A Multi-omics Study of "Healthy" Premature CAD Patients

Recruiting

• Conditions: Coronary Artery Disease

• Registration Number: NCT06362278
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

Brief Summary

The goal of this multi-center observational clinical trial is to investigate the genetic risk factors of patients with premature CAD and none traditional CAD risk factors through a multi-omics approach.

The main questions it aims to answer are:

* Genetic risk factors \& metabolic fingerprints of patients with premature CAD and none traditional CAD risk factors remain unknown.

* How to optimize current primary prevention strategy for this rare CAD subgroup？

Detailed Description

Cardiovascular diseases (CVDs) remain the leading cause of global mortality despite continuous efforts in disease prevention and treatment optimization. In 2022 alone, CVD caused an estimated 19.8 million deaths worldwide, and ischemic heart disease had the highest global age-standardized DALYs of all diseases at 2,275.9 per 100,000. Therefore, research on the etiology and pathogenesis of coronary artery disease (CAD) remains first priority.

It is now widely known that risk factors such as diabetes mellitus, hyperlipidemia, hypertension, smoking, and obesity are closely related to CAD, but they only explain 30%-40% of CAD risk factors, and large-sample cohort and twin studies have concluded that CAD heritability is estimated to be 40% to 60%. With the development of the Human Genome Project and high-throughput sequencing technology, in the past decade, increasingly larger genome-wide association studies (GWAS) have been conducted worldwide and biobanks established. Public sequencing data is increasingly being used as external common controls instead of sequencing new controls in every study. Till now, thousands of mutations related to CAD have been identified. Multiple Polygenic risk scores (PRSs) have been developed to improve the prediction of common, complex cardiovascular diseases like CAD on individual level.

Premature CAD has been proved to have strong link with family history of cardiovascular and cerebral vascular disease, which indicates a strong genetic background of premature CAD. However, there is an even more scarce \& inconspicuous subgroup of premature CAD, defined as premature CAD without common CAD risk factors in this study. First of all, most of those patients were considered "healthy" or "at very low risk of CVDs" before CAD was diagnosed; secondly, genetic risk factors \& metabolic fingerprints of such patients remain unknown; thirdly, we still don't know yet how to optimize current primary prevention strategy for this rare CAD subgroup.

For this regard, we designed this multi-omics study to cover the questions mentioned above.

Study Timeline

• Study First Submitted: 2024-01-05
• Study Start: 2024-03-20
• Status Verified: 2024-04
• Study First Submitted QC: 2024-04-10
• Last Update Submitted: 2024-04-10
• Study First Posted: 2024-04-12
• Last Update Posted: 2024-04-12
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
common & rare variants associated with "healthy" pre-mature CAD phenotype	3 months	Whole-exome study in both patients and matching controls will be pefromed using rare-variant collapsing analyses to findout common \& rare variants accosicated with this phenotype. Relative variants will be further screend \& validated in verification group. If necessary, further casade screening using trios-wes technique will be perfromed within certain families under written consent.
Unique metabolomic fingerprints associated with "healthy" pre-mature CAD phenotype	3 months	Non-targeted metabonomic analysis of plasma will be performed in both patients and matching controls. Relative metabolites will be further screend \& validated in verification group. If necessary, further targeted metabonomic analysis will be performed using redundant serum samples .

Trial Locations

Locations (3)

First Affiliated Hospital of Nanjing Medical University; 🇨🇳 Nanjing, Jiangsu, China

Qilu Hospital of Shangdong University; 🇨🇳 Jinan, Shandong, China

The Second Affiliated Hospital of Zhejiang University Medical College; 🇨🇳 Hangzhou, Zhejiang, China