Lipoprotein Subclasses Associated With High-Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical Trial.
Lipoprotein Subclasses Associated With High-Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical Trial.
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DOI：
10.1161/jaha.122.026662
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发表时间：
2023-01-03
影响因子：
5.4
通讯作者：
Shah, Svati H.
中科院分区：
文献类型：
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作者：
McGarrah, Robert W.;Ferencik, Maros;Giamberardino, Stephanie N.;Hoffmann, Udo;Foldyna, Borek;Karady, Julia;Ginsburg, Geoffrey S.;Kraus, William E.;Douglas, Pamela S.;Shah, Svati H.
超过一半的主要心血管不良事件（MACE）发生在没有阻塞性冠状动脉疾病的情况下，通常归因于高风险冠状动脉粥样硬化斑块（HRP）的破裂。与成像定义的HRP相关的基于血液的生物标志物和预测MACE缺乏。在PROMISE（前瞻性胸痛评估多中心成像研究）试验（N=4019）的生物标志物亚研究中，对可疑有稳定冠状动脉疾病症状的参与者进行了基于核磁共振的脂蛋白颗粒谱分析。主成分分析将相关脂蛋白减少为不相关脂蛋白因子。使用logistic回归模型确定脂蛋白因子和显著相关因子的个体脂蛋白与核心实验室确定的HRP冠状动脉计算机断层造影特征的关系。在PROMISE试验中评估了HRP相关脂蛋白与MACE的关系，并在独立冠状动脉造影生物库（CATHGEN[导管遗传学]）中使用Cox比例风险模型进行了验证。由高密度脂蛋白（HDL）亚类组成的脂蛋白因子与HRP相关。在这些因素中，在多变量模型中，高HDL（比值比[OR]， 0.70 [95% CI, 0.56-0.85]， P<0.001）、中等HDL（比值比[OR]， 0.84 [95% CI, 0.72-0.98]， P=0.028）和HDL大小（比值比[OR]， 0.82 [95% CI, 0.69-0.96]， P=0.018）与HRP相关。在PROMISE中，中等高密度脂蛋白与MACE相关（风险比[HR]， 0.76 [95% CI, 0.63-0.92]； P=0.004），这在CATHGEN生物库中得到了验证（风险比，0.91 [95% CI, 0.88-0.94]； P<0.001）。在PROMISE试验参与者中，大、中等HDL亚类和HDL大小与HRP特征呈负相关，中等HDL亚类与MACE呈负相关。这些发现可能有助于胸痛个体的风险分层，并为HRP的病理生物学提供见解。URL: https://clinicaltrials.gov;唯一标识符：NCT01174550
More than half of major adverse cardiovascular events (MACE) occur in the absence of obstructive coronary artery disease and are often attributed to the rupture of high‐risk coronary atherosclerotic plaque (HRP). Blood‐based biomarkers that associate with imaging‐defined HRP and predict MACE are lacking. Nuclear magnetic resonance–based lipoprotein particle profiling was performed in the biomarker substudy of the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial (N=4019) in participants who had stable symptoms suspicious for coronary artery disease. Principal components analysis was used to reduce the number of correlated lipoproteins into uncorrelated lipoprotein factors. The association of lipoprotein factors and individual lipoproteins of significantly associated factors with core laboratory determined coronary computed tomographic angiography features of HRP was determined using logistic regression models. The association of HRP‐associated lipoproteins with MACE was assessed in the PROMISE trial and validated in an independent coronary angiography biorepository (CATHGEN [Catheterization Genetics]) using Cox proportional hazards models. Lipoprotein factors composed of high‐density lipoprotein (HDL) subclasses were associated with HRP. In these factors, large HDL (odds ratio [OR], 0.70 [95% CI, 0.56–0.85]; P<0.001) and medium HDL (OR, 0.84 [95% CI, 0.72–0.98]; P=0.028) and HDL size (OR, 0.82 [95% CI, 0.69–0.96]; P=0.018) were associated with HRP in multivariable models. Medium HDL was associated with MACE in PROMISE (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P=0.004), which was validated in the CATHGEN biorepository (HR, 0.91 [95% CI, 0.88–0.94]; P<0.001). Large and medium HDL subclasses and HDL size inversely associate with HRP features, and medium HDL subclasses inversely associate with MACE in PROMISE trial participants. These findings may aid in the risk stratification of individuals with chest pain and provide insight into the pathobiology of HRP. URL: https://clinicaltrials.gov; Unique identifier: NCT01174550