Lp(a) predicts peripheral artery disease and coronary disease but not stroke, the EPIC-Norfolk study of 18 720 adults (Arterioscler Thromb Vasc Biol 2012)

Original title: Lipoprotein(a) and risk of coronary, cerebrovascular, and peripheral artery disease: the EPIC-Norfolk prospective population study

Arterioscler Thromb Vasc Biol · 11 October 2012 · 8

Gurdasani D, Sjouke B, Tsimikas S, Hovingh GK, Luben RN, Wainwright NW, Pomilla C, Wareham NJ, Khaw KT, Boekholdt SM, Sandhu MS

This EPIC-Norfolk prospective cohort study measured Lp(a) in 18 720 apparently healthy participants to examine its association with peripheral artery disease (PAD), coronary artery disease (CAD), and ischemic stroke, over 212 981 person-years, during which 2365 CAD, 284 ischemic stroke, and 596 PAD events occurred. Each 2.7-fold increase in Lp(a) was associated with increased risk of PAD (hazard ratio 1.37, 95% CI 1.25-1.50) and CAD (hazard ratio 1.13, 95% CI 1.04-1.22), but not ischemic stroke (hazard ratio 0.91, 95% CI 0.79-1.03), with LDL cholesterol not modifying these associations. The findings show Lp(a) predicts future PAD and CAD events, independent of LDL cholesterol, but not ischemic stroke.

Original abstract

Objective: Although the association between circulating levels of lipoprotein(a) [Lp(a)] and risk of coronary artery disease (CAD) and stroke is well established, its role in risk of peripheral arterial disease (PAD) remains unclear. Here, we examine the association between Lp(a) levels and PAD in a large prospective cohort. To contextualize these findings, we also examined the association between Lp(a) levels and risk of stroke and CAD and studied the role of low-density lipoprotein as an effect modifier of Lp(a)-associated cardiovascular risk.

Methods And Results: Lp(a) levels were measured in apparently healthy participants in the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort. Cox regression was used to quantify the association between Lp(a) levels and risk of PAD, stroke, and CAD outcomes. During 212 981 person-years at risk, a total of 2365 CAD, 284 ischemic stroke, and 596 PAD events occurred in 18 720 participants. Lp(a) was associated with PAD and CAD outcomes but not with ischemic stroke (hazard ratio per 2.7-fold increase in Lp(a) of 1.37, 95% CI 1.25-1.50, 1.13, 95% CI 1.04-1.22 and 0.91, 95% CI 0.79-1.03, respectively). Low-density lipoprotein cholesterol levels did not modify these associations.

Conclusions: Lp(a) levels were associated with future PAD and CAD events. The association between Lp(a) and cardiovascular disease was not modified by low-density lipoprotein cholesterol levels.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.