Wang Shitao, Mei Shuai, Ma Xiaozhu, Wuyun Qidamugai, Zhou Li, Luo Qiushi, Cai Ziyang, Yan Jiangtao
Division of Cardiology, Departments of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan 430030, China.
Biomedicines. 2025 Jul 28;13(8):1838. doi: 10.3390/biomedicines13081838.
: Elevated serum uric acid levels are associated with the occurrence, development, and adverse events of coronary heart disease (CHD) and CHD risk factors. However, the extent of any pathogenic effect of the serum uric acid on CHD and whether CHD risk factors play a confounding or mediating role are still unclear. : The potential causal associations of serum uric acid with CHD were evaluated via cross-trait linkage disequilibrium score regression analysis and Mendelian randomization. The pleiotropy of genetic tools was analyzed via a Bayesian colocalization approach. Moreover, we utilized two-step MR to identify risk factors mediating the relationship between uric acid and CHD. : Mendelian randomization results derived from two genetic instrument selection strategies support that serum uric acid levels have a significant causal relationship with coronary artery disease, stable angina pectoris, and myocardial infarction. This causal relationship was partially mediated by diastolic blood pressure, mean arterial pressure, and serum triglycerides. Transcriptomic analysis revealed that serum uric acid may directly contribute to the development of atherosclerosis by inducing transcriptomic changes in macrophages. : Our findings highlight that the control of serum urate concentration in the long-term management of CHD patients may be necessary. Well-designed clinical trials and foundational research are presently required to furnish conclusive proof regarding the specific clinical scenarios in which adequate reduction in urate concentrations can confer cardiovascular advantages.
血清尿酸水平升高与冠心病（CHD）及其危险因素的发生、发展和不良事件相关。然而，血清尿酸对冠心病的致病作用程度以及冠心病危险因素是否起混杂或中介作用仍不清楚。
通过跨性状连锁不平衡评分回归分析和孟德尔随机化评估血清尿酸与冠心病之间的潜在因果关联。通过贝叶斯共定位方法分析遗传工具的多效性。此外，我们利用两步孟德尔随机化来确定介导尿酸与冠心病关系的危险因素。
来自两种遗传工具选择策略的孟德尔随机化结果支持血清尿酸水平与冠状动脉疾病、稳定型心绞痛和心肌梗死存在显著因果关系。这种因果关系部分由舒张压、平均动脉压和血清甘油三酯介导。转录组分析表明，血清尿酸可能通过诱导巨噬细胞的转录组变化直接促进动脉粥样硬化的发展。
我们的研究结果强调，在冠心病患者的长期管理中，控制血清尿酸盐浓度可能是必要的。目前需要精心设计的临床试验和基础研究，以提供确凿证据，证明在哪些具体临床情况下充分降低尿酸盐浓度可带来心血管益处。
