Evolocumab Alters Transcriptomic Signatures and Identifies Inflammatory Biomarkers in Brain-Heart Syndrome with Coronary Heart Disease History.

A history of coronary heart disease (CHD) increases the risk of Brain-Heart Syndrome (BHS) after acute stroke, partly through heightened inflammatory responses. Evolocumab, a PCSK9 inhibitor, has anti-inflammatory properties, but its transcriptomic effects in BHS patients with CHD remain unclear. This study aims to identify evolocumab-associated transcriptomic changes and inflammation-related biomarkers in this population. Blood samples from 24 BHS patients with CHD history (12 receiving rosuvastatin alone, 12 receiving rosuvastatin plus evolocumab) underwent transcriptomic sequencing. Candidate biomarkers were identified via differential expression and machine learning, with functional enrichment and immune infiltration analyses conducted. Four candidate biomarkers were identified: WHRN (DFNB31), IL12A, and ASB14 were upregulated, while TMED7-TICAM2 was downregulated in the evolocumab combination group. These genes were enriched in pathways related to cell metabolism, signal transduction, and immune regulation. Immune infiltration analysis showed modest but detectable changes in B-cell subsets. External validation confirmed differential expression of these candidate biomarkers in CAD patients. This pilot study provides preliminary insights into the molecular mechanisms of evolocumab in treating Brain-Heart Syndrome with a coronary heart disease history, identifying four inflammation-related biomarkers. These findings suggest potential targets for future investigation; however, given the exploratory nature and small sample size, further experimental and clinical validation is required before any therapeutic application.