Clinical Impact of Familial Hypercholesterolemia on Lower Extremity Artery Disease in Premature Patients

Familial hypercholesterolemia (FH) accelerates systemic atherosclerosis and worsens prognosis from youth. While present in 5%-10% of premature coronary artery disease (pCAD) cases, its prevalence and impact in lower extremity artery disease (LEAD) remain unclear. This study investigated FH prevalence and prognostic impact in premature LEAD (pLEAD).

We retrospectively analyzed LEAD patients aged ≤70 years undergoing first revascularization. FH was diagnosed according to the 2022 Japan Atherosclerosis Society Guidelines, based on dyslipidemia and Achilles tendon thickness. Primary outcomes were survival, amputation-free rate, and secondary intervention-free rate.

Among 66 pLEAD patients (median age 66 years, 76% male), 10 (15%) met the FH criteria. Compared with non-FH patients, FH patients more frequently presented with chronic limb-threatening ischemia (CLTI) (90% vs. 36%, p = 0.001), bilateral lesions (100% vs. 36%, p <0.001), and dialysis dependence (90% vs. 25%, p <0.001). Three-year survival (28% vs. 90%, p <0.001), amputation-free rate (64% vs. 89%, p = 0.028), and secondary intervention-free rate (38% vs. 63%, p = 0.031) were significantly lower in FH patients. In the CLTI subgroup, survival was markedly reduced in FH (17% vs. 71%, p = 0.011).

FH was present in 15% of pLEAD patients and associated with poor outcomes. Routine FH screening, including pCAD history and Achilles tendon evaluation, may improve prognosis.