Lian Huilin, Li Dai, Zeng Youjie, Meng Yi, Chen Ruifang, Guo Ren
Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
Phase I Clinical Research Center, Xiangya Hospital, Central South University, Changsha, 410008, China.
Sci Rep. 2025 Aug 21;15(1):30783. doi: 10.1038/s41598-025-15331-y.
Cardiovascular diseases (CVDs) are major global health threats. This study explores links between anti-allergic drugs and CVD risk, providing valuable insights for clinical pharmacotherapy. Mendelian randomization (MR) analyses were performed on 139 eQTLs for anti-allergic drugs in coronary artery disease (CAD), heart failure (HF), myocardial infarction (MI), and atrial fibrillation (AF) cohorts, with validation in independent cohorts. Sensitivity analyses, transcriptomics analysis, enrichment analysis, and molecular docking were performed to evaluate the robustness of causality, potential pathways and binding affinity. Furthermore, the FAERS database evaluated the cardiovascular adverse events associated with prednisone in combination with cardiovascular drugs. Among the 11 anti-allergic drug targets significantly linked to CVDs, KAT2A inversely correlated with CAD risk, BAZ2B and CYP2C8 with AF risk, and ITGB2, TG and six other eQTLs were associated with HF risk. Notably, prednisone (targeting ITGB2, TG) and loratadine (targeting TSHR) elevated CVD risk, while zafirlukast (targeting KAT2A, POLB, BAZ2B) reduced it. The progression of CVDs may be influenced by the formation of neutrophil extracellular traps and lipid accumulation, which could potentially be affected by the administration of prednisone and similar medications. Molecular docking revealed a strong binding affinity between the cardiovascular candidate drug quercetin and zafirlukast (POLB). Pharmacovigilance analysis indicated an increased risk of adverse cardiovascular outcomes with the concurrent use of prednisone and cardiovascular drugs. The comprehensive analyses indicate that certain anti-allergic drugs may heighten the risk of CVDs, suggesting caution with medications like prednisone.
心血管疾病（CVDs）是全球主要的健康威胁。本研究探讨了抗过敏药物与心血管疾病风险之间的联系，为临床药物治疗提供了有价值的见解。对冠状动脉疾病（CAD）、心力衰竭（HF）、心肌梗死（MI）和心房颤动（AF）队列中139个抗过敏药物的表达定量性状位点（eQTLs）进行了孟德尔随机化（MR）分析，并在独立队列中进行了验证。进行了敏感性分析、转录组学分析、富集分析和分子对接，以评估因果关系的稳健性、潜在途径和结合亲和力。此外，FAERS数据库评估了泼尼松与心血管药物联合使用时的心血管不良事件。在与心血管疾病显著相关的11个抗过敏药物靶点中，KAT2A与CAD风险呈负相关，BAZ2B和CYP2C8与AF风险相关，ITGB2、TG和其他6个eQTLs与HF风险相关。值得注意的是，泼尼松（作用于ITGB2、TG）和氯雷他定（作用于促甲状腺激素受体）会增加心血管疾病风险，而扎鲁司特（作用于KAT2A、POLB、BAZ2B）则会降低心血管疾病风险。心血管疾病的进展可能受到中性粒细胞胞外陷阱形成和脂质积累的影响，而泼尼松和类似药物的使用可能会对其产生潜在影响。分子对接显示心血管候选药物槲皮素与扎鲁司特（POLB）之间具有很强的结合亲和力。药物警戒分析表明，同时使用泼尼松和心血管药物会增加不良心血管事件的风险。综合分析表明，某些抗过敏药物可能会增加心血管疾病的风险，提示对泼尼松等药物应谨慎使用。
