{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:45:47Z","timestamp":1789195547876,"version":"build-2803163510"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":355,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Understanding sex-related cardiovascular differences in those with pre-HFpEF (asymptomatic with normal ejection fraction, elevated natriuretic peptides and structural or functional heart disease) could help explain why females are more likely to develop symptomatic HFpEF compared with males. This study analyses sex-related cardiovascular differences in pre-HFpEF, including measures of cardiovascular stiffness and vascular resistance derived from cardiac magnetic resonance imaging (CMR) and Doppler echocardiography.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>This post hoc analysis of the PARABLE trial enrolled 250 patients with pre-HFpEF. CMR and Doppler echocardiography were used to estimate baseline markers of cardiovascular stiffness and resistance, including effective arterial elastance (EAE), systemic vascular resistance (SVR), total arterial compliance (TAC), left ventricular end diastolic pressure (LVEDP) and left ventricular end diastolic chamber stiffness index (LVSId). The population median age was 72.0 [IQR 68.0; 77.0] years and 38.4% were female. Both sexes had a similar age, blood pressure, HbA1c, renal function and H2FPEF score. Fewer female participants had a diagnosis of diabetes and coronary artery disease. When adjusted for age, hypertension, diabetes, obesity and vascular disease, female participants had higher pulse pressures (62.1 (SD 15.3) vs. 60.1 (SD 12.5) mmHg, P &amp;lt; 0.001) as well as higher median [IQR] levels of LDL-cholesterol (2.50 [2.10; 3.25] vs. 2.00 [1.60; 2.40] mmol\/L, P &amp;lt; 0.001), EAE (1.55 [1.26; 1.84] vs. 1.26 [1.05; 1.51] mmHg\/mL\/m2, P &amp;lt; 0.001), SVR (1609 [1288; 1887] vs. 1336 [1132; 1734] mmHg\/mL\/min2, P = 0.001), LVEDP (18.5 [17.2; 20.1] vs. 18.0 [16.9; 19.3] mmHg, P &amp;lt; 0.001) and LVSId (0.28 [0.24; 0.31] vs 0.24 [0.20; 0.29] mmHg\/mL\/m2, P &amp;lt; 0.001) than males. Females had higher median [IQR] NT-proBNP (176 [95.8; 286] vs. 127 [81.5; 242] pg\/mL, P &amp;lt; 0.001) and lower median [IQR] TAC (1.24 [0.99; 1.58] vs. 1.55 [1.18; 1.91] mL\/mmHg, P &amp;lt; 0.001) than male participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Markers of elevated cardiovascular stiffness and vascular resistance are seen in female versus male participants with pre-HFpEF, suggesting that sex-related pathophysiological mechanisms are present before symptoms of HF develop.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.15228","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T12:15:28Z","timestamp":1741695328000},"page":"2387-2390","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sex-Related Pathophysiological Mechanisms May Be Present Before Symptoms of HFpEF Develop"],"prefix":"10.1093","volume":"12","author":[{"given":"B.","family":"Wong","sequence":"first","affiliation":[{"name":"St. Vincent's University Hospital , Dublin ,","place":["Ireland"]},{"name":"School of Medicine, University College Dublin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.D.","family":"Dodd","sequence":"additional","affiliation":[{"name":"St. Vincent's University Hospital , Dublin ,","place":["Ireland"]},{"name":"School of Medicine, University College Dublin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Gallagher","sequence":"additional","affiliation":[{"name":"School of Medicine, University College Dublin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Dyer","sequence":"additional","affiliation":[{"name":"School of Medicine, University College Dublin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Ryan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Trinity College Dublin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"McDonald","sequence":"additional","affiliation":[{"name":"St. Vincent's University Hospital , Dublin ,","place":["Ireland"]},{"name":"School of Medicine, University College Dublin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7391-2949","authenticated-orcid":false,"given":"M.","family":"Ledwidge","sequence":"additional","affiliation":[{"name":"School of Medicine, University College Dublin , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"2026021804231541400_ehf215228-bib-0001","doi-asserted-by":"publisher","first-page":"e895","DOI":"10.1161\/CIR.0000000000001063","article-title":"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":"145","author":"Heidenreich","year":"2022","journal-title":"Circulation"},{"key":"2026021804231541400_ehf215228-bib-0002","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1002\/ejhf.67","article-title":"Sex-specific cardiovascular structure and function in heart failure with preserved ejection fraction","volume":"16","author":"Gori","year":"2014","journal-title":"Eur J Heart Fail"},{"key":"2026021804231541400_ehf215228-bib-0003","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.cardfail.2021.10.019","article-title":"Arterial stiffness and vascular load in HFpEF: differences among women and men","volume":"28","author":"Lau","year":"2022","journal-title":"J Card Fail"},{"key":"2026021804231541400_ehf215228-bib-0004","doi-asserted-by":"publisher","first-page":"2487","DOI":"10.1002\/ehf2.14422","article-title":"Rising arterial stiffness with accumulating comorbidities associates with heart failure with preserved ejection fraction","volume":"10","author":"Ali","year":"2023","journal-title":"ESC Heart Fail"},{"key":"2026021804231541400_ehf215228-bib-0005","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1001\/jamacardio.2023.0065","article-title":"Effect of sacubitril\/valsartan vs valsartan on left atrial volume in patients with pre-heart failure with preserved ejection fraction: the PARABLE randomized clinical trial","volume":"8","author":"Ledwidge","year":"2023","journal-title":"JAMA Cardiol"},{"key":"2026021804231541400_ehf215228-bib-0006","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1161\/01.cir.102.15.1788","article-title":"Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study","volume":"102","author":"Ommen","year":"2000","journal-title":"Circulation"},{"key":"2026021804231541400_ehf215228-bib-0007","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1002\/ejhf.190","article-title":"Impact of chronic changes in arterial compliance and resistance on left ventricular ageing in humans","volume":"17","author":"Wohlfahrt","year":"2015","journal-title":"Eur J Heart Fail"},{"key":"2026021804231541400_ehf215228-bib-0008","doi-asserted-by":"publisher","first-page":"4297","DOI":"10.1113\/JP272021","article-title":"Physiological adaptations to chronic stress in healthy humans: why might the sexes have evolved different energy utilisation strategies?","volume":"594","author":"Jones","year":"2016","journal-title":"J Physiol"},{"key":"2026021804231541400_ehf215228-bib-0009","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1161\/CIRCULATIONAHA.120.049360","article-title":"Sex differences in blood pressure associations with cardiovascular outcomes","volume":"143","author":"Ji","year":"2021","journal-title":"Circulation"},{"key":"2026021804231541400_ehf215228-bib-0010","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpc.2023.100632","article-title":"Age and sex disparities in blood pressure control and therapeutic inertia: impact of a quality improvement program","volume":"17","author":"Myers","year":"2024","journal-title":"Am J Prev Cardiol"}],"container-title":["ESC Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/12\/3\/2387\/66955841\/eschf_12_3_2387.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/12\/3\/2387\/66955841\/eschf_12_3_2387.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T09:23:25Z","timestamp":1771406605000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eschf\/article\/12\/3\/2387\/8488295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,28]]},"references-count":10,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2,28]]},"published-print":{"date-parts":[[2025,6,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ehf2.15228","relation":{},"ISSN":["2055-5822"],"issn-type":[{"value":"2055-5822","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2025,2,28]]},"assertion":[{"value":"2024-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}