Study of Coronary Calcification in Subjects With Autosomal Dominant Familial Hypercholesterolemia Heterozygous

NCT03501875 | Completed

• 2 other identifiers: P170703J2017-A02904-49
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

Brief Summary

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by elevated plasma levels of LDL-C cholesterol. This early and significant elevation of LDL-C triggers premature atherosclerosis, particularly coronary artery disease. The initiation and management of LDL-C therapies is based on cardiovascular risk assessment. Although this is undoubtedly higher than in normocholesterolemic patients, a significant heterogeneity in heFH patients still persists that is not completely explained. Moreover, the evaluation of cardiovascular risk in patients with heFH is difficult for many reasons: non-validity of risk scores, futility of a risk calculation limited to 10 years in a young patient, late positivity of stress tests . Therefore, there is a clear need for new cardiovascular risk assessment tools to identify higher risk heFH patients who could benefit from early and aggressive treatment. The Coronary Artery Calcium (CAC) Score has been widely studied in the US and validated in European recommendations, and has shown the best reclassification index for patients at intermediate cardiovascular risk. A CAC score of zero is associated with a very low risk of event irrespective of the number of risk factors. Non-calcified plaques are by definition not detected by ACC and patients with CAC = 0 may only have soft non-calcified plaques. The prevalence of these non-calcified plaques in very high-risk patients with acute coronary syndrome is 5%. The prevalence in FH patients is unknown. It has also been shown that the extent of the atherosclerotic burden is related to cardiovascular risk. CAC score has been poorly evaluated in heFH patients. However, hypercholesterolemia and calcifications have been shown to be correlated: supra-aortic calcified masses in homozygous FH patients, early calcifications associated with chronic exposure to high LDL-C (cholesterol burden, equivalent to cigarettes) and finally, the calcifying role of statins. The early increase of LDL-C in patients with genetic forms of FH causes premature cardiovascular damage. Investigators' hypothesis is that patients with FH have earlier coronary atheroma (and thus calcifications and non-calcified plaques) due to exposure early in life to high levels of LDL-cholesterol.

Conditions

Familial Hypercholesterolemia - Heterozygous

Outcome Measures

Primary Outcomes (1)

• Coronary Artery Calcium evaluated by Agatston Score

  Calcium Score

  one day

Secondary Outcomes (3)

• Cholesterol burden

  one day

• Coronary atheromatous plaque

  one day

• Peripheral atherosclerotic burden

  one day

Study Arms (1)

CAC Score

EXPERIMENTAL

CAC Score evaluated by the Agatston method

Radiation: CAC Score

Interventions

CAC Score RADIATION

Computed tomography angiography (CTA) with an injection of iodine-rich contrast material

CAC Score

Eligibility Criteria

• Age: 35 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with a heterozygous form of familial hypercholesterolemia:
• Aged 35 to 60 years old.
• Asymptomatic.
• No sign of ischemia with ECG.
• No personal history of coronary heart disease.
• Treated or untreated by cholesterol lowering treatment.
• Prior clinical examination performed
• Beneficiary of a social protection scheme or beneficiary (excluding AME)
• Informed patient and signed consent form

You may not qualify if:

• Person under tutorship or curatorship, or unable to give consent
• Pregnancy, breastfeeding, woman of childbearing potential in the absence of effective contraception - a urine pregnancy test will be done in hospital on the day of the coroscanner
• Contraindication to CT or injection of iodinated contrast medium or injection of esmolol hydrochloride
• Technical counter-indication: patient diameter\> 70 cm, weight\> 250 kg
• Renal insufficiency (CL \<60)
• Personal history of cardiovascular disease and myocardial infarction
• Type 2 diabetes or uncontrolled diabetes mellitus for more than 5 years
• Uncontrolled hypertension
• Atrial fibrillation, ventricular arrhythmia

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Institute of Cardiometabolism and Nutrition, France: collaborator

Study Sites (1)

Hôpital Pitié-Salpêtrière

Paris, 75013, France

Location

Study Officials

• Antonio GALLO, Dr

  Hôpital Pitié-Salpêtrière, APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2018
• First Posted: April 18, 2018
• Study Start: May 15, 2018
• Primary Completion: June 28, 2021
• Study Completion: June 28, 2021
• Last Updated: September 10, 2021

Record last verified: 2021-09

Locations

FR (1)