Lp(a) raises ischemic stroke risk by about a third, especially in younger patients, a meta-analysis of 20 studies and 90,904 subjects (Atherosclerosis 2015)

Original title: Lipoprotein (a) as a risk factor for ischemic stroke: a meta-analysis

Atherosclerosis · 15 August 2015 · 7

Nave AH, Lange KS, Leonards CO, Siegerink B, Doehner W, Landmesser U, Steinhagen-Thiessen E, Endres M, Ebinger M

This meta-analysis pooled 20 studies comprising 90,904 subjects and 5029 stroke events to determine Lp(a) association with ischemic stroke. Comparing high with low Lp(a), the pooled odds ratio was 1.41 (95% CI 1.26-1.57) across 11 case-control studies, and the pooled risk ratio was 1.29 (95% CI 1.06-1.58) across 9 prospective studies. Study populations with a mean age of 55 or younger showed a higher risk ratio than older populations, while sex-specific risk differences were inconsistent between case-control and prospective designs. The findings show elevated Lp(a) is an independent risk factor for ischemic stroke, potentially more relevant in younger stroke patients, though sex-specific differences and further subgroup research remain open questions.

Original abstract

Objective: Lipoprotein (a) [Lp(a)] harbors atherogenic potential but its role as a risk factor for ischemic stroke remains controversial. We conducted a meta-analysis to determine the relative strength of the association between Lp(a) and ischemic stroke and identify potential subgroup-specific risk differences.

Methods: A systematic search using the MeSH terms "lipoproteins" OR "lipoprotein a" AND "stroke" was performed in PubMed and ScienceDirect for case-control studies from June 2006 and prospective cohort studies from April 2009 until December 20th 2014. Data from eligible papers published before these dates were reviewed and extracted from previous meta-analyses. Studies that assessed the relationship between Lp(a) levels and ischemic stroke and reported generic data-i.e. odds ratio [OR], hazard ratio, or risk ratio [RR]-were eligible for inclusion. Studies that not distinguish between ischemic and hemorrhagic stroke and transient ischemic attack were excluded. Random effects meta-analyses with mixed-effects meta-regression were performed by pooling adjusted OR or RR.

Results: A total of 20 articles comprising 90,904 subjects and 5029 stroke events were eligible for the meta-analysis. Comparing high with low Lp(a) levels, the pooled estimated OR was 1.41 (95% CI, 1.26-1.57) for case-control studies (n = 11) and the pooled estimated RR was 1.29 (95% CI, 1.06-1.58) for prospective studies (n = 9). Sex-specific differences in RR were inconsistent between case-control and prospective studies. Study populations with a mean age of ≤55 years had an increased RR compared to older study populations. Reported Lp(a) contrast levels and ischemic stroke subtype significantly contributed to the heterogeneity observed in the analyses.

Conclusion: Elevated Lp(a) is an independent risk factor for ischemic stroke and may be especially relevant for young stroke patients. Sex-specific risk differences remain conflicting. Further studies in these subgroups may be warranted.

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