Epidemiology
Elevated Lp(a) raises limb amputation risk more than 20-fold in peripheral artery disease, a systematic review of 493,650 subjects across 15 studies (Vasc Med 2022)
Original title: Elevated lipoprotein (a) levels and risk of peripheral artery disease outcomes: A systematic review
This PRISMA-guided systematic review (PROSPERO 289253) identified 15 eligible studies (493,650 subjects) examining elevated Lp(a) and peripheral artery disease (PAD) outcomes. The majority of studies found significant associations: elevated Lp(a) was linked to higher risk of incident claudication (RR 1.20), PAD progression (HR 1.41), restenosis (HR 6.10), PAD-related death and hospitalisation (HR 1.37), limb amputation (HR 22.75), and lower limb revascularisation (HR 1.29 to 2.90). Combined PAD outcomes showed HRs ranging from 1.14 to 2.80 across studies, even after adjusting for traditional risk factors, though heterogeneity in study populations and Lp(a) cut-offs limited precision. The findings support an independent, positive association between elevated Lp(a) and future PAD outcomes, including some of the most severe complications such as amputation.
Original abstract
Background: Despite strong association of elevated lipoprotein (a) (Lp(a)) levels with incident coronary and cerebrovascular disease, data for incident peripheral artery disease (PAD) are less robust. The main objective of the present systematic review was to analyze the association between elevated Lp(a) levels and PAD outcomes.
Methods: This systematic review was performed according to PRISMA guidelines. A literature search was performed to detect randomized clinical trials or observational studies with a cohort design that evaluated the association between Lp(a) levels and PAD outcomes.
Results: Fifteen studies including 493,650 subjects were identified and considered eligible for this systematic review. This systematic review showed that the vast majority of the studies reported a significant association between elevated Lp(a) levels and the risk of PAD outcomes. The elevated Lp(a) levels were associated with a higher risk of incident claudication (RR: 1.20), PAD progression (HR: 1.41), restenosis (HR: 6.10), death and hospitalization related to PAD (HR: 1.37), limb amputation (HR: 22.75), and lower limb revascularization (HR: 1.29 and 2.90). In addition, the presence of elevated Lp(a) values were associated with a higher risk of combined PAD outcomes, with HRs in a range between 1.14 and 2.80, despite adjusting for traditional risk factors. Heterogeneity of results can be explained by different patient populations studied and varying Lp(a) cut-off points of Lp(a) analyzed.
Conclusion: This systematic review suggests that evidence is available to support an independent positive association between Lp(a) levels and the risk of future PAD outcomes. PROSPERO Registration No.: 289253.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.