PCSK9 Polymorphism and Risk of Cardiac Rupture

Maastricht University Medical Centre (MUMC)

Status: Enrolling

Conditions: Gene Polymorphism; Post-Infarction Heart Rupture

Treatments: Genetic: Genetic analysis for PCSK9 polymorphisms

Study type: Observational

Funder types: Other

Identifiers

NCT05503095

IT-VA-237-2021

Details and patient eligibility

About

Protein convertase subtilisin/kexin type 9 (PCSK9) plays a regulatory role in cholesterol homeostasis by promoting low-density lipoprotein receptor (LDLr) degradation. Although the vast majority of the studies have focused on the role of PCSK9 in LDLr expression in the liver, an increasing body of evidence suggests that PCSK9 gene is also present in extra-hepatic tissues. A recent publication showed for the first time that PCSK9 is expressed in the ischemic heart and the expression is highest in the zone bordering the infarcted areas. Furthermore, the expression of PCSK9 is maximal early, at 1 week of ischemia.

Mechanical complications (or cardiac ruptures) are uncommon but potentially lethal sequelae of acute myocardium infarction (AMI) and are commonly associated with early mortality without appropriate surgical intervention. It's unknown why some patients develop these devasting complications following AMI, while others not. Interestingly, studies have shown that post-infarction cardiac rupture affect the border zone between the ischemic and normal area and occur within the first 3 to 5 days after AMI.

Based on the aforementioned observations, it's likely to assume a relationship between PCSK9 expression and the development of post-AMI cardiac rupture. Therefore, the main purpose of the this project is to study the PCSK9 gene polymorphism and its association with cardiac rupture. Investigators hypothesize that PCSK9 expression/secretion and development of post-AMI cardiac rupture may be a part of the dynamic changes at cellular levels occurring in the ischemic heart of genetically predisposed patients.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• clinical diagnosis of acute myocardial infarction with ST sopra-elevation (control group)
• clinical diagnosis of acute myocardial infarction complicated by cardiac rupture

Exclusion criteria

• absence of coronary artery disease

Trial design

100 participants in 2 patient groups

patients who develop cardiac rupture following acute myocardial infarction

Treatment:

Genetic: Genetic analysis for PCSK9 polymorphisms

patients with acute ST-elevation myocardial infarction not complicated by cardiac rupture

Treatment:

Genetic: Genetic analysis for PCSK9 polymorphisms