{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T16:27:50Z","timestamp":1793896070929,"version":"4.8.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"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. Med."],"abstract":"<jats:p>Statin efficacy is settled; the decisive question is in whom absolute benefit exceeds absolute harm by a margin justifying lifelong therapy. Because proportional risk reduction is approximately constant, absolute benefit scales with baseline risk while the principal harm, incident type 2 diabetes, does not, so a threshold must exist below which treatment is unjustified. The PREVENT equations, published in 2023\u20132024 and adopted by the 2026 ACC\/AHA Multisociety dyslipidemia guideline, lower risk estimates and compress the intermediate band to a 10-year risk of 5% to less than 10%, a large, ambiguous stratum populated by patients with metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD affects two in five adults, causes more cardiovascular than hepatic death, and is untreated in about half of eligible patients owing to a now-discredited fear of hepatotoxicity. Existing reviews establish that statins are safe in MASLD and that its cardiovascular risk is excess and graded, but none translates this into a tool for decision-making at the point of care. I advance a testable hypothesis: the fibrosis-4 (FIB-4) index and liver stiffness measurement should function as formal risk-enhancing modifiers subdividing this stratum. Every term of the upgrade rule is specified quantitatively: a two-threshold FIB-4 structure (rule-out below 1.3, or below 2.0 above age 65; rule-in at 2.67 or above, with 1.3\u20132.67 resolved by liver stiffness or coronary artery calcium), liver stiffness thresholds of 8 and 12 kPa, an explicit cardiometabolic-criterion list, and a 30-year PREVENT ASCVD risk of 10% or more. The supporting evidence is observational throughout, and I state plainly what is unestablished, namely that these markers add prognostic information beyond PREVENT and coronary artery calcium; fibrosis is framed as a marker of cumulative cardiometabolic injury, not a causal mediator. I situate the framework alongside resmetirom, incretin therapy, and bempedoic acid, define the fibrosis boundary beyond which competing liver-related mortality invalidates it, and specify a competing-risks validation design aligned to the PREVENT total cardiovascular disease endpoint, externally validated in East Asian and lean-MASLD cohorts. The contribution is a fully specified, falsifiable decision architecture for the stratum where guidelines leave clinicians most uncertain.<\/jats:p>","DOI":"10.3389\/fmed.2026.1926866","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T09:10:19Z","timestamp":1787649019000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A fibrosis-informed refinement of the intermediate-risk stratum for statin allocation: a liver-derived hypothesis anchored to the 2026 PREVENT-based guideline framework"],"prefix":"10.3389","volume":"13","author":[{"given":"Soon Woo","family":"Nam","sequence":"first","affiliation":[{"name":"Hepatobiliary Unit, Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea","place":["Seoul, Republic of 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