Elevated Lp(a) triples stroke-recurrence risk in patients under 60, the BIOSIGNAL study of 1,733 acute stroke patients (Eur Heart J 2021)

Original title: Lipoprotein(a) is associated with large artery atherosclerosis stroke aetiology and stroke recurrence among patients below the age of 60 years: results from the BIOSIGNAL study

Eur Heart J · 7 June 2021 · 8

Arnold M, Schweizer J, Nakas CT, Schütz V, Westphal LP, Inauen C, Pokorny T, Luft A, Leichtle A, Arnold M, Bicvic A, Fischer U et al.

In the prospective, multicentre BIOSIGNAL cohort of 1,733 primarily Caucasian (98.6%) patients with acute ischaemic stroke, Lp(a) measured within 24 hours of symptom onset was independently associated with large artery atherosclerosis (LAA) stroke aetiology (adjusted OR 1.48, 95% CI 1.14-1.90 per log10 Lp(a) increase), with age significantly modifying this association (P for interaction=0.031). In patients under 60, the adjusted odds ratio for LAA stroke was 3.64 (95% CI 1.76-7.52) per log10 Lp(a) increase, or 4.04 (95% CI 1.73-9.43) using the established cut-off of >=100 nmol/L. While Lp(a) was not associated with the 152 recurrent cerebrovascular events in the whole cohort, Lp(a) >=100 nmol/L was associated with increased recurrence risk in patients under 60 (adjusted HR 2.40, 95% CI 1.05-5.47), those with LAA stroke aetiology (HR 2.18, 95% CI 1.08-4.40), or those without known atrial fibrillation (HR 1.60, 95% CI 1.03-2.48). The findings identify elevated Lp(a) as a marker of large artery atherosclerosis stroke and recurrence risk specifically relevant to younger and arteriosclerotic stroke patients.

Original abstract

Aims: Lipoprotein(a) [Lp(a)] is a recognized causal risk factor for atherosclerotic cardiovascular disease but its role for acute ischaemic stroke (AIS) is controversial. In this study, we evaluated the association of Lp(a) with large artery atherosclerosis (LAA) stroke and risk of recurrent cerebrovascular events in AIS patients.

Methods And Results: For this analysis of the prospective, observational, multicentre BIOSIGNAL cohort study we measured Lp(a) levels in plasma samples of 1733 primarily Caucasian (98.6%) AIS patients, collected within 24 h after symptom onset. Primary outcomes were LAA stroke aetiology and recurrent cerebrovascular events (ischaemic stroke or transient ischaemic attack) within 1 year. We showed that Lp(a) levels are independently associated with LAA stroke aetiology [adjusted odds ratio 1.48, 95% confidence interval (CI) 1.14-1.90, per unit log10Lp(a) increase] and identified age as a potent effect modifier (Pinteraction =0.031) of this association. The adjusted odds ratio for LAA stroke in patients aged <60 years was 3.64 (95% CI 1.76-7.52) per unit log10Lp(a) increase and 4.04 (95% CI 1.73-9.43) using the established cut-off ≥100 nmol/l. For 152 recurrent cerebrovascular events, we did not find a significant association in the whole cohort. However, Lp(a) levels ≥100 nmol/l were associated with an increased risk for recurrent events among patients who were either <60 years [adjusted hazard ratio (HR) 2.40, 95% CI 1.05-5.47], had evident LAA stroke aetiology (adjusted HR 2.18, 95% CI 1.08-4.40), or had no known atrial fibrillation (adjusted HR 1.60, 95% CI 1.03-2.48).

Conclusion: Elevated Lp(a) was independently associated with LAA stroke aetiology and risk of recurrent cerebrovascular events among primarily Caucasian individuals aged <60 years or with evident arteriosclerotic disease.

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