Adding Lp(a) boosts prediction of MACE and limb loss after lower-limb revascularisation in diabetic CLTI patients, pushing model AUC as high as 0.98 (Cardiovasc Diabetol 2025)

Original title: Prognostic value of lipoprotein(a) for cardiovascular events after lower limb revascularization in diabetic patients with chronic limb-threatening ischemia

Cardiovasc Diabetol · 10 July 2025 · 7

Biscetti F, Rando MM, Nicolazzi MA, Angelini F, Iezzi R, Eraso LH, Dimuzio PJ, Pitocco D, Massetti M, Gasbarrini A, Flex A

This prospective cohort study followed 158 patients with type 2 diabetes and chronic limb-threatening ischaemia undergoing lower extremity revascularisation over 12 months, to test Lp(a)'s prognostic value for major adverse cardiovascular events (MACE) and limb events (MALE). Events occurred in 74 patients (46.8%), who had markedly higher median Lp(a) than those without (48.0 vs. 8.1 mg/dL, P < 0.01). Lp(a) was independently associated with combined events (HR 1.07, 95% CI 1.04-1.10), MACE (HR 1.08, 95% CI 1.03-1.13), and MALE (HR 1.05, 95% CI 1.02-1.07), all P < 0.01; an empirical cutoff of 29.6 mg/dL conferred a 3.8-fold higher event risk. Adding Lp(a) to the base clinical model markedly improved predictive performance, raising the AUC from 0.74 to 0.98 for the composite outcome, from 0.81 to 0.89 for MACE, and from 0.78 to 0.92 for MALE. The authors conclude Lp(a) is a strong, independent predictor of both cardiovascular and limb outcomes in this high-risk diabetic revascularisation population.

Original abstract

Background: Chronic limb-threatening ischemia (CLTI) presents a major clinical challenge in patients with Type 2 Diabetes Mellitus (T2DM), requiring lower extremity revascularization (LER) to mitigate adverse cardiovascular and limb outcomes. Lipoprotein(a) (Lp(a)) has been implicated in cardiovascular risk, but its role in patients with T2DM and CLTI undergoing revascularization remains unclear. Thus, this study aimed to investigate the prognostic value of Lp(a) levels in diabetic CLTI patients for major adverse cardiovascular events (MACE), major adverse limb events (MALE), or both after LER.

Methods: In this prospective cohort study of 158 individuals with T2DM and CLTI undergoing LER, baseline clinical data were collected, including Lp(a) levels. Patients were followed for occurrence of MACE, MALE, or both over a 12-month period.

Results: During follow-up, 74 patients (46.8%) experienced events (MACE, MALE, or both). Patients with events had significantly higher median Lp(a) levels than those without (48.0 vs. 8.1 mg/dL, p < 0.01). Lp(a) was independently associated with adverse events (HR 1.07, 95% CI 1.04-1.10; p < 0.01). In multivariable analysis, elevated Lp(a) was independently associated with both MACE (HR 1.08, 95% CI 1.03-1.13; p < 0.01) and MALE (HR 1.05, 95% CI 1.02-1.07; p < 0.01). An empirical Lp(a) cutoff of 29.6 mg/dL conferred a 3.8-fold increased risk of events (p < 0.01). Kaplan-Meier survival analysis further confirmed a significantly higher cumulative incidence of events in patients with Lp(a) levels above cutoff (p < 0.01). ROC curve comparison analysis showed that the inclusion of Lp(a) significantly improved the predictive performance of the base clinical model (AUC from 0.74 to 0.98, p < 0.01 for composite outcome; from 0.81 to 0.89, p = 0.03 for MACE; and from 0.78 to 0.92, p < 0.01for MALE).

Conclusions: This study demonstrated that Lp(a) is a strong independent predictor of both cardiovascular and limb events in patients with T2DM undergoing LER for CLTI. These findings support the potential role of Lp(a) as a marker of residual risk in this high-risk population and suggest its utility in risk stratification.

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