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

TL;DR

Familial hypercholesterolemia is linked to worse outcomes in young patients with lower extremity artery disease, suggesting the need for routine screening.

Contribution

This study identifies FH prevalence and its significant impact on pLEAD prognosis, emphasizing the importance of FH screening in LEAD patients.

Findings

FH was present in 15% of premature LEAD patients and was associated with chronic limb-threatening ischemia and dialysis dependence.

FH patients had significantly lower survival, amputation-free, and secondary intervention-free rates compared to non-FH patients.

In CLTI patients, FH was associated with a 17% three-year survival rate versus 71% in non-FH patients.

Abstract

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.

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