{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:37:27Z","timestamp":1791247047326,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Multimorbidity, the coexistence of two or more chronic conditions, is synonymous with heart failure (HF). How risk related to comorbidities compares at individual and population levels is unknown. The aim of this study is to examine the risk related to comorbidities, alone and in combination, both at individual and population levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Using two clinical trials in HF \u2013 the Prospective comparison of ARNI (Angiotensin Receptor\u2013Neprilysin Inhibitor) with ACEI (Angiotensin-Converting Enzyme Inhibitor) to Determine Impact on Global Mortality and morbidity in HF trial (PARADIGM-HF) and the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure trials (ATMOSPHERE) \u2013 we identified the 10 most common comorbidities and examined 45 possible pairs. We calculated population attributable fractions (PAF) for all-cause death and relative excess risk due to interaction with Cox proportional hazard models. Of 15\u2009066 patients in the study, 14\u2009133 (93.7%) had at least one and 11\u2009867 (78.8%) had at least two of the 10 most prevalent comorbidities. The greatest individual risk among pairs was associated with peripheral artery disease (PAD) in combination with stroke (hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.28\u20132.33) and anaemia (HR 1.71; 95% CI 1.39\u20132.11). The combination of chronic kidney disease (CKD) and hypertension had the highest PAF (5.65%; 95% CI 3.66\u20137.61). Two pairs demonstrated significant synergistic interaction (atrial fibrillation with CKD and coronary artery disease, respectively) and one an antagonistic interaction (anaemia and obesity).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In HF, the impact of multimorbidity differed at the individual patient and population level, depending on the prevalence of and the risk related to each comorbidity, and the interaction between individual comorbidities. Patients with coexistent PAD and stroke were at greatest individual risk whereas, from a population perspective, coexistent CKD and hypertension mattered most.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2856","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:13:32Z","timestamp":1681690412000},"page":"687-697","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Impact of Multimorbidity on Mortality in Heart Failure with Reduced Ejection Fraction: Which Comorbidities Matter Most? An Analysis of PARADIGM-HF and ATMOSPHERE"],"prefix":"10.1093","volume":"25","author":[{"given":"Pooja","family":"Dewan","sequence":"first","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Surgery and Physiology, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto , Porto ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawad H.","family":"Butt","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Research Centre, University of Glasgow , Glasgow ,","place":["UK"]},{"name":"Rigshospitalet Copenhagen University Hospital , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark 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