Clinical trial NCT02517944: MYOCARDIAL SILENT INFARCTIONS AND FIBROSIS IN FAMILIAL HYPERCHOLESTEROLEMIA (CHOLCOEUR)
Official title: MYOCARDIAL SILENT INFARCTIONS AND FIBROSIS IN FAMILIAL HYPERCHOLESTEROLEMIA
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Familial Hypercholesterolemia - Heterozygous
Keywords: Familial hypercholesterolemia
Lead sponsor: Institute of Cardiometabolism and Nutrition, France
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2015-08-07
Enrollment: 110
Sex: ALL
Minimum age (years): 40
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 110 subjects divided into:

* 75 patients with heterozygous form at high cardiovascular risk
* 35 controls patients without dyslipidaemia

Brief summary: Patients with familial hypercholesterolemia (FH) at high cardiovascular risk may suffer from silent micro-infarctions (MI) before clinical coronary heart disease manifestations because of the lifetime exposure to elevated serum LDL-cholesterol levels.

The study aims to demonstrate the higher prevalence of silent myocardial infarction in a population of asymptomatic patients with familial hypercholesterolemia at high cardiovascular risk in comparison to control patients using Cardiac Magnetic Resonance sequences of delayed gadolinium enhancement.

Detailed description: To demonstrate the higher prevalence of silent myocardial infarction in a population of asymptomatic patients with familial hypercholesterolemia at high cardiovascular risk in comparison to control patients, the protocol is the following:

* to enroll 75 patients with familial hypercholesterolemia (FH)
* to enroll 35 subjects without FH (control group)
* for each subject, to collect data from his medical file (blood test results) and to perform a cardiac and aortic MRI in order to evaluate the micro-infarction proportion.

The study will be performed according to GCPs and with respect with french laws.

Eligibility criteria: Inclusion criteria:

For patients with heterozygous form of familial hypercholesterolemia:

* Aged between 40 and 60 years
* With an identified genetic mutation (LDL-R, ApoB, PCSK9)
* Asymptomatic,
* With no EKG sign of ischemia
* No personal history of coronary heart disease.
* Treated or untreated by lipid lowering treatment
* High cardiovascular risk identified by 1 of the following criteria:

  1. Current smoking (1 cigarette a day) 2 Family history of very premature onset CHD: first- or second-degree male relative onset before age 45, first- or second-degree female relative onset before age 55 3.Two or more cardiovascular risk factors among this list: increasing age (men \> 30, women \> 40 years of age), LDL-C \> 250 mg/dL, male sex, family history of premature onset CHD, first-degree male relative onset before age 55, first-degree female relative onset before age 65, metabolic syndrome, HDL-C \< 40 mg/dL, hypertension (BP \> 140/or \> 90 mmHg or drug treatment), Lp (a) ≥ 50 mg/dL, tendon xanthoma

For control subjects:

* Aged between 40 and 60 years
* With a normal lipid profile (LDL-C \< 1.6g/L HDL-C \> 0,45g/L and TG \< 4g/L) and untreated by any lipid lowering therapies
* Asymptomatic,
* With EKG showing normal sinus rhythm , no sign of ischemia nor Left Bundle Branch Block
* No personal history of coronary heart disease.
* Control subjects will be matched for age/gender/smoking status and blood pressure

Exclusion criteria:

* Non-affiliation to a healthcare system
* Consent refusal
* Contra-indication to MRI or to gadolinium injection.
* Claustrophobia, metallic devices, pacemaker, mechanical valve implanted before 1985, pregnancy, nursing
* Renal failure
* Technical contra-indication: patient diameter \> 70 cm weight \> 250 kg
* Personal history of cardiovascular disease and myocardial infarction
* Diabetes mellitus
* Uncontrolled hypertension
* TG \< 4 g/L
* Previous use of an Amgen product in the past 12 months

Primary outcomes:
measure: Percentage of patients presenting with at least one micro infarction at RMI
timeFrame: Within 4 weeks after consent signature
Secondary outcomes:
measure: LDL-Cholesterol burden (compared to standard values)
timeFrame: The most recent value within the last 5 years.
measure: Anatomic and functional indexes of the aorta (maximal and minimal areas of aortic lumen, aortic flow)
timeFrame: Within 4 weeks after consent signature
measure: Correlations between LDL-Cholesterol burden & presence of micro infarction, between LDL-Cholesterol burden & myocardial fibrosis, and between LDL-Cholesterol burden & aortic stiffness indexes
timeFrame: 1 year
Other outcomes:
Locations:
city: Paris
country: France
facility: Unité de prévention des maladies cardiovasculaires- Unité INSERM 939 Pôle Cardiologie/Métabolisme Groupe Hospitalier Pitié-Salpêtrière
Study officials:
affiliation: Study principal investigator
name: David Rosenbaum, MD
role: PRINCIPAL_INVESTIGATOR
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