Clinical trial NCT06995183: Heart CT Imaging to Detect Early Coronary Artery Disease in First-Degree Relatives With High or Low Lipoprotein(a) Identified Through Family Screening
Official title: Improved Assessment of Cardiovascular Risk Through Imaging in Relatives Identified By Lipoprotein(a) Cascade Screening
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lipoprotein(a)
Keywords: Lipoprotein(a)
coronary atherosclerosis
subclinical atherosclerosis
coronary artery calcium scoring
coronary computed tomography angiography
cardiovascular risk assessment
primary prevention
coronary artery disease
cascade screening
imaging biomarkers
atherosclerotic cardiovascular disease
lipid disorders
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2025-05-29
Enrollment: 150
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Coronary Atherosclerotic Plaque Detected on CCTA
timeFrame: Day 1
Secondary outcomes:
measure: Number of Participants with Obstructive Coronary Stenosis (≥50% Luminal Narrowing) on CCTA
timeFrame: Day 1
measure: Total Coronary Plaque Volume
timeFrame: Day 1
measure: Calcified and Non-Calcified Plaque Volumes
timeFrame: Day 1
measure: Low-Attenuation Plaque Volume
timeFrame: Day 1
measure: Pericoronary Adipose Tissue (PCAT) Attenuation
timeFrame: Day 1
measure: Number of High-Risk Plaque Features
timeFrame: Day 1
measure: Coronary Artery Calcium (CAC) Score
timeFrame: Day 1
measure: CAD-RADS Classification
timeFrame: Day 1
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: Noord-Holland
Study officials:
References:
citation: 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.