Afanasieva Olga I, Tyurina Alexandra V, Ezhov Marat V, Razova Oxana A, Klesareva Elena A, Pokrovsky Sergei N
Institute of Experimental Cardiology, National Medical Research Center of Cardiology Named after Academician E.I. Chazov, Ministry of Health of the Russian Federation, Academician Chazov str., 15a, 121552 Moscow, Russia.
A.L. Myasnikov Institute of Clinical Cardiology, National Medical Research Center of Cardiology Named after Academician E.I. Chazov, Ministry of Health of the Russian Federation, Academician Chazov str., 15a, 121552 Moscow, Russia.
Diseases. 2023 Oct 18;11(4):145. doi: 10.3390/diseases11040145.
Lipoprotein(a) (Lp(a)) is a genetic risk factor of atherosclerotic cardiovascular diseases (ASCVDs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to vascular inflammation and detected in atherosclerotic plaques. A temporary increase in the circulating concentration of PCSK9 and Lp(a) was shown in patients with myocardial infarction (MI). The aim of this study was to evaluate the role of the apo(a) phenotype and the Lp(a) concentration as well as its complex with PCSK9 in the development of cardiac events and MI in patients with a premature manifestation of coronary heart disease (CHD).
In a prospective study with retrospective data collection, we included 116 patients with premature CHD who were followed for a median of 14 years. The medical history and information on cardiovascular events after an initial exam as well as data on the levels of lipids, Lp(a), PCSK9, PCSK9-Lp(a) complex, and apo(a) phenotype were obtained.
The patients were divided into two groups depending on the presence of a low- (LMW, = 52) or high-molecular weight (HMW, = 64) apo(a) phenotype. LMW apo(a) phenotype (odds ratio 2.3 (1.1 to 4.8), = 0.03), but not elevated Lp(a) (1.9 (0.8-4.6), = 0.13), was an independent predictor for the development of MI after adjustment for sex, age of CHD debut, initial lipids levels, and lipid-lowering treatment. The apo(a) phenotype also determined the relationship between Lp(a) and PCSK9 concentrations. The level of the PCSK9-Lp(a) complex was higher in LMW apo(a) patients.
The LMW apo(a) phenotype is a risk factor for non-fatal MI in a long-term prospective follow-up of patients with premature CHD, and this link could be mediated via PCSK9.
脂蛋白(a)[Lp(a)]是动脉粥样硬化性心血管疾病（ASCVD）的遗传风险因素。前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）与血管炎症相关，并在动脉粥样硬化斑块中被检测到。心肌梗死（MI）患者循环中PCSK9和Lp(a)的浓度会出现短暂升高。本研究的目的是评估载脂蛋白(a)表型、Lp(a)浓度及其与PCSK9的复合物在冠心病（CHD）过早表现患者心脏事件和MI发生发展中的作用。
在一项具有回顾性数据收集的前瞻性研究中，我们纳入了116例过早发生CHD的患者，中位随访时间为14年。获取了初次检查后的病史、心血管事件信息以及血脂、Lp(a)、PCSK9、PCSK9-Lp(a)复合物和载脂蛋白(a)表型水平的数据。
根据是否存在低分子量（LMW，n = 52）或高分子量（HMW，n = 64）载脂蛋白(a)表型，将患者分为两组。在校正性别、CHD发病年龄、初始血脂水平和降脂治疗后，LMW载脂蛋白(a)表型（比值比2.3（1.1至4.8），P = 0.03）而非升高的Lp(a)（1.9（0.8 - 4.6），P = 0.13）是MI发生的独立预测因素。载脂蛋白(a)表型还决定了Lp(a)与PCSK9浓度之间的关系。LMW载脂蛋白(a)患者中PCSK9-Lp(a)复合物水平更高。
在过早发生CHD患者的长期前瞻性随访中，LMW载脂蛋白(a)表型是非致命性MI的危险因素，且这种联系可能通过PCSK-9介导。
