Soon Woo Nam
Among 452 patients, 68 (15%) carried a TTR mutation, 51.5% of whom were symptomatic. The most frequent red flags were sensory neuropathy (62.6%) and family history of cardiomyopathy (51.8%). Tree-based models outperformed other algorithms, with Random Forest selected for its optimal balance between precision and recall. Bilateral carpal tunnel syndrome, family history of neuropathy, and ataxia emerged as the most informative predictors.
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 2023-2024 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 1.3-2.67 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.