Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: MYOCARDIAL SILENT INFARCTIONS AND FIBROSIS IN FAMILIAL HYPERCHOLESTEROLEMIA (CHOLCOEUR)

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: 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

Relevance to patient case: not relevant