MYOCARDIAL SILENT INFARCTIONS AND FIBROSIS IN FAMILIAL HYPERCHOLESTEROLEMIA (CHOLCOEUR)

MYOCARDIAL SILENT INFARCTIONS AND FIBROSIS IN FAMILIAL HYPERCHOLESTEROLEMIA

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.

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.

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