Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Clin Chem. 2021 Jan 8;67(1):131-142. doi: 10.1093/clinchem/hvaa275.
BACKGROUND: Inflammation links to atherosclerosis and its complications in various experimental investigations. Animal studies have implicated numerous inflammatory mediators in the initiation and complication of atherosclerosis. Numerous studies in humans have shown associations of biomarkers of inflammation with cardiovascular events provoked by atheromata. Inflammatory status, determined by the biomarker C-reactive protein, can guide the allocation of statin therapy to individuals without elevated low-density lipoprotein (LDL) concentrations to prevent first ever adverse cardiovascular events. CONTENT: Until recently, no direct evidence has shown that an intervention that selectively limits inflammation can improve outcomes in patients with atherosclerosis. A recent study, based on decades of preclinical investigation, treated patients who had sustained a myocardial infarction and whose LDL was well-controlled on statin treatment with an antibody that neutralizes interleukin-1 beta. This trial, conducted in over 10 000 individuals, showed a reduction in major adverse cardiac events, establishing for the first time the clinical efficacy of an anti-inflammatory intervention in atherosclerosis. Two large subsequent studies have shown that colchicine treatment can also prevent recurrent events in patients recovering from an acute coronary syndrome or in the stable phase of coronary artery disease. These clinical trials have transformed inflammation in atherosclerosis from theory to practice. SUMMARY: Much work remains to optimize further anti-inflammatory interventions, minimize unwanted actions, and refine patient selection. This long road from discovery in the laboratory to successful clinical trials represents a victory for medical science, and opens a new avenue to reducing the risk that remains despite current treatments for atherosclerosis.
背景:在各种实验研究中,炎症与动脉粥样硬化及其并发症有关。动物研究表明,许多炎症介质参与了动脉粥样硬化的发生和并发症。许多人类研究表明,炎症标志物与动脉粥样硬化引起的心血管事件之间存在关联。炎症状态由生物标志物 C 反应蛋白确定,可以指导他汀类药物治疗的分配,无需升高低密度脂蛋白(LDL)浓度,以预防首次不良心血管事件。
内容:直到最近,还没有直接证据表明,选择性限制炎症的干预措施可以改善动脉粥样硬化患者的结局。最近的一项研究基于数十年的临床前研究,对发生心肌梗死且 LDL 在他汀类药物治疗下得到良好控制的患者使用一种中和白细胞介素-1β的抗体进行治疗。这项在超过 10000 名患者中进行的试验显示,主要不良心脏事件减少,首次确立了抗炎干预在动脉粥样硬化中的临床疗效。随后的两项大型研究表明,秋水仙碱治疗也可以预防急性冠脉综合征或冠状动脉疾病稳定期患者的复发事件。这些临床试验将动脉粥样硬化中的炎症从理论转化为实践。
总结:仍有许多工作需要进一步优化抗炎干预措施,减少不必要的作用,并完善患者选择。从实验室的发现到成功的临床试验,这是医学科学的一次胜利,为减少尽管目前治疗动脉粥样硬化仍存在的风险开辟了新途径。
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