{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:48:39Z","timestamp":1790045319506,"version":"4.0.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2015,2,22]],"date-time":"2015-02-22T00:00:00Z","timestamp":1424563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Reagents for measuring NT-proBNP in Val-HeFT and GISSI-HF were kindly provided by Roche Diagnostics GmbH."},{"DOI":"10.13039\/501100004963","name":"the European Commission\u00e2\u20ac\u2122s Seventh Framework Programme","doi-asserted-by":"crossref","award":["under grant agreement No. 305507 (HOMAGE)"],"award-info":[{"award-number":["under grant agreement No. 305507 (HOMAGE)"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The GISSI-HF trial was supported by grants from Societ\u00c3\u00a0 Prodotti Antibiotici (SPA, Italy), Pfizer, Sigma Tau and AstraZeneca."},{"name":"The Val-HeFT trial was funded by Novartis Pharmaceuticals (Switzerland)."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Uncertainties remain on the biological and prognostic significance and therapeutic implications of loss in body weight (W-LOSS) in chronic heart failure (HF) patients. We assessed whether W-LOSS added additional prognostic value to classical clinical risk factors in two separate and large cohorts of patients with chronic HF. The factors associated with W-LOSS were studied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>W-LOSS and estimated plasma volume changes were measured serially in the GISSI-HF (n = 6820) and Val-HeFT trials (n = 4892). In both studies, experiencing at least one episode of \u22655% W-LOSS during the first year of follow-up was considered a sign of wasting. In GISSI-HF, self-reported unintentional W-LOSS \u22652 kg between two consecutive clinical visits within 1 year was also considered a sign of wasting. W-LOSS occurred in 16.4% and 15.7% of the patients enrolled in GISSI-HF and Val-HeFT, respectively (unintentional \u22652 kg W-LOSS occurred in 18.9% in GISSI-HF). In multivariable analyses adjusting for a number of baseline covariates as well as for plasma volume changes, W-LOSS was found to be independently associated with mortality and adverse cardiovascular and non-cardiovascular outcomes, with a significant net reclassification improvement (cfNRI) and an increase in integrated discrimination improvement (IDI). W-LOSS was independently associated with several features representing the severity of HF, including baseline NT-proBNP and high sensitivity C-reactive protein (hsCRP) in Val-HeFT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>W-LOSS was a frequent finding in the GISSI-HF and Val-HeFT trials, associated with multiple patient features, and added additional prognostic information beyond clinical variables of HF severity, including estimated plasma volume changes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.240","type":"journal-article","created":{"date-parts":[[2015,2,22]],"date-time":"2015-02-22T23:53:02Z","timestamp":1424649182000},"page":"424-433","source":"Crossref","is-referenced-by-count":116,"title":["Loss in Body Weight is an Independent Prognostic Factor for Mortality in Chronic Heart Failure: Insights from the GISSI-HF and Val-HeFT Trials"],"prefix":"10.1093","volume":"17","author":[{"given":"Patrick","family":"Rossignol","sequence":"first","affiliation":[{"name":"INSERM, Centre d\u2019Investigations Cliniques-Plurith\u00e9matique 1433 , Nancy ,","place":["France"]},{"name":"Universit\u00e9 de Lorraine \u00a0","place":["France"]},{"name":"INSERM U1116 , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Masson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Research, IRCCS\u2013Istituto di Ricerche Farmacologiche Mario Negri , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Barlera","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Research, IRCCS\u2013Istituto di Ricerche Farmacologiche Mario Negri , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Girerd","sequence":"additional","affiliation":[{"name":"INSERM, Centre d\u2019Investigations Cliniques-Plurith\u00e9matique 1433 , Nancy ,","place":["France"]},{"name":"Universit\u00e9 de Lorraine \u00a0","place":["France"]},{"name":"INSERM U1116 , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Castelnovo","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Research, IRCCS\u2013Istituto di Ricerche Farmacologiche Mario Negri , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"INSERM, Centre d\u2019Investigations Cliniques-Plurith\u00e9matique 1433 , Nancy ,","place":["France"]},{"name":"Universit\u00e9 de Lorraine \u00a0","place":["France"]},{"name":"INSERM U1116 , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Clemenza","sequence":"additional","affiliation":[{"name":"Heart Failure Unit\u2013ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione) , Palermo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Tognoni","sequence":"additional","affiliation":[{"name":"Fondazione Mario Negri Sud , Santa Maria Imbaro ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inder S.","family":"Anand","sequence":"additional","affiliation":[{"name":"Veterans Affairs Medical Center and University of Minnesota , Minneapolis, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay N.","family":"Cohn","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, University of Minnesota Medical School , Minneapolis, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Department of Innovative Clinical Trials, University Medical Centre G\u00f6ttingen , G\u00f6ttingen ,","place":["Germany"]},{"name":"Institute of Diabetes for Older People (IDOP), University of Bedfordshire \u00a0","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Tavazzi","sequence":"additional","affiliation":[{"name":"GVM Hospitals of Care and Research, E.S Health Science Foundation , Cotignola ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Latini","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Research, IRCCS\u2013Istituto di Ricerche Farmacologiche Mario Negri , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,22]]},"reference":[{"key":"2026011921084674600_ejhf240-bib-0001","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/S0735-1097(01)01448-6","article-title":"The relationship between obesity and mortality in patients with heart failure","volume":"38","author":"Horwich","year":"2001","journal-title":"J Am Coll Cardiol"},{"key":"2026011921084674600_ejhf240-bib-0002","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1016\/j.jacc.2008.12.068","article-title":"Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss","volume":"53","author":"Lavie","year":"2009","journal-title":"J Am Coll Cardiol"},{"key":"2026011921084674600_ejhf240-bib-0003","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/S0140-6736(96)07015-8","article-title":"Wasting as independent risk factor for mortality in chronic heart failure","volume":"349","author":"Anker","year":"1997","journal-title":"Lancet"},{"key":"2026011921084674600_ejhf240-bib-0004","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/S0140-6736(03)12892-9","article-title":"Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitors: an observational study","volume":"361","author":"Anker","year":"2003","journal-title":"Lancet"},{"key":"2026011921084674600_ejhf240-bib-0005","doi-asserted-by":"crossref","first-page":"2641","DOI":"10.1093\/eurheartj\/ehn420","article-title":"Weight loss and mortality risk in patients with chronic heart failure in the candesartan in heart failure: assessment of reduction in mortality and morbidity (charm) programme","volume":"29","author":"Pocock","year":"2008","journal-title":"Eur Heart J"},{"key":"2026011921084674600_ejhf240-bib-0006","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.pharmthera.2008.09.009","article-title":"Cardiac cachexia: a systematic overview","volume":"121","author":"von Haehling","year":"2009","journal-title":"Pharmacol Ther"},{"key":"2026011921084674600_ejhf240-bib-0007","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s11897-013-0153-9","article-title":"Mechanisms for cachexia in heart failure","volume":"10","author":"Pureza","year":"2013","journal-title":"Curr Heart Fail Rep"},{"key":"2026011921084674600_ejhf240-bib-0008","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ijcard.2012.10.018","article-title":"Highlights of the mechanistic and therapeutic cachexia and sarcopenia research 2010 to 2012 and their relevance for cardiology","volume":"162","author":"Anker","year":"2013","journal-title":"Int J Cardiol"},{"key":"2026011921084674600_ejhf240-bib-0009","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1172\/JCI102501","article-title":"Water diuresis produced during recumbency by the intravenous infusion of isotonic saline solution","volume":"30","author":"Strauss","year":"1951","journal-title":"J Clin Invest"},{"key":"2026011921084674600_ejhf240-bib-0010","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1016\/S0735-1097(02)01903-4","article-title":"The regulation and measurement of plasma volume in heart failure","volume":"39","author":"Kalra","year":"2002","journal-title":"J Am Coll Cardiol"},{"key":"2026011921084674600_ejhf240-bib-0011","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1016\/j.jacc.2011.04.049","article-title":"Eplerenone survival benefits in heart failure patients post-myocardial infarction are independent from its diuretic and potassium-sparing effects. Insights from an ephesus (eplerenone post-acute myocardial infarction heart failure efficacy and survival study) substudy","volume":"58","author":"Rossignol","year":"2011","journal-title":"J Am Coll Cardiol"},{"key":"2026011921084674600_ejhf240-bib-0012","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/S0140-6736(08)61239-8","article-title":"Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial","volume":"372","author":"Tavazzi","year":"2008","journal-title":"Lancet"},{"key":"2026011921084674600_ejhf240-bib-0013","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1056\/NEJMoa010713","article-title":"A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure","volume":"345","author":"Cohn","year":"2001","journal-title":"N Engl J Med"},{"key":"2026011921084674600_ejhf240-bib-0014","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1161\/CIRCHEARTFAILURE.112.967828","article-title":"Predictors of mortality in 6975 patients with chronic heart failure in the gruppo italiano per lo studio della streptochinasi nell\u2019infarto miocardico-heart failure trial: proposal for a nomogram","volume":"6","author":"Barlera","year":"2013","journal-title":"Circ Heart Fail"},{"key":"2026011921084674600_ejhf240-bib-0015","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4757-3462-1","volume-title":"Regression Modeling Strategies With Applications to Linear Models, Logistic Regression, and Survival Analysis","author":"Harrell","year":"2001"},{"key":"2026011921084674600_ejhf240-bib-0016","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/sim.4085","article-title":"Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers","volume":"30","author":"Pencina","year":"2011","journal-title":"Stat Med"},{"key":"2026011921084674600_ejhf240-bib-0017","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.jacc.2013.09.072","article-title":"Body mass index and mortality in acutely decompensated heart failure across the world: a global obesity paradox","volume":"63","author":"Shah","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"2026011921084674600_ejhf240-bib-0018","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.pcad.2013.10.004","article-title":"Obesity and the obesity paradox in heart failure","volume":"56","author":"Clark","year":"2014","journal-title":"Prog Cardiovasc Dis"},{"key":"2026011921084674600_ejhf240-bib-0019","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jchf.2013.01.006","article-title":"Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure","volume":"1","author":"Lavie","year":"2013","journal-title":"JACC Heart Fail"},{"key":"2026011921084674600_ejhf240-bib-0020","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/chf.12040","article-title":"Analyzing the weight of evidence on the obesity paradox and heart failure\u2014is there a limit to the madness?","volume":"19","author":"Lavie","year":"2013","journal-title":"Congest Heart Fail"},{"key":"2026011921084674600_ejhf240-bib-0021","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/j.jacc.2014.01.022","article-title":"Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox","volume":"63","author":"Lavie","year":"2014","journal-title":"J Am Coll Cardiol."},{"key":"2026011921084674600_ejhf240-bib-0022","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1016\/j.mayocp.2014.04.033","article-title":"The prognostic importance of weight loss in coronary artery disease: a systematic review and meta-analysis","volume":"89","author":"Pack","year":"2014","journal-title":"Mayo Clin Proc"},{"key":"2026011921084674600_ejhf240-bib-0023","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.pcad.2013.09.003","article-title":"Impact of obesity and weight loss on cardiac performance and morphology in adults","volume":"56","author":"Alpert","year":"2014","journal-title":"Prog Cardiovasc Dis"},{"key":"2026011921084674600_ejhf240-bib-0024","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1097\/JCN.0b013e3182a46ba8","article-title":"The link of unintentional weight loss to cardiac event-free survival in patients with heart failure","volume":"29","author":"Song","year":"2014","journal-title":"J Cardiovasc Nurs"},{"key":"2026011921084674600_ejhf240-bib-0025","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1093\/eurjhf\/hft067","article-title":"Increased catabolic activity in adipose tissue of patients with chronic heart failure","volume":"15","author":"Szabo","year":"2013","journal-title":"Eur J Heart Fail"},{"key":"2026011921084674600_ejhf240-bib-0026","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1161\/01.CIR.96.2.526","article-title":"Hormonal changes and catabolic\/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia","volume":"96","author":"Anker","year":"1997","journal-title":"Circulation"},{"key":"2026011921084674600_ejhf240-bib-0027","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/1471-2261-12-77","article-title":"Effects of fish oil supplementation on inflammatory markers in chronic heart failure: a meta-analysis of randomized controlled trials","volume":"12","author":"Xin","journal-title":"BMC Cardiovasc Disord"},{"key":"2026011921084674600_ejhf240-bib-0028","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.metabol.2013.09.017","article-title":"Cross-talk between the heart and adipose tissue in cachectic heart failure patients with respect to alterations in body composition: a prospective study","volume":"63","author":"Christensen","year":"2014","journal-title":"Metabolism"},{"key":"2026011921084674600_ejhf240-bib-0029","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1007\/s12020-012-9836-3","article-title":"Prevalence of cachexia in chronic heart failure and characteristics of body composition and metabolic status","volume":"43","author":"Christensen","year":"2013","journal-title":"Endocrine"},{"key":"2026011921084674600_ejhf240-bib-0030","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/S0735-1097(01)01479-6","article-title":"Circulatory response to fluid overload removal by extracorporeal ultrafiltration in refractory congestive heart failure","volume":"38","author":"Marenzi","year":"2001","journal-title":"J Am Coll Cardiol"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fejhf.240","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/17\/4\/424\/66423570\/eurjhf_17_4_424.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/17\/4\/424\/66423570\/eurjhf_17_4_424.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T02:09:07Z","timestamp":1768874947000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/17\/4\/424\/8426608"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,22]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2015,2,22]]},"published-print":{"date-parts":[[2015,4,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.240","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,4]]},"published":{"date-parts":[[2015,2,22]]}}}