Main Article Content
Abstract
Highlights:
- Around 38.8% of heart failure patients with cachexia died during the 180-1,876-day follow-up period.
- Cachexia increases the risk of mortality in heart failure patients.
Abstract:
Despite the fact that obesity has long been recognized as a risk factor for cardiovascular disease, the mortality rate of heart failure (HF) patients with cachexia is still high. Several studies have been conducted to investigate the association between cachexia and mortality in HF patients. However, the research results vary, as do the diagnostic criteria employed to assess cachexia. This meta-analysis aimed to conclusively summarize the association between cachexia and mortality in HF patients. The data were obtained from prospective or retrospective cohort studies with full texts in English or Indonesian and keywords related to "cachexia," "heart failure," and/ or "mortality". Studies that did not assess mortality in HF patients with cachexia and had no full text accessible were omitted. A literature search was conducted through four databases (PubMed, Web of Science, Scopus, and SAGE Journals) using keywords, reference searches, and/ or other methods on April 2022 in accordance with the Preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data from the selected studies were presented and analyzed using qualitative and quantitative synthesis methods. The Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias in the selected cohort studies. The qualitative synthesis contained nine studies, whereas the quantitative synthesis (meta-analysis) included six studies. Cachexia was found in 16.0% of the 4,697 patients studied. During the 180-1,876-day follow-up period, 33.0% of the patients died, with a mortality rate of 38.8% among the patients with cachexia. The pooled analysis revealed cachexia to be a significant predictor of mortality in HF patients (hazard ratio (HR)=3.84; 95% CI=2.28-6.45; p<0.00001), but with significant heterogeneity (p<0.00001; I2=88%). In conclusion, cachexia worsens HF prognosis.
Keywords
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References
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- Anaszewicz M, BudzyÅ„ski J (2017). Clinical significance of nutritional status in patients with atrial fibrillation: An overview of current evidence. Journal of Cardiology 69, 719–730. doi: 10.1016/j.jjcc.2016.06.014.
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- Carbone S, Lavie CJ, Arena R (2017). Obesity and heart failure: Focus on the obesity paradox. Mayo Clinic Proceedings 92, 266–79. doi: 10.1016/j. mayocp.2016.11.001.
- Castillo-Martínez L, Colín-Ramírez E, Orea-Tejeda A, et al (2012). Cachexia assessed by bioimpedance vector analysis as a prognostic indicator in chronic stable heart failure patients. Nutrition 28, 886–891. doi: 10.1016/j.nut. 2011.11.024.
- Centre for Evidence-Based Medicine (2023). What can I do when a study reports a beta coefficient instead of a hazard ratio? CEBM.
- Drescher C, Konishi M, Ebner N, et al (2015). Loss of muscle mass: Current developments in cachexia and sarcopenia focused on biomarkers and treatment. Journal of Cachexia, Sarcopenia and Muscle 6, 303–311. doi: 10.1002/jcsm.12082.
- Farkas J, von Haehling S, Kalantar-Zadeh K, et al (2013). Cachexia as a major public health problem: frequent, costly, and deadly. Journal of Cachexia, Sarcopenia Muscle 4, 173–178. doi: 10.1007/s13539- 013-0105-y.
- Fatkhullina AR, Peshkova IO, Koltsova EK (2016). The role of cytokines in the development of atherosclerosis. Biochem 81, 1358–1370. doi: 10.1134/S0006297916110134.
- Fulster S, Tacke M, Sandek A, et al (2013). Muscle wasting in patients with chronic heart failure: results from the studies investigating co-morbidities aggravating heart failure (SICA-HF). Europian Heart Journal 34, 512–519. doi: 10.1093/eurheartj/ehs381.
- Haehling S, Anker MS, Anker SD (2016). Prevalence and clinical impact of cachexia in chronic illness in Europe, USA, and Japan: Facts and numbers update 2016. Journal of Cachexia, Sarcopenia and Muscle 7, 507–509. doi: 10.1002/jcsm.12167.
- Hamzeh N, Ghadimi F, Farzaneh R, et al (2017). Obesity, heart failure, and obesity paradox. The Journal of Tehran Heart Center 12, 1–5.
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- Kalantar ZK, Rhee C, Sim JJ, et al (2013). Why cachexia kills: Examining the causality of poor outcomes in wasting conditions. Journal of Cachexia, Sarcopenia and Muscle 4, 89–94. doi: 10.1007/s13539-013-0111-0.
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- Lestari SR, Andrianto A, Nugroho J (2017). Effect of Body Mass Index (BMI) on mortality and readmission of heart failure patients in cardiovascular outpatient care unit at Dr. Soetomo Hospital, Surabaya. Folia Medica Indonesiana 52, 47. doi: 10.20473/fmi.v52i1. 5208.
- Melenovsky V, Kotrc M, Borlaug BA, et al (2013). Relationships between right ventricular function, body composition, and prognosis in advanced heart failure. Journal of the American College of Cardiology 62, 1660–70. doi: 10.1016/j.jacc. 2013.06.046.
- Molnar MZ, Streja E, Kovesdy CP, et al (2011). High platelet count as a link between renal cachexia and cardiovascular mortality in end-stage renal disease patients. American Journal of Clinical Nutrition 94, 945–954. doi: 10.3945/ ajcn.111.014639.
- Okoshi M, Romeiro F, Martinez P, et al (2014). Cardiac cachexia and muscle wasting: Definition, physiopathology, and clinical consequences. Research Reports in Clinical Cardiology. doi: 10.2147/rrcc.S41513.
- Ponikowski P, Voors AA, Anker SD, et al (2016). 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal 37, 2129–200. doi: 10. 1093/eurheartj/ehw128.
- Page, MJ, McKenzie, JE. Bossuyt, P.M, et al (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ, 372. https/doi.org/10.1136/BMJ.N71
- Pureza V, Florea VG (2013). Mechanisms for cachexia in heart failure. Current Heart Failure Reports 10, 307–314. doi: 10.1007/s11897-013-0153-9.
- Raposo André T, Lopes Santos A, Galriça Neto I (2017). Cardiac cachexia syndrome. EMJ Cardiology 101–107. doi: 10.33590/emjcardiol/ 10311709.
- Saboe A, Tiksnadi BB, Purnomowati A, et al (2016). Cardiac cachexia and its impact on survival in heart failure patients. Indonesian Journal of Cardiology 69–74. doi: 10.30701/ijc.v36i2.460.
- Sandek A, Swidsinski A, Schroedl W, et al (2014). Intestinal blood flow in patients with chronic heart failure. Journal of the American College of Cardiology 64, 1092–1102. doi: 10.1016/j.jacc.2014.06.1179.
- Saputri ON, Kalanjati VP, Rahman MA (2020). Body Mass Index (BMI) of children with Tetralogy of Fallot (TOF). Majalah Biomorfologi 30, 14. doi: 10.20473/mbiom.v30i1.2020.14-18.
- Sato Y, Yoshihisa A, Kimishima Y, et al (2020). Prognostic factors in heart failure patients with cardiac cachexia. Journal of Geriatric Cardiology 17, 26–34. doi: 10.11909/j.issn.1671-5411.2020. 01.008.
- Selthofer-Relatić K, Kibel A, Delić-BrkljaÄić D, et al (2019). Cardiac obesity and cardiac cachexia: Is there a pathophysiological link? Journal of Obesity 2019, 1–7. doi: 10.1155/2019/9854085.
- Sharmin S, Kypri K, Khanam M, et al. (2017). Parental supply of alcohol in childhood and risky drinking in adolescence: Systematic review and meta-analysis. International Journal of Environ-mental Research and Public Health 14, 287. doi: 10.3390/ijerph14030287.
- Sobieszek G, Powrózek T, JaroszyÅ„ski A, et al. (2021). Soluble ST2 proteins in male cachectic patients with chronic heart failure. Nutrition, Metabolism and Cardiovascular Disease 31, 886–893. doi: 10.1016/j.numecd.2020.11.014.
- Song EK, Lee Y, Moser DK, et al (2014). The link of unintentional weight loss to cardiac event–free survival in patients with heart failure. Journal of Cardiovascular Nursing 29, 439–447. doi: 10.1097/jcn.0b013e3182a46ba8.
- Soto ME, Pérez-Torres I, Rubio-Ruiz ME, et al (2022). Interconnection between cardiac cachexia and heart failure”Protective role of cardiac obesity. Cells 11, 1039. doi: 10.3390/cells 11061039.
- Sze S, Pellicori P, Kamzi S, et al. (2018). Effect of beta-adrenergic blockade on weight changes in patients with chronic heart failure. International Journal of Cardiology 264, 104–112. doi: 10.1016/j.ijcard.2018.03.089.
- Trullí s JC, Formiga F, Montero M, et al (2013). Impact of weight loss on mortality in chronic heart failure: Findings from the RICA Registry. International Journal of Cardiology 168, 306–311. doi: 10.1016/j.ijcard.2012.09.062.
- Valentova M, Anker SD, von Haehling S (2020). Cardiac cachexia revisited. Heart Failure Clinics 16, 61–69. doi: 10.1016/j.hfc.2019.08.006.
- Valentova M, von Haehling S, Bauditz J, et al. (2016). Intestinal congestion and right ventricular dysfunction: A link with appetite loss, inflammation, and cachexia in chronic heart failure. European Heart Journal 37, 1684–1691. doi: 10.1093/eurheartj/ehw008.
- Vanhoutte G, van de Wiel M, Wouters K, et al. (2016). Cachexia in cancer: What is in the definition? BMJ Open Gastroenterology 3, e000097. doi: 10.1136/bmjgast-2016-000097.
- Virani SS, Alonso A, Aparicio HJ, et al. (2021). Heart disease and stroke statistics”2021 update. Circulation. doi: 10.1161/ cir.0000000 000000950.
- Yancy CW, Jessup M, Bozkurt B, et al (2013). 2013 ACCF/AHA guideline for the management of heart failure. Journal of the American College of Cardiology 62, e147–239. doi: 10.1016/j.jacc. 2013.05.019.
- Zamora E, Díez"López C, Lupón J, et al. (2016). Weight loss in obese patients with heart failure. Journal of the American Heart Association. doi: 10.1161/jaha.115.002468.
References
Amalia R, Dewi IP, Wardhani LFK, et al (2022). Cardiovascular presentation in pheochromo-cytoma: What we should be aware. Siriraj Medical Journal 74, 68–74. doi: 10.33192/ smj.2022.9.
Anaszewicz M, BudzyÅ„ski J (2017). Clinical significance of nutritional status in patients with atrial fibrillation: An overview of current evidence. Journal of Cardiology 69, 719–730. doi: 10.1016/j.jjcc.2016.06.014.
Arámbula-Garza E, Castillo-Martínez L, González- Islas D, et al (2016). Association of cardiac cachexia and atrial fibrillation in heart failure patients. International Journal of Cardiology 223, 863–836. doi: 10.1016/ j.ijcard.2016.08.318.
Araújo JP, Lourenço P, Rocha-Gonçalves F, et al (2011). Nutritional markers and prognosis in cardiac cachexia. International Journal of Cardiology 146, 359–363. doi: 10.1016/j.ijcard. 2009.07.042.
Bangsa NK, Romdoni R, Subagyo S (2021). Clinical symptoms of patient with heart failure in Dr. Soetomo General Hospital: A descriptive study. JUXTA Jurnal Ilmiah Mahasiswa Kedokteran Universitas Airlangga 12, 61. doi: 10.1016/ j.ijcard.2009.07.042.
Carbone S, Lavie CJ, Arena R (2017). Obesity and heart failure: Focus on the obesity paradox. Mayo Clinic Proceedings 92, 266–79. doi: 10.1016/j. mayocp.2016.11.001.
Castillo-Martínez L, Colín-Ramírez E, Orea-Tejeda A, et al (2012). Cachexia assessed by bioimpedance vector analysis as a prognostic indicator in chronic stable heart failure patients. Nutrition 28, 886–891. doi: 10.1016/j.nut. 2011.11.024.
Centre for Evidence-Based Medicine (2023). What can I do when a study reports a beta coefficient instead of a hazard ratio? CEBM.
Drescher C, Konishi M, Ebner N, et al (2015). Loss of muscle mass: Current developments in cachexia and sarcopenia focused on biomarkers and treatment. Journal of Cachexia, Sarcopenia and Muscle 6, 303–311. doi: 10.1002/jcsm.12082.
Farkas J, von Haehling S, Kalantar-Zadeh K, et al (2013). Cachexia as a major public health problem: frequent, costly, and deadly. Journal of Cachexia, Sarcopenia Muscle 4, 173–178. doi: 10.1007/s13539- 013-0105-y.
Fatkhullina AR, Peshkova IO, Koltsova EK (2016). The role of cytokines in the development of atherosclerosis. Biochem 81, 1358–1370. doi: 10.1134/S0006297916110134.
Fulster S, Tacke M, Sandek A, et al (2013). Muscle wasting in patients with chronic heart failure: results from the studies investigating co-morbidities aggravating heart failure (SICA-HF). Europian Heart Journal 34, 512–519. doi: 10.1093/eurheartj/ehs381.
Haehling S, Anker MS, Anker SD (2016). Prevalence and clinical impact of cachexia in chronic illness in Europe, USA, and Japan: Facts and numbers update 2016. Journal of Cachexia, Sarcopenia and Muscle 7, 507–509. doi: 10.1002/jcsm.12167.
Hamzeh N, Ghadimi F, Farzaneh R, et al (2017). Obesity, heart failure, and obesity paradox. The Journal of Tehran Heart Center 12, 1–5.
Higgins, J., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M., & Welch, V. (Eds.). (2022). Cochrane Handbook for Systematic Reviews of Interventions version 6.3. Cochrane. www.training.cochrane.org/handbook
Intan RE, Alkaff FF, Oktaviono YH, et al (2022). Retrospective study of the association between platelet-to-lymphocyte ratio in patients with acute coronary syndrome on admission to a rural referral center in East Java, Indonesia, and the incidence of new symptomatic heart failure at 6 months. Medical Science Monitor. doi: 10.12659/MSM. 935002.
Kalantar ZK, Rhee C, Sim JJ, et al (2013). Why cachexia kills: Examining the causality of poor outcomes in wasting conditions. Journal of Cachexia, Sarcopenia and Muscle 4, 89–94. doi: 10.1007/s13539-013-0111-0.
Kamisaka K, Kamiya K, Iwatsu K, et al (2021). Impact of weight loss in patients with heart failure with preserved ejection fraction: Results from the FLAGSHIP study. ESC Heart Failure 8, 5293–5303. doi: 10.1002/ehf2.13619.
Krysztofiak H, Wleklik M, Migaj J, et al (2020). Cardiac cachexia: A well-known but challenging complication of heart failure. Clinical Intervention in Aging Volume 15, 2041–2051. doi: 10.2147/cia.S273967.
Lestari SR, Andrianto A, Nugroho J (2017). Effect of Body Mass Index (BMI) on mortality and readmission of heart failure patients in cardiovascular outpatient care unit at Dr. Soetomo Hospital, Surabaya. Folia Medica Indonesiana 52, 47. doi: 10.20473/fmi.v52i1. 5208.
Melenovsky V, Kotrc M, Borlaug BA, et al (2013). Relationships between right ventricular function, body composition, and prognosis in advanced heart failure. Journal of the American College of Cardiology 62, 1660–70. doi: 10.1016/j.jacc. 2013.06.046.
Molnar MZ, Streja E, Kovesdy CP, et al (2011). High platelet count as a link between renal cachexia and cardiovascular mortality in end-stage renal disease patients. American Journal of Clinical Nutrition 94, 945–954. doi: 10.3945/ ajcn.111.014639.
Okoshi M, Romeiro F, Martinez P, et al (2014). Cardiac cachexia and muscle wasting: Definition, physiopathology, and clinical consequences. Research Reports in Clinical Cardiology. doi: 10.2147/rrcc.S41513.
Ponikowski P, Voors AA, Anker SD, et al (2016). 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal 37, 2129–200. doi: 10. 1093/eurheartj/ehw128.
Page, MJ, McKenzie, JE. Bossuyt, P.M, et al (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ, 372. https/doi.org/10.1136/BMJ.N71
Pureza V, Florea VG (2013). Mechanisms for cachexia in heart failure. Current Heart Failure Reports 10, 307–314. doi: 10.1007/s11897-013-0153-9.
Raposo André T, Lopes Santos A, Galriça Neto I (2017). Cardiac cachexia syndrome. EMJ Cardiology 101–107. doi: 10.33590/emjcardiol/ 10311709.
Saboe A, Tiksnadi BB, Purnomowati A, et al (2016). Cardiac cachexia and its impact on survival in heart failure patients. Indonesian Journal of Cardiology 69–74. doi: 10.30701/ijc.v36i2.460.
Sandek A, Swidsinski A, Schroedl W, et al (2014). Intestinal blood flow in patients with chronic heart failure. Journal of the American College of Cardiology 64, 1092–1102. doi: 10.1016/j.jacc.2014.06.1179.
Saputri ON, Kalanjati VP, Rahman MA (2020). Body Mass Index (BMI) of children with Tetralogy of Fallot (TOF). Majalah Biomorfologi 30, 14. doi: 10.20473/mbiom.v30i1.2020.14-18.
Sato Y, Yoshihisa A, Kimishima Y, et al (2020). Prognostic factors in heart failure patients with cardiac cachexia. Journal of Geriatric Cardiology 17, 26–34. doi: 10.11909/j.issn.1671-5411.2020. 01.008.
Selthofer-Relatić K, Kibel A, Delić-BrkljaÄić D, et al (2019). Cardiac obesity and cardiac cachexia: Is there a pathophysiological link? Journal of Obesity 2019, 1–7. doi: 10.1155/2019/9854085.
Sharmin S, Kypri K, Khanam M, et al. (2017). Parental supply of alcohol in childhood and risky drinking in adolescence: Systematic review and meta-analysis. International Journal of Environ-mental Research and Public Health 14, 287. doi: 10.3390/ijerph14030287.
Sobieszek G, Powrózek T, JaroszyÅ„ski A, et al. (2021). Soluble ST2 proteins in male cachectic patients with chronic heart failure. Nutrition, Metabolism and Cardiovascular Disease 31, 886–893. doi: 10.1016/j.numecd.2020.11.014.
Song EK, Lee Y, Moser DK, et al (2014). The link of unintentional weight loss to cardiac event–free survival in patients with heart failure. Journal of Cardiovascular Nursing 29, 439–447. doi: 10.1097/jcn.0b013e3182a46ba8.
Soto ME, Pérez-Torres I, Rubio-Ruiz ME, et al (2022). Interconnection between cardiac cachexia and heart failure”Protective role of cardiac obesity. Cells 11, 1039. doi: 10.3390/cells 11061039.
Sze S, Pellicori P, Kamzi S, et al. (2018). Effect of beta-adrenergic blockade on weight changes in patients with chronic heart failure. International Journal of Cardiology 264, 104–112. doi: 10.1016/j.ijcard.2018.03.089.
Trullí s JC, Formiga F, Montero M, et al (2013). Impact of weight loss on mortality in chronic heart failure: Findings from the RICA Registry. International Journal of Cardiology 168, 306–311. doi: 10.1016/j.ijcard.2012.09.062.
Valentova M, Anker SD, von Haehling S (2020). Cardiac cachexia revisited. Heart Failure Clinics 16, 61–69. doi: 10.1016/j.hfc.2019.08.006.
Valentova M, von Haehling S, Bauditz J, et al. (2016). Intestinal congestion and right ventricular dysfunction: A link with appetite loss, inflammation, and cachexia in chronic heart failure. European Heart Journal 37, 1684–1691. doi: 10.1093/eurheartj/ehw008.
Vanhoutte G, van de Wiel M, Wouters K, et al. (2016). Cachexia in cancer: What is in the definition? BMJ Open Gastroenterology 3, e000097. doi: 10.1136/bmjgast-2016-000097.
Virani SS, Alonso A, Aparicio HJ, et al. (2021). Heart disease and stroke statistics”2021 update. Circulation. doi: 10.1161/ cir.0000000 000000950.
Yancy CW, Jessup M, Bozkurt B, et al (2013). 2013 ACCF/AHA guideline for the management of heart failure. Journal of the American College of Cardiology 62, e147–239. doi: 10.1016/j.jacc. 2013.05.019.
Zamora E, Díez"López C, Lupón J, et al. (2016). Weight loss in obese patients with heart failure. Journal of the American Heart Association. doi: 10.1161/jaha.115.002468.