. 1906-1913Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

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

    OBJECTIVES:

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

    METHODS:

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

    RESULTS:

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

    CONCLUSIONS:

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

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