Positive association of lipoprotein(a) and the prevalence of lower extremity arterial disease in MASLD: a cross-sectional study

Lipoprotein(a) [Lp(a)] has been recognized as a genetically determined and independent contributor to atherosclerotic cardiovascular disease. However, its role in lower extremity arterial disease (LEAD) among individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) remains insufficiently studied. Given the overlapping metabolic disturbances in both conditions, such as insulin resistance and lipid abnormalities, a potential relationship between Lp(a) and peripheral vascular injury in MASLD is biologically plausible. This study aimed to investigate the cross-sectional association between circulating Lp(a) concentrations and the presence of LEAD in a well-characterized MASLD population. A total of 468 MASLD patients undergoing routine health check-ups were included. Lp(a) levels were stratified into three categories: <10 mg/dL, 10–30 mg/dL, and ≥ 30 mg/dL. LEAD was diagnosed using duplex ultrasonography. Multivariable logistic regression models were used to assess the relationship between Lp(a) levels and the presence of LEAD, with adjustments for demographic variables, metabolic conditions, and lipid-related parameters. Subgroup analyses were conducted to assess potential effect modification. LEAD was diagnosed in 61.5% (n = 288) of MASLD participants, with a higher prevalence observed across increasing Lp(a) categories (P = 0.015). In fully adjusted models, each 1 mg/dL increase in Lp(a) was associated with higher odds of LEAD (OR = 1.02; 95% CI: 1.00–1.04; P < 0.01). Compared with participants with Lp(a) < 10 mg/dL, those with levels of 10–30 mg/dL and ≥ 30 mg/dL had ORs of 2.00 (95% CI: 1.24–3.22) and 2.15 (95% CI: 1.07–4.34), respectively. Subgroup analyses suggested a stronger association between Lp(a) and LEAD among former or current smokers (P for interaction = 0.031), however, this finding should be interpreted cautiously. Elevated Lp(a) levels were associated with a higher prevalence of LEAD in patients with MASLD. Although the magnitude of association per unit increase was modest, higher Lp(a) concentrations were associated with greater LEAD prevalence. These findings should be interpreted cautiously and viewed as hypothesis-generating, particularly with respect to subgroup analyses. Prospective studies are needed to clarify causality and clinical relevance.