Familial hypercholesterolemia (FH) represents a genetic lipid disorder that frequently triggers premature cardiovascular complications. Subclinical atherosclerosis is characterized by the silent accumulation of fatty plaques within arterial walls well before any overt clinical symptoms emerge. This study explored the prevalence of subclinical atherosclerosis, its arterial distribution, and which factors independently predict its occurrence in people with FH. We conducted a single-center, prospective cross-sectional investigation. The analysis included 215 patients identified as having FH from an initial group of 1145 individuals evaluated using the Dutch Lipid Clinical Network (DLCN) criteria. To detect subclinical atherosclerosis, participants underwent carotid and femoral artery ultrasound and coronary artery calcium scoring. Levels of apolipoprotein A-I, apolipoprotein B, and lipoprotein (a) were quantified through nephelometry. Among the participants, 136 were women (63%), and the average age was 54 years (interquartile range 43–62 years). Visible physical signs of FH (stigmata) appeared in 18% of the group. At the time of screening, only 32% were taking statins, and just 8 patients (4%) had successfully lowered their LDL-C to < 70 mg/dL. Overall, subclinical atherosclerosis was present in 148 individuals (69%). Site-specific involvement included 48% in the coronary arteries, 47.5% at the carotid bifurcation, and 40.5% at the femoral bifurcation. Key independent predictors were older age, male gender, higher pre-treatment LDL-C concentrations, diabetes, and a lower ApoA-I to ApoB ratio. Elevated Lp(a) at or above 30 mg/dL specifically forecasted coronary involvement, diabetes combined with a low ApoA-I/ApoB ratio predicted carotid disease, and smoking was linked to femoral atherosclerosis. Subclinical atherosclerosis occurs frequently in individuals with FH, while adherence to prescribed lipid-lowering medications remains disappointingly low. Incorporating routine screening for subclinical disease could meaningfully shape clinical decision-making by encouraging doctors to follow treatment guidelines more rigorously and helping patients stay committed to therapy.
