Abstract 4142298: Association Between Lp(a) and Cardiovascular Events in Individuals with Peripheral Artery Disease in the Mass General Brigham Lp(a) Registry

Background: Both lipoprotein(a) [Lp(a)] and peripheral artery disease (PAD) are independently associated with atherosclerotic cardiovascular disease (ASCVD) events. Whether elevated Lp(a) provides additional risk stratification among individuals with PAD is less well-established. Methods: The Mass General Brigham (MGB) Lp(a) registry includes all individuals with Lp(a) measured at two tertiary care centers from 2000-2019. Those with a history of PAD were grouped into quartiles according to Lp(a) percentile: 1 st -25 th (Q1, Lp(a) ≤ 14nmol/L), 26 th -50 th (Q2, 14 - 42nmol/L), 51 st -75 th , (Q3, 42-132nmol/L), and 76 th -100 th (Q4, 132-855nmol/L). Outcomes were major adverse cardiovascular events (MACE: composite of cardiovascular death, myocardial infarction, ischemic stroke, or coronary revascularization) and major adverse limb events (MALE: composite of peripheral revascularization [endovascular or surgical], acute limb ischemia, or major lower extremity amputation). Cox proportional hazard modeling was used to assess the association between Lp(a) and the outcomes of interest. Analyses were adjusted for traditional risk factors. Results: Among 3,791 individuals with PAD, (39% female, median age 68 [IQR: 59-77]), 79% had hypertension, 81% had dyslipidemia, and 37% had diabetes. Relative to Q1, those in Q3 and Q4 had a 19% and 26% increased risk of MACE, respectively (adj. HR: 1.19, 95% CI 1.03-1.37, p=0.018; adj. HR: 1.26, 95% CI: 1.09-1.45, p=0.001, Fig, A ). Individuals in Q4 had a 23% higher risk of MALE (adj. HR: 1.23, 1.03-1.48, p=0.022, Fig, B ) relative to those in Q1. The overall event rate (per 1000 patient years) for MACE increased monotonically across all four subgroups while for MALE was increased only for those in the highest Lp(a) group. Conclusions: In individuals with PAD, Lp(a) levels provide additional prognostic information beyond traditional risk factors. Lp(a) above the 50 th percentile was associated with higher risk of MACE, while levels greater than 75 th percentile were associated with an increased risk of both MACE and MALE.