Skip to main content
Top
Published in: Clinical Research in Cardiology 2/2023

Open Access 21-03-2022 | Arterial Occlusive Disease | Original Paper

Coronary artery disease, left ventricular function and cardiac biomarkers determine all-cause mortality in cancer patients—a large monocenter cohort study

Authors: Daniel Finke, Markus B. Heckmann, Susanna Wilhelm, Lukas Entenmann, Hauke Hund, Nina Bougatf, Hugo A. Katus, Norbert Frey, Lorenz H. Lehmann

Published in: Clinical Research in Cardiology | Issue 2/2023

Login to get access

Abstract

Cancer patients are at risk of suffering from cardiovascular diseases (CVD). Nevertheless, the impact of cardiovascular comorbidity on all-cause mortality (ACM) in large clinical cohorts is not well investigated. In this retrospective cohort study, we collected data from 40,329 patients who were subjected to cardiac catherization from 01/2006 to 12/2017 at University Hospital Heidelberg. The study population included 3666 patients with a diagnosis of cancer prior to catherization and 3666 propensity-score matched non-cancer patients according to age, gender, diabetes and hypertension. 5-year ACM in cancer patients was higher with a reduced left ventricular function (LVEF < 50%; 68.0% vs 50.9%) or cardiac biomarker elevation (high-sensitivity cardiac troponin T (hs-cTnT; 64.6% vs 44.6%) and N-terminal brain natriuretic peptide (NT-proBNP; 62.9% vs 41.4%) compared to cancer patients without cardiac risk. Compared to non-cancer patients, NT-proBNP was found to be significantly higher (median NT-proBNP cancer: 881 ng/L, IQR [254; 3983 ng/L] vs non-cancer: 668 ng/L, IQR [179; 2704 ng/L]; p < 0.001, Wilcoxon-rank sum test) and turned out to predict ACM more accurately than hs-cTnT (NT-proBNP: AUC: 0.74; hs-cTnT: AUC: 0.63; p < 0.001, DeLong’s test) in cancer patients. Risk factors for atherosclerosis, such as diabetes and age (> 65 years) were significant predictors for increased ACM in cancer patients in a multivariate analysis (OR diabetes: 1.96 (1.39–2.75); p < 0.001; OR age > 65 years: 2.95 (1.68–5.4); p < 0.001, logistic regression). Our data support the notion, that overall outcome in cancer patients who underwent cardiac catherization depends on cardiovascular comorbidities. Therefore, particularly cancer patients may benefit from standardized cardiac care.

Graphical abstract

Appendix
Available only for authorised users
Literature
3.
go back to reference Bharadwaj A, Potts J, Mohamed MO, Parwani P, Swamy P, Lopez-Mattei JC, Rashid M, Kwok CS, Fischman DL, Vassiliou VS, Freeman P, Michos ED, Mamas MA (2020) Acute myocardial infarction treatments and outcomes in 6.5 million patients with a current or historical diagnosis of cancer in the USA. Eur Heart J 41(23):2183–2193. https://doi.org/10.1093/eurheartj/ehz851CrossRef Bharadwaj A, Potts J, Mohamed MO, Parwani P, Swamy P, Lopez-Mattei JC, Rashid M, Kwok CS, Fischman DL, Vassiliou VS, Freeman P, Michos ED, Mamas MA (2020) Acute myocardial infarction treatments and outcomes in 6.5 million patients with a current or historical diagnosis of cancer in the USA. Eur Heart J 41(23):2183–2193. https://​doi.​org/​10.​1093/​eurheartj/​ehz851CrossRef
7.
go back to reference Tsutamoto T, Hisanaga T, Wada A, Maeda K, Ohnishi M, Fukai D, Mabuchi N, Sawaki M, Kinoshita M (1998) Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. J Am Coll Cardiol 31(2):391–398. https://doi.org/10.1016/s0735-1097(97)00494-4CrossRef Tsutamoto T, Hisanaga T, Wada A, Maeda K, Ohnishi M, Fukai D, Mabuchi N, Sawaki M, Kinoshita M (1998) Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. J Am Coll Cardiol 31(2):391–398. https://​doi.​org/​10.​1016/​s0735-1097(97)00494-4CrossRef
8.
go back to reference Armaiz-Pena GN, Allen JK, Cruz A, Stone RL, Nick AM, Lin YG, Han LY, Mangala LS, Villares GJ, Vivas-Mejia P, Rodriguez-Aguayo C, Nagaraja AS, Gharpure KM, Wu Z, English RD, Soman KV, Shahzad MM, Zigler M, Deavers MT, Zien A, Soldatos TG, Jackson DB, Wiktorowicz JE, Torres-Lugo M, Young T, De Geest K, Gallick GE, Bar-Eli M, Lopez-Berestein G, Cole SW, Lopez GE, Lutgendorf SK, Sood AK (2013) Src activation by beta-adrenoreceptors is a key switch for tumour metastasis. Nat Commun 4:1403. https://doi.org/10.1038/ncomms2413CrossRef Armaiz-Pena GN, Allen JK, Cruz A, Stone RL, Nick AM, Lin YG, Han LY, Mangala LS, Villares GJ, Vivas-Mejia P, Rodriguez-Aguayo C, Nagaraja AS, Gharpure KM, Wu Z, English RD, Soman KV, Shahzad MM, Zigler M, Deavers MT, Zien A, Soldatos TG, Jackson DB, Wiktorowicz JE, Torres-Lugo M, Young T, De Geest K, Gallick GE, Bar-Eli M, Lopez-Berestein G, Cole SW, Lopez GE, Lutgendorf SK, Sood AK (2013) Src activation by beta-adrenoreceptors is a key switch for tumour metastasis. Nat Commun 4:1403. https://​doi.​org/​10.​1038/​ncomms2413CrossRef
15.
go back to reference Eschenhagen T, Force T, Ewer MS, de Keulenaer GW, Suter TM, Anker SD, Avkiran M, de Azambuja E, Balligand JL, Brutsaert DL, Condorelli G, Hansen A, Heymans S, Hill JA, Hirsch E, Hilfiker-Kleiner D, Janssens S, de Jong S, Neubauer G, Pieske B, Ponikowski P, Pirmohamed M, Rauchhaus M, Sawyer D, Sugden PH, Wojta J, Zannad F, Shah AM (2011) Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 13(1):1–10. https://doi.org/10.1093/eurjhf/hfq213CrossRef Eschenhagen T, Force T, Ewer MS, de Keulenaer GW, Suter TM, Anker SD, Avkiran M, de Azambuja E, Balligand JL, Brutsaert DL, Condorelli G, Hansen A, Heymans S, Hill JA, Hirsch E, Hilfiker-Kleiner D, Janssens S, de Jong S, Neubauer G, Pieske B, Ponikowski P, Pirmohamed M, Rauchhaus M, Sawyer D, Sugden PH, Wojta J, Zannad F, Shah AM (2011) Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 13(1):1–10. https://​doi.​org/​10.​1093/​eurjhf/​hfq213CrossRef
16.
go back to reference Alexandre J, Cautela J, Ederhy S, Damaj GL, Salem JE, Barlesi F, Farnault L, Charbonnier A, Mirabel M, Champiat S, Cohen-Solal A, Cohen A, Dolladille C, Thuny F (2020) Cardiovascular toxicity related to cancer treatment: a pragmatic approach to the American and European Cardio-Oncology Guidelines. J Am Heart Assoc 9(18):e018403. https://doi.org/10.1161/JAHA.120.018403CrossRef Alexandre J, Cautela J, Ederhy S, Damaj GL, Salem JE, Barlesi F, Farnault L, Charbonnier A, Mirabel M, Champiat S, Cohen-Solal A, Cohen A, Dolladille C, Thuny F (2020) Cardiovascular toxicity related to cancer treatment: a pragmatic approach to the American and European Cardio-Oncology Guidelines. J Am Heart Assoc 9(18):e018403. https://​doi.​org/​10.​1161/​JAHA.​120.​018403CrossRef
17.
go back to reference McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Skibelund AK, E.S.C.S.D. Group (2021) 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 42(36):3599–3726. https://doi.org/10.1093/eurheartj/ehab368CrossRef McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Skibelund AK, E.S.C.S.D. Group (2021) 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 42(36):3599–3726. https://​doi.​org/​10.​1093/​eurheartj/​ehab368CrossRef
18.
go back to reference Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH, American College of Cardiology, G. American Heart Association Task Force on Practice, A. Society for Cardiovascular, and Interventions, 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention (2011) A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for cardiovascular angiography and interventions. J Am Coll Cardiol 58(24):e44–e122. https://doi.org/10.1016/j.jacc.2011.08.007CrossRef Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH, American College of Cardiology, G. American Heart Association Task Force on Practice, A. Society for Cardiovascular, and Interventions, 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention (2011) A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for cardiovascular angiography and interventions. J Am Coll Cardiol 58(24):e44–e122. https://​doi.​org/​10.​1016/​j.​jacc.​2011.​08.​007CrossRef
19.
go back to reference Celik S, Giannitsis E, Wollert KC, Schwobel K, Lossnitzer D, Hilbel T, Lehrke S, Zdunek D, Hess A, Januzzi JL, Katus HA (2011) Cardiac troponin T concentrations above the 99th percentile value as measured by a new high-sensitivity assay predict long-term prognosis in patients with acute coronary syndromes undergoing routine early invasive strategy. Clin Res Cardiol 100(12):1077–1085. https://doi.org/10.1007/s00392-011-0344-xCrossRef Celik S, Giannitsis E, Wollert KC, Schwobel K, Lossnitzer D, Hilbel T, Lehrke S, Zdunek D, Hess A, Januzzi JL, Katus HA (2011) Cardiac troponin T concentrations above the 99th percentile value as measured by a new high-sensitivity assay predict long-term prognosis in patients with acute coronary syndromes undergoing routine early invasive strategy. Clin Res Cardiol 100(12):1077–1085. https://​doi.​org/​10.​1007/​s00392-011-0344-xCrossRef
20.
go back to reference Januzzi JL Jr, Camargo CA, Anwaruddin S, Baggish AL, Chen AA, Krauser DG, Tung R, Cameron R, Nagurney JT, Chae CU, Lloyd-Jones DM, Brown DF, Foran-Melanson S, Sluss PM, Lee-Lewandrowski E, Lewandrowski KB (2005) The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol 95(8):948–954. https://doi.org/10.1016/j.amjcard.2004.12.032CrossRef Januzzi JL Jr, Camargo CA, Anwaruddin S, Baggish AL, Chen AA, Krauser DG, Tung R, Cameron R, Nagurney JT, Chae CU, Lloyd-Jones DM, Brown DF, Foran-Melanson S, Sluss PM, Lee-Lewandrowski E, Lewandrowski KB (2005) The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol 95(8):948–954. https://​doi.​org/​10.​1016/​j.​amjcard.​2004.​12.​032CrossRef
21.
go back to reference Murphy SL, Xu J, Kochanek KD, Arias E, Tejada-Vera B (2021) Deaths: final data for 2018. Natl Vital Stat Rep 69(13):1–83 Murphy SL, Xu J, Kochanek KD, Arias E, Tejada-Vera B (2021) Deaths: final data for 2018. Natl Vital Stat Rep 69(13):1–83
29.
go back to reference Cartoni C, Niscola P, Breccia M, Brunetti G, D’Elia GM, Giovannini M, Romani C, Scaramucci L, Tendas A, Cupelli L, de Fabritiis P, Foa R, Mandelli F (2009) Hemorrhagic complications in patients with advanced hematological malignancies followed at home: an Italian experience. Leuk Lymphoma 50(3):387–391. https://doi.org/10.1080/10428190802714024CrossRef Cartoni C, Niscola P, Breccia M, Brunetti G, D’Elia GM, Giovannini M, Romani C, Scaramucci L, Tendas A, Cupelli L, de Fabritiis P, Foa R, Mandelli F (2009) Hemorrhagic complications in patients with advanced hematological malignancies followed at home: an Italian experience. Leuk Lymphoma 50(3):387–391. https://​doi.​org/​10.​1080/​1042819080271402​4CrossRef
31.
go back to reference Mrotzek SM, Lena A, Hadzibegovic S, Ludwig R, Al-Rashid F, Mahabadi AA, Mincu RI, Michel L, Johannsen L, Hinrichs L, Schuler M, Keller U, Anker SD, Landmesser U, Rassaf T, Anker MS, Totzeck M (2021) Assessment of coronary artery disease during hospitalization for cancer treatment. Clin Res Cardiol 110(2):200–210. https://doi.org/10.1007/s00392-020-01719-5CrossRef Mrotzek SM, Lena A, Hadzibegovic S, Ludwig R, Al-Rashid F, Mahabadi AA, Mincu RI, Michel L, Johannsen L, Hinrichs L, Schuler M, Keller U, Anker SD, Landmesser U, Rassaf T, Anker MS, Totzeck M (2021) Assessment of coronary artery disease during hospitalization for cancer treatment. Clin Res Cardiol 110(2):200–210. https://​doi.​org/​10.​1007/​s00392-020-01719-5CrossRef
32.
go back to reference Armenian SH, Lacchetti C, Barac A, Carver J, Constine LS, Denduluri N, Dent S, Douglas PS, Durand JB, Ewer M, Fabian C, Hudson M, Jessup M, Jones LW, Ky B, Mayer EL, Moslehi J, Oeffinger K, Ray K, Ruddy K, Lenihan D (2017) Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 35(8):893–911. https://doi.org/10.1200/JCO.2016.70.5400CrossRef Armenian SH, Lacchetti C, Barac A, Carver J, Constine LS, Denduluri N, Dent S, Douglas PS, Durand JB, Ewer M, Fabian C, Hudson M, Jessup M, Jones LW, Ky B, Mayer EL, Moslehi J, Oeffinger K, Ray K, Ruddy K, Lenihan D (2017) Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 35(8):893–911. https://​doi.​org/​10.​1200/​JCO.​2016.​70.​5400CrossRef
33.
go back to reference Pudil R, Mueller C, Celutkiene J, Henriksen PA, Lenihan D, Dent S, Barac A, Stanway S, Moslehi J, Suter TM, Ky B, Sterba M, Cardinale D, Cohen-Solal A, Tocchetti CG, Farmakis D, Bergler-Klein J, Anker MS, Von Haehling S, Belenkov Y, Iakobishvili Z, Maack C, Ciardiello F, Ruschitzka F, Coats AJS, Seferovic P, Lainscak M, Piepoli MF, Chioncel O, Bax J, Hulot JS, Skouri H, Hagler-Laube ES, Asteggiano R, Fernandez TL, de Boer RA, Lyon AR (2020) Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: a position statement from the Cardio-Oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology. Eur J Heart Fail 22(11):1966–1983. https://doi.org/10.1002/ejhf.2017CrossRef Pudil R, Mueller C, Celutkiene J, Henriksen PA, Lenihan D, Dent S, Barac A, Stanway S, Moslehi J, Suter TM, Ky B, Sterba M, Cardinale D, Cohen-Solal A, Tocchetti CG, Farmakis D, Bergler-Klein J, Anker MS, Von Haehling S, Belenkov Y, Iakobishvili Z, Maack C, Ciardiello F, Ruschitzka F, Coats AJS, Seferovic P, Lainscak M, Piepoli MF, Chioncel O, Bax J, Hulot JS, Skouri H, Hagler-Laube ES, Asteggiano R, Fernandez TL, de Boer RA, Lyon AR (2020) Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: a position statement from the Cardio-Oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology. Eur J Heart Fail 22(11):1966–1983. https://​doi.​org/​10.​1002/​ejhf.​2017CrossRef
34.
35.
go back to reference Pavo N, Raderer M, Hulsmann M, Neuhold S, Adlbrecht C, Strunk G, Goliasch G, Gisslinger H, Steger GG, Hejna M, Kostler W, Zochbauer-Muller S, Marosi C, Kornek G, Auerbach L, Schneider S, Parschalk B, Scheithauer W, Pirker R, Drach J, Zielinski C, Pacher R (2015) Cardiovascular biomarkers in patients with cancer and their association with all-cause mortality. Heart 101(23):1874–1880. https://doi.org/10.1136/heartjnl-2015-307848CrossRef Pavo N, Raderer M, Hulsmann M, Neuhold S, Adlbrecht C, Strunk G, Goliasch G, Gisslinger H, Steger GG, Hejna M, Kostler W, Zochbauer-Muller S, Marosi C, Kornek G, Auerbach L, Schneider S, Parschalk B, Scheithauer W, Pirker R, Drach J, Zielinski C, Pacher R (2015) Cardiovascular biomarkers in patients with cancer and their association with all-cause mortality. Heart 101(23):1874–1880. https://​doi.​org/​10.​1136/​heartjnl-2015-307848CrossRef
36.
go back to reference Romano S, Fratini S, Ricevuto E, Procaccini V, Stifano G, Mancini M, Di Mauro M, Ficorella C, Penco M (2011) Serial measurements of NT-proBNP are predictive of not-high-dose anthracycline cardiotoxicity in breast cancer patients. Br J Cancer 105(11):1663–1668. https://doi.org/10.1038/bjc.2011.439CrossRef Romano S, Fratini S, Ricevuto E, Procaccini V, Stifano G, Mancini M, Di Mauro M, Ficorella C, Penco M (2011) Serial measurements of NT-proBNP are predictive of not-high-dose anthracycline cardiotoxicity in breast cancer patients. Br J Cancer 105(11):1663–1668. https://​doi.​org/​10.​1038/​bjc.​2011.​439CrossRef
42.
go back to reference Finke D, Romann SW, Heckmann MB, Hund H, Bougatf N, Kantharajah A, Katus HA, Muller OJ, Frey N, Giannitsis E, Lehmann LH (2021) High-sensitivity cardiac troponin T determines all-cause mortality in cancer patients: a single-centre cohort study. ESC Heart Fail. https://doi.org/10.1002/ehf2.13515CrossRef Finke D, Romann SW, Heckmann MB, Hund H, Bougatf N, Kantharajah A, Katus HA, Muller OJ, Frey N, Giannitsis E, Lehmann LH (2021) High-sensitivity cardiac troponin T determines all-cause mortality in cancer patients: a single-centre cohort study. ESC Heart Fail. https://​doi.​org/​10.​1002/​ehf2.​13515CrossRef
Metadata
Title
Coronary artery disease, left ventricular function and cardiac biomarkers determine all-cause mortality in cancer patients—a large monocenter cohort study
Authors
Daniel Finke
Markus B. Heckmann
Susanna Wilhelm
Lukas Entenmann
Hauke Hund
Nina Bougatf
Hugo A. Katus
Norbert Frey
Lorenz H. Lehmann
Publication date
21-03-2022
Publisher
Springer Berlin Heidelberg
Published in
Clinical Research in Cardiology / Issue 2/2023
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-022-02001-6

Other articles of this Issue 2/2023

Clinical Research in Cardiology 2/2023 Go to the issue