Diagnostic accuracy of peripheral ultrasound in familial hypercholesterolemia: A systematic review and meta-analysis

BACKGROUND: Familial hypercholesterolemia is characterized by lifelong exposure to high cholesterol levels and premature atherosclerotic cardiovascular disease. Unequivocal atherosclerosis on imaging reclassifies patients from high to very high risk. OBJECTIVE: The aim of this systematic review is to evaluate the diagnostic accuracy of carotid ultrasound and femoral ultrasound compared to cardiac computed tomography, for detecting subclinical atherosclerosis in adults with familial hypercholesterolemia with no history or symptoms of atherosclerotic disease. METHODS: Studies published in full length in English were identified through a bibliographic database search in eight databases and two trial registers supplemented with backward and forward citation (updated 14 August, 2026). Studies were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool and synthesized using a generalized linear mixed model. The protocol was registered on Open Science Framework, osf.io/89z4a. RESULTS: Thirteen studies were included in the systematic review and three studies in the meta-analysis. Pooled prevalence estimates were 68.5% [62.2;74.5] for carotid plaques, 56.5% [48.3;64.5%] for femoral plaques, and a composite measure of coronary artery disease 46.2% [33.4;59.2]. Peripheral ultrasound demonstrated a high sensitivity of 78.9% [51.5;93.0] and low specificity of 32.0% [14.0;57.6]. CONCLUSIONS: A small amount of very low-quality evidence was identified highlighting the need for further studies to determine the best test-and-treat strategy for this patient group. The current evidence suggests that carotid and femoral ultrasound are unsuitable as replacement tests for cardiac computed tomography but could potentially play a role as triage test for risk stratification.