Study of the Determinants of Coronary Atherosclerosis in Familial Hypercholesterolemia (ATHERO-FH Study) (ATHERO-FH)

Study of the Determinants of Coronary Atherosclerosis in Familial Hypercholesterolemia

The goal of this study (interventional clinical research not involving a health product) is to assess the prevalence of subclinical coronary atherosclerosis diagnosed by coronary CT angiography in heart failure patients in primary prevention, across different levels of cardiovascular risk defined by coronary artery calcium (CAC) score percentiles (based on data from the MESA study): low risk (≤25th percentile for age, sex, and ethnicity), intermediate risk (25th < CAC ≤ 75th percentile), and high risk (>75th percentile). The Patients will attend an on-site visit at inclusion (and must undergo a coronary CT angiography within 6 months following this visit), will be contacted by phone at 1 year and 2 years, and will return for an on-site visit at 30 months.

Study Overview

• Status: Recruiting
• Conditions: Familial Hypercholesterolemias; Atherosclerotic Cardiovascular Disease (ASCVD)
• Intervention / Treatment: Other: Coronary CT scan with CAC score measurement

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bertrand CARIOU, Pr; Phone Number: +33 2 53 48 27 10; Email: bertrand.cariou@chu-nantes.fr

Study Locations

• France
  • Dijon, France
    • Recruiting
    • CHU Dijon Bourgogne
    • Contact: Yves COTTIN; Phone Number: +33 3 80 29 35 36; Email: yves.cottin@chu-dijon.fr
    • Principal Investigator: Yves COTTIN
  • Lille, France
    • Not yet recruiting
    • CHRU LILLE
    • Principal Investigator: cecile yelnik
    • Contact: Cécile YELNIK; Phone Number: +33 3 20 44 59 62; Email: cecile.yelnik@chu-lille.fr
  • Lyon, France
    • Recruiting
    • Hospices Civils de Lyon
    • Principal Investigator: Sybil CHARRIERE
    • Contact: Sybil CHARRIERE; Phone Number: +33 4 27 85 66 66; Email: sybil.charriere@chu-lyon.fr
  • Marseille, France
    • Not yet recruiting
    • Hôpital de la Conception, AP-HM
    • Contact: Sophie BELIARD-LASSERRE; Phone Number: +33 4 91 38 36 50; Email: Sophie.beliard@ap-hm.fr
    • Principal Investigator: Sophie BELIARD-LASSERRE
  • Nantes, France
    • Recruiting
    • CHU Nantes
    • Contact: Bertrand CARIOU, Pr; Phone Number: +33 2 53 48 27 10; Email: bertrand.cariou@chu-nantes.fr
    • Principal Investigator: Bertrand CARIOU CARIOU
  • Paris, France
    • Recruiting
    • Hôpital de la Pitié-Salpêtrière, AP-HP
    • Principal Investigator: Antonio Gallo
    • Contact: Antonio GALLO; Phone Number: +33 1 42 17 57 85; Email: Antonio.gallo@aphp.fr
  • Paris, France
    • Recruiting
    • Hôpital Saint-Antoine, AP-HP
    • Principal Investigator: FRANCK BOCCARA
    • Contact: Franck BOCCARA; Phone Number: +33 1 49 28 24 49; Email: franck.boccara@aphp.fr
  • Rennes, France
    • Recruiting
    • CHU Rennes
    • Principal Investigator: François PAILLARD
    • Contact: François PAILLARD; Phone Number: +33 2 99 28 25 40; Email: francois.paillard@chu-rennes.fr
  • Strasbourg, France
    • Recruiting
    • CHU Strasbourg
    • Principal Investigator: Alain Pradignac
    • Contact: Alain PRADIGNAC; Phone Number: +33 3 88 12 75 89; Email: alain.pradignac@chru-strasbourg.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Person willing to sign the study consent form
• Person affiliated with a current social security scheme
• Person with a definite diagnosis of Familial Hypercholesterolemia, defined by a Dutch Lipid Clinic Network (DLCN) clinical-biological score > 8 and/or an identified causal mutation in the LDL receptor (LDLR) gene, apolipoprotein B100 gene, PCSK9 gene, or apolipoprotein E gene
• Male aged 40 years or older, or female aged 50 years or older
• Ability to understand French for questionnaire completion
• Person not taking any lipid-lowering medication or on a stable dose of lipid-lowering therapy for at least one month prior to inclusion (three months for PCSK9 inhibitors) at Visit 1
• Person not taking any antihypertensive medication or on a stable dose of antihypertensive therapy for at least one month at Visit 1
• Person not taking any antidiabetic medication or on a stable dose of antidiabetic therapy for at least 3 months at Visit 1

Exclusion Criteria:

• Subject with a technical contraindication for coronary CT scan: patient diameter > 70 cm and/or weight > 250 kg
• Patient with a history of atherosclerotic cardiovascular event (myocardial infarction, ischemic heart disease, coronary revascularization, ischemic stroke, carotid endarterectomy, lower limb arterial revascularization)
• Patient allergic to iodinated contrast agents
• Severe renal insufficiency: estimated glomerular filtration rate (eGFR) according to the CKD-EPI formula ≤ 30 ml/min
• Subject with active cancer or in remission for less than 3 years
• Subject who has received oral or intravenous corticosteroid therapy within the last 6 months
• Subject with untreated or poorly controlled hypothyroidism
• Subject receiving immunosuppressive or anticancer therapy
• Subject refusing to participate
• Subject under guardianship, curatorship, or judicial protection, or without social insurance coverage
• Pregnant woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Single arm; Visit 1: Inclusion Visit: Verification of eligibility criteria. Consent form signing, collection of clinical information, and completion of questionnaires. Fasting blood draw for biological analyses and biobanking. Collection of urine and stool samples (optional). POpmeter (optional), Fibroscan (optional), completion of the CONSTANCES and SF36 questionnaires. Visit 2 (30 months): Collection of the CAC score result (dated less than 6 months prior). Collection of clinical information and completion of questionnaires. Fasting blood draw for biological analyses and biobanking. Collection of urine and stool samples (optional). pOpmeter (optional), Fibroscan (optional), completion of the CONSTANCES and SF36 questionnaires. Major cardiovascular events will be collected from patients during telephone calls at 1 and 2 years, and during the 30-month visit.

Other: Coronary CT scan with CAC score measurement; Coronary CT scan with CAC score measurement (on the same day or within 6 months after the inclusion visit).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of subclinical coronary atherosclerosis	The criterion defining the presence of subclinical coronary atherosclerosis is the presence of at least one coronary stenosis greater than 50% in a main artery on coronary CT angiography	At the time of performing the coronary CT scan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of factors associated with the presence or absence of subclinical coronary atherosclerosis (coronary stenosis > 50% on coronary CT scan).	The anthropometric data collected as part of the current study will be comparable to the data collected as part of the SAFIR study	30 months
Identification of factors associated with the presence or absence of subclinical coronary atherosclerosis (coronary stenosis > 50% on coronary CT scan).	The clinic data collected as part of the current study will be comparable to the data collected as part of the SAFIR study	30 months
Identification of factors associated with the presence or absence of subclinical coronary atherosclerosis (coronary stenosis > 50% on coronary CT scan).	The drug treatments collected as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with the presence or absence of subclinical coronary atherosclerosis (coronary stenosis > 50% on coronary CT scan).	The genetic data collected as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with the presence or absence of subclinical coronary atherosclerosis (coronary stenosis > 50% on coronary CT scan).	The biological data collected as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with the presence or absence of subclinical coronary atherosclerosis (coronary stenosis > 50% on coronary CT scan).	Arterial Doppler ultrasound of the carotid arteries and lower limbs as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with the presence or absence of subclinical coronary atherosclerosis (coronary stenosis > 50% on coronary CT scan).	Pulse wave velocity measured by the pOpmeter as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with the presence or absence of subclinical coronary atherosclerosis (coronary stenosis > 50% on coronary CT scan).	Hepatic steatosis as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with the presence or absence of subclinical coronary atherosclerosis (coronary stenosis > 50% on coronary CT scan).	Hepatic fibrosis as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with the presence or absence of subclinical coronary atherosclerosis (coronary stenosis > 50% on coronary CT scan).	Nutritional data as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with the presence or absence of subclinical coronary atherosclerosis (coronary stenosis > 50% on coronary CT scan).	Physical activity as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with the presence or absence of subclinical coronary atherosclerosis (coronary stenosis > 50% on coronary CT scan).	Quality of life as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with a coronary calcium score less than or equal to the 25th percentile	The anthropometric data collected as part of the current study will be comparable to the data collected as part of the SAFIR study	30 months
Identification of factors associated with a coronary calcium score less than or equal to the 25th percentile	The clinic data collected as part of the current study will be comparable to the data collected as part of the SAFIR study	30 months
Identification of factors associated with a coronary calcium score less than or equal to the 25th percentile	The drug treatments collected as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with a coronary calcium score less than or equal to the 25th percentile	The genetic data collected as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with a coronary calcium score less than or equal to the 25th percentile	The biological data collected as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with a coronary calcium score less than or equal to the 25th percentile	Arterial Doppler ultrasound of the carotid arteries and lower limbs as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with a coronary calcium score less than or equal to the 25th percentile	Pulse wave velocity measured by the pOpmeter as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with a coronary calcium score less than or equal to the 25th percentile	Hepatic steatosis as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with a coronary calcium score less than or equal to the 25th percentile	Hepatic fibrosis as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with a coronary calcium score less than or equal to the 25th percentile	Nutritional data as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with a coronary calcium score less than or equal to the 25th percentile	Physical activity as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Identification of factors associated with a coronary calcium score less than or equal to the 25th percentile	Quality of life as part of the current study will be comparable to the data collected as part of the SAFIR study.	30 months
Study of the association between the characteristics of coronary atheroma plaque on coronary CT and major cardiovascular events at 30 months.	Semi-quantitative visual quantification of coronary stenoses on CT coronary angiography according to the CAD-RADS v2.0 classification and visual characterization of high-risk plaque features (vulnerability).	30 months
Study of the association between the characteristics of coronary atheroma plaque on coronary CT and major cardiovascular events at 30 months.	Quantification of total coronary atherosclerotic plaque, calcified and non-calcified, and by artery	30 months
Study of the association between the presence of subclinical atherosclerosis (coronary stenosis > 50% on CT coronary angiography) and major cardiovascular events at 30 months	Assess the association between the presence of significant coronary stenosis (>50% on a major artery) on coronary CT and the following major cardiovascular events: Acute coronary syndrome or myocardial infarction; Coronary revascularization: angioplasty or bypass; Ischemic stroke; Carotid endarterectomy; Revascularization of a lower limb artery: angioplasty or bypass; Amputation related to PAD; Cardiovascular death	30 months
Study of the association between the percentile of the coronary calcium score and major cardiovascular events and overall mortality at 30 months	Assess the occurrence of major cardiovascular events and mortality according to the percentile of the coronary calcium score.	30 months
Study of the association between arterial stiffness and major cardiovascular events and overall mortality at 30 months.	Assess the occurrence of major cardiovascular events and mortality according to the measurement of arterial stiffness evaluated by pulse wave velocity measured with the pOpmeter	30 months
Study of the association between the presence of hepatic steatosis and major cardiovascular events and overall mortality at 30 months	Evaluer la survenue des événements cardiovasculaires majeurs et la mortalité en fonction de la stéatose hépatique	30 months
Study of the association between the presence of liver fibrosis and major cardiovascular events and all-cause mortality at 30 months	Assess the occurrence of major cardiovascular events and mortality according to the presence of liver fibrosis	30 months

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: France 2030 program; European Union Next Generation

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2025
• Primary Completion (Estimated): March 25, 2027
• Study Completion (Estimated): September 25, 2029

Study Registration Dates

• First Submitted: April 29, 2025
• First Submitted That Met QC Criteria: April 29, 2025
• First Posted (Actual): May 7, 2025

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Familial hypercholesterolemia; atherosclerotic cardiovascular disease
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Arteriosclerosis; Arterial Occlusive Diseases; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hyperlipoproteinemia Type II; Atherosclerosis
• Other Study ID Numbers: RC24_0343; 2025-A00453-46 (Registry Identifier: National number)

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