Elevated Lp(a) associated with large artery atherosclerosis stroke and risk of recurrent stroke

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

Literature - Arnold M, Schweizer J, Nakas CT et al. - Eur Heart J. 2021 Mar 8;ehab081. doi: 10.1093/eurheartj/ehab081.

Introduction and methods

Up to 25% of strokes are recurrent strokes which are more likely to be fatal or lead to disability compared to first strokes [1]. Optimal secondary prevention depends on the underlying etiology of the stroke. However, the underlying etiology remains undetermined in approximately 30% of cases [2]. Especially in a younger population, recognized vascular risk factors may not have developed yet but so far unknown risk factors may play a role in the development of stroke. There is a growing body of evidence that Lp(a) is causally associated with ASCVD [3-9]. However, evidence of the association of Lp(a) with stroke recurrence or stroke etiology is scarce. This study investigated the association of Lp(a) with large artery atherosclerosis (LAA) stroke and risk of recurrent cerebrovascular events (acute ischemic stroke [AIS] or TIA) within 1 year after index AIS.

BIOSIGNAL is a prospective, observational, multicenter cohort study to evaluate selected blood biomarkers in 1759 patients with AIS. Blood biomarkers were measured within 24h from symptom onset. Median age was 74 (IQR 64–82) years, 342 (19.4%) participants were <60 years, 736 (42%) were female and 1711 (98.6%) were Caucasian. Outcomes were LAA stroke according to the TOAST (Trial of Org 10172 in Acute Stroke Treatment) [10] and CCS (Causative Classification System) [11] classification on hospital discharge and time to recurrent ischemic cerebrovascular event (AIS or TIA) during 1-year follow-up after the index stroke.

Main results

  • Lp(a) was independently associated with LAA stroke etiology (adjusted OR 1.48, 95%CI 1.14-1.90, per unit log10-Lp(a) increase).
  • There was a significant interaction between Lp(a) and age for LAA stroke in the multivariable model (P for interaction=0.031). The adjusted OR for LAA stroke in patients <60 years was 3.64 (95%CI 1.76-7.52, P< 0.001, per unit log10 Lp(a) increase). In contrast, in patients aged ≥60 years the association was not significant (adjusted OR 1.26, 95%CI 0.96-1.64, P=0.1).
  • When Lp(a) was used as a dichotomized variable with a cut-off value of 100 nmol/l, the adjusted OR for LAA stroke was 1.77 (95%CI 1.26–2.47, P<0.01) in the whole cohort, 4.04 (95% CI 1.73-9.43, P<0.01) in patients aged <60 years and 1.48 (95%CI 1.02-2.13, P=0.04) in patients aged ≥60 years.
  • In total 152 (8.64%) of patients experienced an AIS (n=116) or TIA (n=36) during 1-year follow-up after the index stroke.
  • There was no significant association between dichotomized Lp(a) with a cut-off level of 100 nmol/l and the occurrence of a recurrent ischemic cerebrovascular event in the whole cohort (HR 1.40, 95%CI 0.94-2.07, P=0.09). However, a significant association with AIS or TIA was found in patients aged >60 years (adjusted HR 2.4, 95%CI 1.05-5.47, P=0.04) independent of etiological classification. There was no significant association between dichotomized Lp(a) and recurrence of an ischemic cerebrovascular event in patients aged ≥60 years (adjusted HR 1.23, 95%CI 0.78-1.92, P=0.37).
  • Lp(a) levels ≥100 nmol/l were associated with recurrent cerebrovascular events in patients with a LAA stroke etiology (adjusted HR 2.18, 95%CI 1.08–4.40, P=0.03), but not in patients with non-LAA strokes. Lp(a) levels ≥100 nmol/l were also associated with recurrent cerebrovascular events in patients without an AF diagnosis (adjusted HR 1.60, 95%CI 1.03–2.48, P=0.04), whereas no significant association was found in patients with known or newly diagnosed AF.


Elevated Lp(a) was independently associated with LAA stroke etiology and risk of recurrent AIS or TIA in patients <60 years.


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Find this article online at Am Heart J.

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