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

NCT06362278 | Recruiting

• 1 other identifier: 026
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 3

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？

Conditions

Coronary Artery Disease

Keywords

coronary artery disease; multi-omics; premature

Outcome Measures

Primary Outcomes (2)

• common & rare variants associated with "healthy" pre-mature CAD phenotype

  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

  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

Study Arms (3)

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

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

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

Interventions

multi-omics studies OTHER

15cc peripheral venous blood will be collected for multi-omics studies, including whole-exome study, transcriptomics \& metabolomics studies.

cases group; matching controls group; verification group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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
• Confirmed diagnosis of Obstructive CAD (≥50% diameter stenosis in a major epicardial vessel) through coronary angiography
• 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.
• 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
• Coronary artery stenosis was ruled out through either coronary angiography or coronary CTA.

You may not qualify if:

• Patients with hypertension (grade 1-3)
• Patients with type 1 or type 2 diabetes mellitus
• BMI \>28.0 Kg/m\^2
• 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)
• Smoker (Smoking for more than 6 consecutive or cumulative months in a lifetime, whether quit smoking or not)
• Patients with hyperuricemia or gout
• eGFR\<60 ml/min·1.73m\^2
• Patients with structural heart diseases, inherited cardiomyopathies \& arrhythmias

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (3)

First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210000, China

RECRUITING

Qilu Hospital of Shangdong University

Jinan, Shandong, 250012, China

ACTIVE NOT RECRUITING

The Second Affiliated Hospital of Zhejiang University Medical College

Hangzhou, Zhejiang, 310009, China

ACTIVE NOT RECRUITING

Related Publications (11)

• Mensah GA, Fuster V, Murray CJL, Roth GA; Global Burden of Cardiovascular Diseases and Risks Collaborators. Global Burden of Cardiovascular Diseases and Risks, 1990-2022. J Am Coll Cardiol. 2023 Dec 19;82(25):2350-2473. doi: 10.1016/j.jacc.2023.11.007. No abstract available.

  PMID: 38092509 BACKGROUND

• Kessler T, Vilne B, Schunkert H. The impact of genome-wide association studies on the pathophysiology and therapy of cardiovascular disease. EMBO Mol Med. 2016 Jul 1;8(7):688-701. doi: 10.15252/emmm.201506174. Print 2016 Jul.

  PMID: 27189168 BACKGROUND

• O'Sullivan JW, Raghavan S, Marquez-Luna C, Luzum JA, Damrauer SM, Ashley EA, O'Donnell CJ, Willer CJ, Natarajan P; American Heart Association Council on Genomic and Precision Medicine; Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease. Polygenic Risk Scores for Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2022 Aug 23;146(8):e93-e118. doi: 10.1161/CIR.0000000000001077. Epub 2022 Jul 18.

  PMID: 35862132 BACKGROUND

• Muse ED, Chen SF, Torkamani A. Monogenic and Polygenic Models of Coronary Artery Disease. Curr Cardiol Rep. 2021 Jul 1;23(8):107. doi: 10.1007/s11886-021-01540-0.

  PMID: 34196841 BACKGROUND

• Saadatagah S, Varughese MG, Nambi V. Coronary Artery Disease Risk Prediction in Young Adults: How Can We Overcome the Dominant Effect of Age? Curr Atheroscler Rep. 2023 Jun;25(6):257-265. doi: 10.1007/s11883-023-01106-1. Epub 2023 May 17.

  PMID: 37195598 BACKGROUND

• Vilne B, Schunkert H. Integrating Genes Affecting Coronary Artery Disease in Functional Networks by Multi-OMICs Approach. Front Cardiovasc Med. 2018 Jul 17;5:89. doi: 10.3389/fcvm.2018.00089. eCollection 2018.

  PMID: 30065929 BACKGROUND

• Collet JP, Zeitouni M, Procopi N, Hulot JS, Silvain J, Kerneis M, Thomas D, Lattuca B, Barthelemy O, Lavie-Badie Y, Esteve JB, Payot L, Brugier D, Lopes I, Diallo A, Vicaut E, Montalescot G; ACTION Study Group. Long-Term Evolution of Premature Coronary Artery Disease. J Am Coll Cardiol. 2019 Oct 15;74(15):1868-1878. doi: 10.1016/j.jacc.2019.08.1002.

  PMID: 31601367 BACKGROUND

• Navas-Nacher EL, Colangelo L, Beam C, Greenland P. Risk factors for coronary heart disease in men 18 to 39 years of age. Ann Intern Med. 2001 Mar 20;134(6):433-9. doi: 10.7326/0003-4819-134-6-200103200-00007.

  PMID: 11255518 BACKGROUND

• Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema MD, Munoz D, Smith SC Jr, Virani SS, Williams KA Sr, Yeboah J, Ziaeian B. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Sep 10;140(11):e596-e646. doi: 10.1161/CIR.0000000000000678. Epub 2019 Mar 17. No abstract available.

  PMID: 30879355 BACKGROUND

• Singh A, Collins BL, Gupta A, Fatima A, Qamar A, Biery D, Baez J, Cawley M, Klein J, Hainer J, Plutzky J, Cannon CP, Nasir K, Di Carli MF, Bhatt DL, Blankstein R. Cardiovascular Risk and Statin Eligibility of Young Adults After an MI: Partners YOUNG-MI Registry. J Am Coll Cardiol. 2018 Jan 23;71(3):292-302. doi: 10.1016/j.jacc.2017.11.007. Epub 2017 Nov 12.

  PMID: 29141201 BACKGROUND

• Wojcik GL, Murphy J, Edelson JL, Gignoux CR, Ioannidis AG, Manning A, Rivas MA, Buyske S, Hendricks AE. Opportunities and challenges for the use of common controls in sequencing studies. Nat Rev Genet. 2022 Nov;23(11):665-679. doi: 10.1038/s41576-022-00487-4. Epub 2022 May 17.

  PMID: 35581355 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

15cc peripheral venous blood will be gathered from each participant for multi-omics studies including: 1）5cc collected with EDTA-K2 tubes for whole-exome study, 2) 5cc collected with PAXGENE tubes for transcriptomics study, 3) 5cc collected with lithium heparin tubes for metabolomics study.

MeSH Terms

Conditions

Coronary Artery Disease; Premature Birth

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Chunjian Li, PHD

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chunjian Li, PHD

CONTACT

+86 13701465229; lijay@njmu.edu.cn

Qiang Huang, MD

CONTACT

+86 15261659317; hq_elife@stu.njmu.edu.cn

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Cardiology

Study Record Dates

• First Submitted: January 5, 2024
• First Posted: April 12, 2024
• Study Start: March 20, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 12, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)