Endotoxin and immune activation in chronic heart failure: a prospective cohort study
Abstract
Background Immune activation in patients with chronic heart failure may be secondary to endotoxin (lipopolysaccharide) action. We investigated the hypothesis that altered gut permeability with bacterial translocation and endotoxaemia would be increased in patients with oedema secondary to congestive heart failure.Methods We compared 20 patients who had chronic heart failure with recent-onset peripheral oedema (mean age 64 years [SD 10], New York Heart Association [NYHA] class 3.3 [0.7]), 20 stable non-oedematous patients with chronic heart failure (mean age 63 years [19], NYHA class 2.6 [0.7]), and 14 healthy volunteers (mean age 55 years [16]). Biochemical markers of endotoxaemia, inflammation, and immune activation were measured. Ten patients were studied within 1 week of complete resolution of oedema. Five patients survived longer than 6 months and were restudied again after remaining free of oedema for more than 3 months.Findings Mean endotoxin concentrations were higher in oedematous patients with chronic heart failure than in stable patients with chronic heart failure (0.74 [SD 0.45] vs 0.37 EU/mL [0.23], p=0.0009) and controls (0.46 EU/mL [0.21], p=0.02). Oedematous patients had the highest concentrations of several cytokines. After short-term diuretic treatment, endotoxin concentrations decreased from 0.84 EU/mL [0.49] to 0.45 EU/mL [0.21], p<0.05) but cytokines remained raised. After freedom of oedema for more than 3 months after oedema resolved, endotoxin concentrations remained unchanged from the previous visit (0.49 EU/mL [0.06], p=0.45).Interpretation Raised concentrations of endotoxin and cytokines are found in patients with chronic heart failure during acute oedematous exacerbation. Intensified diuretic treatment can normalise endotoxin concentrations. Our preliminary findings suggest that endotoxin may trigger immune activation in patients with chronic heart failure during oedematous episodes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Patients with decompensated heart failure have higher endotoxin levels in the blood compared to stable patients.
“Patients with decompensated heart failure have higher endotoxin levels in the blood compared to stable patients25.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [25]
Endotoxin levels in patients with heart failure are reduced with diuretic or antibiotic therapy, but plasma cytokine levels have not always been observed to change.
“Interestingly, while endotoxin levels in patients with heart failure have been shown to be reduced with diuretic or antibiotic therapy, plasma cytokine levels have not always been observed to change, suggesting a sustained effect as the disease process is triggered38,46.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [38]
Patients with decompensated heart failure have higher blood levels of endotoxin.
“Patients with decompensated heart failure have higher blood levels of endotoxin38.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [38]
Cites
Elevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart Failure
Levine, B., Kalman, J., Mayer, L., Fillit, H. M., & Packer, M. (1990) · New England Journal of Medicine · doi:10.1056/nejm199007263230405 · Cited by 2,582 · see citing works
High serum procalcitonin concentrations in patients with sepsis and infection
Assicot, M., Bohuon, C., Gendrel, D., Raymond, J., Carsin, H., & Guilbaud, J. (1993) · The Lancet · doi:10.1016/0140-6736(93)90277-n · Cited by 2,195 · see citing works
Structure and Function of Lipopolysaccharide Binding Protein
Schumann, R. R., Leong, S. R., Flaggs, G., Gray, P. W., Wright, S. D., Mathison, J. C., Tobias, P. S., & Ulevitch, R. J. (1990) · Science · doi:10.1126/science.2402637 · Cited by 1,672 · see citing works
Self-citationToll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling
Yang, R.-B., Mark, M., Gray, A., Huang, A., Xie, M.-H., Zhang, M., Goddard, A., Wood, W., Gurney, A., & Godowski, P. (1998) · Nature · doi:10.1038/26239 · Cited by 1,319 · see citing works
Tumor Necrosis Factor-α and Tumor Necrosis Factor Receptors in the Failing Human Heart
Torre‐Amione, G., Kapadia, S. R., Lee, J. J., Durand, J., Bies, R. D., Young, J. B., & Mann, D. L. (1996) · Circulation · doi:10.1161/01.cir.93.4.704 · Cited by 991 · see citing works
Anker, S. D., Chua, T. P., Ponikowski, P., Harrington, D., Swan, J. W., Kox, W. J., Poole-Wilson, P. A., & Coats, A. J. S. (1997) · Circulation · doi:10.1161/01.cir.96.2.526 · Cited by 800 · see citing works
Self-citationCD14: Cell surface receptor and differentiation marker
Ziegler-Heitbrock, H. W. L., & Ulevitch, R. J. (1993) · Immunology Today · doi:10.1016/0167-5699(93)90212-4 · Cited by 585 · see citing works
Keith, M. E., Geranmayegan, A., Sole, M. J., Kurian, R., Robinson, A., Omran, A., & Jeejeebhoy, K. N. (1998) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(98)00101-6 · Cited by 556 · see citing works
Exercise limitation in chronic heart failure: Central role of the periphery
Clark, A. L., Poole-Wilson, P. A., & Coats, A. J. S. (1996) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(96)00323-3 · Cited by 523 · see citing works
Self-citationRandow, F., Syrbe, U., Meisel, C., Krausch, D., Zuckermann, H., Platzer, C., & Volk, H. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.5.1887 · Cited by 446 · see citing works
Self-citationElevated soluble CD14 receptors and altered cytokines in chronic heart failure
Anker, S. D., Egerer, K. R., Volk, H.-D., Kox, W. J., Poole-Wilson, P. A., & Coats, A. J. S. (1997) · The American Journal of Cardiology · doi:10.1016/s0002-9149(97)00159-8 · Cited by 392 · see citing works
Self-citationLPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria.
Lamping, N., Dettmer, R., Schröder, N. W. J., Pfeil, D., Hallatschek, W., Burger, R., & Schumann, R. R. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2338 · Cited by 345 · see citing works
Self-citationInduction of Interleukin 6 (IL-6) by Hypoxia in Vascular Cells
Yan, S. F., Tritto, I., Pinsky, D. J., Liao, H., Huang, J. G., Fuller, G. M., Brett, J., May, L. T., & Stern, D. M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.19.11463 · Cited by 345 · see citing works
Munger, M. A., Johnson, B., Amber, I. J., Callahan, K. S., & Gilbert, E. M. (1996) · The American Journal of Cardiology · doi:10.1016/s0002-9149(97)89206-5 · Cited by 237 · see citing works
Gomez-Jimenez, J., Salgado, A., Mourelle, M., Martín, M. C., Segura, R., Peracaula, R., & Moncada, S. (1995) · Critical Care Medicine · doi:10.1097/00003246-199502000-00009 · Cited by 205 · see citing works
Anker, 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 · see citing works
Self-citationLipopolysaccharide (LPS)-binding Proteins BPI and LBP Form Different Types of Complexes with LPS
Tobias, P. S., Soldau, K., Iovine, N. M., Elsbach, P., & Weiss, J. P. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.30.18682 · Cited by 122 · see citing works
Lamping, N., Hoess, A., Yu, B., Park, T. C., Kirschning, C. J., Pfeil, D., Reuter, D., Wright, S. D., Herrmann, F., & Schumann, R. R. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.10.4648 · Cited by 121 · see citing works
Self-citationEndotoxin Tolerance after Severe Injury and Its Regulatory Mechanisms
Keel, M. J. B., Schregenberger, N., Steckholzer, U., Ungethüm, U., Kenney, J. S., Trentz, O., & Ertel, W. (1996) · doi:10.1097/00005373-199609000-00008 · Cited by 100 · see citing works
Anker, S. D., Volterrani, M., Egerer, K., et al. (1998) · QJM · doi:10.1093/qjmed/91.3.199 · Cited by 84 · see citing works
Self-citationWagner, D. R., McTiernan, C. F., Sanders, V. J., & Feldman, A. M. (1998) · Circulation · doi:10.1161/01.cir.97.6.521 · Cited by 81 · see citing works
Sautner, T., Wessely, C., Riegler, M. F., et al. (1998) · Annals of Surgery · doi:10.1097/00000658-199808000-00014 · Cited by 73 · see citing works
Vonhof, S., Brost, B. C., Stille‐Siegener, M., Grumbach, I. M., Kreuzer, H., & Figulla, H. R. (1998) · International Journal of Cardiology · doi:10.1016/s0167-5273(97)00332-x · Cited by 64 · see citing works
Vanderheyden, M. (1998) · European Heart Journal · doi:10.1053/euhj.1997.0828 · Cited by 57 · see citing works
Eggesbø, J. B., Hjermann, I., Lund, P. K., et al. (1994) · Cytokine · doi:10.1016/1043-4666(94)90080-9 · Cited by 45 · see citing works
Lipopolysaccharide induces cell shrinkage in rabbit ventricular cardiac myocytes
Lew, W. Y. W., Ryan, J., & Yasuda, S. (1997) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1997.272.6.h2989 · Cited by 14 · see citing works
Direct action of endotoxin on cardiac muscle.
Starr, R. G., As, L., Gc, P., et al. (1995) · PubMed · Cited by 10 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Gut microbiota and cardiovascular disease.
Witkowski, M., Weeks, T. L., & Hazen, S. L. (2020) · Circulation Research · doi:10.1161/circresaha.120.316242 · Cited by 1,051 · see citing works
Plasma Cytokine Parameters and Mortality in Patients With Chronic Heart Failure
Rauchhaus, M., Doehner, W., Francis, D. P., Davos, C., Kemp, M., Liebenthal, C., Niebauer, J., Hooper, J., Volk, H.-D., Coats, A. J. S., et al. (2000) · Circulation · doi:10.1161/01.cir.102.25.3060 · Cited by 810 · see citing works
Self-citationDietary metabolism, the gut microbiome, and heart failure
Tang, W. H. W., Li, D. Y., & Hazen, S. L. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0108-7 · Cited by 789 · see citing works
Erridge, C., Attina, T., Spickett, C. M., & Webb, D. J. (2007) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.5.1286 · Cited by 776 · see citing works
Altered intestinal function in patients with chronic heart failure
Sandek, A., Bauditz, J., Swidsinski, A., Buhner, S., Weber-Eibel, J., von Haehling, S., Schroedl, W., Karhausen, T., Doehner, W., Rauchhaus, M., et al. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.07.016 · Cited by 661 · see citing works
Self-citationInflammatory mediators in chronic heart failure: an overview
Anker, S. D., & von Haehling, S. (2004) · Heart · doi:10.1136/hrt.2002.007005 · Cited by 627 · see citing works
Self-citationSurvival advantages of obesity in dialysis patients
Kalantar-Zadeh, K., Abbott, K. C., Salahudeen, A. K., Kilpatrick, R. D., & Horwich, T. B. (2005) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.3.543 · Cited by 610 · see citing works
Obesity and the Obesity Paradox in Heart Failure
Horwich, T. B., Fonarow, G. C., & Clark, A. L. (2018) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2018.05.005 · Cited by 392 · see citing works
Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability
de Punder, K., & Pruimboom, L. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00223 · Cited by 321 · see citing works
Anemia predicts mortality in severe heart failure
Mozaffarian, D., Nye, R., & Levy, W. C. (2003) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(03)00425-x · Cited by 294 · see citing works
Systemic inflammation in heart failure – The whys and wherefores
Yndestad, A., Kristian Damås, J., Øie, E., Ueland, T., Gullestad, L., & Aukrust, P. (2006) · Heart Failure Reviews · doi:10.1007/s10741-006-9196-2 · Cited by 294 · see citing works
Protein nutrition and malnutrition in CKD and ESRD
Zha, Y., & Qian, Q. (2017) · Nutrients · doi:10.3390/nu9030208 · Cited by 292 · see citing works
The importance of the gastrointestinal system in the pathogenesis of heart failure
Krack, A., Sharma, R., Figulla, H. R., & Anker, S. D. (2005) · European Heart Journal · doi:10.1093/eurheartj/ehi389 · Cited by 280 · see citing works
Self-citationIntersections Between Microbiome and Heart Failure: Revisiting the Gut Hypothesis
Nagatomo, Y., & Tang, W. H. W. (2015) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2015.09.017 · Cited by 259 · see citing works
Hoeper, M. M., Benza, R. L., Corris, P., de Perrot, M., Fadel, E., Keogh, A. M., Kühn, C., Savale, L., & Klepetko, W. (2019) · European Respiratory Journal · doi:10.1183/13993003.01906-2018 · Cited by 216 · see citing works
Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk
Neves, A. L., Coelho, J., Couto, L., Leite-Moreira, A., & Roncon-Albuquerque, R. (2013) · Journal of Molecular Endocrinology · doi:10.1530/jme-13-0079 · Cited by 211 · see citing works
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 · see citing works
Self-citationCostanza, A. C., Moscavitch, S. D., Faria Neto, H. C. C., & Mesquita, E. T. (2015) · International Journal of Cardiology · doi:10.1016/j.ijcard.2014.11.034 · Cited by 182 · see citing works
Maes, M., Ruckoanich, P., Chang, Y. S., Mahanonda, N., & Berk, M. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.06.008 · Cited by 169 · see citing works
Many good reasons to have STAT3 in the heart
Hilfiker-Kleiner, D., Hilfiker, A., & Drexler, H. (2005) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.02.003 · Cited by 115 · see citing works
Arutyunov, G. P., Kostyukevich, O. I., Serov, R. A., Rylova, N. V., & Bylova, N. A. (2008) · International Journal of Cardiology · doi:10.1016/j.ijcard.2007.11.103 · Cited by 103 · see citing works
Marlicz, W., Łoniewski, I., Grimes, D. S., & Quigley, E. M. (2014) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2014.07.015 · Cited by 91 · see citing works
Krack, A., Richartz, B. M., Gastmann, A., Greim, K., Lotze, U., Anker, S. D., & Figulla, H. R. (2004) · European Journal of Heart Failure · doi:10.1016/j.ejheart.2004.03.002 · Cited by 83 · see citing works
Self-citationHow are Cytokines Activated in Heart Failure?
Paulus, W. J. (1999) · European Journal of Heart Failure · doi:10.1016/s1388-9842(99)00049-5 · Cited by 72 · see citing works
Mamic, P., Heidenreich, P. A., Hedlin, H., Tennakoon, L., & Staudenmayer, K. L. (2016) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2016.06.005 · Cited by 59 · see citing works
The effect of n-3 fatty acids on C-reactive protein levels in patients with chronic renal failure
Madsen, T., Schmidt, E. B., & Christensen, J. H. (2007) · Journal of Renal Nutrition · doi:10.1053/j.jrn.2007.03.003 · Cited by 52 · see citing works
The Role of Microbiota in Cardiovascular Risk: Focus on Trimethylamine Oxide
Al-Rubaye, H., Perfetti, G., & Kaski, J.-C. (2019) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2018.06.005 · Cited by 43 · see citing works
Inflammation and chronic heart failure–potential therapeutic role of intravenous immunoglobulin
Aukrust, P., Yndestad, A., Damås, J. K., & Gullestad, L. (2004) · Autoimmunity Reviews · doi:10.1016/s1568-9972(03)00103-4 · Cited by 37 · see citing works
Nguyen, M., Gautier, T., Masson, D., Bouhemad, B., & Guinot, P.-G. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12072579 · Cited by 25 · see citing works
“Once perfusion is restored, treating venous congestion may help to reduce the endotoxin burden [48].”
BackgroundPlasma concentrations of bacterial lipopolysaccharide: a marker of infection or inflammation?
Rauchhaus, M., & Anker, S. D. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)00750-6 · Cited by 5 · see citing works
Self-citation
- Authors
- Niebauer, J., Volk, H.-D., Kemp, M., Dominguez, M., Schumann, R. R., Rauchhaus, M., Poole-Wilson, P. A., Coats, A. J., & Anker, S. D.
- Affiliations
- Imperial College London (GB)
- Charité – Universitätsmedizin Berlin (DE)
- Harefield Hospital (GB)
- Max Delbrück Center (DE)
- Corresponding author
- Anker, Stefan D
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 1999-05
- Volume
- 353
- Issue
- 9167
- Pages
- 1838-1842
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2160000314
- Cited by
- 877
- References
- 27
- Citations by year
- 2026: 16 · 2025: 29 · 2024: 28 · 2023: 41 · 2022: 31 · 2021: 38 · 2020: 32 · 2019: 25 · 2018: 33 · 2017: 35 · 2016: 25 · 2015: 21 · 2014: 25 · 2013: 35 · 2012: 27
- FWCI
- 27.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- chronic heart failure, endotoxin, lipopolysaccharide, endotoxemia, immune activation, peripheral edema, congestive heart failure, intestinal permeability, bacterial translocation, cytokines, inflammation, diuretic therapy
- MeSH terms
- Lipopolysaccharide-Binding Protein, Acute-Phase Proteins, Carrier Proteins, Diuretics, Edema, Cardiac, Endotoxins, Heart Failure, Humans, Membrane Glycoproteins, Middle Aged, Prospective Studies, Time Factors, Cohort Studies, Cytokines, Bacterial Translocation, Endotoxemia
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
