Top-quartile Lp(a) raises MACE risk 30% and limb-event risk 19% in peripheral artery disease patients, Mass General Brigham registry of 3,757 finds (Eur J Prev Cardiol 2025)

Original title: Association between lipoprotein(a) and cardiovascular events in patients with peripheral artery disease: the Mass General Brigham Lp(a) registry

Eur J Prev Cardiol · 18 September 2025 · 8

McClintick DJ, Biery DW, Berman AN, Besser S, Shiyovich A, Singh A, Huck DM, Weber BN, Cardoso R, Bonaca MP, Januzzi JL, Gerhard-Herman MD et al.

The Mass General Brigham Lp(a) registry, drawing on all individuals with Lp(a) measured at two tertiary care centres from 2000 to 2019, identified 3,757 patients with peripheral artery disease (39% female, median age 68, IQR 58-77), stratified into Lp(a) quartiles (Q1 at or below 14 nmol/L up to Q4 at 132-855 nmol/L), to assess the association with major adverse cardiovascular events (MACE) and major lower-extremity events (MALE). Compared with the lowest quartile, patients in the third and fourth quartiles had 24% and 30% higher adjusted MACE risk, respectively (adjusted HR 1.24, P = 0.005; adjusted HR 1.30, P = 0.001), and those in the fourth quartile had 19% higher MALE risk (adjusted HR 1.19, P = 0.043). This large, long-observed PAD cohort confirms elevated Lp(a) as a prognostic marker for both cardiovascular and limb-specific outcomes, supporting its measurement for risk stratification in this high-risk population.

Original abstract

Aims: Both lipoprotein(a) [Lp(a)] and peripheral artery disease (PAD) are associated with ischaemic events. We sought to assess the association between Lp(a) and major adverse cardiovascular events (MACE) and major lower extremity events (MALE) among patients with baseline PAD.

Methods And Results: The Mass General Brigham (MGB) Lp(a) registry includes all individuals with Lp(a) measured at two tertiary care centres from 2000 to 2019. Those with PAD were grouped according to Lp(a) percentile: 1st-25th [Q1, Lp(a) ≤ 14 nmol/L], 26th-50th (Q2, 14-<42 nmol/L), 51st-75th (Q3, 42-<132 nmol/L), and 76th-100th (Q4, 132-855 nmol/L). Outcomes were MACE [composite of cardiovascular (CV) death, myocardial infarction, or coronary revascularization] and MALE (composite of peripheral revascularization, acute limb ischaemia, or major lower extremity amputation). Cox proportional hazard modelling was used to assess the association between Lp(a) and the outcomes of interest after adjusting for traditional risk factors. Among 3757 individuals with PAD [39% female, median age 68 (IQR: 58-77)], individuals with Lp(a) levels in the third and fourth quartiles had a 24 and 30% increased hazard of MACE, respectively [adj. hazard ratio (HR): 1.24, P = 0.005; adj. HR: 1.30, P = 0.001] when compared with those in the first quartile. Individuals in the fourth quartile had a 19% greater hazard of MALE (adj. HR: 1.19, P = 0.043).

Conclusion: Elevated Lp(a) in patients with PAD was associated with an increased risk of both MACE and MALE. Accordingly, measurement of Lp(a) may convey important prognostic value and allow for further risk stratification within this high-risk population.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.