{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T06:47:09Z","timestamp":1792306029407,"version":"4.4.0"},"reference-count":149,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Obesity or excess visceral adiposity plays a fundamental role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF), but it is not clear that an expanded adipose tissue mass contributes importantly to the evolution and progression of heart failure with reduced ejection fraction (HFrEF). Whereas central adiposity characterizes most patients with HFpEF, obesity was not a remarkable feature of HFrEF in the large-scale trials carried out in the 1980s and 1990s, and studies typically characterized obesity as a protective factor against adverse outcomes. In the general community without apparent heart disease, the finding of obesity or central adiposity precedes and predicts the subsequent occurrence of HFpEF, but not HFrEF. The mass of epicardial adipose tissue\u2014an important source of cardioactive molecules\u2014is expanded in HFpEF, but it is diminished in HFrEF, and the decrease has adverse prognostic significance. An increased waist-to-height ratio (a marker of excess abdominal adiposity) is more strongly associated with adverse heart failure outcomes in HFpEF than in HFrEF. Systemic inflammation [as reflected by elevations of high-sensitivity C-reactive protein (hsCRP)] in the general community presages the development of HFpEF, but not HFrEF, presumably because excess adiposity augments hsCRP in HFpEF, whereas increases in hsCRP in HFrEF may be related to coexisting atherosclerosis or clinical congestion. Whereas obesity is the principal determinant of serum levels of leptin and adiponectin in HFpEF, cardiac and neurohormonal signalling may drive circulating levels of these adipokines in HFrEF. Central obesity identifies patients more likely to respond to mineralocorticoid receptor antagonists in both HFpEF and in HFrEF, but this feature also identifies patients more likely to respond neprilysin inhibition or sodium-glucose cotransporter 2 inhibitors if they have HFpEF, but not HFrEF. Weight loss by incretin-based drugs lowers systolic blood pressure in patients with HFpEF, but potentially not with HFrEF, and such weight loss is accompanied by a reduced risk of worsening heart failure events in patients with HFpEF, but without a similar benefit in HFrEF. Taken collectively, these observations raise important questions about the potential role of obesity and visceral adiposity as contributing factors in the evolution and progression of HFrEF.<\/jats:p>","DOI":"10.1093\/eurheartj\/ehaf645","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T11:34:03Z","timestamp":1754998443000},"page":"12-21","source":"Crossref","is-referenced-by-count":22,"title":["Do obesity and visceral adiposity promote heart failure with reduced ejection fraction?"],"prefix":"10.1093","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1828-2387","authenticated-orcid":false,"given":"Milton","family":"Packer","sequence":"first","affiliation":[{"name":"Baylor Heart and Vascular Institute, Baylor University Medical Center , 621 North Hall Street, Dallas, TX 75226 ,","place":["USA"]},{"name":"Imperial College , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"2026010418522284500_ehaf645-B1","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1093\/eurheartj\/ehaf057","article-title":"Near-universal prevalence of central adiposity in heart failure with preserved ejection fraction: the PARAGON-HF trial","volume":"46","author":"Peikert","year":"2025","journal-title":"Eur Heart J"},{"key":"2026010418522284500_ehaf645-B2","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1016\/j.jacc.2025.03.530","article-title":"Disentangling the impact of adiposity from insulin resistance in heart failure with preserved ejection fraction","volume":"85","author":"Reddy","year":"2025","journal-title":"J Am Coll Cardiol"},{"key":"2026010418522284500_ehaf645-B3","doi-asserted-by":"publisher","first-page":"e2231878","DOI":"10.1001\/jamanetworkopen.2022.31878","article-title":"Subclinical risk factors for heart failure with preserved and reduced ejection fraction among Black adults","volume":"5","author":"Zhao","year":"2022","journal-title":"JAMA Netw Open"},{"key":"2026010418522284500_ehaf645-B4","doi-asserted-by":"publisher","first-page":"e002711","DOI":"10.1136\/openhrt-2024-002711","article-title":"Adiposity, fat-free mass and incident heart failure in 500","volume":"11","author":"Oguntade","year":"2024","journal-title":"Open Heart"},{"key":"2026010418522284500_ehaf645-B5","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/j.jchf.2018.07.009","article-title":"Adiposity and incident heart failure and its subtypes: MESA (Multi-Ethnic Study of Atherosclerosis)","volume":"6","author":"Rao","year":"2018","journal-title":"JACC Heart Fail"},{"key":"2026010418522284500_ehaf645-B6","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1093\/eurheartj\/ehaa823","article-title":"Pathophysiologic importance of visceral adipose tissue in women with heart failure and preserved ejection fraction","volume":"42","author":"Sorimachi","year":"2021","journal-title":"Eur Heart J"},{"key":"2026010418522284500_ehaf645-B7","doi-asserted-by":"publisher","first-page":"e010618","DOI":"10.1161\/CIRCHEARTFAILURE.123.010618","article-title":"Obesity-related biomarkers are associated with exercise intolerance and HFpEF","volume":"16","author":"Ramirez","year":"2023","journal-title":"Circ Heart Fail"},{"key":"2026010418522284500_ehaf645-B8","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1016\/S0140-6736(24)00469-0","article-title":"Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials","volume":"403","author":"Butler","year":"2024","journal-title":"Lancet"},{"key":"2026010418522284500_ehaf645-B9","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1056\/NEJMoa2410027","article-title":"Tirzepatide for heart failure with preserved ejection fraction and obesity","volume":"392","author":"Packer","year":"2025","journal-title":"N Engl J Med"},{"key":"2026010418522284500_ehaf645-B10","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/0735-1097(92)90167-L","article-title":"The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure","volume":"20","author":"Packer","year":"1992","journal-title":"J Am Coll Cardiol"},{"key":"2026010418522284500_ehaf645-B11","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1097\/CRD.0b013e31815d29e9","article-title":"Does body mass index really matter in the management of heart failure?: a review of the literature","volume":"16","author":"Sagar","year":"2008","journal-title":"Cardiol Rev"},{"key":"2026010418522284500_ehaf645-B12","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1136\/bmj.321.7255.215","article-title":"Do patients with suspected heart failure and preserved left ventricular systolic function suffer from \u201cdiastolic heart failure\u201d or from misdiagnosis? 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