01 June 2026 : Clinical Research
[In Press] Machine-Learning-Based Evaluation of the Prognostic Significance of the Non-High-Density Lipoprotein to High-Density Lipoprotein Cholesterol Ratio in Critical Ischemic Stroke
Xiaolong Wang1ABCDEF, Hongwei Liu12ABCDEF, Shengwei Gao1ABCDEF, Yonglai Zhang3ABDEFG, Xuan Chen1ABCDEFG, Ke Shi4ABCDEFDOI: 10.12659/MSM.953117
Med Sci Monit In Press; DOI: 10.12659/MSM.953117
Available online: 2026-06-01, In Press, Corrected Proof
Publication in the "In-Press" formula aims at speeding up the public availability of the pending manuscript while waiting for the final publication. The assigned DOI number is active and citable. The availability of the article in the Medline, PubMed and PMC databases as well as Web of Science will be obtained after the final publication according to the journal schedule
Abstract
BACKGROUND
This study examined associations of the non-high-density lipoprotein to high-density lipoprotein cholesterol ratio (NHHR) with short-term (28-day) and long-term (365-day) mortality in critically ill patients with ischemic stroke.
MATERIAL AND METHODS
This retrospective cohort study utilized data from the MIMIC-IV database and focused on critically ill patients with ischemic stroke. Cox proportional hazards, restricted cubic spline, and Kaplan-Meier analyses were performed to examine the relationship between NHHR and mortality. Machine learning models were developed to improve predictive performance; model discrimination and clinical utility were evaluated using time-dependent receiver operating characteristic curves and decision curve analysis.
RESULTS
Overall, 2492 critically ill patients with ischemic stroke were included. For 28-day mortality, NHHR levels below 2.122 were associated with a 24.9% increase in risk per unit decrease, whereas values above 2.122 conferred a 13.0% increase in risk per unit increment. For 365-day mortality, NHHR levels below 2.111 were associated with a 20.9% increase in mortality risk per unit decrease; values above this threshold were associated with a 14.1% increase in risk per unit increase. Among 6 machine learning algorithms, the random survival forest model demonstrated the best performance, demonstrating superior discrimination, calibration, and clinical utility for predicting both short- and long-term mortality.
CONCLUSIONS
In critically ill patients with ischemic stroke, NHHR demonstrated a nonlinear and independent association with mortality; the lowest risk was observed at intermediate values. Random survival forest modeling supports NHHR as a robust and clinically meaningful prognostic biomarker in this population.
Keywords: Cholesterol, HDL; Cholesterol, LDL; Ischemic Stroke; Machine Learning; Neurology; Prognosis
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