One-Year Outcomes in PAD Patients With Elevated Lipoprotein(a): A Propensity-Matched Analysis

Abstract

Lipoprotein(a) (Lp(a)) is a genetically determined, proatherogenic lipoprotein linked to increased cardiovascular risk. Although elevated Lp(a) levels have been implicated in peripheral artery disease (PAD) development, their prognostic significance in patients with established PAD remains unclear. To evaluate whether elevated Lp(a) independently predicts short-term cardiovascular and limb outcomes in patients with established PAD. Using the TriNetX Research Network, we conducted a retrospective cohort study of adults with PAD between January 1, 2010, and January 1, 2025. Patients with Lp(a) measurements were stratified by Lp(a) levels (≥50 mg/dL vs <50 mg/dL). A 1:1 propensity score matching (PSM) controlled for demographics and cardiovascular comorbidities. Primary outcomes included 1-year rates of myocardial infarction, stroke, major adverse cardiovascular events (MACE), all-cause mortality, and major adverse limb events (MALE). Among 1,790,984 PAD patients, 3,397 (0.2%) had elevated Lp(a). After PSM, 2 balanced cohorts of 3,397 patients were analyzed. In the unmatched cohort, elevated Lp(a) was associated with higher rates of myocardial infarction, stroke, and MACE, but paradoxically lower all-cause mortality and major adverse limb events (MALE). However, in the matched cohort, these differences were no longer statistically significant, suggesting the initial findings were likely driven by baseline differences and confounding. In patients with established PAD, elevated Lp(a) was not independently associated with increased short-term cardiovascular or limb events after accounting for comorbidities. These findings suggest that Lp(a)’s prognostic value may be limited in secondary prevention settings but could remain relevant for primary prevention and risk stratification. Further prospective studies are needed to assess the utility of Lp(a)-lowering therapies in PAD populations.