CHU de Nantes, l'Institut du Thorax, Department of Endocrinology, 44000 Nantes, France; CHU de Nantes, l'Institut du Thorax, Center of Clinical Investigation, 44000 Nantes, France; Inserm UMR 1087, CNRS UMR 6291, Université de Nantes, l'Institut du Thorax, 44000 Nantes, France.
CHU de Nantes, l'Institut du Thorax, Department Cardiology, 44000 Nantes, France.
Diabetes Metab. 2017 Dec;43(6):529-535. doi: 10.1016/j.diabet.2017.07.009. Epub 2017 Aug 31.
Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations have been shown to be positively associated with LDL cholesterol (LDL-C), but the relationship between PCSK9 and coronary atherosclerosis lesions remains unclear.
This study aims to investigate the correlation between serum PCSK9 levels and coronary damage severity in patients hospitalized for acute coronary syndrome (ACS).
In this prospective proof-of-concept study, coronary lesions were assessed using SYNTAX scores. Serum PCSK9 concentrations were measured on admission (Day 0) for ACS by Elisa, and on every day of hospitalization. Spearman's correlations were used to determine the association between PCSK9 levels, SYNTAX score and metabolic parameters.
A total of 174 patients (mean age: 59±14 years, 79% male) with ACS (on Day 0, 119 patients were not taking statins, but 55 were) were included. After initiation of high-intensity statin therapy, serum PCSK9 concentrations increased significantly, reaching maximum levels on Day 2 (+31% vs. Day 0), and remained stable up to Day 4 (P<0.001, by mixed model). Serum PCSK9 on Day 0 was associated with LDL-C (rho=0.226, P=0.017) and apolipoprotein B (rho=0.282, P=0.005) in the statin-naïve group only, and with triglycerides and non-HDL-C in all groups. More important, PCSK9 levels on Day 0 were positively associated with SYNTAX scores in the statin-naïve group (rho=0.239, P=0.009), but not in the statin-treated group (P=NS). This association was maintained after adjusting for LDL-C (P=0.014) and major CV risk factors (P=0.008).
Serum PCSK9 levels are positively associated with severity of coronary artery lesions independently of LDL-C concentrations in patients hospitalized for ACS. This reinforces the potential importance of PCSK9 inhibition in the management of ACS.
血清前蛋白转化酶枯草溶菌素 9（PCSK9）浓度与 LDL 胆固醇（LDL-C）呈正相关，但 PCSK9 与冠状动脉粥样硬化病变之间的关系尚不清楚。
本研究旨在探讨急性冠状动脉综合征（ACS）住院患者血清 PCSK9 水平与冠状动脉损伤严重程度的相关性。
在这项前瞻性概念验证研究中，采用 SYNTAX 评分评估冠状动脉病变。入院时（ACS 第 0 天）通过 ELISA 测量血清 PCSK9 浓度，并在住院期间的每天测量。采用 Spearman 相关分析确定 PCSK9 水平、SYNTAX 评分和代谢参数之间的关联。
共纳入 174 例 ACS 患者（平均年龄：59±14 岁，79%为男性）（第 0 天，119 例未服用他汀类药物，但 55 例服用）。开始高强度他汀类药物治疗后，血清 PCSK9 浓度显著升高，第 2 天达到最高水平（+31%，与第 0 天相比，P<0.001，采用混合模型），并在第 4 天保持稳定（P<0.001，采用混合模型）。在他汀类药物初治组中，第 0 天的血清 PCSK9 与 LDL-C（rho=0.226，P=0.017）和载脂蛋白 B（rho=0.282，P=0.005）相关，而在所有组中，与甘油三酯和非 HDL-C 相关。更重要的是，在他汀类药物初治组中，第 0 天的 PCSK9 水平与 SYNTAX 评分呈正相关（rho=0.239，P=0.009），但在他汀类药物治疗组中无相关性（P=NS）。在校正 LDL-C（P=0.014）和主要心血管危险因素（P=0.008）后，这种相关性仍然存在。
在 ACS 住院患者中，血清 PCSK9 水平与冠状动脉病变严重程度呈正相关，独立于 LDL-C 浓度。这进一步证实了 PCSK9 抑制在 ACS 管理中的潜在重要性。
