超重/肥胖人群合并心血管代谢疾病多靶点药物治疗机制及策略

Mechanisms and strategies of multi-targeted pharmacotherapy for cardiometabolic diseases in overweight/obese populations

摘要:

超重/肥胖合并心血管代谢疾病已成为全球突出公共卫生问题,其病理机制以内脏脂肪病理重构、多器官交互损伤及神经-内分泌失衡为核心,形成“代谢紊乱-器官损伤-炎症激活”的恶性循环。文章系统综述了超重/肥胖与心血管代谢疾病的核心关联机制,重点阐述以胰高血糖素样肽1受体激动剂(GLP-1RA)为代表的新型药物的治疗机制与临床应用,并创新性地提出其在动脉粥样硬化性心血管疾病一级、二级、三级预防中的分层应用价值,前瞻性地探讨双靶点、三靶点激动剂的协同治疗策略,填补现有综述对“全周期风险管理”阐述不足的空白。同时,探讨如何应对当前临床应用面临的个体疗效异质性、长期安全性数据不足、药物可及性受限及联合治疗策略待优化等挑战,旨在为肥胖合并心血管代谢疾病的全周期、分层级风险管理提供区别于传统单一减重视角的循证依据。

Abstract:

Overweight/obesity complicated by cardiometabolic diseases constitutes a pressing global health crisis. The pathological cascade hinges on visceral adipose tissue remodeling, inter-organ detrimental crosstalk, and neuroendocrine imbalance, creating a vicious cycle of metabolic disorder, organ injury, and inflammatory activation. This systematic review examines the mechanistic nexus between obesity and cardiometabolic disorders, focusing on the therapeutic mechanisms and clinical applications of glucagon-like peptide-1 receptor agonists (GLP1RA) as representative novel agents. Specifically, we elaborate on their stratified application value in the primary, secondary and tertiary prevention of atherosclerotic cardiovascular disease (ASCVD), and prospectively discuss synergistic therapeutic strategies of dualtarget and tripletarget agonists, filling the gap of inadequate elaboration on “fullcycle risk management” in existing reviews. Meanwhile, we discuss how to cope with current challenges in clinical application, including heterogeneity of individual therapeutic responses, insufficient longterm safety data, limited drug accessibility, and pending optimization of combination therapy strategies. This study aims to provide evidence for fullcycle and hierarchical risk management of obesity combined with cardiometabolic diseases, which differs from the traditional single perspective of weight loss.