The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Elevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart Failure
Open accessAbstract
BACKGROUND AND METHODS: Although cachexia often accompanies advanced heart failure, little is known about the causes of the cachectic state. To assess the potential role of tumor necrosis factor in the pathogenesis of cardiac cachexia, we measured serum levels of the factor in 33 patients with chronic heart failure, 33 age-matched healthy controls, and 9 patients with chronic renal failure. RESULTS: Mean (+/- SEM) serum levels of tumor necrosis factor were higher in the patients with heart failure (115 +/- 25 U per milliliter) than in the healthy controls (9 +/- 3 U per milliliter; P less than 0.001). Nineteen of the patients with chronic heart failure had serum levels of tumor necrosis factor greater than or equal to 39 U per milliliter (greater than 2 SD above the mean value for the control group), whereas the remaining 14 patients had serum levels of tumor necrosis factor below this level. The patients with high levels of tumor necrosis factor were more cachectic than those with low levels (82 +/- 3 vs. 95 +/- 6 percent of ideal body weight, respectively; P less than 0.05) and had more advanced heart failure, as evidenced by their higher values for plasma renin activity (2.92 +/- 0.53 vs. 1.06 +/- 0.53 ng per liter per second [10.5 +/- 1.9 vs. 3.8 +/- 1.9 ng per milliliter per hour]; P less than 0.01) and lower serum sodium concentration (135 +/- 1 vs. 138 +/- 1 mmol per liter; P less than 0.05). The group with high levels of tumor necrosis factor also had lower hemoglobin levels (7.82 +/- 0.2 vs. 8.69 +/- 0.4 mmol per liter [12.6 +/- 0.4 vs. 14.0 +/- 0.6 g per deciliter]) and higher values for blood urea nitrogen (19.5 +/- 2.2 vs. 12.5 +/- 1.8 mmol per liter) than the group with low levels of tumor necrosis factor (P less than 0.05 for both). The high levels of tumor necrosis factor were not due solely to decreased renal clearance, however, since the levels in the patients with heart failure were considerably higher than those in the nine patients with chronic renal failure (115 +/- 25 vs. 45 +/- 25 U per milliliter; P less than 0.05). CONCLUSIONS: These findings indicate that circulating levels of tumor necrosis factor are increased in cachectic patients with chronic heart failure and that this elevation is associated with the marked activation of the renin-angiotensin system seen in patients with end-stage cardiac disease.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“in patients with congestive heart failure, the levels of pro-inflammatory cytokines, especially TNF, IL-6, and IL-1, are markedly elevated, and the TNF level is a negative prognostic factor”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [191]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Mosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104
T Cell Growth Factor: Parameters of Production and a Quantitative Microassay for Activity
Gillis, S. A., Ferm, M. M., Ou, W., & Smith, K. A. (1978) · The Journal of Immunology · doi:10.4049/jimmunol.120.6.2027 · Cited by 3,273
Shock and Tissue Injury Induced by Recombinant Human Cachectin
Tracey, K. J., Beutler, B., Lowry, S. F., Merryweather, J., Wolpe, S., Milsark, I. W., Hariri, R. J., Fahey, T. J., Zentella, A., Albert, J. D., et al. (1986) · Science · doi:10.1126/science.3764421 · Cited by 2,549
Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities.
Le, J., & Vilček, J. (1987) · PubMed · Cited by 1,327
Friedberg, C. K. (1966) · Biblioteca Digital (Real Academia Nacional de Medicina) · Cited by 1,308
Waage, A., Halstensen, A. I., & Espevik, T. (1987) · The Lancet · doi:10.1016/s0140-6736(87)91728-4 · Cited by 1,085
Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo.
Beutler, B., Milsark, I. W., & Cerami, A. (1985) · The Journal of Immunology · doi:10.4049/jimmunol.135.6.3972 · Cited by 771
Tumor Necrosis Factor and Interleuktn-1 in the Serum of Children with Severe Infectious Purpura
Girardin, E. P., Grau, G. E., Dayer, J., Roux-Lombard, P., the J5 Study Group*, & Lambert, P.-H. (1988) · New England Journal of Medicine · doi:10.1056/nejm198808183190703 · Cited by 737
Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation.
Tracey, K. J., He, W., Manogue, K. R., Fong, Y., HESSE, D. G., Nguyen, H. T., Kuo, G. C., Beutler, B., Cotran, R. S., & Cerami, A. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.167.3.1211 · Cited by 730
Lähdevirta, J., Maury, C. P. J., Teppo, A., & Repo, H. (1988) · The American Journal of Medicine · doi:10.1016/0002-9343(88)90576-1 · Cited by 717
Research works printed but not linked: 4
- Packer, 1987, Circulation, 75, IV-80
- Bertani, 1989, Am J Pathol, 134, 419
- Pessina, 1987, Lymphokine Res, 6, 35
- Le, 1987, Lab Invest, 56, 234
Cited by
Sorted by citations
Items 201–300 of 1,003
Sex Differences in Muscle Wasting
Anderson, L. J., Liu, H. M., & Garcia, J. M. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-70178-3_9 · Cited by 226
Problems encountered during anti-tumour necrosis factor therapy
Desai, S. B., & Fürst, D. E. (2006) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2006.06.002 · Cited by 221
Administration of Anti-TNF Antibody Improves Left Ventricular Function in Septic Shock Patients
Vincent, J., Bakker, J., Marécaux, G., Schandené, L., Kahn, R. J., & Dupont, É. (1992) · CHEST Journal · doi:10.1378/chest.101.3.810 · Cited by 220
Li, X., Moody, M. R., Engel, D., Walker, S., Clubb, F. J., Sivasubramanian, N., Mann, D. L., & Reid, M. B. (2000) · Circulation · doi:10.1161/01.cir.102.14.1690 · Cited by 217
Hare, J. M., Loh, E., Creager, M. A., & Colucci, W. S. (1995) · Circulation · doi:10.1161/01.cir.92.8.2198 · Cited by 219
Risk stratification in chronic heart failure
Cowburn, P. (1998) · European Heart Journal · doi:10.1053/euhj.1997.0820 · Cited by 219
“Circulating levels of the cytokine, tumour necrosis factor, are increased in cachectic patients with chronic heart failure([109]).”
BackgroundKatz, S. D., Rao, R., Berman, J. W., Schwarz, M., Demopoulos, L. A., Bijou, R., & LeJemtel, T. H. (1994) · Circulation · doi:10.1161/01.cir.90.1.12 · Cited by 217
Sliwa, K. S., Skudicky, D., Candy, G. P., Wisenbaugh, T. W., & Sareli, P. (1998) · The Lancet · doi:10.1016/s0140-6736(97)09338-0 · Cited by 216
Cardiac remodeling and failure
Fedak, P. W. M., Verma, S., Weisel, R. D., & Li, R. (2005) · Cardiovascular Pathology · doi:10.1016/j.carpath.2004.12.002 · Cited by 219
Circulating Interleukin-6 in Severe Heart Failure
MacGowan, G. A., Mann, D. L., Kormos, R. L., Feldman, A. M., & Murali, S. (1997) · The American Journal of Cardiology · doi:10.1016/s0002-9149(96)00063-x · Cited by 214
Macrophage autophagy in macrophage polarization, chronic inflammation and organ fibrosis
Wen, J.-H., Li, D.-Y., Liang, S., Yang, C., Tang, J., & Liu, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.946832 · Cited by 219
TLR4-mediated inflammatory activation of human coronary artery endothelial cells by LPS
Zeuke, S. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00512-6 · Cited by 212
Spinale, F. G. (2000) · Cardiovascular Research · doi:10.1016/s0008-6363(99)00431-9 · Cited by 211
Sharma, R. K. (2004) · European Heart Journal · doi:10.1016/j.ehj.2004.04.023 · Cited by 208
Ruffolo, R. R., & Feuerstein, G. Z. (1998) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199800003-00005 · Cited by 210
Çavuşoğlu, E. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehl153 · Cited by 208
“CHF on presentation (N) (%) 9 (8.7) 18 (17.3) 34 (32.7) ,0.0001 MI on presentation (N) (%) 26 ( 25 ) 28 (26.9) 28 (26.9) 0.936 ASA use (N) (%) 94 (90.4) 89 (85.6) 87 (83.7) 0.342 Beta-blocker use (N) (%) 78 (75.0) 70 (67.3) 69 (66.4) 0.3313 ACE-inhibitor use (N) (%) 64 (61.5) 60 (57.7) 54 (51.9) 0.37 Statin use (N) (%…”
InfluentialCachexia and Sarcopenia: Emerging Syndromes of Importance in Dogs and Cats
Freeman, L. M. (2011) · Journal of Veterinary Internal Medicine · doi:10.1111/j.1939-1676.2011.00838.x · Cited by 226
“TNF and IL-1 also cause cardiac myocyte hypertrophy and fibrosis and have negative inotropic effects that may contribute to progression of the underlying disease.(73,74) Their mechanism appears to be primarily through the nuclear factor-jB (NF-jB) pathway, which has numerous effects, including increased muscle proteol…”
BackgroundInflammatory and Atherosclerotic Interactions in the Depleted Uremic Patient
Stenvinkel, P. (2000) · Blood Purification · doi:10.1159/000014479 · Cited by 207
Tumor necrosis factor-alpha in human arterial wall with atherosclerosis
Rus, F., Niculescu, F. I., & Vlaicu, R. (1991) · Atherosclerosis · doi:10.1016/0021-9150(91)90066-c · Cited by 207
Risk Factors for Heart Failure
Lawson, C. A., Zaccardi, F., Squire, I. B., Okhai, H., Davies, M. J., Huang, W., Mamas, M. A., Lam, C. S. P., Khunti, K., & Kadam, U. T. (2020) · Circulation Heart Failure · doi:10.1161/circheartfailure.119.006472 · Cited by 212
Circulating adiponectin concentrations in patients with congestive heart failure
George, J., Patal, S., Wexler, D., Sharabi, Y., Peleg, E., Kamari, Y., Grossman, E., Sheps, D., Keren, G., & Roth, A. (2006) · Heart · doi:10.1136/hrt.2005.083345 · Cited by 204
Takano, H., Zou, Y., Hasegawa, H., Akazawa, H., Nagai, T., & Komuro, I. (2003) · Antioxidants and Redox Signaling · doi:10.1089/152308603770380098 · Cited by 205
“The plasma concentration of tumor necrosis factor-a (TNF-a ) is elevated in many cardiac diseases, including heart failure, and TNF-a exerts a negative inotropic effect on the heart (29, 33, 43).”
Florea, V., Rieger, A. C., DiFede, D. L., El-Khorazaty, J. A., Natsumeda, M., Banerjee, M. N., Tompkins, B. A., Khan, A., Schulman, I. H., Landin, A. M., et al. (2017) · Circulation Research · doi:10.1161/circresaha.117.311827 · Cited by 205
“Our present study yielded similar results, as both doses reduced serum levels of TNF-α, a proinflammatory cytokine and marker of heart disease progression.(29) Together, these results support the idea that MSCs exert their therapeutic benefits in part through anti-inflammatory effects.”
Anker, S. D., Swank, J. W., Volterrani, M., Chua, T. P., Clark, A. L., Poole-Wilson, P. A., & Coats, A. J. S. (1997) · European Heart Journal · doi:10.1093/oxfordjournals.eurheartj.a015229 · Cited by 205
Mechanisms for the transition from physiological to pathological cardiac hypertrophy
Oldfield, C. J., Duhamel, T. A., & Dhalla, N. S. (2019) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2019-0566 · Cited by 219
“In patients with heart failure, TNF- levels have been reported to be elevated (Fang et al. 2017; Levine et al. 1990) and TNF- gene expression is positively correlated with level, severity, and etiology of disease in this population (Eskandari et al. 2018).”
BackgroundCytokines and Cardiac Contractile Function
Kelly, R. A., & Smith, T. W. (1997) · Circulation · doi:10.1161/01.cir.95.4.778 · Cited by 204
Niebauer, J., Pflaum, C. D., Clark, A. L., Strasburger, C. J., Hooper, J., Poole-Wilson, P. A., Coats, A. J. S., & Anker, S. D. (1998) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(98)00226-5 · Cited by 199
The Role of Monocytes and Inflammation in the Pathophysiology of Heart Failure
Wrigley, B., Lip, G. Y. H., & Shantsila, E. (2011) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfr122 · Cited by 202
“Human studies Levine et al.(4) Observational study: circulating levels of TNF increased in CHF and were highest in the most advanced disease”
BackgroundInfluentialChronic Chagas' Disease Cardiomyopathy Patients Display an Increased IFN-γ Response to Infection
Abel, L. C. J., Rizzo, L. V., Ianni, B. M., Albuquerque, F., Bacal, F., Carrara, D., Bocchi, E. A., Teixeira, H. C., Mady, C., Kalil, J. E., et al. (2001) · Journal of Autoimmunity · doi:10.1006/jaut.2001.0523 · Cited by 196
Tsutamoto, T., Wada, A., Maeda, K., Mabuchi, N., Hayashi, M., Tsutsui, T., Ohnishi, M., Sawaki, M., Fujii, M., Matsumoto, T., et al. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(99)00594-x · Cited by 196
“ular remodeling (15–21), are increased in plasma in CHF patients (12,22,23).”
BackgroundListing, J., Strangfeld, A., Kekow, J., Schneider, M., Kapelle, A., Wassenberg, S., & Zink, A. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23281 · Cited by 196
Cardiorenal syndrome: pathophysiology and potential targets for clinical management
Hatamizadeh, P., Fonarow, G. C., Budoff, M. J., Darabian, S., Kovesdy, C. P., & Kalantar‐Zadeh, K. (2012) · Nature Reviews Nephrology · doi:10.1038/nrneph.2012.279 · Cited by 205
Hausenloy, D. J., Lecour, S., & Yellon, D. M. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3360 · Cited by 198
“…low physiological levels of TNF do not seem to alter the function of the heart (85), an increase in TNF, as observed in myocardial infarction (24, 50, 109) or heart failure (76), exerts a negative inotropic effect and leads to contractile dysfunction in a concentration-dependent manner (114, 135).”
Nutritional and Anti-Inflammatory Interventions in Chronic Heart Failure
Kalantar‐Zadeh, K., Anker, S. D., Horwich, T. B., & Fonarow, G. C. (2008) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2008.03.007 · Cited by 196
Schulze, P. C., Kratzsch, J., Linke, A., Schoene, N., Adams, V., Gielen, S., Erbs, S., Möbius‐Winkler, S., & Schuler, G. C. (2003) · European Journal of Heart Failure · doi:10.1016/s1388-9842(02)00177-0 · Cited by 193
Cardiac troponin I as diagnostic and prognostic marker in severe heart failure
La Vecchia, L., Mezzena, G., Zanolla, L., Paccanaro, M., Varotto, L., Bonanno, C., & Ometto, R. (2000) · The Journal of Heart and Lung Transplantation · doi:10.1016/s1053-2498(00)00120-0 · Cited by 191
Long-term Survival After Heart Failure
Goldberg, R. J. (2007) · Archives of Internal Medicine · doi:10.1001/archinte.167.5.490 · Cited by 194
“A growing body of evidence suggests that the cause of cardiac cachexia among patients with severe HF is multifactorial.(23,24) The observed increase in mortality among patients with decompensated HF and their weight loss also may be a result of multiple factors, including weight reduction, severity of the underlying H…”
BackgroundIwai‐Kanai, E., Hasegawa, K., Araki, M., Kakita, T., Morimoto, T., & Sasayama, S. (1999) · Circulation · doi:10.1161/01.cir.100.3.305 · Cited by 192
Conraads, V. M. (2002) · European Heart Journal · doi:10.1053/euhj.2002.3239 · Cited by 191
Yu, X., Deng, L., Wang, D., Li, N., Chen, X., Cheng, X. C., Jin, Y., Gao, X., Liao, M., Wang, M., et al. (2012) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2012.10.002 · Cited by 190
“In the past years, clinical observations have indicated elevated tumor necrosis factor-α (TNF-α) in the plasma of patients with AMI which contributed to myocardial injury and dysfunction [3–5].”
BackgroundAnker, S. D., Clark, A. L., Kemp, M., Salsbury, C., Teixeira, M. M., Hellewell, P. G., & Coats, A. J. S. (1997) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(97)00262-3 · Cited by 190
Biomarkers of inflammation in heart failure
Bozkurt, B., Mann, D. L., & Deswal, A. M. (2009) · Heart Failure Reviews · doi:10.1007/s10741-009-9140-3 · Cited by 189
“Circulating levels of TNF, IL-6, and IL-18 are elevated in patients with HF (Table 2) [1, 6, 10–12, 17–30].”
BackgroundResultInfluentialGlezeva, N., & Baugh, J. A. (2013) · Heart Failure Reviews · doi:10.1007/s10741-013-9405-8 · Cited by 194
“Initial evidence showing a role for inflammation in hypertensive cardiac remodelling and heart disease came from experimental and clinical observations of immune– inflammatory activation in patients with established chronic HF [32].”
BackgroundLongrois, D., Balligand, J., KELLY, R., & SMITH, T. (1995) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(08)80015-6 · Cited by 189
Peschel, T., Schönauer, M., Thiele, H., Anker, S., Schuler, G., & Niebauer, J. (2003) · European Journal of Heart Failure · doi:10.1016/s1388-9842(03)00104-1 · Cited by 187
Tumor Necrosis Factor-α and Mortality in Heart Failure
Dunlay, S. M., Weston, S. A., Redfield, M. M., Killian, J. M., & Roger, V. L. (2008) · Circulation · doi:10.1161/circulationaha.107.759191 · Cited by 187
Proinflammatory cytokines and skeletal muscle
te, U. S., & Schulze, P. C. (2004) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200405000-00005 · Cited by 193
Anderson, H. D. I., Rahmutula, D., & Gardner, D. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309552200 · Cited by 186
The British Society for Rheumatology biologic DMARD safety guidelines in inflammatory arthritis
Holroyd, C., Seth, R., Bukhari, M., Malaviya, A., Holmes, C., Curtis, E., Chan, C. K. Y., Yusuf, M. A., Litwic, A., Smolen, S., et al. (2018) · Rheumatology · doi:10.1093/rheumatology/key208 · Cited by 166
Duda, M. K., O’Shea, K. M., Tintinu, A., Xu, W., Khairallah, R. J., Barrows, B. R., Chess, D. J., Azimzadeh, A. M., Harris, W. S., Sharov, V. G., et al. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn310 · Cited by 181
Bradham, W. S. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00503-x · Cited by 185
Frantz, S., Falcão‐Pires, I., Balligand, J., Bauersachs, J. K., Brutsaert, D. L., Ciccarelli, M., Dawson, D. K., Windt, L. J. D., Giacca, M., Hamdani, N., et al. (2018) · European Journal of Heart Failure · doi:10.1002/ejhf.1138 · Cited by 193
Regulating the regulator: NF-κB signaling in heart
Hall, G., Hasday, J. D., & Rogers, T. B. (2006) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2006.07.006 · Cited by 183
The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction
Packer, M. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.06.055 · Cited by 213
Self-citationPotent and Long-Lasting Vasodilatory Effects of Adrenomedullin in Humans
Nakamura, M., Yoshida, H., Makita, S., Arakawa, N., Niinuma, H., & Hiramori, K. (1997) · Circulation · doi:10.1161/01.cir.95.5.1214 · Cited by 183
Increased endogenous nitric oxide synthase inhibitor in patients with congestive heart failure
Usui, M., Matsuoka, H., Miyazaki, H., Ueda, S., Okuda, S., & Imaizumi, T. (1998) · Life Sciences · doi:10.1016/s0024-3205(98)00225-2 · Cited by 232
Heart Failure, Redox Alterations, and Endothelial Dysfunction
López-Farré, A. J., & Casado, S. (2001) · Hypertension · doi:10.1161/hy1201.099612 · Cited by 184
THE ROLE OF TNF IN CARDIOVASCULAR DISEASE
Ferrari, R. (1999) · Pharmacological Research · doi:10.1006/phrs.1998.0463 · Cited by 182
The Role of Cytokines in Regulating Protein Metabolism and Muscle Function
Zoico, E., & Roubenoff, R. (2002) · Nutrition Reviews · doi:10.1301/00296640260085949 · Cited by 179
IL-10 attenuates TNF- -induced NF B pathway activation and cardiomyocyte apoptosis
Dhingra, S., Sharma, A. N., Arora, R. C., Slezák, J., & Singal, P. K. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp040 · Cited by 181
Takano, H., Nagai, T., Asakawa, M., Toyozaki, T., Oka, T., Komuro, I., Saito, T., & Masuda, Y. (2000) · Circulation Research · doi:10.1161/01.res.87.7.596 · Cited by 182
Mechanisms of Disease: erythropoietin resistance in patients with both heart and kidney failure
van der Putten, K., Braam, B. G., Jie, K. E., & Gaillard, S. (2007) · Nature Reviews Nephrology · doi:10.1038/ncpneph0655 · Cited by 182
“Increased levels of TNF and IL-6 have also been measured in patients with heart failure”
BackgroundEffects of exercise training in patients with congestive heart failure: A critical review
McKelvie, R. S., Teo, K. K., McCartney, N., Humen, D. P., Montague, T. J., & Yusuf, S. (1995) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(94)00428-s · Cited by 180
Nitric oxide and excitation–contraction coupling
Hare, J. M. (2003) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(03)00143-3 · Cited by 179
Role of inflammation in the progression of heart failure
Yndestad, A., Damås, J. K., Øie, E., Ueland, T., Gullestad, L. L., & Aukrust, P. (2007) · Current Cardiology Reports · doi:10.1007/bf02938356 · Cited by 177
“In 1990, Levine et al. [ 2 ] demonstrated that patients with chronic HF had increased circulating levels of the inflammatory cytokine tumor necrosis factor (TNF)-(z [2], a finding that subsequently led to the introduction of a cardioinflammatory model for HF, raising the possibility that cytokines and other inflammato…”
BackgroundInfluentialAcute Kidney Injury and Extrarenal Organ Dysfunction
Yap, S. C., Lee, H. T., & Warner, D. S. (2012) · Anesthesiology · doi:10.1097/aln.0b013e31824f951b · Cited by 178
“overexpress both IL-6 and its receptor, IL-6R were also found to have ventricular hypertrophy.(59)”
BackgroundDeBoer, M. D., Zhu, X., Levasseur, P. R., Meguid, M. M., Suzuki, S., Inui, A., Taylor, J. E., Halem, H. A., Dong, J. Z., Datta, R., et al. (2007) · Endocrinology · doi:10.1210/en.2007-0016 · Cited by 178
Drexler, H., Kästner, S., Strobel, A., Studer, R., Brodde, O. ‐., & Hasenfuss, G. P. (1998) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(98)00336-2 · Cited by 177
“ated with systemic and cardiac cytokine activation (9,10) which,”
BackgroundTumor necrosis factor receptor-2 (TNFR2): an overview of an emerging drug target
Medler, J., & Wajant, H. (2019) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2019.1586886 · Cited by 177
“association (NYHA) classification of heart diseases [67].”
Briasoulis, Α., Androulakis, E. S., Christophides, T., & Tousoulis, D. (2016) · Heart Failure Reviews · doi:10.1007/s10741-016-9533-z · Cited by 183
“Several therapeutic approaches have been proposed to modify the inflammatory status of patients with HF, but the results coming from large studies are disappointing [59, 60].”
Role of nitric oxide in the regulation of myocardial function
Hare, J. M., & Colucci, W. S. (1995) · Progress in Cardiovascular Diseases · doi:10.1016/s0033-0620(05)80004-0 · Cited by 175
Prognostic Value of High-Sensitivity C-Reactive Protein in Heart Failure: A Systematic Review
Araújo, J. P., Lourenço, P., Azevedo, A., Friões, F., Rocha‐Gonçalves, F., Ferreira, A., & Bettencourt, P. (2008) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2008.10.030 · Cited by 177
Gastrointestinal and Liver Issues in Heart Failure
Sundaram, V., & Fang, J. C.-T. (2016) · Circulation · doi:10.1161/circulationaha.115.020894 · Cited by 179
“immune activation, and levels of proinflammatory cytokines predict HF survival.(15,16) However, the direct pathological link between the two has yet to be clearly elucidated.”
BackgroundDessap, A. M., Hoüel, R., Soustelle, C., Kirsch, M. E. W., Thébert, D., & Loisance, D. Y. (2001) · The Annals of Thoracic Surgery · doi:10.1016/s0003-4975(01)02486-9 · Cited by 173
Kittleson, M. M., Minhas, K. M., Irizarry, R. A., Ye, S. Q., Edness, G., Breton, E., Conte, J. V., Tomaselli, G. F., Garcia, J. G. N., & Hare, J. M. (2005) · Physiological Genomics · doi:10.1152/physiolgenomics.00255.2004 · Cited by 173
“Levels of TNF have been shown to be upregulated in chronic heart failure (34), and increasing levels of TNF have been correlated with disease severity (40).”
BackgroundSharma, R., Coats, A. J. S., & Anker, S. D. (2000) · International Journal of Cardiology · doi:10.1016/s0167-5273(99)00186-2 · Cited by 172
Insulin says NO to cardiovascular disease
Yu, Q., Gao, F., & Ma, X. L. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvq349 · Cited by 172
Adams, V. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00228-6 · Cited by 172
“Recently, we and others have demonstrated an in- patients with CHF [18–21].”
ResultOstrow, A. M., Freeze, H. H., & Rychik, J. R. (2006) · The Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2006.02.048 · Cited by 171
The oral microbiome in the pathophysiology of cardiovascular disease
Tonelli, A., Lumngwena, E. N., & Ntusi, N. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00825-3 · Cited by 184
Song, W. (2000) · Cardiovascular Research · doi:10.1016/s0008-6363(99)00395-8 · Cited by 169
ESPEN Guidelines on Enteral Nutrition: Cardiology and Pulmonology
Anker, S. D., John, M., Pedersen, P. U., Raguso, C. A., Cicoira, M., Dardai, E., Laviano, A., Ponikowski, P. P., Schols, A. M. W. J., Becker, H. F., et al. (2006) · Clinical Nutrition · doi:10.1016/j.clnu.2006.01.017 · Cited by 170
“Neuroendocrine and immunological disturbances underly the altered balance between anabolism and catabolism in these patients(4) with increased plasma levels of catecholamines, cortisol, aldosterone, and rennin,(11) steroid and growth hormone resistance,(12,13) and activation of cytokines.(14,15) Protein malabsorption…”
BackgroundTumor necrosis factor-alpha is released from the isolated heart undergoing ischemia and reperfusion
Gurevitch, J., Frolkis, I., Yuhas, Y., Paz, Y., Matsa, M., Mohr, R., & Yakirevich, V. (1996) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(96)00105-2 · Cited by 168
Characteris Tics and Causes of Immune Dysfunction Related to Uremia and Dialysis
Hauser, A. B., Stinghen, A. E. M., Kato, S., Bucharles, S. G. E., Aita, C. A. M., Yuzawa, Y., & Pecoits‐Filho, R. (2008) · Peritoneal Dialysis International · doi:10.1177/089686080802803s34 · Cited by 168
“This activation could be explained by bacterial or endotoxin translocation in patients with severe gut edema as a result of extreme volume overload (27), which in turn may lead to increased production of proinflammatory cytokines (28).”
BackgroundTumour necrosis factor alpha in severe congestive cardiac failure.
Dutka, D. P., Elborn, J. S., Delamere, F. M., Shale, D. J., & Morris, G. K. (1993) · Heart · doi:10.1136/hrt.70.2.141 · Cited by 168
Bergamini, C., Cicoira, M., Rossi, A., & Vassanelli, C. (2009) · European Journal of Heart Failure · doi:10.1093/eurjhf/hfp042 · Cited by 166
Richards, M., Nicholls, M. G., Yandle, T. G., Ikram, H., Espiner, E. A., Turner, J. G., Buttimore, R. C., Lainchbury, J. G., Elliott, J. M., Frampton, C. M., et al. (1999) · Heart · doi:10.1136/hrt.81.2.114 · Cited by 166
Aukrust, P., Gullestad, L. L., Ueland, T., Damås, J. K., & Yndestad, A. (2005) · Annals of Medicine · doi:10.1080/07853890510007232 · Cited by 171
“(3), numerous studies have demonstrated that HF patients have raised plasma/serum levels of inflammatory cytokines such as tumor necrosis factor (TNF)a, interleukin (IL)1b, IL-6 as well as several chemokines, e.”
BackgroundKassiri, Z., Oudit, G. Y., Sanchez, O. H., Dawood, F., Mohammed, F. F., Nuttall, R. K., Edwards, D. R., Liu, P. P., Backx, P. H., & Khokha, R. (2005) · Circulation Research · doi:10.1161/01.res.0000178789.16929.cf · Cited by 165
Yamada, T., Matsumori, A., & Sasayama, S. (1994) · Circulation · doi:10.1161/01.cir.89.2.846 · Cited by 164
Cardiac Troponins in Dogs and Cats
Langhorn, R., & Willesen, J. L. (2015) · Journal of Veterinary Internal Medicine · doi:10.1111/jvim.13801 · Cited by 178
Molecular mechanisms of angiotensin II-induced vascular injury
Ruiz‐Ortega, M., Rupérez, M., Esteban, V., & Egido, J. (2003) · Current Hypertension Reports · doi:10.1007/s11906-003-0014-0 · Cited by 163
“High levels of TNF-α have also been found in endothelial cells of human atheroma plaques [ 23 ].”
BackgroundThe Nutrition Implications of Cardiac Cachexia
Freeman, L. M., & Roubenoff, R. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1994.tb01358.x · Cited by 163
Increased Sensitivity to Nitric Oxide Synthase Inhibition in Patients With Heart Failure
Hare, J. M., Givertz, M. M., Creager, M. A., & Colucci, W. S. (1998) · Circulation · doi:10.1161/01.cir.97.2.161 · Cited by 163
“of TNF-a and IL-6 are increased in patients with heart failure.(29,30) Recently, Torre-Amione et al(31) and Habib et al(22) have further demonstrated that the expression of TNF-a is”
BackgroundMelenovský, V., Kotrč, M., Borlaug, B. A., Marek, T., Kovář, J., Málek, I., & Kautzner, J. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.06.046 · Cited by 159
“Tumor necrosis factor– alpha, a cytokine elevated in cardiac cachexia (41), has potent negative inotropic effects (42) and is correlated with”
BackgroundMcMurray, J. J. V., KJEKSHUS, J. K., Gullestad, L. L., Dunselman, P., Hjalmarson, Å. C., Wedel, H., Lindberg, M., Waagstein, F., Grande, P., Hradec, J., et al. (2009) · Circulation · doi:10.1161/circulationaha.109.849117 · Cited by 162
Lopshire, J. C., Zhou, X., Dusa, C., Ueyama, T., Rosenberger, J. G., Courtney, N., Ujhelyi, M. R., Mullen, T. J., Das, M. K., & Zipes, D. P. (2009) · Circulation · doi:10.1161/circulationaha.108.812412 · Cited by 161
Aßmus, B., Cremer, S., Kirschbaum, K., Culmann, D., Kiefer, K. C., Dorsheimer, L., Rasper, T., Abou‐El‐Ardat, K., Herrmann, E. M., Berkowitsch, A., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa845 · Cited by 168
Verghese, G. M., Ware, L. B., Matthay, B. A., & Matthay, M. A. (1999) · Journal of Applied Physiology · doi:10.1152/jappl.1999.87.4.1301 · Cited by 161
“Second, levels of circulating TNF-a, a cytokine that has been shown to upregulate alveolar fluid clearance experimentally (50), are elevated in patients with chronic congestive heart failure (16, 34).”
BackgroundThe Inflammasome in Myocardial Injury and Cardiac Remodeling
Toldo, S. A., Mezzaroma, E., Mauro, A. G., Salloum, F. N., Tassell, B. W. V., & Abbate, A. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.5989 · Cited by 165
“Accordingly, patients with HF have elevated plasma levels of inflammatory biomarkers that are direct predictors of worse prognosis (43, 66, 76).”
Metadata
- Authors
- Levine, B., Kalman, J., Mayer, L., Fillit, H. M., & Packer, M.
- Affiliations
- City University of New York (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1990-07-26
- Volume
- 323
- Issue
- 4
- Pages
- 236-241
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2324476825
- Cited by
- 2,582
- References
- 55
- Citations by year
- 2026: 21 · 2025: 43 · 2024: 49 · 2023: 34 · 2022: 70 · 2021: 63 · 2020: 64 · 2019: 64 · 2018: 59 · 2017: 64 · 2016: 58 · 2015: 70 · 2014: 75 · 2013: 73 · 2012: 79
- FWCI
- 29.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (7r01hl025055-11, 5r01ca041583-06, 5k04hl001229-02)
- National Heart, Lung, and Blood Institute (KO4-HL-01229, R01-HL-25055)
- National Cancer Institute (R01-CA41583)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Keywords
- TNF-α, chronic heart failure, cardiac cachexia, serum cytokines, plasma renin activity, serum sodium, hemoglobin, blood urea nitrogen, chronic kidney disease, cytokine clearance, advanced heart failure, weight loss, inflammation in heart failure, anemia of heart failure, hyperuricemia, hyperkalemia
- MeSH terms
- Adult, Aged, Aged, 80 and over, Chronic Disease, Female, Heart Failure, Hemoglobins, Humans, Male, Middle Aged, Renin, Sodium, Tumor Necrosis Factor-alpha
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
