Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium

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Abstract

Aims

Our aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively.

Methods and results

Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, we analysed individual level data from 10 prospective population-based studies including 74 738 participants. We investigated the value of adding troponin I levels to conventional risk factors for prediction of cardiovascular disease by calculating measures of discrimination ( C-index) and net reclassification improvement (NRI). We further tested the clinical implication of statin therapy based on troponin concentration in 12 956 individuals free of cardiovascular disease in the JUPITER study. Troponin I remained an independent predictor with a hazard ratio of 1.37 for cardiovascular mortality, 1.23 for cardiovascular disease, and 1.24 for total mortality. The addition of troponin I information to a prognostic model for cardiovascular death constructed of ESC SCORE variables increased the C-index discrimination measure by 0.007 and yielded an NRI of 0.048, whereas the addition to prognostic models for cardiovascular disease and total mortality led to lesser C-index discrimination and NRI increment. In individuals above 6 ng/L of troponin I, a concentration near the upper quintile in BiomarCaRE (5.9 ng/L) and JUPITER (5.8 ng/L), rosuvastatin therapy resulted in higher absolute risk reduction compared with individuals <6 ng/L of troponin I, whereas the relative risk reduction was similar.

Conclusion

In individuals free of cardiovascular disease, the addition of troponin I to variables of established risk score improves prediction of cardiovascular death and cardiovascular disease.

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Most cited references 18

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Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial.

Eoin O'Connell, Elaine Tallon, Kenneth McDonald … (2013)

Prevention strategies for heart failure are needed. To determine the efficacy of a screening program using brain-type natriuretic peptide (BNP) and collaborative care in an at-risk population in reducing newly diagnosed heart failure and prevalence of significant left ventricular (LV) systolic and/or diastolic dysfunction. The St Vincent's Screening to Prevent Heart Failure Study, a parallel-group randomized trial involving 1374 participants with cardiovascular risk factors (mean age, 64.8 [SD, 10.2] years) recruited from 39 primary care practices in Ireland between January 2005 and December 2009 and followed up until December 2011 (mean follow-up, 4.2 [SD, 1.2] years). Patients were randomly assigned to receive usual primary care (control condition; n=677) or screening with BNP testing (n=697). Intervention-group participants with BNP levels of 50 pg/mL or higher underwent echocardiography and collaborative care between their primary care physician and specialist cardiovascular service. The primary end point was prevalence of asymptomatic LV dysfunction with or without newly diagnosed heart failure. Secondary end points included emergency hospitalization for arrhythmia, transient ischemic attack, stroke, myocardial infarction, peripheral or pulmonary thrombosis/embolus, or heart failure. A total of 263 patients (41.6%) in the intervention group had at least 1 BNP reading of 50 pg/mL or higher. The intervention group underwent more cardiovascular investigations (control, 496 per 1000 patient-years vs intervention, 850 per 1000 patient-years; incidence rate ratio, 1.71; 95% CI, 1.61-1.83; P<.001) and received more renin-angiotensin-aldosterone system-based therapy at follow-up (control, 49.6%; intervention, 56.5%; P=.01). The primary end point of LV dysfunction with or without heart failure was met in 59 (8.7%) of 677 in the control group and 37 (5.3%) of 697 in the intervention group (odds ratio [OR], 0.55; 95% CI, 0.37-0.82; P = .003). Asymptomatic LV dysfunction was found in 45 (6.6%) of 677 control-group patients and 30 (4.3%) of 697 intervention-group patients (OR, 0.57; 95% CI, 0.37-0.88; P = .01). Heart failure occurred in 14 (2.1%) of 677 control-group patients and 7 (1.0%) of 697 intervention-group patients (OR, 0.48; 95% CI, 0.20-1.20; P = .12). The incidence rates of emergency hospitalization for major cardiovascular events were 40.4 per 1000 patient-years in the control group vs 22.3 per 1000 patient-years in the intervention group (incidence rate ratio, 0.60; 95% CI, 0.45-0.81; P = .002). Among patients at risk of heart failure, BNP-based screening and collaborative care reduced the combined rates of LV systolic dysfunction, diastolic dysfunction, and heart failure. clinicaltrials.gov Identifier: NCT00921960.

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Net reclassification improvement: computation, interpretation, and controversies: a literature review and clinician's guide.

Ewout W. Steyerberg, Moniek Vedder, Jacqueline Witteman … (2014)

The net reclassification improvement (NRI) is an increasingly popular measure for evaluating improvements in risk predictions. This article details a review of 67 publications in high-impact general clinical journals that considered the NRI. Incomplete reporting of NRI methods, incorrect calculation, and common misinterpretations were found. To aid improved applications of the NRI, the article elaborates on several aspects of the computation and interpretation in various settings. Limitations and controversies are discussed, including the effect of miscalibration of prediction models, the use of the continuous NRI and “clinical NRI,” and the relation with decision analytic measures. A systematic approach toward presenting NRI analysis is proposed: Detail and motivate the methods used for computation of the NRI, use clinically meaningful risk cutoffs for the category-based NRI, report both NRI components, address issues of calibration, and do not interpret the overall NRI as a percentage of the study population reclassified. Promising NRI findings need to be followed with decision analytic or formal cost-effectiveness evaluations.

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Prognostic value of cardiac troponin I measured with a highly sensitive assay in patients with stable coronary artery disease.

Marc Pfeffer, Eugene Braunwald, Torbjørn Omland … (2013)

The aims of this study were to assess the prognostic value of cardiac troponin I levels, measured with a new high-sensitivity assay, in low-risk patients with stable coronary artery disease (CAD) and to contrast its determinants and prognostic merit with that of high-sensitivity cardiac troponin T (hs-TnT). New, highly sensitive cardiac troponin assays permit evaluation of the association between troponin levels and outcomes in patients with stable CAD. High-sensitivity cardiac troponin I (hs-TnI) levels at baseline were assessed in 3,623 patients with stable CAD and preserved systolic function enrolled in the PEACE (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy) trial. In total, 98.5% of patients had hs-TnI concentrations higher than the detection level (1.2 pg/ml). hs-TnI correlated moderately with hs-TnT (r = 0.44) and N-terminal pro-B-type natriuretic peptide (r = 0.39) but only weakly with age (r = 0.17) and estimated glomerular filtration rate (r = -0.11). During a median follow-up period of 5.2 years, 203 patients died of cardiovascular causes or were hospitalized for heart failure, and 209 patients had nonfatal myocardial infarctions. In analyses adjusting for conventional risk markers, N-terminal pro-B-type natriuretic peptide, and hs-TnT, hs-TnI levels in the fourth compared with the 3 lower quartiles were associated with the incidence of cardiovascular death or heart failure (hazard ratio: 1.84; 95% confidence interval: 1.30 to 2.61; p < 0.001). [corrected]. There was a [corrected] weaker association with nonfatal myocardial infarction (hazard ratio: 1.37; 95% confidence interval: 0.98 to 1.92; p = 0.066). [corrected]. In the same models, hs-TnT concentrations were associated with the incidence of cardiovascular death or heart failure but not of myocardial infarction. In patients with stable CAD, hs-TnI concentrations are associated with cardiovascular risk independently of conventional risk markers and hs-TnT. (Prevention of Events With Angiotensin-Converting Enzyme Inhibitor Therapy [PEACE]; NCT00000558). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): Eur Heart J

Journal ID (iso-abbrev): Eur. Heart J

Journal ID (publisher-id): eurheartj

Journal ID (hwp): ehj

Title: European Heart Journal

Publisher: Oxford University Press

ISSN (Print): 0195-668X

ISSN (Electronic): 1522-9645

Publication date (Print): 07 August 2016

Publication date (Electronic): 12 May 2016

Publication date PMC-release: 12 May 2016

Volume: 37

Issue: 30 , Focus Issue on Troponin

Pages: 2428-2437

Affiliations

[1 ]University Heart Center Hamburg, Clinic for General and Interventional Cardiology , Hamburg, Germany

[2 ]German Center for Cardiovascular Research (DZHK e.V.), partner site Hamburg , Lübeck, Kiel, Hamburg, Germany

[3 ]National Institute for Health and Welfare , Helsinki, Finland

[4 ]Department of Medicine II, Preventive Cardiology and Preventive Medicine, University Medical Center of the Johannes Gutenberg-University Mainz , Mainz, Germany

[5 ]University Medical Center of the Johannes Gutenberg-University Mainz, Center for Thrombosis and Haemostasis (CTH) , Mainz, Germany

[6 ]German Center for Cardiovascular Research (DZHK), Partner Site Rhein-Main , Mainz, Germany

[7 ]University Medical Center Mainz, Institute for Clinical Chemistry and Laboratory Medicine , Mainz, Germany

[8 ]Department of Public Health, Faculty of Health and Medical Science, University of Copenhagen , Copenhagen, Denmark

[9 ]Research Centre for Prevention and Health , Capital Region, Denmark

[10 ]Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology II , München, Germany

[11 ]German Center for Cardiovascular Research (DZHK e.V.), Partner Site Munich Heart Alliance , München, Germany

[12 ]University Medicine Greifswald, Institute for Clinical Chemistry and Laboratory Medicine , Greifswald, Germany

[13 ]German Center for Cardiovascular Research (DZHK e.V.), Partner Site Greifswald , Greifswald, Germany

[14 ]Chronic Disease Epidemiology and Prevention Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare , Helsinki, Finland

[15 ]Department of Clinical and Experimental Medicine, Research Centre in Epidemiology and Preventive Medicine, University of Insubria , Varese, Italy

[16 ]Department of Laboratory Medicine, Hospital of Desio, University of Milano Bicocca , Desio (MB), Italy

[17 ]IRCCS Istituto Neurologico Mediterraneo Neuromed, Department of Epidemiology and Prevention, Laboratory of Molecular and Nutritional Epidemiology , Pozzilli, Isernia, Italy

[18 ]Queens University of Belfast, UK Clinical Research Collaboration Centre of Excellence for Public Health , Belfast, UK

[19 ]Queens University of Belfast, Centre for Public Health Belfast , Belfast, UK

[20 ]Brigham and Women's Hospital , Cardiovascular and Preventive Medicine Divisions, Boston, USA

[21 ]University of Ulm Medical Centre , Department of Internal Medicine II-Cardiology, Ulm, Germany

[22 ]German Heart Centre Munich, Technical University of Munich , München, Germany

Author notes

[* ]Corresponding author. Tel: +49 407410 56800, Fax: +49 407410 53622, Email: s.blankenberg@ 123456uke.de

[†]

Authors contributed equally as first author of the manuscript.

[‡]

Authors contributed equally as last author of the manuscript.

Article

Publisher ID: ehw172

DOI: 10.1093/eurheartj/ehw172

PMC ID: 4982535

PubMed ID: 27174290

SO-VID: 13a58194-defb-4c45-b632-3275e32a882c

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

History

Date received : 23 October 2015

Date revision received : 12 February 2016

Date accepted : 24 March 2016

Funding

Funded by: the European Union Seventh Framework Programme;

Award ID: FP7/2007–2013

Award ID: HEALTH-F2-2011-278913

Funded by: European Union FP 7 project CHANCES;

Award ID: HEALTH-F3-2010-242244

Funded by: the Medical Research Council London;

Award ID: G0601463

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Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium

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Abstract

Aims

Methods and results

Conclusion

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Cardiovascular Innovations and Applications

Most cited references 18

Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial.

Net reclassification improvement: computation, interpretation, and controversies: a literature review and clinician's guide.

Prognostic value of cardiac troponin I measured with a highly sensitive assay in patients with stable coronary artery disease.

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Cited by 71

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