The Danish Familial Hypercholesterolemia Organized Coronary Screening Trial

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.

Inclusion Criteria:Patients diagnosed with genetically or clinically FH (DLCN score > 6) between the age of 20 and 70 are eligible patients in DANFOCOS.Exclusion Criteria: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 treatmentLife expectancy < 5 years.Secondary dyslipidemiaDysregulated diabetesDysregulated hypothyreosis TSH > 4,0 IU/L.Combined hyperlipidemia: TG > 4 mmol/LNefrotic syndrome: proteinuria > 3 g/L and s-albumin < 30 g/lHistory of primary billiary cirrhosisLow-carb-high-fat diet.Pharmacological induced dyslipidemia