Prevalence of Carotid Atherosclerotic Plaques and Stenosis in Adults with Familial Hypercholesterolemia Needs Reappraisal: Systematic Review and Meta-Analysis

<b>Background:</b> This systematic review and meta-analysis aimed to assess the burden of carotid atherosclerosis, including the prevalence of carotid plaques and stenosis, among individuals with familial hypercholesterolemia (FH). <b>Methods:</b> PubMed, Embase, and Scopus were searched up to 3 August 2025 to identify full-text, peer-reviewed articles published in English reporting the prevalence of carotid atherosclerotic plaques and/or stenosis in adult (≥18 years) patients with either a clinical or genetic diagnosis of FH. The methodological quality of the included studies was assessed using the Mixed Methods Appraisal Tool. Results were synthesized using random-effects meta-analysis and presented as pooled prevalence estimates with 95% confidence intervals (95% CI) displayed in forest plots. Publication bias was assessed using the Doi plot and the Luis Furuya-Kanamori index. <b>Results:</b> For the analysis of carotid plaque prevalence, seventeen studies including a total of 2870 patients were included (weighted age 47.2 ± 13.4 years, 47.3% male). No statistical difference in the pooled prevalence of carotid plaques was observed between clinically and genetically diagnosed FH (both 53%; 95% CI: 40-65%), however sub-analyses suggested a higher plaque burden in genetic FH. For the analysis of carotid stenosis prevalence, four studies comprising 704 participants were included; however, the available data were less consistent, yielding a pooled prevalence of 9% (95% CI: 0-40%). In conclusion, the results should be interpreted with caution due to several limitations, including the relatively low quality of the included studies, potential publication bias, considerable heterogeneity between the studies, and low to moderate certainty of evidence for the pooled estimates. These findings further emphasize the need for large-scale, standardized, multicenter studies to better characterize the burden of carotid atherosclerosis in this population.