Coronary artery calcium scoring and coronary computed tomography angiography in familial hypercholesterolemia:...

Familial hypercholesterolemia is a prevalent genetic disorder characterized by lifelong elevated LDL-cholesterol (LDL-C), resulting in increased risk of premature atherosclerosis and cardiovascular events. General and familial hypercholesterolemia-specific risk scores (SAFEHEART-RE, Montreal-FH, and FH risk score) are insufficient to capture the interindividual variability in cardiovascular risk. Current guidelines and consensus statements recognize the potential value of coronary computed tomography in familial hypercholesterolemia, although specific guidance on timing and modality remains limited. This review evaluates the evidence and role of coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA) for improved cardiovascular risk stratification and therapeutic guidance.

Although elevated CACS is highly prevalent among patients with heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH), younger familial hypercholesterolemia patients may exhibit exclusively noncalcified plaque, and because most are treated with statins, which may increase coronary calcification, CACS should be interpreted with caution. CCTA provides comprehensive assessment of plaque burden, stenosis, and high-risk features, which are associated with adverse cardiovascular outcomes. CCTA may support therapy intensification by identifying patients with substantial coronary plaque burden, while the absence of detectable atherosclerosis should not justify withholding guideline-recommended lipid-lowering therapy (LLT).

CCTA may provide additional information on atherosclerotic burden in familial hypercholesterolemia. In HeFH, evidence is currently insufficient to support routine CCTA screening at specific ages or intervals. CCTA at approximately 30 years of age in men and 40 years of age in women may represent a proposed strategy requiring prospective evaluation. In children with HoFH, screening is recommended at least once after the age of 3. Follow-up imaging should be individualized according to clinical indication, imaging findings, treatment response and radiation-associated risks.