{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T00:13:28Z","timestamp":1793578408660,"version":"4.5.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Cardiovascular-kidney-metabolic (CKM) multimorbidity is prevalent among individuals with heart failure (HF), but whether cardiac structure and function, clinical outcomes, and treatment response to sacubitril\/valsartan vary in relation to CKM status is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In this PARAGON-HF post-hoc analysis, we evaluated the impact of CKM multimorbidity (atherosclerotic cardiovascular [CV] disease, chronic kidney disease, and type 2 diabetes) on cardiac structure and function, clinical outcomes, and treatment effects of sacubitril\/valsartan versus valsartan. The primary outcome was a composite of total HF hospitalizations and CV death. Secondary outcomes included the individual components of the primary outcome and a composite kidney outcome (sustained estimated glomerular filtration rate reduction of \u226550%, end-stage kidney disease, or kidney-related death). At baseline, 35.2% had one CKM condition, 33.3% had two, 15.9% had three, and only 15.6% had HF alone. CKM multimorbidity was associated with higher septal and posterior wall thickness, lower global longitudinal strain, higher E\/e', and worse right ventricular function. Total HF hospitalizations or CV death increased with greater CKM multimorbidity, with the highest relative risk observed with three CKM conditions (rate ratio 3.06, 95% confidence interval 2.33\u20134.03), compared with HF alone. Treatment effects of sacubitril\/valsartan were consistent irrespective of the number of CKM conditions for the primary endpoint (pinteraction\u2009=\u20090.75), CV death (pinteraction\u2009=\u20090.82), total HF hospitalizations (pinteraction\u2009=\u20090.67), and the composite kidney endpoint (pinteraction\u2009=\u20090.99).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cardiovascular-kidney-metabolic multimorbidity was common in PARAGON-HF and associated with adverse changes in cardiac structure and function and with a stepwise increase in risk of clinical outcomes. Treatment effects of sacubitril\/valsartan were consistent irrespective of CKM burden.<\/jats:p>\n                    <jats:p>Clinical Trial Registration: ClinicalTrials.gov \u00a0NCT01920711.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3304","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T02:50:11Z","timestamp":1719456611000},"page":"1762-1774","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Cardiovascular-Kidney-Metabolic Overlap in Heart Failure with Preserved Ejection Fraction: Cardiac Structure and Function, Clinical Outcomes, and Response to Sacubitril\/Valsartan in PARAGON-HF"],"prefix":"10.1093","volume":"26","author":[{"given":"Mats C.H.","family":"Lassen","sequence":"first","affiliation":[{"name":"Cardiovascular Division, Brigham and Women's Hospital , Boston, MA ,","place":["USA"]},{"name":"Department of Cardiology, Herlev and Gentofte Hospital, 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