Coronary CT Screening of Patients With Familial Hypercholesterolemia - The Prevalence of Subclinical Atherosclerosis in Familial Hypercholesterolemia in the Region of Southern Denmark
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- CACS
研究概览
简要总结
Familial hypercholesterolemia (FH) is the most common inherited cause of atherosclerotic cardiovascular disease (ASCVD) with a prevalence of approximately one in 200 individuals, however only few of the estimated 30.000 patients with FH in Denmark has been diagnosed. FH is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and a high risk of premature ASCVD in particular coronary artery disease. The presence of atherosclerosis measured by cardiac computed tomography (CT) is a reliable predictor of future cardiovascular events and may help guide clinicians with regard to the lifestyle modifying therapies and lipid-lowering treatment. However, the prevalence and degree of coronary atherosclerosis in Danish FH patients without symptoms of ASCVD is unknown.
Therefore, the invetigators aimed to:
- Screen FH patients in a Danish setting for subclinical coronary atherosclerosis to improve lipid-lowering treatment and,
- Test if coronary CT screening can help to reach LDL-C therapy goals and reduce smoking.
This study will consist of a local cross sectional pilotstudy including 100 asymptomatic FH patients recruited from the lipid clinic at Odense University Hospital and hereafter a regional cross-sectional on approximately 600 asymptomatic FH patients in the Region of Southern Denmark recruited from the lipid clinics trough the national patient registry. In the pilot study, patients will undergo lipid analysis and non-contrast / contrast CT for description of coronary arterial calcium, and plaque morphology in this patient group. This will provide knowledge for planning the regional cross sectional study describing subclinical atherosclerosis in this population. Patients will furthermore be randomized to see their coronary CT scan or not. Mean LDL-C change and smoking status will be evaluated one year after.
The benefit of finding subclinical atherosclerotic disease with the possibility to improve lipid-lowering treatment for prevention of future premature ischemic heart disease is considered to outweigh the minor radiation exposure in this trial. If LDL-C is reduced significantly and smoking reduction is significant trough a simple intervention as showing the CT scan to the patient, this study can provide knowledge whether CT screening of this patient group should be considered in Denmark.
详细描述
- Introduction:
Familial hypercholesterolemia (FH) is the most common inherited cause of atherosclerotic cardiovascular disease (ASCVD) with a prevalence of 1/200. More than 30.000 patients in Denmark are expected to have FH, however, few of these patients is diagnosed.
Patients with FH may have up to a 13-fold higher risk of coronary artery disease compared to the background population. However, FH can be treated with appropriate lipid-lowering treatment, and early initiation of lipid-lowering treatment may lower the risk of ASCVD to be comparable with individuals without FH. Early diagnosis and initiation of lifestyle modifying therapies and lipid-lowering treatment is of major importance to lower the risk of ASCVD in FH patients and their affected relatives. However, limited knowledge exist on whether risk stratification using objective measures of coronary artery atherosclerosis may be used to identify FH patients that require more intensive lipid-lowering treatment than others.
FH should be suspected in individuals with severely elevated low-density lipoprotein - cholesterol (LDL-C) in, or in families with premature ASCVD. A diagnosis of FH is most often based on clinical scores such as the Simon Broome Criteria or the Dutch Lipid Clinical Network (DLCN) Criteria, which both include information on genetic testing for pathogenic FH mutations as an important part of making a definite diagnosis of FH.
The lipid-lowering treatment in most FH patients include statins and ezetimibe. Proprotein-convertase-subtilisin/kexin-type 9 (PCSK9)-inhibitors are very potent and has been shown to reduce atherosclerotic plaques, but these agents are currently very expensive and their use in FH patients in the context of primary prevention is limited to patients with highly elevated LDL-C despite standard treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with genetically or clinically FH (DLCN score > 6) between the age of 20 and 70 are eligible patients in DANFOCOS.
排除标准
- •History of ASCVD defined as myocardialinfarction, procedural revascularisation, CABG and/or objective evidence if ischaemia (exercise stress test, stress echocardiography, myocardial perfusion scintigraphy, stress cardiac magnetic resonance, coronary angiography, cardiac CT), angina pectoris, ischaemic stroke or a medically (aspirin, clopidogrel, persantin) treated transitory ischaemic attack, and symptomatic peripheral vascular disease with ankle-brachial index below 0.9 or procedural revascularisation.
- •Current Pregnancy or planning pregnancy (due to radiation issues)
- •eGFR < 60 ml/min/1,73 m2 (due to CT-contrast)
- •Prior allergic reaction to CT-contrast.
- •PCSK9-inhibitor treatment
- •Life expectancy < 5 years.
- •Secondary dyslipidemia
- •Dysregulated diabetes
- •Dysregulated hypothyreosis TSH > 4,0 IU/L.
- •Combined hyperlipidemia: TG > 4 mmol/L
- •Nefrotic syndrome: proteinuria > 3 g/L and s-albumin < 30 g/l
- •History of primary billiary cirrhosis
- •Low-carb-high-fat diet.
- •Pharmacological induced dyslipidemia
- •Findings on Coronary CT leads to exclusion
- •Three vessels disease
- •Left main coronary artery stenosis
- •Proximal left anterior descending coronary artery stenosis
- •Proximal right coronary artery stenosis
结局指标
主要结局
CACS
时间窗: 18 months
Median CACS of the population
Coronary arterial calcium score (CACS)
时间窗: 18 months
Mean CACS of the population
Plaque composition
时间窗: 18 months
proportion of soft and calcified plaques
Plaque volume (mean)
时间窗: 18 months
Mean size of plaques described in mm.
Plaque volume (median)
时间窗: 18 months
Median size of plaques described in mm.
Severity of stenosis (proportion of stenosis)
时间窗: 18 months
Percentage of vessel lumen compromised by plaque described as proportion of minor, moderate and severe stenosis.
Severity of stenosis (number of stenosis)
时间窗: 18 months
Percentage of vessel lumen compromised by plaque described as number of minor, moderate and severe stenosis.
次要结局
- Change in LDL-C levels.(12 months)
- Change in smoking status(12 months)
- Change in mean consumption cigarettes per day(12 months)
- Prevalence of femoral and carotid plaques(18 months)