Heart CT Imaging to Detect Early Coronary Artery Disease in First-Degree Relatives With High or Low Lipoprotein(a) Identified Through Family Screening (IMAGE-LPA)

Improved Assessment of Cardiovascular Risk Through Imaging in Relatives Identified By Lipoprotein(a) Cascade Screening

Lipoprotein(a), or Lp(a), is a type of cholesterol that can increase the risk of heart and blood vessel disease. Many people are unaware they have high Lp(a), since it is not routinely measured and usually causes no symptoms on its own. However, elevated Lp(a) levels tend to run in families, meaning that close relatives of individuals with high Lp(a) are more likely to have it as well.

At Amsterdam UMC, family members of patients with high Lp(a) are invited for cascade screening, which includes testing for Lp(a) and other cardiovascular risk factors. From this screened group, a selection of individuals with either high or low Lp(a) levels are invited to participate in the IMAGE-LPA study.

In IMAGE-LPA, participants undergo a comprehensive cardiovascular evaluation, including blood tests and heart imaging using CT scans. Two types of scans are performed: (1) a calcium score scan to detect early calcium buildup in the heart's arteries (an early marker of atherosclerosis), and (2) coronary CT angiography to assess for plaque and narrowing in the coronary arteries.

The goal of the study is to compare individuals with high versus low Lp(a) identified through cascade screening, to determine whether high Lp(a) levels are associated with early signs of heart disease in this patient group.

The study does not involve any medications or invasive procedures. The findings may help clarify whether heart imaging can improve early detection in individuals with high Lp(a), and guide future strategies for preventing cardiovascular disease in families affected by this inherited risk factor.

Study Overview

• Status: Recruiting
• Conditions: Lipoprotein(a)

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Maxim E Annink, MD MSc LLM; Phone Number: +31205669111; Email: m.e.annink@amsterdamumc.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105AZ
      • Recruiting
      • Amsterdam UMC
      • Contact: Maxim E Annink, MD MSc LLM; Phone Number: +31205669111; Email: m.e.annink@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Participants will be selected from first-degree relatives of patients with elevated Lipoprotein(a) who previously participated in the Lp(a) familial cascade screening program at the Amsterdam UMC Vascular Medicine outpatient clinic. All participants have been screened for Lp(a) levels as part of routine clinical care and have indicated willingness to be contacted for future research. Eligible individuals are middle-aged or older and have no history of clinically manifest atherosclerotic cardiovascular disease.

Description

In order to be eligible to participate in this study in the elevated Lp(a) subgroup, a subject must meet all of the following inclusion criteria:

• Man or woman ≥50 years of age;
• Lp(a) level ≥ 150 nmol/L;
• Identified as having elevated Lp(a) through Lp(a) family cascade screening at the Amsterdam UMC Vascular Medicine outpatient clinic;
• Able and willing to provide informed consent;
• Able to comply with study requirements.

In order to be eligible to participate in this study in the Low Lp(a) subgroup, a subject must meet all of the following inclusion criteria:

• Man or woman ≥50 years of age;
• Lp(a) level < 50 nmol/L;
• Identified as having elevated Lp(a) through Lp(a) family cascade screening at the Amsterdam UMC Vascular Medicine outpatient clinic;
• Able and willing to provide informed consent;
• Able to comply with study requirements.

A potential subject who meets any of the following criteria will be excluded from participation in this study (both subgroups):

• Renal insufficiency, defined as eGFR < 30 ml/min
• History of ASCVD (acute coronary syndrome, history of myocardial infarction, stable or unstable angina pectoris or coronary or other arterial revascularization, stroke, transient ischemic attack or peripheral artery disease including aortic aneurysm, all of atherosclerotic origin)
• History of atrial fibrillation
• Prior and current use of statins
• Any other treatment or clinically relevant condition that could interfere with the conduct or interpretation of the study in the opinion of the investigator
• Unable or unwilling to provide informed consent
• Unable to comply with study requirements.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
High Lp(a); Individuals aged 50 years or older who were identified with elevated Lipoprotein(a) levels (≥150 nmol/L) through familial cascade screening at the Amsterdam UMC Vascular Medicine outpatient clinic. These participants have no history of clinical atherosclerotic cardiovascular disease and are undergoing imaging to assess subclinical coronary atherosclerosis.
Low Lp(a); Age- and sex-matched individuals aged 50 years or older with normal Lipoprotein(a) levels (<50 nmol/L), identified through the same familial cascade screening program. These participants also have no history of clinical atherosclerotic cardiovascular disease and serve as controls to compare the prevalence of subclinical coronary plaque.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Coronary Atherosclerotic Plaque Detected on CCTA	Assessment of the presence or absence of any coronary artery plaque as detected by coronary computed tomography angiography (CCTA). Plaque is defined as within and/or adjacent to the vessel lumen distinguishable from the lumen and surrounding tissue.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Obstructive Coronary Stenosis (≥50% Luminal Narrowing) on CCTA	Measured by CCTA. Obstructive stenosis is defined as luminal narrowing of ≥50% in any major coronary artery, based on visual assessment and automated quantification.	Day 1
Total Coronary Plaque Volume	Total plaque volume (in mm³) across all coronary segments, quantified using FDA-approved software (Cleerly Inc.) from CCTA scans. Includes both calcified and non-calcified plaque.	Day 1
Calcified and Non-Calcified Plaque Volumes	Volumes (in mm³) of calcified and non-calcified coronary plaque separately measured using semi-automated quantification of CCTA images. Non-calcified plaque includes fibrous and lipid-rich components.	Day 1
Low-Attenuation Plaque Volume	Volume (in mm³) of coronary plaque with CT attenuation <30 HU, measured on CCTA. Low-attenuation plaque is associated with high-risk morphology and vulnerability.	Day 1
Pericoronary Adipose Tissue (PCAT) Attenuation	Mean CT attenuation (in Hounsfield Units) of adipose tissue surrounding coronary arteries, as a surrogate of coronary inflammation. Measured on CCTA at the proximal right coronary artery.	Day 1
Number of High-Risk Plaque Features	CCTA-based count of high-risk plaque features per patient, including positive remodeling, napkin-ring sign, low-attenuation plaque, and spotty calcification. A higher count suggests greater risk of future events.	Day 1
Coronary Artery Calcium (CAC) Score	Agatston CAC score obtained from non-contrast CT scan preceding CCTA. Score quantifies coronary calcification. Scale: 0-400+; higher score = more calcification, worse outcome	Day 1
CAD-RADS Classification	Coronary Artery Disease Reporting and Data System (CAD-RADS) score, a standardized grading system for coronary stenosis severity based on CCTA. Scores range from 0 (no plaque) to 5 (severe stenosis ≥70%).	Day 1

Collaborators and Investigators

• Sponsor: E.S.stroes

Publications and helpful links

General Publications

• Annink ME, Janssen ES, Reeskamp LF. Effectiveness of cascade screening for elevated lipoprotein(a), an underdiagnosed family disorder. Curr Opin Lipidol. 2024 Dec 1;35(6):290-296. doi: 10.1097/MOL.0000000000000951. Epub 2024 Sep 18.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 16, 2025
• First Submitted That Met QC Criteria: May 27, 2025
• First Posted (Actual): May 29, 2025

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: coronary artery disease; subclinical atherosclerosis; Lipoprotein(a); primary prevention; coronary atherosclerosis; atherosclerotic cardiovascular disease; coronary computed tomography angiography; lipid disorders; cascade screening; imaging biomarkers; cardiovascular risk assessment; coronary artery calcium scoring
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Coronary Artery Disease
• Other Study ID Numbers: 2024.1104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared because participants did not provide explicit consent for their data to be shared beyond the scope of the approved study. Data sharing was not included as part of the informed consent process.

Drug and device information, study documents

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