Short summary

Familial hypercholesterolemia is a common but underdiagnosed and undertreated cause for premature ahterosclerotic cardiovascular disease. The risc of developing cardiovascluar events in people with familial hypercholesterolemia is highly variable. Imaging is shown to improve risc stratification for optimization in treatment. We aim to describe the amount of familial hypercholesterolemia patients with subclinical atherosclerosis in our lipid clinic, and if imaging can improve their treatment.

Rationale

Introduction 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 20 % 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 lifestyle modifying therapies and lipid-lowering treatment. However, the prevalence and degree of coronary atherosclerosis in Danish FH patients without symptoms or history of ASCVD is unknown. Therefore, we aim 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 be done in a pilot setting on 100 patients.

Method This is a cross-sectional study including 100 FH patients (no history of ASCVD) from the lipid clinic at Odense University Hospital from the age of 20-70 equally distributed on age and sex. Participants will undergo lipid analysis, vascular ultrasound measuring carotid and femoral plaque score and non-contrast / contrast CT for description of coronary arterial calcium and plaque morphology by AutoPlaque. The patients are randomized to see their coronary CT in an embedded randomized controlled trial. Mean LDL-C change, smoking and anxiety will be evaluated one year after, and analyzed using STATA with Students T-test for changes in LDL-C levels and selfreported anxiety. Vascular ultrasound are compared with coronary CT calculating sensitivity and specificity for detection of ASCVD.

This study will describe the amount of patients eligible for more intensive lipid lowering tretment after imaging is performed according to changes in LDL-C treatment target depending on imaging results.

Furthermore the study will describe if visualization of the coronary arteries lfor the patient eads to reduction in LDL-C target, adding knowledge to whether imaging, including visualization of the coronary vessels, could benefit asymptomatic FH patients. Sensitivity for detection of coronary atherosclerosis by vascular ultrasound in this group will be described too.

Trial registration number: clinicaltrials.gov number: NCT05758779

Description of the cohort

Familial Hypercholesterolemia Patients with a Durch Clinical lipid Networs Score of 6 or above, recruited from the lipid clinic at Odense University Hospital

Data and biological material

Questionary and data from patient journal.

Blod samples including cholesterol analysis, lipoprotein(a), Hba1c, kreatinkinase, ALAT and kidney parameters. Blood sample for a biobank.

Imaging. Echocardiography, peripheral vascular ultrasound, Coronary CT with and without contrast

Collaborating researchers and departments

Department of cardiology Aalborg University Hospital

• MD. PhD Christian Sørensen Bork