Clinical trial NCT03234127: Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia
Official title: Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Homozygous Familial Hypercholesterolemia
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2017-07-31
Enrollment: 562
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The main objective of SAFIR is to identify the atherosclerotic genetic factors in these patients, which will identify new therapeutic targets for the treatment of CV and Familial Hypercholesterolemia diseases. In addition, SAFIR will allow the identification of new CV protection biomarkers, which will be useful tools for the development of a personalized medicine for the management of dyslipidemias.

Detailed description: The objective of the SAFIR study is to perform non-invasive coronary vascular phenotyping of familial hypercholesterolemia (FH) families by performing a coronary calcium score and then to detect protective genetic factors in patients who do not have a significant atheroma despite a perturbed biological phenotype.

The investigators will also conduct biochemical, lipidemic and metabolomic analyzes to identify a signature of biomarkers protective of cardiovascular risk in FH patients.

The investigators will use the French FH register, which already includes 3889 patients, to identify these "protected" FH families within the main reference centers for the management of FH for inclusion and follow-up of patients.

Eligibility criteria: Inclusion Criteria:

* Patient agreeing to sign the consent of the study and the consent of biocollection
* Patient suffering from a familial hypercholesterolemia with a clinically-biologic score DLCN (Dutch Lipid Clinic Network, Annex 2)\> 8 and / or a causative mutation identified in the LDL receptor genes, apolipoprotein B100 or Of PCSK9.
* Men ≥ 40 years of age; Female ≥ 50 years
* Patient affiliated to an existing social insurance

The inclusion criteria to be met in the population with known coronary atheroma:

* Subject in secondary prevention of an atheromatous disease: coronary event or ischemic heart disease, irrespective of the result of the coronary calcium score; Ischemic stroke with proven carotid atheromatosis; revascularization (angioplasty, bypass surgery) or amputation in PAD
* Primary prevention topic CV with calcium score ≥ 400 Agatston units

Inclusion criteria to be met in the population without cardiovascular risk:

- No cardiovascular event (including MI, coronary revascularization, angina, stroke \&, Transiant ischemic attack of atheromatous origin, PAD) with: For women between 50 and 65 years, a nil calcium score \* For women between 65 and 75 years of age, a calcium score\*\* ≤ 10 Agatston units For women over 75 years of age, a calcium score\*\* ≤ 20 Agatston units For men between 40 and 55 years of age, a nil calcium score\* for men For men between 55 and 70 years of age, a calcium score\*\* ≤ 10 Agatston units For men over 70 years of age, a calcium score\*\* ≤ 20 Agatston units

* 40 year old men and 50 year old women: less than 6 months old
* 41 year old men and 51 year old women: under 1 year old
* 42 year old men and 52 year old women: under 2 years old
* 43 year old men and 53 year old women: under 3 years old
* 44 year old men and 54 year old women: under 4 years old

  * Less than 5 years

Inclusion criteria to be met in the related population with familial hypercholesterolemia :

* Patient agreeing to sign the consent of the study and the consent of biocollection
* Patient suffering from a familial hypercholesterolemia with a clinically-biologic score DLCN (Dutch Lipid Clinic Network, Annex 2)\> 8 and / or a causative mutation identified in the LDL receptor genes, apolipoprotein B100 or Of PCSK9.
* Men or Female ≥ 30 years
* Patient affiliated to an existing social insurance

Inclusion criteria to be met in the related population without familial hypercholesterolemia :

* Patient agreeing to sign the consent of the study and the consent of biocollection
* Patient not suffering from a familial hypercholesterolemia related to one of the members of the population suffering from familial hypercholesterolemia without cardiovascular risk
* Men or Female ≥ 18 years
* Patient affiliated to an existing social insurance

Exclusion Criteria:

* Subject suffering from active cancer or progressive neoplasia
* Subject treated with recent corticosteroid therapy
* Subjects with unsubstituted or poorly controlled hypothyroidism (TSH\> normal)
* Subject receiving immunosuppressive or anti-cancer treatment
* Subject refusing to participate
* Subjects under tutelage, curatorship or a safeguard of justice or without social insurance

The exclusion criterion for all populations except the related population without familial hypercholesterolemia:

- Subject with no "definite" familial hypercholesterolemia according to the DLCN score (≤8), after auction. The purpose of the auction will be to rule on the causal nature of an identified mutation.

Primary outcomes:
measure: Identification of genes associated with the resistance to development of coronary atherosclerosis in subjects with heterozygous familial hypercholesterolemia
timeFrame: 3 years
Secondary outcomes:
measure: Identification of new biochemical, lipidemic, metabolomic and metagenomic biomarkers associated with cardiovascular protection in FH patients.
timeFrame: 3 years
measure: Association of arterial stiffness (reflected by the pulse wave velocity) with the development of coronary atherosclerosis in FH patients
timeFrame: 3 years
measure: Association of atherosclerosis of supra-aortic trunks (AST) with the development of coronary atherosclerosis in FH patients
timeFrame: 3 years
measure: Association of atherosclerosis of the lower limbs with the development of coronary atherosclerosis (PAD) in FH patients
timeFrame: 3 years
measure: Association between aortic valvular score and development of coronary atherosclerosis in FH patients
timeFrame: 3 years
measure: Association between coronary calcium score and aortic valvular score in HF patients
timeFrame: 3 years
Other outcomes:
Locations:
city: Dijon
country: France
facility: Le Bocage Hospital
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: Louis Pradel Cardiovascular Hospital
city: Marseille
country: France
facility: La Conception Hospital
city: Nantes
country: France
facility: Nantes University Hospital
city: Paris
country: France
facility: Saint-Antoine Hospital
city: Paris
country: France
facility: Pitié-Salpêtrière Hospital
city: Rennes
country: France
facility: Rennes University Hospital
city: Toulouse
country: France
facility: Toulouse Hospital
Study officials:
References: