Detection of Coronary Artery Calcifications by Whole Blood Transcriptome Analyzed by Artificial InTelligence Algorithms (CAC-TRAIT)

Detection of Coronary Artery Calcifications by Whole Blood Transcriptome Analyzed by Artificial InTelligence Algorithms. (CAC-TRAIT Study)

The goal of this observational study is to determine the diagnostic accuracy of peripheral whole blood transcriptomes analyzed by an artificial intelligence algorithm to detect the presence and extent of coronary calcification in individuals without a history of known cardiovascular disease.

The main question it aims to answer is:

1. Will the proposed method predict the presence and extent of coronary artery calcification from the peripheral whole-blood transcriptomes?

Study Overview

• Status: Completed
• Conditions: Atherosclerosis; Atheroscleroses, Coronary; Atherosclerotic Plaque

Detailed Description

This study will be a prospective observational single-site study. A convenience sample will be carried out to include 800 patients who attend the Clinic, to undergo a cardiac CT without contrast (coronary calcium score), either for a medical indication or volunteers for an assessment of cardiovascular risk. The study will have a baseline stage in which a clinical evaluation will be performed, blood samples will be drawn for transcriptome analysis and laboratory analysis. Then, a DNA sample obtained by swabbing the buccal mucosa will be taken. Subsequently, a non-contrast gated cardiac CT will be performed to assess the presence and extent of coronary calcification and other outcomes of interest. At the end of patient enrollment, biological samples will be sequenced for in silico evaluation of the results. Finally, a 5-year clinical (telephone) follow-up will be carried out to collect data on the incidence of fatal and non-fatal cardiovascular events.

• Study Type: Observational
• Enrollment (Actual): 800

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma de Buenos Aires, Argentina, C1426EOB
    • Clinica Sagrada Familia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Men and women between 30 and 75 years attending the institution for a non-contrast cardiac CT scan (coronary calcium score) either by medical indication or voluntary for cardiovascular risk assessment.

Description

Inclusion Criteria:

• Men and women between 30 and 75 years attending the institution for a non-contrast cardiac CT scan (coronary calcium score) either by medical indication or voluntary for cardiovascular risk assessment.
• Signature of the informed consent form

Exclusion Criteria:

• Previously known chronic renal or hepatic insufficiency.
• Active chronic lung disease, defined as exacerbated asthma, exacerbated chronic obstructive pulmonary disease (COPD), or pulmonary fibrosis.
• Active and/or previous cardiovascular disease, defined as previous acute myocardial infarction, stable or unstable angina, cerebrovascular accident, history of vascular interventions (coronary or another territory), heart failure, severe cardiomyopathies, or valvulopathies.
• Uncontrolled hyper or hypothyroidism.
• Suprarenal insufficiency.
• Previous surgeries in the last 3 months.
• Severe trauma in the last 6 months, defined as one that involved bone fractures and/or surgical interventions.
• Known active cancer disease or under treatment (acute or preventive), or history of cancer disease without criteria for a cure.
• Known autoimmune disease active or in treatment.
• Ongoing pregnancy, postpartum period of fewer than 12 months, or breastfeeding.
• Other serious illnesses with an estimated life expectancy of fewer than 12 months (according to the investigators).
• Temperature greater than 37.5°C recorded by a thermometer or any acute infection caused by viruses or bacteria confirmed by a health professional in the previous 30 days.
• Pathologies under immunosuppressive treatment

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Presence / absence of CAC; Participants with or without a level/extension of CAC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary artery calcium score	Coronary artery calcium (CAC) score (Agatston units) stratified with increasing risk according to the Society of Cardiovascular Computed Tomography Guidelines as CAC=0; CAC 1-99; CAC 100-299; and CAC≥300.	At baseline (cross-sectional assessment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary artery calcium score	Percentile Agatston score: according to age and sex with a increasing risk ranging from 1 to 99 th percentile.	At baseline (cross-sectional assessment)
Coronary artery calcium score (number of segments)	Number of segments with coronary calcifications ranging from 0 to 17 segments.	At baseline (cross-sectional assessment)
Aortic valve calcium	Aortic valve calcification score (Agatston units) as a continuous variable with increasing risk and without preestablished thresholds	At baseline (cross-sectional assessment)
Thoracic aorta calcium	Thoracic aorta calcification score (Agatston units) as a continuous variable with increasing risk and without preestablished thresholds	At baseline (cross-sectional assessment)
Epicardial adipose tissue (volume)	cm2/m2	At baseline (cross-sectional assessment)
Epicardial adipose tissue (density)	density, Q1-Q4: quartiles percentage	At baseline (cross-sectional assessment)
Fatty liver	liver attenuation <48 Hounsfield units	At baseline (cross-sectional assessment)
Neutrophil to lymphocyte ratio	hematological parameter for systemic inflammation and stress	At baseline (cross-sectional assessment)
High-sensitive C reactive protein (CRP)	mg/dl	At baseline (cross-sectional assessment)
Repolarization abnormalities	Number of participants with repolarization abnormalities on a 12-lead ECG, defined as ST segment depression or pathological T wave inversion.	At baseline (cross-sectional assessment)
Left ventricular hypertrophy	Number of participants with left ventricular hypertrophy on a 12-lead ECG, defined by positive Sokolow-Lyon or Cornell criteria.	At baseline (cross-sectional assessment)
Intraventricular conduction abnormalities	Number of participants with intraventricular conduction abnormalities on a 12-lead ECG, stratified by the presence of left bundle branch block; right bundle branch block and left posterior fascicular block; right bundle branch block and left anterior fascicular block or right bundle branch block; or left anterior fascicular block.	At baseline (cross-sectional assessment)
Percent electron density relative to water (%EDW)	percent electron density relative to water, available for direct evaluation with dedicated software in all scans acquired using a dual-layer spectral CT scanner).	At baseline (cross-sectional assessment)
Death	Number of participants with report of death from any cause	year 1 through 5
Acute ischemic syndrome	Number of participants with non fatal diagnosis of acute myocardial infarction or unstable angina	year 1 through 5
Heart failure	Number of participants with non fatal new diagnosis of heart failure with preserved or impaired ventricular function	year 1 through 5
Vascular revascularization	Number of participants with performance of myocardial revascularization surgery, coronary angioplasty or peripheral vascular angioplasty	year 1 through 5
cerebrovascular event	Number of participants with non fatal diagnosis of cerebrovascular accident ("stroke") or transient ischemic attack	year 1 through 5
Cancer	Number of participants with new diagnosis of any type of cancer	year 1 through 5

Collaborators and Investigators

• Sponsor: Santiago Gabriel Miriuka
• Collaborators: Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia
• Investigators: Principal Investigator: Santiago G Miriuka, MD MSc PhD, MultiplAI Health LTD

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2022
• Primary Completion (Actual): January 24, 2024
• Study Completion (Actual): January 24, 2024

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 15, 2022
• First Posted (Actual): November 16, 2022

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: artificial intelligence; primary prevention; risk stratification; transcriptomics; Cardiovascular disease (CVD) screening; general population; no history of CVD; subclinical
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Atherosclerosis; Plaque, Atherosclerotic
• Other Study ID Numbers: CCT2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No