Study of Coronary Calcification in Subjects With Autosomal Dominant Familial Hypercholesterolemia Heterozygous
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 270
- 试验地点
- 2
- 主要终点
- Coronary Artery Calcium evaluated by Agatston Score
研究概览
简要总结
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.
详细描述
The CAC score has demonstrated very powerful predictive power, particularly in asymptomatic populations.
- The CAC score can:
1.1- Identify subjects with high cardiovascular risk According to prospective studies, it is estimated that a CAC score> 400 is a CHD equivalent, with 10-year event rates exceeding 20% in asymptomatic patients. Prospective studies in young patients with a family history of cardiovascular disease or dyslipidaemia showed a higher risk of cardiovascular disease in those with a CAC score of 0.
1.2- Identify subjects with low cardiovascular risk Regardless of the presence of risk factors, meta-analyses have repeatedly shown the high negative predictive power associated with a CAC = 0. The absence of calcified plaque presents an extraordinarily low risk at 10 years (1.1% at 1.7%) regardless of the number of risk factors Regardless of the presence of risk factors, meta-analyses have repeatedly shown the high negative predictive power associated with a CAC = 0 with an annual mortality rate of 0.87 compared to 1.92 in those with CAC between 1 and 10. Finally, recent studies have questioned the indication of a statin in non-HeFH patients with CAC = 0.
Non-calcified plaques are not, by definition, detected by CAC tests and patients with CAC = 0 may only exhibit soft, non-calcified plaques. The prevalence of these non-calcified plaques in high-risk patients with acute coronary syndrome is 5% . The prevalence in heHF patients is unknown. 2. Description of the population to be studied and justification of their choice. Recruitment of patients with familial hypercholesterolemia will be carried out at the Cardiovascular Prevention Unit of the Pitié-Salpêtrière Hospital and in the Cardiology Department of Saint-Antoine Hospital. Patients will be included in the study when they come for their usual consultation or as part of their cardiovascular assessment in day hospitalization. 3. Brief description of the product (s) or experimental act (s)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •Participation in another interventional research involving the human person or being in the exclusion period following previous research involving the human person, if applicable
结局指标
主要结局
Coronary Artery Calcium evaluated by Agatston Score
时间窗: one day
Calcium Score
次要结局
- Peripheral atherosclerotic burden(one day)
- Coronary atheromatous plaque(one day)
- Cholesterol burden(one day)