多重载脂蛋白小组通过识别受益于靶向PCSK9抑制剂治疗的患者,改善心血管事件预测和心血管结局。

IF 7.4 1区 医学 Q1 HEMATOLOGY
Esther Reijnders, Patrick Bossuyt, J Wouter Jukema, L Renee Ruhaak, Fred Romijn, Michael Szarek, Stella Trompet, Deepak Bhatt, Vera Bittner, Rafael Diaz, Sergio Fazio, Irena Stevanovic, Shaun Goodman, Robert Harrington, Harvey White, Philippe Gabriel Steg, Gregory Schwartz, Christa Cobbaert
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引用次数: 0

摘要

背景:尽管使用高强度他汀类药物可达到低密度脂蛋白胆固醇目标,但仍存在残留的心血管风险。传统的风险评分是次优的。本研究评估了9-plex载脂蛋白面板在近期接受他汀类药物治疗的急性冠状动脉综合征患者中的预后效用,以及它在预测alirocumab治疗效果中的作用,alirocumab是一种PCSK9(蛋白转化酶枯草杆菌素/ keexin 9型)抑制剂,可实现精准医学。方法:采用质谱法分析来自ODYSSEY OUTCOMES试验(https://www.clinicaltrials.gov;唯一识别码:NCT01663402) 11843名参与者的基线血清样本,测定Apo(a)、Apo AI、Apo AII、Apo AIV、ApoB、Apo CI、Apo CII、Apo CIII、ApoE。使用逻辑回归,根据基线载脂蛋白和脂质浓度估计中位随访2.9年期间主要不良心血管事件(MACE)和全因死亡的概率。通过比较3种模型的曲线下面积(AUC)来评估临床表现:载脂蛋白组、脂质组(总胆固醇、高密度脂蛋白胆固醇和甘油三酯)和两者的组合。此外,还开发了通过载脂蛋白面板估计alirocumab治疗益处的预测模型。结果:载脂蛋白组对MACE预后的AUC (95% CI)为0.648(0.626-0.670),而脂质组的AUC为0.579(0.557-0.602)。对于全因死亡,载脂蛋白组的AUC为0.699(0.664-0.733),而脂质组的AUC为0.599(0.564-0.635)。结论:在优化的他汀类药物治疗的急性冠状动脉综合征患者中,多重载脂蛋白组可以更好地预测MACE和全因死亡,而不是血脂。该小组还预测了alirocumab的治疗效果。现在需要进一步验证这种方法,如果得到证实和改进,它可能导致未来更好的疾病预测和管理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Multiplex Apolipoprotein Panel Improves Cardiovascular Event Prediction and Cardiovascular Outcome by Identifying Patients Who Benefit From Targeted PCSK9 Inhibitor Therapy.

Background: Residual cardiovascular risk remains, despite achieving low-density lipoprotein cholesterol targets with high-intensity statins. Traditional risk scores are suboptimal. This study evaluated the prognostic utility of a 9-plex apolipoprotein panel in recent patients with acute coronary syndrome on statins and its role in predicting treatment benefit by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, enabling precision medicine.

Methods: Baseline serum samples from 11 843 participants in the ODYSSEY OUTCOMES trial (https://www.clinicaltrials.gov; Unique identifier: NCT01663402) were analyzed using mass spectrometry to measure Apo(a), Apo AI, Apo AII, Apo AIV, ApoB, Apo CI, Apo CII, Apo CIII, ApoE. Using logistic regression, probabilities of major adverse cardiovascular events (MACE) and all-cause death over a median follow-up of 2.9 years were estimated based on baseline apolipoproteins and lipid concentrations. Clinical performance was assessed by comparing the area under the curve (AUC) of 3 models: the apolipoprotein panel, the lipid panel (total cholesterol, high-density lipoprotein cholesterol, and triglycerides), and a combination. In addition, prediction models estimating the treatment benefit of alirocumab by the apolipoprotein panel were developed.

Results: The prognostic performance of the apolipoprotein panel for MACE showed an AUC (95% CI) of 0.648 (0.626-0.670), compared with 0.579 (0.557-0.602) for the lipid panel. For all-cause death, the apolipoprotein panel had an AUC of 0.699 (0.664-0.733), while the lipid panel had an AUC of 0.599 (0.564-0.635). Adding the apolipoprotein panel significantly improved the performance of the conventional lipid panel (P<0.0001): AUC, 0.659 (0.637-0.681) for MACE and 0.724 (0.691-0.756) for all-cause death. Higher risk for MACE based on the baseline apolipoprotein panel was found to predict greater treatment benefit with alirocumab.

Conclusions: A multiplex apolipoprotein panel led to better prediction of MACE and all-cause death, beyond lipids, in patients with postacute coronary syndrome on optimized statin therapy. The panel also predicts the treatment benefit of alirocumab. Further validation of this approach is now needed, and if confirmed and improved, it could lead to better disease prediction and management in the future.

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来源期刊
CiteScore
15.60
自引率
2.30%
发文量
337
审稿时长
2-4 weeks
期刊介绍: The journal "Arteriosclerosis, Thrombosis, and Vascular Biology" (ATVB) is a scientific publication that focuses on the fields of vascular biology, atherosclerosis, and thrombosis. It is a peer-reviewed journal that publishes original research articles, reviews, and other scholarly content related to these areas. The journal is published by the American Heart Association (AHA) and the American Stroke Association (ASA). The journal was published bi-monthly until January 1992, after which it transitioned to a monthly publication schedule. The journal is aimed at a professional audience, including academic cardiologists, vascular biologists, physiologists, pharmacologists and hematologists.
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