Platelets. 2026 Dec;37(1):2743142. doi: 10.1080/09537104.2026.2743142. Epub 2026 Oct 8.
ABSTRACT
BACKGROUND: In aspirin-treated unstable angina (UA), heterogeneity in on-treatment arachidonic acid (AA)-induced platelet aggregation and cholesterol reduction contributes to residual ischemic risk. Insomnia is prevalent in coronary disease, yet its association with specific aspirin-sensitive platelet aggregation kinetics and lipid parameters remains undefined.
METHODS: In a cross-sectional cohort of 198 aspirin-treated UA patients, 38 routine hematologic or biochemical variables including AA-induced platelet aggregation indices were analyzed using principal component analysis (PCA) and unsupervised phenotyping (k-means and hierarchical clustering). Elastic-net logistic regression and machine learning classifiers were used for multivariable modeling, and performance was estimated by cross-validation. Correlation-network analysis and Shapley additive explanations (SHAP) supported interpretability.
RESULTS: Unsupervised analyses consistently identified two phenotypes. Insomnia was enriched in a platelet-lipid phenotype characterized by lower platelet aggregation indices and a lower lipid marker profile. The K-nearest neighbors (KNN) model demonstrated strong cross-validated discrimination (AUC = 0.934; average precision = 0.923), while all four classifiers converged with AUC > 0.925. After age matching, elastic-net logistic regression retained only AA-induced maximal platelet aggregation (PmaxAggR) and total cholesterol (CHOL) as independent predictors, with odds ratios of 0.927 and 0.340, respectively (both p < .001). Inflammatory markers, including neutrophil count and monocyte count, were no longer selected. Network analysis placed insomnia within the platelet-lipid module linked to PMaxAggR, CHOL, and some other platelet or lipid indices.
CONCLUSIONS: In age-matched, aspirin-treated UA patients, insomnia is independently associated with reduced PMaxAggR and lower CHOL, with inflammatory markers no longer significant after age-balancing. These findings delineate an age-independent platelet-cholesterol axis linked to insomnia, potentially reflecting shared autonomic and neurobiological dysregulation, and motivate sleep evaluation as part of platelet-reactivity phenotyping in this population.
PMID:42845035 | DOI:10.1080/09537104.2026.2743142