Study of Coronary Calcification in Subjects With Autosomal Dominant Familial Hypercholesterolemia Heterozygous (FH-CALC)
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|ClinicalTrials.gov Identifier: NCT03501875|
Recruitment Status : Active, not recruiting
First Posted : April 18, 2018
Last Update Posted : February 5, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Familial Hypercholesterolemia - Heterozygous||Radiation: CAC Score||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||300 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Study of Coronary Calcification in Subjects With Autosomal Dominant Familial Hypercholesterolemia Heterozygous|
|Actual Study Start Date :||May 15, 2018|
|Estimated Primary Completion Date :||February 1, 2021|
|Estimated Study Completion Date :||May 1, 2021|
Experimental: CAC Score
CAC Score evaluated by the Agatston method
Radiation: CAC Score
Computed tomography angiography (CTA) with an injection of iodine-rich contrast material
- Coronary Artery Calcium evaluated by Agatston Score [ Time Frame: one day ]Calcium Score
- Cholesterol burden [ Time Frame: one day ]Total and LDL cholesterol before treatment (at diagnosis) (age at diagnosis) + yearly total and LDL-cholesterol on treatment (after diagnosis)
- Coronary atheromatous plaque [ Time Frame: one day ]Coronary computed tomography angiography: evaluation of atherosclerotic load according to the CAD-RADS classification
- Peripheral atherosclerotic burden [ Time Frame: one day ]Carotid and femoral intima-media thickness
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03501875
|Paris, France, 75013|
|Principal Investigator:||Antonio GALLO, Dr||Hôpital Pitié-Salpêtrière, APHP|