Division of Cardiovascular Medicine, Department of Medicine University of California San Diego San Diego CA.
David Geffen School of Medicine at University of California, Los Angeles CA Los Angeles.
J Am Heart Assoc. 2023 Jun 6;12(11):e028892. doi: 10.1161/JAHA.122.028892. Epub 2023 Jun 1.
Management of elevated low-density lipoprotein cholesterol (LDL-C) is central to preventing atherosclerotic cardiovascular disease (ASCVD) and key to reducing the risk of ASCVD events. Current guidelines on the management of blood cholesterol recommend statins as first-line therapy for LDL-C reduction according to an individual's ASCVD risk and baseline LDL-C levels. The addition of nonstatin lipid-lowering therapy to statins to achieve intensive LDL-C lowering is recommended for patients at very high risk of ASCVD events, including patients with familial hypercholesterolemia who have not achieved adequate LDL-C lowering with statins alone. Despite guideline recommendations and clinical trial evidence to support the use of lipid-lowering therapies for ASCVD risk reduction, most patients at high or very high risk do not meet LDL-C thresholds. This review explores the challenges associated with LDL-C lowering in contemporary clinical practice and proposes a framework for rethinking the binary definition of ASCVD, shifting from "primary" versus "secondary" prevention to a "continuum of risk." The approach considers the role of plaque burden and progression in subclinical disease and emphasizes the importance of early risk assessment and treatment for preventing first cardiovascular events. Patients at high risk of ASCVD events who require significant LDL-C lowering should be considered for combination therapies comprising statin and nonstatin agents. Practical guidance for the pharmacological management of elevated LDL-C, both now and in the future, is provided.
管理升高的低密度脂蛋白胆固醇(LDL-C)是预防动脉粥样硬化性心血管疾病(ASCVD)的核心,也是降低 ASCVD 风险的关键。目前关于血液胆固醇管理的指南建议,根据个体的 ASCVD 风险和基线 LDL-C 水平,他汀类药物是降低 LDL-C 的一线治疗药物。对于 ASCVD 事件发生风险极高的患者,包括单独使用他汀类药物未能使 LDL-C 充分降低的家族性高胆固醇血症患者,建议在他汀类药物的基础上联合使用非他汀类降脂药物以达到强化 LDL-C 降低的目标。尽管指南建议和临床试验证据支持使用降脂疗法降低 ASCVD 风险,但大多数处于高风险或极高风险的患者并未达到 LDL-C 阈值。本文探讨了当代临床实践中降低 LDL-C 所面临的挑战,并提出了重新思考 ASCVD 二元定义的框架,从“一级”和“二级”预防转向“风险连续谱”。该方法考虑了斑块负荷和亚临床疾病进展的作用,并强调了早期风险评估和治疗在预防首次心血管事件中的重要性。对于 ASCVD 事件风险高且需要显著降低 LDL-C 的患者,应考虑联合使用他汀类药物和非他汀类药物的联合治疗。本文提供了目前和未来升高 LDL-C 的药物治疗的实用指南。
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