Lipoprotein (a) Level As a Risk Factor for Stroke and Its Subtype: A Systematic Review and Meta-analysis

Overview

Journal Sci Rep

Specialty Science

Date 2021 Aug 3

PMID 34341405

Citations 18

Authors

Pradeep Kumar

Priyanka Swarnkar

Shubham Misra

Manabesh Nath

Affiliations

Soon will be listed here.

Abstract

The role of lipoprotein-A [Lp (a)] as a risk factor for stroke is less well documented than for coronary heart disease. Hence, we conducted a systematic review and meta-analysis for the published observational studies in order to investigate the association of Lp (a) levels with the risk of stroke and its subtypes. In our meta-analysis, 41 studies involving 7874 ischemic stroke (IS) patients and 32,138 controls; 13 studies for the IS subtypes based on TOAST classification and 7 studies with 871 Intracerebral hemorrhage (ICH) cases and 2865 control subjects were included. A significant association between increased levels of Lp (a) and risk of IS as compared to control subjects was observed (standardized mean difference (SMD) 0.76; 95% confidence interval (CIs) 0.53-0.99). Lp (a) levels were also found to be significantly associated with the risk of large artery atherosclerosis (LAA) subtype of IS (SMD 0.68; 95% CI 0.01-1.34) as well as significantly associated with the risk of ICH (SMD 0.65; 95% CI 0.13-1.17) as compared to controls. Increased Lp (a) levels could be considered as a predictive marker for identifying individuals who are at risk of developing IS, LAA and ICH.

Citing Articles

Predicting new-onset stroke with machine learning: development of a model integrating traditional Chinese and western medicine.

Wang L, Shi J, Miao L, Chen Y, Wei J, Jia M Front Pharmacol. 2025; 16:1546878.

PMID: 40061953 PMC: 11885310. DOI: 10.3389/fphar.2025.1546878.

Lipoprotein(a) and thromboembolism: current state of knowledge and unsolved issues.

Konieczynska M, Natorska J, Zabczyk M, Undas A Arch Med Sci. 2025; 20(6):1770-1783.

PMID: 39967936 PMC: 11831339. DOI: 10.5114/aoms/197357.

Atherogenic circulating lipoproteins in ischemic stroke.

Benitez S, Puig N, Camps-Renom P, Sanchez-Quesada J Front Cardiovasc Med. 2024; 11:1470364.

PMID: 39713216 PMC: 11659270. DOI: 10.3389/fcvm.2024.1470364.

Lipoprotein (a): Underrecognized Risk with a Promising Future.

Manzato M, Wright R, Jaffe A, Vasile V Rev Cardiovasc Med. 2024; 25(11):393.

PMID: 39618878 PMC: 11607505. DOI: 10.31083/j.rcm2511393.

Frequency of lipoprotein(a) testing and its levels in Pakistani population.

Batool H, Khan M, Ain Q, Chughtai O, Khan M, Khan M Glob Cardiol Sci Pract. 2024; 2024(4):e202437.

PMID: 39351483 PMC: 11439424. DOI: 10.21542/gcsp.2024.37.

References

Schreiner P, Chambless L, Brown S, Watson R, Toole J, Heiss G . Lipoprotein(a) as a correlate of stroke and transient ischemic attack prevalence in a biracial cohort: the ARIC Study. Atherosclerosis Risk in Communities. Ann Epidemiol. 1994; 4(5):351-9. DOI: 10.1016/1047-2797(94)90068-x. View

Nguyen T, ELLEFSON R, Hodge D, Bailey K, Kottke T, Abu-Lebdeh H . Predictive value of electrophoretically detected lipoprotein(a) for coronary heart disease and cerebrovascular disease in a community-based cohort of 9936 men and women. Circulation. 1997; 96(5):1390-7. DOI: 10.1161/01.cir.96.5.1390. View

Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M . Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015; 4:1. PMC: 4320440. DOI: 10.1186/2046-4053-4-1. View

van Kooten F, van Krimpen J, Dippel D, Hoogerbrugge N, Koudstaal P . Lipoprotein(a) in patients with acute cerebral ischemia. Stroke. 1996; 27(7):1231-5. DOI: 10.1161/01.str.27.7.1231. View

Zhang W, Zhang X . Prognostic value of serum lipoprotein(a) levels in patients with acute ischemic stroke. Neuroreport. 2013; 25(4):262-6. DOI: 10.1097/WNR.0000000000000094. View

Tascilar N, Dursun A, Ankarali H, Mungan G, Sumbuloglu V, Ekem S . Relationship of apoE polymorphism with lipoprotein(a), apoA, apoB and lipid levels in atherosclerotic infarct. J Neurol Sci. 2008; 277(1-2):17-21. DOI: 10.1016/j.jns.2008.09.034. View

Aronis K, Zhao D, Hoogeveen R, Alonso A, Ballantyne C, Guallar E . Associations of Lipoprotein(a) Levels With Incident Atrial Fibrillation and Ischemic Stroke: The ARIC (Atherosclerosis Risk in Communities) Study. J Am Heart Assoc. 2017; 6(12). PMC: 5779047. DOI: 10.1161/JAHA.117.007372. View

Nave A, Lange K, Leonards C, Siegerink B, Doehner W, Landmesser U . Lipoprotein (a) as a risk factor for ischemic stroke: a meta-analysis. Atherosclerosis. 2015; 242(2):496-503. DOI: 10.1016/j.atherosclerosis.2015.08.021. View

de la Pena-Diaz A, Cardoso-Saldana G, Zamora-Gonzalez J, Barinagarrementeria F, Izaguirre R, Loyau S . Functional approach to investigate Lp(a) in ischaemic heart and cerebral diseases. Eur J Clin Invest. 2003; 33(2):99-105. DOI: 10.1046/j.1365-2362.2003.01114.x. View

10.

Slowik A, Iskra T, Turaj W, Hartwich J, Dembinska-Kiec A, Szczudlik A . LDL phenotype B and other lipid abnormalities in patients with large vessel disease and small vessel disease. J Neurol Sci. 2003; 214(1-2):11-6. DOI: 10.1016/s0022-510x(03)00166-7. View

11.

Santos-Silva A, Rebelo I, Castro E, Belo L, Catarino C, Monteiro I . Erythrocyte damage and leukocyte activation in ischemic stroke. Clin Chim Acta. 2002; 320(1-2):29-35. DOI: 10.1016/s0009-8981(02)00039-6. View

12.

Petersen N, Schmied A, Zeller J, Plendl H, Deuschl G, Zunker P . Lp(a) lipoprotein and plasminogen activity in patients with different etiology of ischemic stroke. Cerebrovasc Dis. 2006; 23(2-3):188-93. DOI: 10.1159/000097640. View

13.

Bevan S, Traylor M, Adib-Samii P, Malik R, Paul N, Jackson C . Genetic heritability of ischemic stroke and the contribution of previously reported candidate gene and genomewide associations. Stroke. 2012; 43(12):3161-7. DOI: 10.1161/STROKEAHA.112.665760. View

14.

Tang Y, Geng D . Associations of plasma LP(a), Hcy and D-D levels with the subtype of ischemic cerebrovascular disease. Medicine (Baltimore). 2019; 98(11):e14910. PMC: 6426500. DOI: 10.1097/MD.0000000000014910. View

15.

Albucher J, Ferrieres J, Ruidavets J, Guiraud-Chaumeil B, Perret B, Chollet F . Serum lipids in young patients with ischaemic stroke: a case-control study. J Neurol Neurosurg Psychiatry. 2000; 69(1):29-33. PMC: 1736997. DOI: 10.1136/jnnp.69.1.29. View

16.

Ferretti G, Bacchetti T, Johnston T, Banach M, Pirro M, Sahebkar A . Lipoprotein(a): A missing culprit in the management of athero-thrombosis?. J Cell Physiol. 2017; 233(4):2966-2981. DOI: 10.1002/jcp.26050. View

17.

Dhamija R, Gaba P, Arora S, Kaintura A, Kumar M, Bhattacharjee J . Homocysteine and lipoprotein (a) correlation in ischemic stroke patients. J Neurol Sci. 2009; 281(1-2):64-8. DOI: 10.1016/j.jns.2009.02.341. View

18.

Sun L, Li Z, Zhang H, Ma A, Liao Y, Wang D . Pentanucleotide TTTTA repeat polymorphism of apolipoprotein(a) gene and plasma lipoprotein(a) are associated with ischemic and hemorrhagic stroke in Chinese: a multicenter case-control study in China. Stroke. 2003; 34(7):1617-22. DOI: 10.1161/01.STR.0000078370.12085.02. View

19.

Fu H, Zhang D, Zhu R, Cui L, Qiu L, Lin S . Association between lipoprotein(a) concentration and the risk of stroke in the Chinese Han population: a retrospective case-control study. Ann Transl Med. 2020; 8(5):212. PMC: 7154407. DOI: 10.21037/atm.2020.01.38. View

20.

Rigal M, Ruidavets J, Viguier A, Petit R, Perret B, Ferrieres J . Lipoprotein (a) and risk of ischemic stroke in young adults. J Neurol Sci. 2006; 252(1):39-44. DOI: 10.1016/j.jns.2006.10.004. View