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

Author:

Arnold Markus1ORCID,Schweizer Juliane1,Nakas Christos T23ORCID,Schütz Valerie1,Westphal Laura P1ORCID,Inauen Corinne1,Pokorny Thomas1,Luft Andreas1,Leichtle Alexander2ORCID,Arnold Marcel4,Bicvic Antonela14ORCID,Fischer Urs4,De Marchis Gian Marco5,Bonati Leo H5ORCID,Müller Mandy D5,Kahles Timo6ORCID,Nedeltchev Krassen6,Cereda Carlo W7ORCID,Kägi Georg8,Bustamante Alejandro9,Montaner Joan9ORCID,Ntaios George10ORCID,Foerch Christian11ORCID,Spanaus Katharina12ORCID,von Eckardstein Arnold12,Katan Mira1ORCID

Affiliation:

1. Department for Neurology, University Hospital Zurich, Zurich, Switzerland

2. Department of Clinical Chemistry, Inselspital, University Hospital and University of Bern, Bern, Switzerland

3. Laboratory of Biometry, University of Thessaly, Volos, Greece

4. Department for Neurology, Inselspital, University Hospital and University of Bern, Bern, Switzerland

5. Department for Neurology & Stroke Center, University Hospital of Basel & University of Basel, Basel, Switzerland

6. Department of Neurology, Cantonal Hospital Aarau, Switzerland

7. Neurocentro della Svizzera Italiana, Stroke Center EOC, Lugano, Switzerland

8. Department of Neurology, Cantonal Hospital St, Gallen, Switzerland

9. Department for Neurology, Vall d'Hebron Institute of Research (VHIR), Universitat Autónoma de Barcelona, Spain

10. Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece

11. Department of Neurology, University Hospital of Frankfurt, Frankfurt am Main, Germany

12. Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland

Abstract

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.

Funder

Kurt und Senta Hermann Stiftung

Swiss National Science Foundation

EMDO foundation

Swiss Heart Foundation

University Hospital Zurich

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine

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