{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:03:31Z","timestamp":1790071411768,"version":"4.0.1"},"reference-count":24,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Pers. Med.","JPM"],"abstract":"<jats:p>Background: Patient heterogeneity in routine biomarkers is often collapsed into a single physiological reserve score, but whether that one-dimensional representation holds across acute and chronic settings\u2014or whether it obscures biomarker-defined subgroups relevant to individualized care\u2014is unclear. Methods: We harmonized routine biomarkers (BMI, blood pressure, eGFR, LDL, total cholesterol, and HbA1c) across two cohorts from the same health system: an acute cardiorenal syndrome cohort and a chronic outpatient cohort treated with dapagliflozin and\/or semaglutide, excluding 15 patients common to both. We tested whether these biomarkers supported a one-factor structure via exploratory factor analysis, then a categorical alternative via Gaussian mixture modeling, assessed six-month class persistence in the chronic cohort, and applied the derived classes to the acute cohort for descriptive independent cohort application. Results: A one-factor representation was not supported (KMO = 0.485; covariance concentrated in two definitionally related variable pairs). Gaussian mixture modeling favored a two-class solution, distinguished mainly by LDL, total cholesterol, HbA1c, and diastolic blood pressure. Class assignment showed moderate six-month agreement (\u03ba = 0.46) in a subgroup enriched for closer monitoring. In the acute cohort, class structure was not clearly associated with age, BNP, ejection fraction, length of stay, CKD stage, HF phenotype, NYHA class, or comorbidities; associations with outcomes were descriptive, not causal. Conclusions: Rather than reducing to a single reserve score, these biomarkers were better described by an exploratory two-class, biomarker-defined phenotype structure that captured observable patient heterogeneity, showed moderate short-term persistence, and was not clearly related to acute illness severity. These findings are specific to the biomarkers and cohorts studied and should not be generalized without independent replication.<\/jats:p>","DOI":"10.3390\/jpm16090481","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:04:17Z","timestamp":1790067857000},"page":"481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory Biomarker-Defined Phenotypic Heterogeneity Beyond a Single Physiological Reserve Construct"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5530-486X","authenticated-orcid":false,"given":"Muneera O.","family":"AlTaweel","sequence":"first","affiliation":[{"name":"Department of Cardiac Sciences, King Abdulaziz Hospital, MNGHA, King Abdullah Military City, Al-Mubarraz 36248, Al-Ahsa, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center\u2014Eastern Region (KAIMRC-ER), King Abdullah Military City, Al-Mubarraz 36428, Al-Ahsa, Saudi Arabia"},{"name":"King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), MNGHA, King Abdullah Military City, Al-Mubarraz 36428, Al-Ahsa, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aftab","family":"Ahmed Jalbani","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, King Abdulaziz Hospital, MNGHA, King Abdullah Military City, Al-Mubarraz 36248, Al-Ahsa, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Fahad","family":"Memon","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, King Abdulaziz Hospital, MNGHA, King Abdullah Military City, Al-Mubarraz 36248, Al-Ahsa, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Ayman","family":"Aly Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, King Abdulaziz Hospital, MNGHA, King Abdullah Military City, Al-Mubarraz 36248, Al-Ahsa, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Paras","family":"Memon","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, King Abdulaziz Hospital, MNGHA, King Abdullah Military City, Al-Mubarraz 36248, Al-Ahsa, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Islam","family":"Elnasharty","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, King Abdulaziz Hospital, MNGHA, King Abdullah Military City, Al-Mubarraz 36248, Al-Ahsa, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Amin","family":"Elshehawey","sequence":"additional","affiliation":[{"name":"Department of Cardiac Sciences, King Abdulaziz Hospital, MNGHA, King Abdullah Military City, Al-Mubarraz 36248, Al-Ahsa, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Ali","family":"Al Qarni","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center\u2014Eastern Region (KAIMRC-ER), King Abdullah Military City, Al-Mubarraz 36428, Al-Ahsa, Saudi Arabia"},{"name":"King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), MNGHA, King Abdullah Military City, Al-Mubarraz 36428, Al-Ahsa, Saudi Arabia"},{"name":"Endocrinology and Metabolism, Department of Medicine, King Abdulaziz Hospital, MNGHA, King Abdullah Military City, Al-Mubarraz 36428, Al-Ahsa, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wasserman, M.R., Bakerjian, D., and Linnebur, S. 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