Effect of PCSK9 E670G and R46L Polymorphisms on Major Adverse Cardio-Cerebrovascular Events in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Abstract

Major adverse cardio-cerebrovascular events (MACCE) in ST-segment elevation myocardial infarction (STEMI) are still high, although there have been advances in pharmacology and interventional procedures. Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a serine protease regulating lipid metabolism associated with inflammation in acute coronary syndrome. The MACCE is possibly related to polymorphisms in PCSK9. A prospective cohort observational study was designed to confirm the association between polymorphism of E670G and R46L in the PCSK9 gene with MACCE in STEMI. The Cox proportional hazards model and Spearman correlation were utilized in the study. The Genotyping of PCSK9 and ELISA was assayed.Sixty-five of 423 STEMI patients experienced MACCE in 6 months. The E670G polymorphism in PCSK9 was associated with MACCE (hazard ratio = 45.40; 95% confidence interval: 5.30–390.30; p = 0.00). There was a significant difference of PCSK9 plasma levels in patients with previous statin consumption (310 [220–1,220] pg/mL) versus those free of any statins (280 [190–1,520] pg/mL) (p = 0.001).E670G polymorphism of PCSK9 was associated with MACCE in STEMI within a 6-month follow-up. The plasma PCSK9 level was higher in statin users.

Effects of PCSK9 Inhibition on Coronary Atherosclerosis Regression of Nontarget Lesions after Primary Percutaneous Coronary Intervention in Acute Coronary Syndrome Patients

“…PCSK9 is also detected in atherosclerotic plaques, contributing to the development and progression of atherosclerosis and thrombosis through a process involving platelet activation, leukocyte recruitment, as well as clot formation, and so on [ 17 ]. PCSK9 has been reported to regulate inflammation-related lipid metabolism in ACS, and its polymorphisms may be related to MACE [ 18 ]. PCSK9 is expressed in various cell types involved in the development and progression of atherosclerosis and can be detected in human atherosclerotic plaques [ 19 ].…”

Predictive Value of Plasma PCSK9 Levels for Degree of Atherosclerosis and Major Adverse Cardiovascular and Cerebrovascular Events in Older Adult Patients with Non-Alcoholic Fatty Liver Disease

“…29 Furthermore, PCSK9 levels greater than 310 ng/mL were associated with more severe coronary artery stenosis and a higher incidence of MACCE at follow-up. 30 The difference in traditional atherosclerosis risk factors in different Gensini score subgroups was not statistically significant in this study, possibly because the selected patients were older adults. Theocharidou et al reported that PCSK9 was associated with higher morbidity, mortality, and risk of major clinical adverse events in patients with NAFLD.…”

Correlations of PCSK9 and LDLR Gene Polymorphisms and Serum PCSK9 Levels With Atherosclerosis and Lipid Metabolism in Patients on Maintenance Hemodialysis

“…6 Proprotein convertase subtilisin/kexin type 9 (PCSK9) refers to a serine protease-modulating lipid metabolism associated with inflammation in acute coronary syndrome. 7 Discovered in 2003, PCSK9 subsequently emerges as an innovative target for low-density lipoprotein cholesterol (LDL-C)lowering treatment. 8 PCSK9 performs a crucial role in myocardial infarction 9 and in the regulation of lipid metabolism.…”