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

April 10, 2024 updated by: Chunjian Li, The First Affiliated Hospital with Nanjing Medical University

A Multi-omics Study of Patients With Premature Coronary Artery Disease in the Absence of Common Risk Factors

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？

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

160

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210000
        • Recruiting
        • First Affiliated Hospital of Nanjing Medical University
        • Contact:
    • Shandong
      • Jinan, Shandong, China, 250012
        • Active, not recruiting
        • Qilu Hospital of Shangdong University
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310009
        • Active, not recruiting
        • The Second Affiliated Hospital of Zhejiang University Medical College

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

In-patients from cardiology department of either following 3 hospitals: a) The First Affiliated Hospital of Nanjing Medical University; b) Qilu Hospital of Shandong University; c) The Second Affiliated Hospital Zhejiang University School of Medicine. Those patients who meet the criteria for cases or controls and willing to give an informed consent will be enrolled.

Description

Inclusion Criteria for cases:

  1. In-patients from cardiology department of either following 3 hospitals: a) The First Affiliated Hospital of Nanjing Medical University; b) Qilu Hospital of Shandong University; c) The Second Affiliated Hospital Zhejiang University School of Medicine
  2. Confirmed diagnosis of Obstructive CAD (≥50% diameter stenosis in a major epicardial vessel) through coronary angiography
  3. Age of the patient when Obstructive CAD was for the first time diagnosed should be no more than 45 years old for the male and 55 years old for the female.

Inclusion Criteria for controls:

  1. In-patients from cardiology department of either following 3 hospitals: a) The First Affiliated Hospital of Nanjing Medical University; b) Qilu Hospital of Shandong University; c) The Second Affiliated Hospital Zhejiang University School of Medicine
  2. Coronary artery stenosis was ruled out through either coronary angiography or coronary CTA.

Exclusion Criteria for both cases and controls:

  1. Patients with hypertension (grade 1-3)
  2. Patients with type 1 or type 2 diabetes mellitus
  3. BMI >28.0 Kg/m^2
  4. Patients with non-ideal blood lipids level on admission(defined as either LDL-C≥2.6mmol/L OR non-HDL cholesterol≥3.4mmol/L OR Lipoprotein(a) ≥300mg/L)
  5. Smoker (Smoking for more than 6 consecutive or cumulative months in a lifetime, whether quit smoking or not)
  6. Patients with hyperuricemia or gout
  7. eGFR<60 ml/min·1.73m^2
  8. Patients with structural heart diseases, inherited cardiomyopathies & arrhythmias
  9. Other reasons a participant considered unsuitable for inclusion by researchers.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
cases group
In-patients from cardiology department of The First Affiliated Hospital with Nanjing Medical University will be screened using inclusion/exclusion criteria for patients. Among the patients who meet the criteria and willing to give an informed consent, 30 patients with youngest CAD-diagnosed-age will be enrolled as cases.
Other: multi-omics studies
15cc peripheral venous blood will be collected for multi-omics studies, including whole-exome study, transcriptomics & metabolomics studies.
matching controls group
In-patients from cardiology department of The First Affiliated Hospital with Nanjing Medical University will be screened using inclusion/exclusion criteria for controls. 30 controls matched in gender and age will be enrolled as matching controls.
Other: multi-omics studies
15cc peripheral venous blood will be collected for multi-omics studies, including whole-exome study, transcriptomics & metabolomics studies.
verification group
In-patients from cardiology departments of all 3 centers will be screened using inclusion/exclusion criteria. Other than previous 60 participants, about another 100 patients and controls in total who meet the criteria and willing to give an informed consent will be enrolled as verification group.
Other: multi-omics studies
15cc peripheral venous blood will be collected for multi-omics studies, including whole-exome study, transcriptomics & metabolomics studies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
common & rare variants associated with "healthy" pre-mature CAD phenotype
Time Frame: 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.
3 months
Unique metabolomic fingerprints associated with "healthy" pre-mature CAD phenotype
Time Frame: 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 .
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Investigators

  • Principal Investigator: Chunjian Li, PHD, The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 20, 2024

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

January 5, 2024

First Submitted That Met QC Criteria

April 10, 2024

First Posted (Actual)

April 12, 2024

Study Record Updates

Last Update Posted (Actual)

April 12, 2024

Last Update Submitted That Met QC Criteria

April 10, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 026

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual level data will not be published until further permission granted from domestic Human Genetic Resource Administration.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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