{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T05:10:15Z","timestamp":1782537015167,"version":"3.54.5"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic kidney disease (CKD) substantially increases the risk of heart failure with preserved ejection fraction (HFpEF). In this study, we quantified prospective, stage-specific incidence and evaluated whether biologically anchored, multimarker domains improve prediction beyond clinical factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a single-center, prospective cohort study (2019\u20132024) of adults with CKD G1\u2013G5 (not on dialysis) with a 36-month follow-up. Incident HFpEF was adjudicated by two cardiologists using Heart Failure Association\u2014Pre-test assessment, Echocardiography and natriuretic peptide score, Functional testing, Final aetiology (HFA-PEFF) criteria with atrial fibrillation\u2013adjusted natriuretic peptide thresholds, and death was treated as a competing event. Baseline biomarkers were grouped into five domains\u2014cardiac stretch, myocyte injury, fibrosis\/remodeling, renal injury\/function, and inflammation\u2014and standardized to domain\n                      <jats:italic>z<\/jats:italic>\n                      -scores. We estimated incidence per 100 person-years and adjusted associations using Cox and Fine\u2013Gray models. Incremental value was assessed with changes in the C-statistic (\n                      <jats:italic>\u0394<\/jats:italic>\n                      C), continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration, with all metrics bootstrap-validated and false discovery rate control applied for domain tests.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 920 participants (mean age 64\u2009\u00b1\u200912 years; 43% women), 68 HFpEF events occurred over 2,582 person-years, corresponding to 2.63 [95% confidence intervals (CI) 2.01\u20133.26] events per 100 person-years. Incidence increased with CKD stage\u2014G1 0.29%, G2 1.16%, G3a 1.76%, G3b 3.14%, G4 4.46%, and G5 6.93%\u2014and with albuminuria\u2014A1 1.32%, A2 2.42%, and A3 4.87%. Adjusted hazard ratios were 1.32 (1.17\u20131.49) per CKD stage and 1.41 (1.20\u20131.66) per albuminuria category. Per 1 SD, domains associated with higher risk were stretch 1.45 (1.23\u20131.72), fibrosis\/remodeling 1.34 (1.13\u20131.59), injury 1.26 (1.07\u20131.48), renal 1.22 (1.04\u20131.43), and inflammation 1.17 (0.99\u20131.37). Adding biomarker domains improved discrimination from 0.72 to 0.79 (\n                      <jats:italic>\u0394<\/jats:italic>\n                      C 0.07, 95% CI 0.03\u20130.10), with continuous NRI 0.20 and IDI 0.055.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In CKD, HFpEF incidence increases stepwise with CKD stage and albuminuria. Domain-based biomarker profiling, particularly cardiac stretch and fibrosis\/remodeling, provides prognostic information beyond clinical factors, supporting a biologically anchored and parsimonious approach to risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2025.1728415","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T06:49:48Z","timestamp":1773384588000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Incidence of new-onset HFpEF across CKD stages and Its association with cardio-renal, inflammatory, and fibrotic biomarkers"],"prefix":"10.3389","volume":"12","author":[{"given":"Kun","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Nephrology, ZiBo Central Hospital","place":["Zibo, Shandong, 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