International Journal of Cardiology 191 (2015) 229–230
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Elevated high-sensitive cardiac troponin T levels are associated with low skeletal muscle mass in abdominal surgical oncology patients at risk for coronary artery disease Jeroen L.A. van Vugt a,b,⁎, Djamila Boerma b, Ineke M. Dijkstra c, Thomas L. Bollen d, Frank D. Eefting e, Jan N.M. IJzermans a, Peter G. Noordzij f a
Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands Department of Surgery, St Antonius Hospital, Nieuwegein, The Netherlands c Department of Clinical Chemistry, St Antonius Hospital, Nieuwegein, The Netherlands d Department of Radiology, St Antonius Hospital, Nieuwegein, The Netherlands e Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands f Department of Anesthesiology, Intensive Care and Pain Medicine, St Antonius Hospital, Nieuwegein, The Netherlands b
a r t i c l e
i n f o
Article history: Received 22 April 2015 Accepted 7 May 2015 Available online 8 May 2015 Keywords: Sarcopenia Cachexia Cancer Muscle mass Myocardial injury Cardiac troponin
(i.e. postoperative mortality rate N 3%), demonstrated that 31% of the study participants had elevated baseline high-sensitive cardiac troponin T (hs-cTnT) levels (i.e. ≥ 0.014 μg L− 1) [7]. We hypothesized that abdominal cancer patients with a low skeletal muscle mass are at increased risk for preoperative (baseline) myocardial injury, as expressed in elevated troponin levels, compared with patients with a normal skeletal muscle mass. Therefore, we conducted a post-hoc analysis of patients enrolled into the MICOLON study who underwent abdominal surgery for cancer and had an abdominal CT scan available. Patients eligible for the MICOLON study were aged ≥ 45 year and had at least one major or two minor cardiac risk factors [7]. Hs-cTnT
Up to 80% of patients with advanced cancer are affected by cancerinduced cachexia, a clinical condition that results in skeletal muscle wasting with or without accompanying loss of adipose tissue [1]. Patients with congestive heart failure are also prone to skeletal muscle wasting [2]. Visa versa, animal studies suggest that cancer not only can induce skeletal muscle wasting, but can also induce cardiac muscle wasting [3,4]. Therefore, it is suggested that bilateral effects exist; on the one hand heart failure may result in skeletal muscle wasting, and on the other hand cancer-induced cachexia may lead to cardiac muscle wasting, possibly resulting in further deterioration of cardiac function [3]. This could be an explanation for the similar symptomatology (i.e. dyspnea, fatigue, impaired exercise capacity, and weight loss) and shared risk factors to develop cachexia of cancer and chronic heart failure patients [5,6]. The MICOLON study, investigating myocardial injury and non-cardiac complications after major abdominal surgery
⁎ Corresponding author at: Department of Surgery, Erasmus University Medical Center, Wytemaweg 80, 3015 CE Rotterdam, The Netherlands. E-mail address: [email protected] (J.L.A. van Vugt).
http://dx.doi.org/10.1016/j.ijcard.2015.05.035 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
Fig. 1. Preoperative hs-cTnT level and L3 muscle index showed a significant negative correlation (p = 0.029). Dotted line: hs-cTnT level of 0.014 μg L−1.
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J.L.A. van Vugt et al. / International Journal of Cardiology 191 (2015) 229–230
Table 1 Multivariable logistic regression analysis using a stepwise method (Forward: Conditional) for risk factors for elevated preoperative hs-cTnT levels (≥0.014 μg L−1). Bold values indicate significance at p b 0.05.
Sarcopenia (yes) Age (years) Gender (male) BMI (kg2/m2) Medical history of congestive heart failure Medical history of atrial fibrillation Preoperative eGFR (ml/min/1.73 m2) ASA classification POSSUM†
Univariate OR (95% CI)
p-Value
Multivariable OR (95% CI)
p-Value
10.00 (3.28–30.50) 1.23 (1.14–1.32) 1.89 (0.80–4.50) 0.88 (0.8–0.97) 7.28 (1.44–36.71) 4.30 (1.57–11.77) 0.97 (0.96–0.99) 3.04 (1.40–6.59) 1.07 (1.02–1.11)
b0.001 b0.001 0.150 0.011 0.016 0.005 0.001 0.005 0.004
11.75 (2.60–53.05) 1.22 (1.12–1.34)
0.001 b0.001
22.53 (2.03–250.15)
0.011
0.96 (0.94–0.99)
0.002
Abbreviations: BMI: body mass index; eGFR: estimated glomerular filtration rate; ASA: American Society of Anesthesiologists; POSSUM: Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity; OR: odds ratio; CI: confidence interval.
measurements were performed in blood samples collected after induction of general anesthesia using the fifth generation Elecsys Troponin T high sensitive assay on an automated Cobas 6000 platform (Roche Diagnostics, Germany). Hs-cTnT levels ≥0.014 μg L−1 were considered elevated. The cross-sectional skeletal muscle area (cm2) was assessed at the level of the third lumbar vertebra (L3) on preoperative abdominal computed tomography (CT) scans on a transverse slice showing both transversal processes, using MeVisLab FatSeg (MeVis Medical Solutions, Bremen, Germany). The distinction between different tissues was based on Hounsfield units (HU). For skeletal muscle, a threshold range of −30 to +150 HU was used. Measurements included the psoas, paraspinal, transverse abdominal, external oblique, internal oblique, and rectus abdominis muscles. The cross-sectional muscle area was corrected for height, as is conventional for body composition measurements. This resulted in the L3 muscle index (cm2/m2). Patients were classified as sarcopenic (i.e. low skeletal muscle mass) and non-sarcopenic according to sex-specific cutoff values defined by Prado et al. (38.5 cm2/m2 for women and 52.4 cm2/m2 for men) [8]. Measurements were performed by a medically trained member of the study group who was blinded for outcomes. Written informed consent was obtained from each patient. The study has been approved by the local medical ethical committee and was performed according to the ethical guidelines of the 1975 Declaration of Helsinki. In total, 126 patients were eligible for this study. Forty-five (35.7%) patients had elevated preoperative hs-cTnT levels and 82 (65.1%) of patients were sarcopenic. Preoperative hs-cTnT and L3 muscle index showed a significant negative correlation (R2 = 0.038; p = 0.029) (Fig. 1). Patients with elevated hs-cTnT levels showed a significantly lower L3 muscle index (44.2 cm2/m2 versus 48.5 cm2/m2; p = 0.001) and higher rate of sarcopenia (91.1% versus 8.9%; p b 0.001) compared with patients with normal baseline hs-cTnT levels. Moreover, nineteen of the sarcopenic patients (23.2%) had a hs-cTnT level ≥0.020 μg L−1 compared with two of the non-sarcopenic patients (4.5%), p = 0.007. These differences remained significant in males, whereas the differences were non-significant in females. Besides higher age, history of congestive heart failure and a low estimated glomerular filtration rate (eGFR), sarcopenia was independently associated with elevated preoperative troponin levels (adjusted odds ratio 11.8 [95% confidence interval 2.6–53.1]; p = 0.001) in a multivariable stepwise forward (Forward: Conditional) logistic regression model for risk factors for elevated hs-cTnT (Table 1). Our findings demonstrate that low skeletal muscle mass is independently associated with elevated baseline cardiac troponin levels in a
cohort of abdominal surgical oncology patients at risk for coronary artery disease, particularly in males. This supports the hypothesis of bilateral effects of cancer induced muscle wasting and heart failure in humans. Conflicts of interest The authors report no relationships that could be construed as a conflict of interest. Acknowledgments The authors would like to thank Wiro J. Niessen and Marcel Koek from the Department of Radiology and Medical Informatics, Erasmus University Medical Center, Rotterdam, the Netherlands, for providing the FatSeg software program and technical support; Ewout M. van de Garde from the Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, the Netherlands, for statistical advice; and all investigators, collaborators and participants of the MICOLON study. References [1] K. Fearon, F. Strasser, S.D. Anker, I. Bosaeus, E. Bruera, R.L. Fainsinger, et al., Definition and classification of cancer cachexia: an international consensus, Lancet Oncol. 12 (2011) 489–495. [2] A.J. Coats, Research on cachexia, sarcopenia and skeletal muscle in cardiology, J. Cachex. Sarcopenia Muscle 3 (2012) 219–223. [3] S.M. Kazemi-Bajestani, H. Becher, K. Fassbender, Q. Chu, V.E. Baracos, Concurrent evolution of cancer cachexia and heart failure: bilateral effects exist, J. Cachex. Sarcopenia Muscle 5 (2014) 95–104. [4] J. Springer, A. Tschirner, A. Haghikia, S. von Haehling, H. Lal, A. Grzesiak, et al., Prevention of liver cancer cachexia-induced cardiac wasting and heart failure, Eur. Heart J. 35 (2014) 932–941. [5] L. Cramer, B. Hildebrandt, T. Kung, K. Wichmann, J. Springer, W. Doehner, et al., Cardiovascular function and predictors of exercise capacity in patients with colorectal cancer, J. Am. Coll. Cardiol. 64 (2014) 1310–1319. [6] W. Doehner, S. von Haehling, S.D. Anker, M. Lainscak, Neurohormonal activation and inflammation in chronic cardiopulmonary disease: a brief systematic review, Wien. Klin. Wochenschr. 121 (2009) 293–296. [7] P.G. Noordzij, O. van Geffen, I.M. Dijkstra, D. Boerma, A.J. Meinders, T.C. Rettig, et al., High-sensitive cardiac troponin T measurements in prediction of non-cardiac complications after major abdominal surgery, Br. J. Anaesth. (2015 Mar 3)http://dx. doi.org/10.1093/bja/aev027. [8] C.M. Prado, V.E. Baracos, L.J. McCargar, T. Reiman, M. Mourtzakis, K. Tonkin, et al., Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment, Clin. Cancer Res. 15 (2009) 2920–2926.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Elevated high-sensitive cardiac troponin T levels are associated with low skeletal muscle mass in abdominal surgical oncology patients at risk for coronary artery disease Jeroen L.A. van Vugt a,b,⁎, Djamila Boerma b, Ineke M. Dijkstra c, Thomas L. Bollen d, Frank D. Eefting e, Jan N.M. IJzermans a, Peter G. Noordzij f a
Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands Department of Surgery, St Antonius Hospital, Nieuwegein, The Netherlands c Department of Clinical Chemistry, St Antonius Hospital, Nieuwegein, The Netherlands d Department of Radiology, St Antonius Hospital, Nieuwegein, The Netherlands e Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands f Department of Anesthesiology, Intensive Care and Pain Medicine, St Antonius Hospital, Nieuwegein, The Netherlands b
a r t i c l e
i n f o
Article history: Received 22 April 2015 Accepted 7 May 2015 Available online 8 May 2015 Keywords: Sarcopenia Cachexia Cancer Muscle mass Myocardial injury Cardiac troponin
(i.e. postoperative mortality rate N 3%), demonstrated that 31% of the study participants had elevated baseline high-sensitive cardiac troponin T (hs-cTnT) levels (i.e. ≥ 0.014 μg L− 1) [7]. We hypothesized that abdominal cancer patients with a low skeletal muscle mass are at increased risk for preoperative (baseline) myocardial injury, as expressed in elevated troponin levels, compared with patients with a normal skeletal muscle mass. Therefore, we conducted a post-hoc analysis of patients enrolled into the MICOLON study who underwent abdominal surgery for cancer and had an abdominal CT scan available. Patients eligible for the MICOLON study were aged ≥ 45 year and had at least one major or two minor cardiac risk factors [7]. Hs-cTnT
Up to 80% of patients with advanced cancer are affected by cancerinduced cachexia, a clinical condition that results in skeletal muscle wasting with or without accompanying loss of adipose tissue [1]. Patients with congestive heart failure are also prone to skeletal muscle wasting [2]. Visa versa, animal studies suggest that cancer not only can induce skeletal muscle wasting, but can also induce cardiac muscle wasting [3,4]. Therefore, it is suggested that bilateral effects exist; on the one hand heart failure may result in skeletal muscle wasting, and on the other hand cancer-induced cachexia may lead to cardiac muscle wasting, possibly resulting in further deterioration of cardiac function [3]. This could be an explanation for the similar symptomatology (i.e. dyspnea, fatigue, impaired exercise capacity, and weight loss) and shared risk factors to develop cachexia of cancer and chronic heart failure patients [5,6]. The MICOLON study, investigating myocardial injury and non-cardiac complications after major abdominal surgery
⁎ Corresponding author at: Department of Surgery, Erasmus University Medical Center, Wytemaweg 80, 3015 CE Rotterdam, The Netherlands. E-mail address: [email protected] (J.L.A. van Vugt).
http://dx.doi.org/10.1016/j.ijcard.2015.05.035 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
Fig. 1. Preoperative hs-cTnT level and L3 muscle index showed a significant negative correlation (p = 0.029). Dotted line: hs-cTnT level of 0.014 μg L−1.
230
J.L.A. van Vugt et al. / International Journal of Cardiology 191 (2015) 229–230
Table 1 Multivariable logistic regression analysis using a stepwise method (Forward: Conditional) for risk factors for elevated preoperative hs-cTnT levels (≥0.014 μg L−1). Bold values indicate significance at p b 0.05.
Sarcopenia (yes) Age (years) Gender (male) BMI (kg2/m2) Medical history of congestive heart failure Medical history of atrial fibrillation Preoperative eGFR (ml/min/1.73 m2) ASA classification POSSUM†
Univariate OR (95% CI)
p-Value
Multivariable OR (95% CI)
p-Value
10.00 (3.28–30.50) 1.23 (1.14–1.32) 1.89 (0.80–4.50) 0.88 (0.8–0.97) 7.28 (1.44–36.71) 4.30 (1.57–11.77) 0.97 (0.96–0.99) 3.04 (1.40–6.59) 1.07 (1.02–1.11)
b0.001 b0.001 0.150 0.011 0.016 0.005 0.001 0.005 0.004
11.75 (2.60–53.05) 1.22 (1.12–1.34)
0.001 b0.001
22.53 (2.03–250.15)
0.011
0.96 (0.94–0.99)
0.002
Abbreviations: BMI: body mass index; eGFR: estimated glomerular filtration rate; ASA: American Society of Anesthesiologists; POSSUM: Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity; OR: odds ratio; CI: confidence interval.
measurements were performed in blood samples collected after induction of general anesthesia using the fifth generation Elecsys Troponin T high sensitive assay on an automated Cobas 6000 platform (Roche Diagnostics, Germany). Hs-cTnT levels ≥0.014 μg L−1 were considered elevated. The cross-sectional skeletal muscle area (cm2) was assessed at the level of the third lumbar vertebra (L3) on preoperative abdominal computed tomography (CT) scans on a transverse slice showing both transversal processes, using MeVisLab FatSeg (MeVis Medical Solutions, Bremen, Germany). The distinction between different tissues was based on Hounsfield units (HU). For skeletal muscle, a threshold range of −30 to +150 HU was used. Measurements included the psoas, paraspinal, transverse abdominal, external oblique, internal oblique, and rectus abdominis muscles. The cross-sectional muscle area was corrected for height, as is conventional for body composition measurements. This resulted in the L3 muscle index (cm2/m2). Patients were classified as sarcopenic (i.e. low skeletal muscle mass) and non-sarcopenic according to sex-specific cutoff values defined by Prado et al. (38.5 cm2/m2 for women and 52.4 cm2/m2 for men) [8]. Measurements were performed by a medically trained member of the study group who was blinded for outcomes. Written informed consent was obtained from each patient. The study has been approved by the local medical ethical committee and was performed according to the ethical guidelines of the 1975 Declaration of Helsinki. In total, 126 patients were eligible for this study. Forty-five (35.7%) patients had elevated preoperative hs-cTnT levels and 82 (65.1%) of patients were sarcopenic. Preoperative hs-cTnT and L3 muscle index showed a significant negative correlation (R2 = 0.038; p = 0.029) (Fig. 1). Patients with elevated hs-cTnT levels showed a significantly lower L3 muscle index (44.2 cm2/m2 versus 48.5 cm2/m2; p = 0.001) and higher rate of sarcopenia (91.1% versus 8.9%; p b 0.001) compared with patients with normal baseline hs-cTnT levels. Moreover, nineteen of the sarcopenic patients (23.2%) had a hs-cTnT level ≥0.020 μg L−1 compared with two of the non-sarcopenic patients (4.5%), p = 0.007. These differences remained significant in males, whereas the differences were non-significant in females. Besides higher age, history of congestive heart failure and a low estimated glomerular filtration rate (eGFR), sarcopenia was independently associated with elevated preoperative troponin levels (adjusted odds ratio 11.8 [95% confidence interval 2.6–53.1]; p = 0.001) in a multivariable stepwise forward (Forward: Conditional) logistic regression model for risk factors for elevated hs-cTnT (Table 1). Our findings demonstrate that low skeletal muscle mass is independently associated with elevated baseline cardiac troponin levels in a
cohort of abdominal surgical oncology patients at risk for coronary artery disease, particularly in males. This supports the hypothesis of bilateral effects of cancer induced muscle wasting and heart failure in humans. Conflicts of interest The authors report no relationships that could be construed as a conflict of interest. Acknowledgments The authors would like to thank Wiro J. Niessen and Marcel Koek from the Department of Radiology and Medical Informatics, Erasmus University Medical Center, Rotterdam, the Netherlands, for providing the FatSeg software program and technical support; Ewout M. van de Garde from the Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, the Netherlands, for statistical advice; and all investigators, collaborators and participants of the MICOLON study. References [1] K. Fearon, F. Strasser, S.D. Anker, I. Bosaeus, E. Bruera, R.L. Fainsinger, et al., Definition and classification of cancer cachexia: an international consensus, Lancet Oncol. 12 (2011) 489–495. [2] A.J. Coats, Research on cachexia, sarcopenia and skeletal muscle in cardiology, J. Cachex. Sarcopenia Muscle 3 (2012) 219–223. [3] S.M. Kazemi-Bajestani, H. Becher, K. Fassbender, Q. Chu, V.E. Baracos, Concurrent evolution of cancer cachexia and heart failure: bilateral effects exist, J. Cachex. Sarcopenia Muscle 5 (2014) 95–104. [4] J. Springer, A. Tschirner, A. Haghikia, S. von Haehling, H. Lal, A. Grzesiak, et al., Prevention of liver cancer cachexia-induced cardiac wasting and heart failure, Eur. Heart J. 35 (2014) 932–941. [5] L. Cramer, B. Hildebrandt, T. Kung, K. Wichmann, J. Springer, W. Doehner, et al., Cardiovascular function and predictors of exercise capacity in patients with colorectal cancer, J. Am. Coll. Cardiol. 64 (2014) 1310–1319. [6] W. Doehner, S. von Haehling, S.D. Anker, M. Lainscak, Neurohormonal activation and inflammation in chronic cardiopulmonary disease: a brief systematic review, Wien. Klin. Wochenschr. 121 (2009) 293–296. [7] P.G. Noordzij, O. van Geffen, I.M. Dijkstra, D. Boerma, A.J. Meinders, T.C. Rettig, et al., High-sensitive cardiac troponin T measurements in prediction of non-cardiac complications after major abdominal surgery, Br. J. Anaesth. (2015 Mar 3)http://dx. doi.org/10.1093/bja/aev027. [8] C.M. Prado, V.E. Baracos, L.J. McCargar, T. Reiman, M. Mourtzakis, K. Tonkin, et al., Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment, Clin. Cancer Res. 15 (2009) 2920–2926.
