Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atherosclerosis- resistance | Other | FH Patient without atherosclerosis |
|
| Control | Other | FH patient with atheroclerosis |
|
| the related population without familial hypercholesterolemia | Other | No FH patient |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Whole Genome Sequencing | Genetic | Whole Genome Sequencing Biomarkers analyses |
|
| Measure | Description | Time Frame |
|---|---|---|
| Identification of genes associated with the resistance to development of coronary atherosclerosis in subjects with heterozygous familial hypercholesterolemia | Identification of functional genetic variants by a Whole Genome Sequencing (WGS) approach in case-control analysis (FH without and with advanced coronary atherosclerosis) and/or family analysis (protected and affected relatives) | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Identification of new biochemical, lipidemic, metabolomic and metagenomic biomarkers associated with cardiovascular protection in FH patients. | Lipidic panel, phosphocalcic panel, Ceramides, Alipoproteins, Lp(a), lipidomic, LDL size, Phospholipids, TMAO, Carnitin, Cholin, microbiota, metabolomic, LDL Ox, Sterols, Isoprostan, oxidation, inflammation, cytokins, oxidative stress. | 3 years |
Not provided
Inclusion Criteria:
The inclusion criteria to be met in the population with known coronary atheroma:
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
Inclusion criteria to be met in the related population with familial hypercholesterolemia :
Inclusion criteria to be met in the related population without familial hypercholesterolemia :
Exclusion Criteria:
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Le Bocage Hospital | Dijon | 29079 | France | |||
| CHRU de Lille |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000090542 | Homozygous Familial Hypercholesterolemia |
| ID | Term |
|---|---|
| D006938 | Hyperlipoproteinemia Type II |
| D008052 | Lipid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
Not provided
Not provided
| ID | Term |
|---|---|
| D000073336 | Whole Genome Sequencing |
| ID | Term |
|---|---|
| D017422 | Sequence Analysis, DNA |
| D017421 | Sequence Analysis |
| D005821 | Genetic Techniques |
| D008919 | Investigative Techniques |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Association of arterial stiffness (reflected by the pulse wave velocity) with the development of coronary atherosclerosis in FH patients | Measurement of arterial stiffness measured by popmeter® (pulse wave velocity) | 3 years |
| Association of atherosclerosis of supra-aortic trunks (AST) with the development of coronary atherosclerosis in FH patients | Measurement of ASD through arterial Doppler ultrasonography (Intra-media thickness (IMT), degree of stenosis (ESCT), plaque) | 3 years |
| Association of atherosclerosis of the lower limbs with the development of coronary atherosclerosis (PAD) in FH patients | Measurement of lower extremity involvement by arterial doppler ultrasonography | 3 years |
| Association between aortic valvular score and development of coronary atherosclerosis in FH patients | Measurement of coronary calcium score and aortic valvular score (optional) by a thoracic CT scan | 3 years |
| Association between coronary calcium score and aortic valvular score in HF patients | Measurement of coronary calcium score and aortic valvular score (optional) by a thoracic CT scan | 3 years |
| Lille |
| 59037 |
| France |
| Louis Pradel Cardiovascular Hospital | Lyon | 69677 | France |
| La Conception Hospital | Marseille | 13285 | France |
| Nantes University Hospital | Nantes | 44093 | France |
| Saint-Antoine Hospital | Paris | 75012 | France |
| Pitié-Salpêtrière Hospital | Paris | 75013 | France |
| Rennes University Hospital | Rennes | 35033 | France |
| Toulouse Hospital | Toulouse | 31059 | France |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006951 | Hyperlipoproteinemias |
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |