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This review summarizes circulating inflammatory mediators in HFpEF, explores how comorbidities shape distinct immune signatures, and discusses current and emerging treatment strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Findings<\/jats:title>\n                    <jats:p>Comorbidities, including hypertension, obesity, type 2 diabetes, and chronic kidney disease, drive distinct immune profiles in HFpEF through dysregulated cytokine signaling. Circulating mediators, including IL-6, IL-1\u03b2, TNF-\u03b1, soluble ST2, and CRP, reflect this comorbidity-driven immune activation and predict adverse outcomes. Current therapies, e.g. SGLT2 inhibitors, mineralocorticoid receptor antagonists, and angiotensin receptor-neprilysin inhibitors, display anti-inflammatory effects but benefit only specific subgroups. Emerging inflammation-targeted strategies, including anti-IL-6 or anti-IL-1\u03b2, NLRP3 inflammasome modulation and myeloperoxidase inhibition, are under clinical investigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>Linking immune profiles to HFpEF phenogroups may enable precision medicine by refining risk stratification and tailoring therapies, moving beyond the current one-size-fits-all approach.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11897-026-00745-0","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:43:25Z","timestamp":1773391405000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comorbidity-Driven Inflammation in HFpEF: Immune Profiling and Therapeutic Targets"],"prefix":"10.1007","volume":"23","author":[{"given":"Ellaline","family":"Cami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"Verghote","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Pecetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arantxa","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebba","family":"Brakenhielm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth AV","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Van Empel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"745_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.947147","volume":"13","author":"C Li","year":"2022","unstructured":"Li C, Qin D, Hu J, Yang Y, Hu D, Yu B. 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