Original Article
Arthritis Care & Research DOI 10.1002/acr.22547
Cardiac biomarkers in systemic sclerosis: contribution of high-sensitivity cardiac troponin in addition to N-terminal pro-brain natriuretic peptide Jérôme Avouac (MD, PhD), Christophe Meune (MD, PhD), Camille Chenevier-Gobeaux (PharmD, PhD), Didier Borderie (MD, PhD), Guillaume Lefevre (MD), André Kahan (MD, PhD), Yannick Allanore (MD, PhD). Jérôme Avouac and Yannick Allanore: Paris Descartes University, Sorbonne Paris Cité, Rheumatology A department, Cochin Hospital, Paris, France and Paris Descartes University, INSERM U1016 and CNRS UMR8104, Cochin Institute, Paris, France Christophe Meune: Paris 13 University, University Hospital of Paris-Seine-Saint-Denis, Cardiology Department, Bobigny, France and UMR 942, Paris, France Camille Chenevier-Gobeaux and Didier Borderie: Clinical Chemistry Laboratory, Cochin and Hôtel-Dieu Hospitals, Paris, France Guillaume Lefevre: Clinical Chemistry and Hormonology Department, Tenon Hospital, Paris, France André Kahan: Paris Descartes University, Sorbonne Paris Cité, Rheumatology A department, Cochin Hospital, Paris, France Key Indexing Terms: systemic sclerosis, cardiac involvement, pulmonary hypertension, biomarker, high sensitivity cardiac troponin, NT-proBNP, myocardial injury, myocardial dysfunction The authors declare to have no conflicts of interest. Funding: This research received no funding Corresponding author: Dr. Jérôme Avouac, MD, PhD Service de Rhumatologie A, Hôpital Cochin Université Paris Descartes 27 rue du Faubourg Saint-Jacques 75014 Paris, France Telephone: + 33 1 58.41.25.63 Fax: + 33 1 58.41.26.24 e-mail: [email protected] Running Head: Cardiac biomarkers in systemic sclerosis Word count: Abstract words: 230; Manuscript words: 2929; number of tables and figures: 6, Supplemental file: 2
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/acr.22547 © 2015 American College of Rheumatology Received: Apr 4, 2015; Revised: Dec 15, 2015; Accepted: Jam 06, 2015
This article is protected by copyright. All rights reserved.
Arthritis Care & Research
Page 2 of 29
Abstract Objective: i) To measure plasma concentrations of high-sensitivity cardiac troponin T (HScTnT) and N-terminal fragment of pro-BNP (NT-proBNP) in patients with systemic sclerosis (SSc) and age-sex matched healthy controls, ii) To examine the contribution of traditional cardiovascular risk factor and SSc features to the concentrations of these two cardiac biomarkers. Methods: Plasma HS-cTnT and NT-proBNP concentrations were measured using electrochemiluminescence and sandwich immunoassay, respectively. Results: we included 161 unrelated SSc patients and 213 matched controls. HS-cTnT and NT-proBNP plasma levels were significantly increased in SSc patients versus controls (p14 ng/L. Increased NT-proBNP concentrations were only associated with the presence of precapillary PH (p30 kg/m2, treated/untreated hypertension, known/symptoms of coronary artery disease, diabetes, dyslipidemia, and plasma creatinine values above the normal range. The local ethics committees approved the study and all the subjects gave written informed consent. Clinical assessment: Detailed information was collected in all participating patients, including age, sex, cutaneous SSc subset, disease duration (date of first non-Raynaud’s symptom), history of digital ulceration, and current and past medication use, which was obtained from information provided by patients, and based on the review of medical records. Laboratory assessments: Laboratory studies were obtained at baseline, on the morning of hospital admission. They included complete blood cell count, Westergren erythrocyte sedimentation rate (ESR, considered elevated above 28mm Hour-1), C-reactive protein level (CRP, considered elevated above 10mg/l), serum creatinine concentration, and tests for antinuclear, anticentromere antibodies (both detected in immunofluorescence on Hep2 cells) and antitopoisomerase I antibodies (counter immuno-electrophoresis).
John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.
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Page 7 of 29
Arthritis Care & Research
Pulmonary and cardiac assessment: Pulmonary involvement was assessed by chest radiography, computed tomography, measurements of forced vital capacity (FVC) and the carbon monoxide diffusion capacity (DLCO). Echocardiography was performed by a senior cardiologist (CM) according to the American Society of Echocardiography recommendations. In particular, left ventricular ejection fraction (LVEF) was determined using the Simpson method and systolic PAP (sPAP) was based on the tricuspid and/or pulmonary regurgitation, adding 10 mmHg for auricular pressure. Right heart catheterization (RHC) was systematically performed in case of suspicion of pulmonary hypertension, which was considered in patients with a) an estimated echocardiographic systolic pulmonary arterial pressure (sPAP, based on transtricuspid gradient, assessed by continuous doppler flow, adding 10 mmHg for right atrial pressure) >40 mmHg OR b) a DLCO
Arthritis Care & Research DOI 10.1002/acr.22547
Cardiac biomarkers in systemic sclerosis: contribution of high-sensitivity cardiac troponin in addition to N-terminal pro-brain natriuretic peptide Jérôme Avouac (MD, PhD), Christophe Meune (MD, PhD), Camille Chenevier-Gobeaux (PharmD, PhD), Didier Borderie (MD, PhD), Guillaume Lefevre (MD), André Kahan (MD, PhD), Yannick Allanore (MD, PhD). Jérôme Avouac and Yannick Allanore: Paris Descartes University, Sorbonne Paris Cité, Rheumatology A department, Cochin Hospital, Paris, France and Paris Descartes University, INSERM U1016 and CNRS UMR8104, Cochin Institute, Paris, France Christophe Meune: Paris 13 University, University Hospital of Paris-Seine-Saint-Denis, Cardiology Department, Bobigny, France and UMR 942, Paris, France Camille Chenevier-Gobeaux and Didier Borderie: Clinical Chemistry Laboratory, Cochin and Hôtel-Dieu Hospitals, Paris, France Guillaume Lefevre: Clinical Chemistry and Hormonology Department, Tenon Hospital, Paris, France André Kahan: Paris Descartes University, Sorbonne Paris Cité, Rheumatology A department, Cochin Hospital, Paris, France Key Indexing Terms: systemic sclerosis, cardiac involvement, pulmonary hypertension, biomarker, high sensitivity cardiac troponin, NT-proBNP, myocardial injury, myocardial dysfunction The authors declare to have no conflicts of interest. Funding: This research received no funding Corresponding author: Dr. Jérôme Avouac, MD, PhD Service de Rhumatologie A, Hôpital Cochin Université Paris Descartes 27 rue du Faubourg Saint-Jacques 75014 Paris, France Telephone: + 33 1 58.41.25.63 Fax: + 33 1 58.41.26.24 e-mail: [email protected] Running Head: Cardiac biomarkers in systemic sclerosis Word count: Abstract words: 230; Manuscript words: 2929; number of tables and figures: 6, Supplemental file: 2
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/acr.22547 © 2015 American College of Rheumatology Received: Apr 4, 2015; Revised: Dec 15, 2015; Accepted: Jam 06, 2015
This article is protected by copyright. All rights reserved.
Arthritis Care & Research
Page 2 of 29
Abstract Objective: i) To measure plasma concentrations of high-sensitivity cardiac troponin T (HScTnT) and N-terminal fragment of pro-BNP (NT-proBNP) in patients with systemic sclerosis (SSc) and age-sex matched healthy controls, ii) To examine the contribution of traditional cardiovascular risk factor and SSc features to the concentrations of these two cardiac biomarkers. Methods: Plasma HS-cTnT and NT-proBNP concentrations were measured using electrochemiluminescence and sandwich immunoassay, respectively. Results: we included 161 unrelated SSc patients and 213 matched controls. HS-cTnT and NT-proBNP plasma levels were significantly increased in SSc patients versus controls (p14 ng/L. Increased NT-proBNP concentrations were only associated with the presence of precapillary PH (p30 kg/m2, treated/untreated hypertension, known/symptoms of coronary artery disease, diabetes, dyslipidemia, and plasma creatinine values above the normal range. The local ethics committees approved the study and all the subjects gave written informed consent. Clinical assessment: Detailed information was collected in all participating patients, including age, sex, cutaneous SSc subset, disease duration (date of first non-Raynaud’s symptom), history of digital ulceration, and current and past medication use, which was obtained from information provided by patients, and based on the review of medical records. Laboratory assessments: Laboratory studies were obtained at baseline, on the morning of hospital admission. They included complete blood cell count, Westergren erythrocyte sedimentation rate (ESR, considered elevated above 28mm Hour-1), C-reactive protein level (CRP, considered elevated above 10mg/l), serum creatinine concentration, and tests for antinuclear, anticentromere antibodies (both detected in immunofluorescence on Hep2 cells) and antitopoisomerase I antibodies (counter immuno-electrophoresis).
John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.
6
Page 7 of 29
Arthritis Care & Research
Pulmonary and cardiac assessment: Pulmonary involvement was assessed by chest radiography, computed tomography, measurements of forced vital capacity (FVC) and the carbon monoxide diffusion capacity (DLCO). Echocardiography was performed by a senior cardiologist (CM) according to the American Society of Echocardiography recommendations. In particular, left ventricular ejection fraction (LVEF) was determined using the Simpson method and systolic PAP (sPAP) was based on the tricuspid and/or pulmonary regurgitation, adding 10 mmHg for auricular pressure. Right heart catheterization (RHC) was systematically performed in case of suspicion of pulmonary hypertension, which was considered in patients with a) an estimated echocardiographic systolic pulmonary arterial pressure (sPAP, based on transtricuspid gradient, assessed by continuous doppler flow, adding 10 mmHg for right atrial pressure) >40 mmHg OR b) a DLCO
