{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:47:55Z","timestamp":1782276475461,"version":"3.54.5"},"reference-count":137,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Hypertension is among the most important modifiable risk factors associated with heart failure with preserved ejection fraction (HFpEF) development and progression, yet guideline-directed blood pressure (BP) targets (&lt;130\/80 mmHg) and sodium\u2013glucose co-transporter 2 inhibitor (SGLT2i) therapies lack dedicated randomized controlled trials (RCTs) in this specific group of patients. This narrative review synthesizes 2024 ESC\/ESH and 2025 JSH meta-analyses, discussing the proposed pathophysiological framework linking hypertension-associated remodeling with HFpEF. Post hoc analyses from landmark trials (EMPEROR-Preserved, DELIVER) demonstrate consistent heart failure (HF) event reductions with SGLT2i (pooled HR 0.79, 95% CI 0.67\u20130.93), complemented by modest systolic BP lowering (\u22122.3 mmHg) and biomarker insights. Soluble ST2 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) may contribute to risk stratification in HFpEF populations when interpreted in conjuction with imaging findings and clinical context; however, neither biomarker is specific for hypertension-mediated remodeling. Critical evidence gaps persist: heterogeneous BP thresholds across international guidelines, limited device therapy data (renal denervation showing \u22128.5 mmHg sustained reduction), and real-world implementation barriers among elderly\/comorbid Europeans (adherence &lt; 50%, polypharmacy risks). Hellenic HF Registry data highlight frailty prevalence (68% in patients &gt; 75 years) complicating aggressive BP management. The review addresses phenotype-specific challenges through precision medicine approaches incorporating phenomapping and multi-biomarker panels (NRI 0.28 improvement). We advocate for dedicated HFpEF RCTs evaluating intensive vs. standard BP targets, SGLT2i sequencing with antihypertensives, and European real-world registries to bridge the translational gap. These strategies aim to transform guideline recommendations into optimized, patient-centered care for the rapidly expanding hypertensive HFpEF population.<\/jats:p>","DOI":"10.3390\/medicina62071222","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"1222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypertensive Heart Failure with Preserved Ejection Fraction: Guidelines vs. Randomized Controlled Trials Evidence Gaps"],"prefix":"10.3390","volume":"62","author":[{"given":"Georgios","family":"Mavraganis","sequence":"first","affiliation":[{"name":"First Cardiology Clinic, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"Department of Clinical Therapeutics, School of Medicine, Alexandra Hospital, National and Kapodistrian University of Athens Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5598-9950","authenticated-orcid":false,"given":"Christos","family":"Fragoulis","sequence":"additional","affiliation":[{"name":"First Cardiology Clinic, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Georgiopoulos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, Alexandra Hospital, National and Kapodistrian University of Athens Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2692-095X","authenticated-orcid":false,"given":"Kyriaki","family":"Mavromoustakou","sequence":"additional","affiliation":[{"name":"First Cardiology Clinic, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriakos","family":"Dimitriadis","sequence":"additional","affiliation":[{"name":"First Cardiology Clinic, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0706-4424","authenticated-orcid":false,"given":"Konstantinos","family":"Aznaouridis","sequence":"additional","affiliation":[{"name":"First Cardiology Clinic, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6340-3996","authenticated-orcid":false,"given":"Christina","family":"Chrysohoou","sequence":"additional","affiliation":[{"name":"First Cardiology Clinic, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimon","family":"Stamatelopoulos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, Alexandra Hospital, National and Kapodistrian University of Athens Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7636-6725","authenticated-orcid":false,"given":"Konstantinos","family":"Tsioufis","sequence":"additional","affiliation":[{"name":"First Cardiology Clinic, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","first-page":"e674","article-title":"Correction to: 2022 AHA\/ACC\/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"146","author":"Heidenreich","year":"2023","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jacc.2013.02.092","article-title":"A novel paradigm for heart failure with preserved ejection fraction: Comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation","volume":"62","author":"Paulus","year":"2013","journal-title":"J. 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